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  1. Chelation Therapy for Mercury Poisoning

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    Rong Guan

    2009-01-01

    Full Text Available Chelation therapy has been the major treatment for heavy metal poisoning. Various chelating agents have been developed and tested for treatment of heavy metal intoxications, including mercury poisoning. It has been clearly shown that chelating agents could rescue the toxicity caused by heavy metal intoxication, but the potential preventive role of chelating agents against heavy metal poisoning has not been explored much. Recent paper by Siddiqi and colleagues has suggested a protective role of chelating agents against mercury poisoning, which provides a promising research direction for broader application of chelation therapy in prevention and treatment of mercury poisoning.

  2. Chelation Therapy for Mercury Poisoning

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    Rong Guan; Han Dai

    2009-01-01

    Chelation therapy has been the major treatment for heavy metal poisoning. Various chelating agents have been developed and tested for treatment of heavy metal intoxications, including mercury poisoning. It has been clearly shown that chelating agents could rescue the toxicity caused by heavy metal intoxication, but the potential preventive role of chelating agents against heavy metal poisoning has not been explored much. Recent paper by Siddiqi and colleagues has suggested a protective role o...

  3. Combination therapies in iron chelation

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    Raffaella Origa

    2014-12-01

    Full Text Available The availability of oral iron chelators and new non-invasive methods for early detection and treatment of iron overload, have significantly improved the life expectancy and quality of life of patients with b thalassemia major. However, monotherapy is not effective in all patients for a variety of reasons. We analyzed the most relevant reports recently published on alternating or combined chelation therapies in thalassemia major with special attention to safety aspects and to their effects in terms of reduction of iron overload in different organs, improvement of complications, and survival. When adverse effects, such as gastrointestinal upset with deferasirox or infusional site reactions with deferoxamine are not tolerable and organ iron is in an acceptable range, alternating use of two chelators (drugs taken sequentially on different days, but not taken on the same day together may be a winning choice. The association deferiprone and deferoxamine should be the first choice in case of heart failure and when dangerously high levels of cardiac iron exist. Further research regarding the safety and efficacy of the most appealing combination treatment, deferiprone and deferasirox, is needed before recommendations for routine clinical practice can be made.

  4. Metal ions, Alzheimer's disease and chelation therapy.

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    Budimir, Ana

    2011-03-01

    In the last few years, various studies have been providing evidence that metal ions are critically involved in the pathogenesis of major neurological diseases (Alzheimer, Parkinson). Metal ion chelators have been suggested as potential therapies for diseases involving metal ion imbalance. Neurodegeneration is an excellent target for exploiting the metal chelator approach to therapeutics. In contrast to the direct chelation approach in metal ion overload disorders, in neurodegeneration the goal seems to be a better and subtle modulation of metal ion homeostasis, aimed at restoring ionic balance. Thus, moderate chelators able to coordinate deleterious metals without disturbing metal homeostasis are needed. To date, several chelating agents have been investigated for their potential to treat neurodegeneration, and a series of 8-hydroxyquinoline analogues showed the greatest potential for the treatment of neurodegenerative diseases.

  5. Importance of iron chelation therapy

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    A. Varoğlu

    2011-12-01

    Full Text Available It is necessary to remember that today patients have different options of chelation treatment, as desferrioxamine, deferiprone and deferasirox are available. However, a patient has to be compliant with treatments. They have always to remember that too much iron causes different complications and could be a barrier for a definitive cure from thalassemia. 由于出现了去铁胺、去铁酮和去铁斯若等药物,病人现在可以选择不同的螯合治疗方式。 然而,病人必须适应这几种治疗方式。 他们必须时刻记住太多的铁元素会引发多种并发症,并对地中海贫血的彻底治疗造成阻碍。

  6. IRON CHELATION THERAPY IN THALASSEMIA SYNDROMES

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    Paolo Cianciulli

    2009-06-01

    Full Text Available Transfusional hemosiderosis is a frequent complication in patients with transfusion dependent chronic diseases such as  thalassemias and severe type of sickle cell diseases. As there are no physiological mechanisms to excrete the iron contained in transfused red cells (1 unit of blood contains approximately 200 mg of iron the excess of iron is stored in various organs. Cardiomyopathy is the most severe complication covering more than 70% of the causes of death of thalassemic patients. Although the current reference standard iron chelator deferoxamine (DFO has been used clinically for over four decades, its effectiveness is limited by a demanding therapeutic regimen that leads to poor compliance. Despite poor compliance, because of the inconvenience of subcutaneous infusion, DFO improved considerably the survival and quality of life of patients with thalassemia. Deferiprone since 1998 and Deferasirox since 2005 were licensed for clinical use. The oral chelators have a better compliance because of oral use, a comparable efficacy to DFO in iron excretion and probably a better penetration to myocardial cells. Considerable increase in iron excretion was documented with combination therapy of DFO and Deferiprone. The proper use of the three chelators will improve the prevention and treatment of iron overload, it will reduce  complications, and improve survival and quality of life of transfused patients

  7. Myelodysplastic Syndromes and Iron Chelation Therapy

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    Angelucci, Emanuele; Urru, Silvana Anna Maria; Pilo, Federica; Piperno, Alberto

    2017-01-01

    Over recent decades we have been fortunate to witness the advent of new technologies and of an expanded knowledge and application of chelation therapies to the benefit of patients with iron overload. However, extrapolation of learnings from thalassemia to the myelodysplastic syndromes (MDS) has resulted in a fragmented and uncoordinated clinical evidence base. We’re therefore forced to change our understanding of MDS, looking with other eyes to observational studies that inform us about the relationship between iron and tissue damage in these subjects. The available evidence suggests that iron accumulation is prognostically significant in MDS, but levels of accumulation historically associated with organ damage (based on data generated in the thalassemias) are infrequent. Emerging experimental data have provided some insight into this paradox, as our understanding of iron-induced tissue damage has evolved from a process of progressive bulking of organs through high-volumes iron deposition, to one of ‘toxic’ damage inflicted through multiple cellular pathways. Damage from iron may, therefore, occur prior to reaching reference thresholds, and similarly, chelation may be of benefit before overt iron overload is seen. In this review, we revisit the scientific and clinical evidence for iron overload in MDS to better characterize the iron overload phenotype in these patients, which differs from the classical transfusional and non-transfusional iron overload syndrome. We hope this will provide a conceptual framework to better understand the complex associations between anemia, iron and clinical outcomes, to accelerate progress in this area. PMID:28293409

  8. Nanoparticle and iron chelators as a potential novel Alzheimer therapy.

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    Liu, Gang; Men, Ping; Perry, George; Smith, Mark A

    2010-01-01

    Current therapies for Alzheimer disease (AD) such as the acetylcholinesterase inhibitors and the latest NMDA receptor inhibitor, Namenda, provide moderate symptomatic delay at various stages of the disease, but do not arrest the disease progression or bring in meaningful remission. New approaches to the disease management are urgently needed. Although the etiology of AD is largely unknown, oxidative damage mediated by metals is likely a significant contributor since metals such as iron, aluminum, zinc, and copper are dysregulated and/or increased in AD brain tissue and create a pro-oxidative environment. This role of metal ion-induced free radical formation in AD makes chelation therapy an attractive means of dampening the oxidative stress burden in neurons. The chelator desferrioxamine, FDA approved for iron overload, has shown some benefit in AD, but like many chelators, it has a host of adverse effects and substantial obstacles for tissue-specific targeting. Other chelators are under development and have shown various strengths and weaknesses. Here, we propose a novel system of chelation therapy through the use of nanoparticles. Nanoparticles conjugated to chelators show unique ability to cross the blood-brain barrier (BBB), chelate metals, and exit through the BBB with their corresponding complexed metal ions. This method may provide a safer and more effective means of reducing the metal load in neural tissue, thus attenuating the harmful effects of oxidative damage and its sequelae. Experimental procedures are presented in this chapter.

  9. Μethods of iron chelation therapy: a bibliographic review

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    Maria Agapiou

    2012-01-01

    Full Text Available "Iron Chelation Therapy" is a term used to describe the procedure of removing excess iron from the body, which is applied after a total of approximately 20 blood transfusions or when serum ferritin levels rise above 1000 ng/ml. Aim: The purpose of the present paper is a retrospective search in bibliography, concerning the methods of iron chelation treatment for patients with hemochromatosis owing to their undergoing multiple blood transfusions. Method: The methology followed, included the search for review and research studies, in electronic databases as well as scientific haematology journals, mostly regarding recent entries in greek and international bibliography. Results: According to the bibliography, chelation therapy compounds have significantly changed the patients' clinical features and have substantially improved their quality of life, along with their outcome over time. However, the level of patient compliance to treatment still remains the basic problem of iron chelation therapy. Conclusions: Even though the discovery of orally administered chelating agents can qualify as an auspicious accomplishment, research fields should cover a much wider spectrum, in order to improve the effectiveness of iron chelation treatment.

  10. Efficacy of chelation therapy to remove aluminium intoxication.

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    Fulgenzi, Alessandro; De Giuseppe, Rachele; Bamonti, Fabrizia; Vietti, Daniele; Ferrero, Maria Elena

    2015-11-01

    There is a distinct correlation between aluminium (Al) intoxication and neurodegenerative diseases (ND). We demonstrated how patients affected by ND showing Al intoxication benefit from short-term treatment with calcium disodium ethylene diamine tetraacetic acid (EDTA) (chelation therapy). Such therapy further improved through daily treatment with the antioxidant Cellfood. In the present study we examined the efficacy of long-term treatment, using both EDTA and Cellfood. Slow intravenous treatment with the chelating agent EDTA (2 g/10 mL diluted in 500 mL physiological saline administered in 2 h) (chelation test) removed Al, which was detected (using inductively coupled plasma mass spectrometry) in urine samples collected from patients over 12 h. Patients that revealed Al intoxication (expressed in μg per g creatinine) underwent EDTA chelation therapy once a week for ten weeks, then once every two weeks for a further six or twelve months. At the end of treatment (a total of 22 or 34 chelation therapies, respectively), associated with daily assumption of Cellfood, Al levels in the urine samples were analysed. In addition, the following blood parameters were determined: homocysteine, vitamin B12, and folate, as well as the oxidative status e.g. reactive oxygen species (ROS), total antioxidant capacity (TAC), oxidized LDL (oxLDL), and glutathione. Our results showed that Al intoxication reduced significantly following EDTA and Cellfood treatment, and clinical symptoms improved. After treatment, ROS, oxLDL, and homocysteine decreased significantly, whereas vitamin B12, folate and TAC improved significantly. In conclusion, our data show the efficacy of chelation therapy associated with Cellfood in subjects affected by Al intoxication who have developed ND.

  11. Iron Chelation

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    Skip to main content Menu Donate Treatments Therapies Iron Chelation Iron chelation therapy is the main treatment ... have iron overload and need treatment. What is iron overload? Iron chelation therapy is used when you ...

  12. REGIONAL SIDEROSIS: A NEW CHALLENGE FOR IRON CHELATION THERAPY

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    Zvi Ioav Cabantchik

    2013-12-01

    Full Text Available The traditional role of iron chelation therapy has been to reduce body iron burden via chelation of excess metal from organs and fluids and its excretion via biliary-fecal and/or urinary routes. In their present use for hemosiderosis, chelation regimens might not be suitable for treating disorders of iron maldistribution, as those are characterized by toxic islands of siderosis appearing in a background of normal or subnormal iron levels (e.g. sideroblastic anemias, neuro- and cardio-siderosis in Friedreich ataxia- and neurosiderosis in Parkinson’s disease. We aimed at clearing local siderosis from aberrant labile metal that promotes oxidative damage, without interfering with essential local functions or with hematological iron-associated properties. For this purpose we introduced a conservative mode of iron chelation based on dual activity based on scavenging labile metal but also redeploying it to cell acceptors or to physiological transferrin. The scavenging and redeployment mode of action was designed both for correcting aberrant iron distribution and also for minimizing/preventing systemic loss of chelated metal. We first examine cell models that recapitulate iron maldistribution and associated dysfunctions identified with Friedreich ataxia and Parkinson’s disease and use them to explore the ability of the double-acting agent deferiprone, an orally active chelator, to mediate iron scavenging and redeployment and thereby causing functional improvement. We subsequently evaluate the concept in translational models of disease and finally assess its therapeutic potential in prospective double-blind pilot clinical trials. We claim that any chelator applied to diseases of regional siderosis, cardiac, neuronal or endocrine ought to preserve both systemic and regional iron levels. The proposed deferiprone-based therapy has provided a paradigm for treating regional types of siderosis without affecting hematological parameters and systemic

  13. Chelation therapy in intoxications with mercury, lead and copper

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    Cao, yang; Skaug, Marit Aralt; Andersen, Ole;

    2015-01-01

    mobilize deposits of mercury as well as of lead into the urine. These drugs can be administered orally and have relatively low toxicity compared to the classical antidote dimercaptopropanol (BAL). d-Penicillamine has been widely used in copper overload, although 2,3-dimercaptosuccinic acid......In the present review we provide an update of the appropriate use of chelating agents in the treatment of intoxications with compounds of mercury, lead and copper. The relatively new chelators meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto-propanesulphonate (DMPS) can effectively...... or tetrathiomolybdate may be more suitable alternatives today. In copper-toxicity, a free radical scavenger might be recommended as adjuvant to the chelator therapy...

  14. Combined Chelation Therapy with Deferasirox and Deferoxamine in Thalassemia

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    Lal, Ashutosh; Porter, John; Sweeters, Nancy; Ng, Vivian; Evans, Patricia; Neumayr, Lynne; Kurio, Gregory; Harmatz, Paul; Vichinsky, Elliott

    2012-01-01

    Iron overload is the primary cause of mortality and morbidity in thalassemia major despite advances in chelation therapy. We performed a pilot clinical trial to evaluate the safety and efficacy of combined therapy with deferasirox (DFX, 20-30 mg/kg daily) and deferoxamine (DFO, 35-50 mg/kg on 3-7 days/week) in 22 patients with persistent iron overload or organ damage. In the 18 subjects completing 12 months of therapy, median liver iron concentration decreased by 31% from 17.4 mg/g (range 3.9...

  15. Red Blood Cell Transfusion Independence Following the Initiation of Iron Chelation Therapy in Myelodysplastic Syndrome

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    Maha A. Badawi

    2010-01-01

    Full Text Available Iron chelation therapy is often used to treat iron overload in patients requiring transfusion of red blood cells (RBC. A 76-year-old man with MDS type refractory cytopenia with multilineage dysplasia, intermediate-1 IPSS risk, was referred when he became transfusion dependent. He declined infusional chelation but subsequently accepted oral therapy. Following the initiation of chelation, RBC transfusion requirement ceased and he remained transfusion independent over 40 months later. Over the same time course, ferritin levels decreased but did not normalize. There have been eighteen other MDS patients reported showing improvement in hemoglobin level with iron chelation; nine became transfusion independent, nine had decreased transfusion requirements, and some showed improved trilineage myelopoiesis. The clinical features of these patients are summarized and possible mechanisms for such an effect of iron chelation on cytopenias are discussed.

  16. Brazilian Thalassemia Association protocol for iron chelation therapy in patients under regular transfusion

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    Monica Pinheiro de Almeida Verissimo

    2013-01-01

    Full Text Available In the absence of an iron chelating agent, patients with beta-thalassemia on regular transfusions present complications of transfusion-related iron overload. Without iron chelation therapy, heart disease is the major cause of death; however, hepatic and endocrine complications also occur. Currently there are three iron chelating agents available for continuous use in patients with thalassemia on regular transfusions (desferrioxamine, deferiprone, and deferasirox providing good results in reducing cardiac, hepatic and endocrine toxicity. These practice guidelines, prepared by the Scientific Committee of Associação Brasileira de Thalassemia (ABRASTA, presents a review of the literature regarding iron overload assessment (by imaging and laboratory exams and the role of T2* magnetic resonance imaging (MRI to control iron overload and iron chelation therapy, with evidence-based recommendations for each clinical situation. Based on this review, the authors propose an iron chelation protocol for patients with thalassemia under regular transfusions.

  17. MRI marrow observations in thalassemia: the effects of the primary disease, transfusional therapy, and chelation

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    Levin, T.L. [Department of Pediatric Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital, New York, NY (United States); Sheth, S.S. [Department of Pediatrics, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital, 3959 Broadway, New York, NY 10032 (United States); Ruzal-Shapiro, C. [Department of Pediatric Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital, New York, NY (United States); Abramson, S. [Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Piomelli, S. [Department of Pediatrics, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital, 3959 Broadway, New York, NY 10032 (United States); Berdon, W.E. [Department of Pediatric Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital, New York, NY (United States)

    1995-11-01

    The magnetic resonance bone marrow patterns in thalassemia were evaluated to determine changes produced by transfusion and chelation therapy. Thirteen patients had T1- and T2-weighted images of the spine, pelvis and femurs. Three received no therapy (age range 2.5-3 years). Three were ``hypertransfused`` (transfused to maintain a hemoglobin greater than 10 g/dl) and not chelated because of age (age range 6 months-8 years). Seven were ``hypertransfused`` and chelated (age range 12-35 years). Signal characteristics of marrow were compared with those of surrounding muscle and fat. Fatty marrow (isointense with subcutaneous fat) was compared with red marrow (hypointense to fat and slightly hyperintense to muscle). Marrow hypointense to muscle was identified as iron deposition within red marrow. The untreated group demonstrated signal consistent with red marrow throughout the central and peripheral skeleton. Hypertransfused but not chelated patients demonstrated marked iron deposition in the central and peripheral skeleton. Hypertransfused and chelated patients demonstrated iron deposition in the central skeleton and a mixed appearance of marrow in the peripheral skeleton. The MR appearance of marrow in thalassemia is a reflection of the patient`s transfusion and chelation therapy. Iron deposition occurs despite chelation therapy in sites of active red marrow. As red marrow retreats centrally with age, so does the pattern of iron deposition. The long-term biological effects of this iron deposition are unknown. (orig.). With 8 figs., 1 tab.

  18. Chelation therapy and cardiovascular disease: connecting scientific silos to benefit cardiac patients.

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    Peguero, Julio G; Arenas, Ivan; Lamas, Gervasio A

    2014-08-01

    Medical practitioners have treated atherosclerotic disease with chelation therapy for over 50 years. Lack of strong of evidence led conventional practitioners to abandon its use in the 1960s and 1970s. This relegated chelation therapy to complementary and alternative medicine practitioners, who reported good anecdotal results. Concurrently, the epidemiologic evidence linking xenobiotic metals with cardiovascular disease and mortality gradually accumulated, suggesting a plausible role for chelation therapy. On the basis of the continued use of chelation therapy without an evidence base, the National Institutes of Health released a Request for Applications for a definitive trial of chelation therapy. The Trial to Assess Chelation Therapy (TACT) was formulated as a 2 × 2 factorial randomized controlled trial of intravenous EDTA-based chelation vs. placebo and high-dose oral multivitamins and multiminerals vs. oral placebo. The composite primary endpoint was death, reinfarction, stroke, coronary revascularization, or hospitalization for angina. A total of 1708 post-MI patients who were 50 years or older with a creatinine of 2.0 or less were enrolled and received 55,222 infusions of disodium EDTA or placebo with a median follow-up of 55 months. Patients were on evidence-based post-MI medications including statins. EDTA proved to be safe. EDTA chelation therapy reduced cardiovascular events by 18%, with a 5-year number needed to treat (NNT) of 18. Prespecified subgroup analysis revealed a robust benefit in patients with diabetes mellitus with a 41% reduction in the primary endpoint (5-year NNT = 6.5), and a 43% 5-year relative risk reduction in all-cause mortality (5-year NNT = 12). The magnitude of benefit is such that it suggests urgency in replication and implementation, which could, due to the excellent safety record, occur simultaneously.

  19. Iron chelation therapy in transfusion-dependent thalassemia patients: current strategies and future directions

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    Saliba AN

    2015-06-01

    Full Text Available Antoine N Saliba, Afif R Harb, Ali T Taher Department of Internal Medicine, Division of Hematology/Oncology, American University of Beirut, Beirut, Lebanon Abstract: Transfusional iron overload is a major target in the care of patients with transfusion-dependent thalassemia (TDT and other refractory anemias. Iron accumulates in the liver, heart, and endocrine organs leading to a wide array of complications. In this review, we summarize the characteristics of the approved iron chelators, deferoxamine, deferiprone, and deferasirox, and the evidence behind the use of each, as monotherapy or as part of combination therapy. We also review the different guidelines on iron chelation in TDT. This review also discusses future prospects and directions in the treatment of transfusional iron overload in TDT whether through innovation in chelation or other therapies, such as novel agents that improve transfusion dependence. Keywords: thalassemia, transfusion-dependent thalassemia, iron overload, iron chelation therapy, transfusion

  20. Chelation therapy in Wilson's disease: from D-penicillamine to the design of selective bioinspired intracellular Cu(I) chelators.

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    Delangle, Pascale; Mintz, Elisabeth

    2012-06-01

    Wilson's disease is an orphan disease due to copper homeostasis dysfunction. Mutations of the ATP7B gene induces an impaired functioning of a Cu-ATPase, impaired Cu detoxification in the liver and copper overload in the body. Indeed, even though copper is an essential element, which is used as cofactor by many enzymes playing vital roles, it becomes toxic when in excess as it promotes cytotoxic reactions leading to oxidative stress. In this perspective, human copper homeostasis is first described in order to explain the mechanisms promoting copper overload in Wilson's disease. We will see that the liver is the main organ for copper distribution and detoxification in the body. Nowadays this disease is treated life-long by systemic chelation therapy, which is not satisfactory in many cases. Therefore the design of more selective and efficient drugs is of great interest. A strategy to design more specific chelators to treat localized copper accumulation in the liver will then be presented. In particular we will show how bioinorganic chemistry may help in the design of such novel chelators by taking inspiration from the biological copper cell transporters.

  1. ELECTED PROBLEMS RELATED TO ENVIRONMENTAL HEAVY METALS EXPOSURE AND CHELATION THERAPY

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    Anna Skoczyńska

    2010-09-01

    Full Text Available Background: Exposure to heavy metals leads to functional and metabolic disturbances and many of them are included in pathogenesis of common diseases (arterial hypertension, atherosclerosis, neurodegenerative processes. In this context new therapeutic and prophylactic strategies are necessary. Patients diagnosed with chronic heavy metals intoxication usually require chelation to increase mobilisation of metals from tissues and elimination of them via urine. Acute poisoning with toxic metal may be difficult to diagnosis, especially in case of accidental intoxication or suicidal intention. Patients also require chelation after causative factor is identified. Objectives: To describe some problems connected with toxicity of metals poisoning and to review pharmacologic therapies that could have a role in poisoning with metals. Methods: A review of the literature was carried out and expert opinion expressed. Results/conclusion: Chelation is a common therapy in case of poisoning with toxic metals but it is satisfied only partially. A combined therapy with structurally different chelators or long-term acting chelators could become viable alternatives in the future. A combined therapy with an antioxidant plus chelator may be a good choice in patients chronically poisoned with metals. Exposure to lead should be taken into account during estimation of global cardiovascular risk.

  2. The Management of Iron Chelation Therapy: Preliminary Data from a National Registry of Thalassaemic Patients

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    Ceci, Adriana; Mangiarini, Laura; Felisi, Mariagrazia; Bartoloni, Franco; Ciancio, Angela; Capra, Marcello; D'Ascola, Domenico; Cianciulli, Paolo; Filosa, Aldo

    2011-01-01

    Thalassaemia and other haemoglobinopathies constitute an important health problem in Mediterranean countries, placing a tremendous emotional, psychological, and economic burden on their National Health systems. The development of new chelators in the most recent years had a major impact on the treatment of thalassaemia and on the quality of life of thalassaemic patients. A new initiative was promoted by the Italian Ministry of Health, establishing a Registry for thalassaemic patients to serve as a tool for the development of cost-effective diagnostic and therapeutic approaches and for the definition of guidelines supporting the most appropriate management of the iron-chelating therapy and a correct use of the available iron-chelating agents. This study represents the analysis of the preliminary data collected for the evaluation of current status of the iron chelation practice in the Italian thalassaemic population and describes how therapeutic interventions can widely differ in the different patients' age groups. PMID:21738864

  3. The Management of Iron Chelation Therapy: Preliminary Data from a National Registry of Thalassaemic Patients

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    Adriana Ceci

    2011-01-01

    Full Text Available Thalassaemia and other haemoglobinopathies constitute an important health problem in Mediterranean countries, placing a tremendous emotional, psychological, and economic burden on their National Health systems. The development of new chelators in the most recent years had a major impact on the treatment of thalassaemia and on the quality of life of thalassaemic patients. A new initiative was promoted by the Italian Ministry of Health, establishing a Registry for thalassaemic patients to serve as a tool for the development of cost-effective diagnostic and therapeutic approaches and for the definition of guidelines supporting the most appropriate management of the iron-chelating therapy and a correct use of the available iron-chelating agents. This study represents the analysis of the preliminary data collected for the evaluation of current status of the iron chelation practice in the Italian thalassaemic population and describes how therapeutic interventions can widely differ in the different patients' age groups.

  4. Public health department response to mercury poisoning: the importance of biomarkers and risks and benefits analysis for chelation therapy.

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    McKay, Charles A

    2013-12-01

    Chelation therapy is often used to treat mercury poisoning. Public health personnel are often asked about mercury toxicity and its treatment. This paper provides a public health department response to use of a mercury-containing cosmetic in Minnesota, a perspective on two unpublished cases of chelation treatment for postulated mercury toxicity, and comments on the use of a nonsystemic treatment for removal of mercury following the Iraqi seed coat poisoning incident. Physicians should evaluate sources of exposure, biomarkers, and risks and benefits before recommending chelation therapy for their patients. Potential risks to chelation therapy and its little understood subtle or latent effects are areas of public health concern.

  5. Catechol-Bisphosphonate Conjugates:New Potential Chelating Agents for Metal Intoxication Therapy

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    Guang Yu XU; Chun Hao YANG; Bo LIU; Xi Han WU; Yu Yuan XIE

    2004-01-01

    In a quest for better chelating therapy drugs for the treatment of intoxication by Fe, Al, or actinides, two new series of mixed catechol-bisphosphonate through amide linkage were synthesized.Benzyl group was used as protecting group to avoid the breakage of amide by acid hydrolysis or imcomplete reaction in silylation-dealkylation using bromotrimethylsilane.

  6. Essential trace metal excretion from rats with lead exposure and during chelation therapy.

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    Victery, W; Miller, C R; Goyer, R A

    1986-02-01

    Urinary excretion of lead, zinc, calcium, magnesium, iron, copper, sodium, and potassium was measured in rats daily for 1 week after a 6-week exposure to 10,000 micrograms/ml lead in drinking water. Beginning on the third day, half of the lead-exposed and control rats were injected intraperitoneally with calcium disodium ethylenediaminetetraacetate (EDTA) daily for 3 days. Whole blood, plasma, and kidney metal concentrations were determined from samples obtained at the end of the experiment. Exposure to lead increased urinary excretion, not only of lead, but also of calcium, magnesium, zinc, copper, and iron. Excretion of sodium and potassium was not altered. Chelation therapy further increased excretion of lead, zinc, copper, and iron, but not magnesium. The increase in calcium excretion during chelation treatment (beyond that resulting from lead exposure per se) was accounted for by the Ca content of CaNa2-EDTA. EDTA treatment increased renal concentration of zinc but lowered renal concentration of lead, copper, and iron. These multimetal alterations may have implications for essential metal supplementation, particularly zinc, in persons being given chelation agents for excess lead exposure and in infants and children with low-level lead exposure not necessarily requiring chelation therapy.

  7. Safety and Outcomes of Open-Label Deferasirox Iron Chelation Therapy for Mucormycosis▿

    OpenAIRE

    2009-01-01

    We sought to describe the safety profile of open-label, adjunctive deferasirox iron chelation therapy in eight patients with biopsy-proven mucormycosis. Deferasirox was administered for an average of 14 days (range, 7 to 21) at 5 to 20 mg/kg of body weight/day. The only adverse effects attributable to deferasirox were rashes in two patients. Deferasirox treatment was not associated with changes in renal or liver function, complete blood count, or transplant immunosuppressive levels. Thus, def...

  8. Safety and Outcomes of Open-Label Deferasirox Iron Chelation Therapy for Mucormycosis▿

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    Spellberg, Brad; Andes, David; Perez, Mario; Anglim, Anne; Bonilla, Hector; Mathisen, Glenn E.; Walsh, Thomas J.; Ibrahim, Ashraf S.

    2009-01-01

    We sought to describe the safety profile of open-label, adjunctive deferasirox iron chelation therapy in eight patients with biopsy-proven mucormycosis. Deferasirox was administered for an average of 14 days (range, 7 to 21) at 5 to 20 mg/kg of body weight/day. The only adverse effects attributable to deferasirox were rashes in two patients. Deferasirox treatment was not associated with changes in renal or liver function, complete blood count, or transplant immunosuppressive levels. Thus, deferasirox appears safe as an adjunctive therapy for mucormycosis. PMID:19433555

  9. Evaluation of the potential role of chelation therapy in treatment of low to moderate lead exposures

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    Chisolm, J.J. Jr. (Johns Hopkins School of Medicine, Baltimore, MD (USA))

    1990-11-01

    In the overall long-term management of lead poisoning, chelation therapy can have short-term benefits; however, these benefits must be accompanied by drastic reduction in environmental exposure to lead if therapy is to have any long-term benefit. This discussion is limited to calcium disodium ethylenediaminetetraacetate (CaNa{sub 2}EDTA), the chelating agent that has been the mainstay of treatment of lead poisoning for the past 38 years, and to meso-2,3-dimercaptosuccinic acid (DMSA), a new and promising oral chelating agent, which is an orphan drug and is currently classified as an investigational new drug by the US Food and Drug Administration. With both drugs, multiple courses of treatment will be needed if any substantial reduction in body lead burden is to be achieved. A major limitation of CaNa{sub 2}EDTA is the enormous diuresis of zinc that it produces. DMSA produces a comparable diuresis of lead, a greater decrease in blood lead, and has negligible influence on the urinary losses of zinc, copper, iron, and calcium. Limited experience to date in man has revealed no significant adverse side effects of DMSA. In animals, DMSA will promptly reduce the concentration of lead in brain and kidney, in particular. By contrast, similar 5-day courses of CaNa{sub 2}EDTA do not produce any net reduction in brain lead. This is important, as the brain is the critical organ of the adverse effects of lead in children. If the efficacy of DMSA is to be comprehensively evaluated ethically in children, new and more sensitive neurochemical, electrophysiologic, or other markers must be developed.

  10. Oral iron chelators.

    Science.gov (United States)

    Kwiatkowski, Janet L

    2010-02-01

    Effective chelation therapy can prevent or reverse organ toxicity related to iron overload, yet cardiac complications and premature death continue to occur, largely related to difficulties with compliance in patients who receive parenteral therapy. The use of oral chelators may be able to overcome these difficulties and improve patient outcomes. A chelator's efficacy at cardiac and liver iron removal and side-effect profile should be considered when tailoring individual chelation regimens. Broader options for chelation therapy, including possible combination therapy, should improve clinical efficacy and enhance patient care.

  11. Clinical assessment of quality of life of the patients with chronic blood transfusion and chelation therapy

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    Tamil Selvan

    2014-01-01

    Full Text Available Background: The patient with hemoglobinopathy like thalassemia major (TM, bone marrow dysfunction, and sickle cell disease are requiring chronic blood transfusion for their life time to survive. Among these, TM is one of the most common hemoglobinopathy worldwide. Objective: This study is done to assess the quality of life (QOL of the patients with chronic blood transfusion and chelation therapy. Materials and Methods: The QOL scores were obtained through the self-administered SF-36 questionnaire. The study subjects were asked to answer the SF-36 questionnaire once every 3 months. Results: After 6 months, the SF 36 general health mean score was 63.58 ± 12.98 (P < 0.05. The highest mean score was 69.37 ± 11.61. The mean difference after the final reviews was statistically significant. Conclusion: The preponderance of scores used to assess QOL suggests that there is a direct and independent effect on QOL when treated with transfusion and iron-chelation therapy.

  12. Manganese (II) Chelate Functionalized Copper Sulfide Nanoparticles for Efficient Magnetic Resonance/Photoacoustic Dual-Modal Imaging Guided Photothermal Therapy.

    Science.gov (United States)

    Liu, Renfa; Jing, Lijia; Peng, Dong; Li, Yong; Tian, Jie; Dai, Zhifei

    2015-01-01

    The integration of diagnostic and therapeutic functionalities into one nanoplatform shows great promise in cancer therapy. In this research, manganese (II) chelate functionalized copper sulfide nanoparticles were successfully prepared using a facile hydrothermal method. The obtained ultrasmall nanoparticles exhibit excellent photothermal effect and photoaoustic activity. Besides, the high loading content of Mn(II) chelates makes the nanoparticles attractive T1 contrast agent in magnetic resonance imaging (MRI). In vivo photoacoustic imaging (PAI) results showed that the nanoparticles could be efficiently accumulated in tumor site in 24 h after systematic administration, which was further validated by MRI tests. The subsequent photothermal therapy of cancer in vivo was achieved without inducing any observed side effects. Therefore, the copper sulfide nanoparticles functionalized with Mn(II) chelate hold great promise as a theranostic nanomedicine for MR/PA dual-modal imaging guided photothermal therapy of cancer.

  13. New developments and controversies in iron metabolism and iron chelation therapy.

    Science.gov (United States)

    Kontoghiorghe, Christina N; Kontoghiorghes, George J

    2016-03-26

    haemochromatosis, thalassaemia intermedia and ex-thalassaemia transplanted patients who are safely treated with venesection. Iron chelating drugs can override normal regulatory pathways, correct iron imbalance and minimise iron toxicity. The use of iron chelating drugs as main, alternative or adjuvant therapy is in progress in many conditions, especially those with non established or effective therapies.

  14. ATOX1 gene silencing increases susceptibility to anticancer therapy based on copper ionophores or chelating drugs.

    Science.gov (United States)

    Barresi, Vincenza; Spampinato, Giorgia; Musso, Nicolò; Trovato Salinaro, Angela; Rizzarelli, Enrico; Condorelli, Daniele Filippo

    2016-03-01

    Copper is a catalytic cofactor required for the normal function of many enzymes involved in fundamental biological processes but highly cytotoxic when in excess. Therefore its homeostasis and distribution is strictly regulated by a network of transporters and intracellular chaperones. ATOX1 (antioxidant protein 1) is a copper chaperone that plays a role in copper homeostasis by binding and transporting cytosolic copper to ATPase proteins in the trans-Golgi network. In the present study the Caco-2 cell line, a colon carcinoma cell line, was used as an in vitro model to evaluate if ATOX1 deficiency could affect sensitivity to experimentally induced copper dyshomeostasis. Silencing of ATOX1 increased toxicity of a short treatment with a high concentration of Cu(2+). Copper ionophores, such as 5-chloro-8-hydroxyquinoline, induced a copper-dependent cell toxicity which was significantly potentiated after ATOX1 silencing. The copper chelator TPEN (N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine) produced a form of cell toxicity that was reversed by the addition of Cu(2+). ATOX1 silencing increased Caco-2 cell sensitivity to TPEN toxicity. Our results suggest the possibility of a therapy with copper-chelating or ionophore drugs in subtypes of tumors showing specific alterations in ATOX1 expression.

  15. Predictors of non-adherence to follow-up visits and deferasirox chelation therapy among jordanian adolescents with Thalassemia major.

    Science.gov (United States)

    Al-Kloub, Manal Ibrahim; A Bed, Mona A; Al Khawaldeh, Omar A; Al Tawarah, Yasin M; Froelicher, Erika Sivarajan

    2014-10-01

    Poor adherence to treatment can have negative effects on outcomes and heath care cost. However, little is known about the factors that impact adherence to deferasirox chelation therapy. The aims of this study were to identify rates and predictors of non-adherence to medical regimen among thalassemia major adolescents on deferasirox oral chelation therapy by using subjective (self-reporting) and objective (serum ferritin and follow-up visits) measures. Convenient samples of 164 adolescents, aged 12-19 years were recruited from three National Thalassemia Centers in Jordan. Patients were interviewed using a four-section questionnaire and the medical records were checked. Results indicated that rate of adherence according to self-report was (73%); while to follow-up medical appointments and serum ferritin level rates was 57% and 47%, respectively. One-third of participant adolescents (n = 52) were psychologically impaired. Multivariate analysis showed that factors affecting adolescent non-adherence to deferasirox chelation therapy is different from that affecting adherence to follow-up visits. In general, adolescents more than 16 years old, presence of sibling with thalassemia, lack of parental monitoring, lower family income, decrease frequency of blood transfusion, and psychological impairment were found significant predictors of non-adherence among adolescents. Disease knowledge was not associated with adherence status of the adolescents. Clinician should be aware of high prevalence of low adherence to chelation therapy during adolescent years. Nurses need to regularly assess, monitor, and promote adherence behavior that might impact patients' outcomes.

  16. [Iron chelation therapy and its influence on the alleviation of EPO resistance in MDS patients].

    Science.gov (United States)

    Zhang, Yao; Xiao, Chao; Gu, Shu-Cheng; Chang, Chun-Kang

    2014-08-01

    This study was aimed to investigate the changes of erythropoietin (EPO), hemoglobin(Hb) and recombinant EPO (rEPO) levels in MDS patients receiving iron chelation therapy, and to explore the relationship between EPO and serum ferritin(SF). A total of 172 MDS patients and 30 healthy controls were studied. The levels of SF, EPO, serum iron (SI), total iron binding capacity (TIBC), C-reaction protein (CRP) and Hb were measured respectively, the level of SF was adjusted according to the changes of CRP. Among them, there were 34 cases of low-risk (SF>1 000 mg/L) receiving deferoxamine therapy, whose changes of SF, EPO, SI, TIBC, Hb levels were detected and compared before and after treatment. Besides, the difference in the incidence of EPO resistance in iron overload group and non-iron overload group was assessed before and after therapy, and 58 cases of low-risk and EPOEPO in non-iron overload group was higher than that in the normal control group (997.44 ± 473.48 vs 467.27 ± 238.49, P EPO in iron overload group was higher than that in non-iron overload group and control group (3257.59 ± 697.19 vs 997.44 ± 473.48, P = 0.012, 3257.59 ± 697.19 vs 467.27 ± 238.49, P = 0.002). Otherwise, the incidence of EPO resistance in iron overload group was higher than that in non-iron overload group (18/35 vs 2/23, P = 0.001), and the level of EPO and SF was positively related to each other in iron overload group (r = 0.310,P = 0.036). After receiving iron chelation therapy, the levels of SF, SI, TIBC and EPO in iron overload group were significantly lower than that before therapy (3942.38 ± 641.82 vs 2266.35 ± 367.31, P = 0.028;48.61 ± 10.65 vs 28.52 ± 12.61, P = 0.034;59.84 ± 12.62 vs 33.76 ± 15.43, P = 0.045;3808.01 ± 750.22 vs 1954.78 ± 473.18, P = 0.042). Moreover, the level of Hb increased (35 ± 18 vs 57 ± 21, P = 0.046) and the EPO resistance in some patients was decreased. It is concluded that iron chelation therapy can improve the efficacy of EPO to alleviate

  17. The proceedings of the 17th International Conference on Chelation: application of effective chelation therapies in iron loading and non iron loading conditions, and the gap in the prevention and treatment policies on thalassemia between developed and developing countries.

    Science.gov (United States)

    Kontoghiorghes, George J

    2009-01-01

    Substantial progress in the use of chelating drugs for the treatment of iron overload and of non iron loading conditions has been presented during the 17th International Conference on Chelation (ICOC) held in November 2007 at Shenzhen, China. Major challenges lie ahead for the prevention and treatment of thalassemia in China, India, Thailand, Indonesia and many other developing countries where millions of heterozygote thalassemia carriers live and thousands of homozygote thalassemia patients are born annually. The progressive improvement of the economic climate in developing countries will increase the demand and resources for more prenatal and antenatal diagnoses, transfusions and chelation therapy in forthcoming years. Despite the major advances in diagnosis and treatment in developed countries, the vast majority of thalassemia patients in developing countries die untreated because they cannot afford the cost of transfusions and chelation therapy. New approaches and infrastructures and more efforts are needed to overcome the difficulties of supplying new techniques and treatments to patients in developing countries. International and local organizations need to be persuaded to act collectively and effectively to improve chelation and related treatments for thalassemia and other conditions, especially at this time that universally effective and inexpensive chelation therapies can be applied.

  18. Antioxidant and Metal Chelation-Based Therapies in the Treatment of Prion Disease.

    Science.gov (United States)

    Brazier, Marcus W; Wedd, Anthony G; Collins, Steven J

    2014-04-21

    Many neurodegenerative disorders involve the accumulation of multimeric assemblies and amyloid derived from misfolded conformers of constitutively expressed proteins. In addition, the brains of patients and experimental animals afflicted with prion disease display evidence of heightened oxidative stress and damage, as well as disturbances to transition metal homeostasis. Utilising a variety of disease model paradigms, many laboratories have demonstrated that copper can act as a cofactor in the antioxidant activity displayed by the prion protein while manganese has been implicated in the generation and stabilisation of disease-associated conformers. This and other evidence has led several groups to test dietary and chelation therapy-based regimens to manipulate brain metal concentrations in attempts to influence the progression of prion disease in experimental mice. Results have been inconsistent. This review examines published data on transition metal dyshomeostasis, free radical generation and subsequent oxidative damage in the pathogenesis of prion disease. It also comments on the efficacy of trialed therapeutics chosen to combat such deleterious changes.

  19. Antioxidant and Metal Chelation-Based Therapies in the Treatment of Prion Disease

    Directory of Open Access Journals (Sweden)

    Marcus W. Brazier

    2014-04-01

    Full Text Available Many neurodegenerative disorders involve the accumulation of multimeric assemblies and amyloid derived from misfolded conformers of constitutively expressed proteins. In addition, the brains of patients and experimental animals afflicted with prion disease display evidence of heightened oxidative stress and damage, as well as disturbances to transition metal homeostasis. Utilising a variety of disease model paradigms, many laboratories have demonstrated that copper can act as a cofactor in the antioxidant activity displayed by the prion protein while manganese has been implicated in the generation and stabilisation of disease-associated conformers. This and other evidence has led several groups to test dietary and chelation therapy-based regimens to manipulate brain metal concentrations in attempts to influence the progression of prion disease in experimental mice. Results have been inconsistent. This review examines published data on transition metal dyshomeostasis, free radical generation and subsequent oxidative damage in the pathogenesis of prion disease. It also comments on the efficacy of trialed therapeutics chosen to combat such deleterious changes.

  20. Chelation in Metal Intoxication

    Directory of Open Access Journals (Sweden)

    Swaran J.S. Flora

    2010-06-01

    Full Text Available Chelation therapy is the preferred medical treatment for reducing the toxic effects of metals. Chelating agents are capable of binding to toxic metal ions to form complex structures which are easily excreted from the body removing them from intracellular or extracellular spaces. 2,3-Dimercaprol has long been the mainstay of chelation therapy for lead or arsenic poisoning, however its serious side effects have led researchers to develop less toxic analogues. Hydrophilic chelators like meso-2,3-dimercaptosuccinic acid effectively promote renal metal excretion, but their ability to access intracellular metals is weak. Newer strategies to address these drawbacks like combination therapy (use of structurally different chelating agents or co-administration of antioxidants have been reported recently. In this review we provide an update of the existing chelating agents and the various strategies available for the treatment of heavy metals and metalloid intoxications.

  1. Subclinical renal abnormalities in young thalassemia major and intermedia patients and its relation to chelation therapy

    Directory of Open Access Journals (Sweden)

    Amira A.M. Adly

    2014-10-01

    Conclusion: Subclinical renal affection can start earlier in TM patients compared to TI. Poor chelation is associated with early signs of renal affection. Periodic renal assessment of those patients is mandatory as they may be affected by hidden renal dysfunction.

  2. Iron Chelation Therapy with Deferasirox in the Management of Iron Overload in Primary Myelofibrosis

    Science.gov (United States)

    Elli, Elena Maria; Belotti, Angelo; Aroldi, Andrea; Parma, Matteo; Pioltelli, Pietro; Pogliani, Enrico Maria

    2014-01-01

    Deferasirox (DSX) is the principal option currently available for iron-chelation-therapy (ICT), principally in the management of myelodysplastic syndromes (MDS), while in primary myelofibrosis (PMF) the expertise is limited. We analyzed our experience in 10 PMF with transfusion-dependent anemia, treated with DSX from September 2010 to December 2013. The median dose tolerated of DSX was 750 mg/day (10 mg/kg/day), with 3 transient interruption of treatment for drug-related adverse events (AEs) and 3 definitive discontinuation for grade 3/4 AEs. According to IWG 2006 criteria, erythroid responses with DSX were observed in 4/10 patients (40%), 2 of them (20%) obtaining transfusion independence. Absolute changes in median serum ferritin levels (Delta ferritin) were greater in hematologic responder (HR) compared with non-responder (NR) patients, already at 6 months of ICT respect to baseline. Our preliminary data open new insights regarding the benefit of ICT not only in MDS, but also in PMF with the possibility to obtain an erythroid response, overall in 40 % of patients. HR patients receiving DSX seem to have a better survival and a lower incidence of leukemic transformation (PMF-BP). Delta ferritin evaluation at 6 months could represent a significant predictor for a different survival and PMF-BP. However, the tolerability of the drug seems to be lower compared to MDS, both in terms of lower median tolerated dose and for higher frequency of discontinuation for AEs. The biological mechanism of action of DSX in chronic myeloproliferative setting through an independent NF-κB inhibition could be involved, but further investigations are required. PMID:24959339

  3. IRON CHELATION THERAPY WITH DEFERASIROX IN THE MANAGEMENT OF IRON OVERLOAD IN PRIMARY MYELOFIBROSIS

    Directory of Open Access Journals (Sweden)

    Elena Maria Elli

    2014-05-01

    Full Text Available Deferasirox (DSX is the principal option currently available for iron-chelation-therapy (ICT, principally in the management of myelodysplastic syndromes (MDS, while in primary myelofibrosis (PMF the expertise is limited. We analyzed our experience in 10 PMF with transfusion-dependent anemia, treated with DSX from September 2010 to December 2013. The median dose tolerated of DSX was 750 mg/day (10 mg/kg/day, with 3 transient interruption of treatment for drug-related adverse events (AEs and 3 definitive discontinuation for grade 3/4 AEs. According to IWG 2006 criteria, erythroid responses with DSX were observed in 4/10 patients (40%, 2 of them (20% obtaining transfusion independence. Absolute changes in median serum ferritin levels (Delta ferritin were greater in hematologic responder (HR compared with non-responder (NR  patients, already at 6 months of ICT respect to baseline. Our preliminary data open new insights regarding the benefit of ICT not only in MDS, but also in PMF with the possibility to obtain an erythroid response, overall in 40 % of patients. HR patients receiving DSX seem to have a better survival and a lower incidence of leukemic transformation (PMF-BP. Delta ferritin evaluation at 6 months could represent a significant predictor for a different survival and PMF-BP.  However, the tolerability of the drug seems to be lower compared to MDS, both in terms of lower median tolerated dose and for higher frequency of discontinuation for AEs. The biological mechanism of action of DSX in chronic myeloproliferative setting through an independent NF-κB inhibition could be involved, but further investigations are required.

  4. Effect of succimer chelation therapy on postural balance and gait outcomes in children with early exposure to environmental lead.

    Science.gov (United States)

    Bhattacharya, Amit; Shukla, Rakesh; Auyang, Edward D; Dietrich, Kim N; Bornschein, Robert

    2007-05-01

    This study investigated the influence of succimer chelation therapy in eliminating and/or minimizing lead-associated impairments of motor functions such as postural balance and locomotion or gait activities. In this study, postural balance and functional locomotion or gait were quantitated in 161 children in Cincinnati enrolled in a randomized, placebo-controlled, double blind clinical trial. In comparison to the placebo group, the succimer therapy group showed significantly decreased postural sway during dynamic task performance implying improved postural balance. The results from locomotion tests demonstrated significant improvements in functional tasks of obstacle crossing and normal walking in the succimer treated group. While some beneficial neuromotor effects of succimer therapy were observed in the present study there remains several unanswered questions such as how long these effects will persist and how succimer therapy modifies lead-associated cerebellar deficits manifesting as perturbations in vestibular and/or proprioception systems for postural balance and functional locomotion.

  5. Hematological improvement during iron-chelation therapy in myelodysplastic syndromes: the experience of the "Rete Ematologica Lombarda".

    Science.gov (United States)

    Molteni, Alfredo; Riva, Marta; Pellizzari, Annamaria; Borin, Lorenza; Freyrie, Alessandra; Freyre, Alessandra; Greco, Rosa; Ubezio, Marta; Bernardi, Massimo; Fariciotti, Alessio; Nador, Guido; Nichelatti, Michele; Ravano, Emanuele; Morra, Enrica

    2013-10-01

    To analyze the unpredicted event of hematological improvement (HI) during iron-chelation therapy (ICT), we reviewed a series of 53 myelodysplastic patients with transfusion dependency in a retrospective study involving 8 centers afferent to the "Rete Ematologica Lombarda". According to the IWG response criteria published in the year 2000, we observed erythroid responses in 19 patients (35.1%), 5 major (9.2%) and 14 minor (25.9%). In the assessable patients, platelet response was 8/13 (61%) and neutrophil response was 13/17 (76.4%). Only in patients with erythroid improvement, multilineage responses were observed. Apparently, patients with greater erythropoiesis dysfunction may take more advantage.

  6. Subclinical renal abnormalities in young thalassemia major and intermedia patients and its relation to chelation therapy

    OpenAIRE

    Adly, Amira A.M.; Dalia N. Toaima; Noha Refaat Mohamed; Karim Mahmoud Abu El Seoud

    2014-01-01

    Background: Limited data are available about renal involvement in thalassemia patients. Renal dysfunction in these patients seems to be multifactorial attributed mainly to long standing anemia, chronic hypoxia, iron overload and toxicity of iron chelators. Objective: To assess the frequency of subclinical glomerular and tubular dysfunctions in children and adolescents with β-thalassemia major and intermedia, and to correlate these findings with the degree of iron overload and type of chela...

  7. Chelation therapy for treatment of systemic intoxication with uranium: A review.

    Science.gov (United States)

    Šömen Joksić, Agnes; Katz, Sidney A

    2015-01-01

    Elevated levels of naturally occurring uranium have been found in small geographic areas throughout the world. Exposure of the general public to uranium is most often by the ingestion of food and water containing natural uranium from the hydrogeological environment, but this likelihood is remote. However, the risk is increased in regions where uranium is mined, milled, processed and/or fabricated as well as in the vicinity of former battlefields where depleted uranium munitions were deployed. Exposure in such cases is by the inhalation route. Internalized uranium is a long-term hazard the toxicity of which depends upon the dose and the dose rate as well as other parameters such as the chemical form and site of deposition of the uranium and the physiology of the host. The radiological toxicity and the chemical toxicity of uranium and its compounds are responsible for kidney damage and lung cancer. The vulnerable groups are the very young and the very old, individuals predisposed to hypertension or osteoporosis and individuals with chronic kidney disease. Those subject to long-term exposure from internalized uranium are a greater risk for the long-term implications. The accumulation of uranium may be mitigated by decreasing its absorption, distribution and deposition and increasing its elimination with chelating agents. The formation of soluble chelates may enhance the mobilization of uranium deposited in tissue and expedite its transport to and elimination from the renal system. The focus of this review is on the use of chelating agents to enhance decorporation of uranium thereby reducing the risk of intoxication.

  8. A systematic comparative evaluation of 90Y-labeled bifunctional chelators for their use in targeted therapy.

    Science.gov (United States)

    Chakravarty, Rubel; Chakraborty, Sudipta; Dash, Ashutosh

    2014-02-01

    This paper describes a systematic comparative evaluation of five commonly used bifunctional chelators, namely,p-isothiocyanato benzyl derivatives of diethylenetriaminepentacetic acid (DTPA-NCS), trans-cyclohexyl diethylenetriaminepentaceticacid (CHX-A″-DTPA-NCS), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NCS), 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA-NCS), and 3,6,9,15-tetraazabicyclo [9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (PCTA-NCS), on the basis of their ability to complex 90Y at room temperature, in vitro and in vivo stability and clearance pattern in biological system. The results of the experiments carried out revealed that CHX-A″-DTPA-NCS was the most promising option as it could be radiolabeled with 90Y at room temperature with highest specific activity and demonstrated high in vitro stability in human serum and in presence of challenging metal ions commonly present inhuman plasma. The clearance pattern in Swiss mice revealed that 90Y-CHX- A″-DTPA-NCS cleared through the kidneys with minimum retention in any other major organ. Thus, the use of cyclohexyl-DTPA based bifunctional chelators would increase the scope of making 90Y-labeled agents suitable for targeted therapy.

  9. Effect of Systemic Iron Overload and a Chelation Therapy in a Mouse Model of the Neurodegenerative Disease Hereditary Ferritinopathy

    Science.gov (United States)

    Li, Wei; Goodwin, Charles B.; Richine, Briana; Acton, Anthony; Chan, Rebecca J.; Peacock, Munro; Muhoberac, Barry B.; Ghetti, Bernardino; Vidal, Ruben

    2016-01-01

    Mutations in the ferritin light chain (FTL) gene cause the neurodegenerative disease neuroferritinopathy or hereditary ferritinopathy (HF). HF is characterized by a severe movement disorder and by the presence of nuclear and cytoplasmic iron-containing ferritin inclusion bodies (IBs) in glia and neurons throughout the central nervous system (CNS) and in tissues of multiple organ systems. Herein, using primary mouse embryonic fibroblasts from a mouse model of HF, we show significant intracellular accumulation of ferritin and an increase in susceptibility to oxidative damage when cells are exposed to iron. Treatment of the cells with the iron chelator deferiprone (DFP) led to a significant improvement in cell viability and a decrease in iron content. In vivo, iron overload and DFP treatment of the mouse model had remarkable effects on systemic iron homeostasis and ferritin deposition, without significantly affecting CNS pathology. Our study highlights the role of iron in modulating ferritin aggregation in vivo in the disease HF. It also puts emphasis on the potential usefulness of a therapy based on chelators that can target the CNS to remove and redistribute iron and to resolubilize or prevent ferritin aggregation while maintaining normal systemic iron stores. PMID:27574973

  10. The effects of succimer chelation therapy on auditory function in rhesus monkeys.

    Science.gov (United States)

    Lasky, R E; Luck, M L; Laughlin, N K

    2001-01-01

    Sixty-six female rhesus monkeys were randomly assigned to three lead exposure conditions (none, from birth to 1 year, and from birth to 2 years) by two chelation treatment (succimer and no succimer) conditions. Blood lead levels were maintained at 35-40 microg/dl beginning shortly after birth and continuing for 1 or 2 years postnatally. There were two separate chelation regimes: 53 and 65 weeks of age. Lead and lead-vehicle dosing were discontinued while succimer was administered. Succimer (or placebo) was administered orally at a dose of 30 mg/kg/day (divided into three doses per day) for 5 days and for 14 additional days at 20 mg/kg/day (divided into two doses per day) for a total 19-day treatment regimen. Auditory function was assessed in these monkeys at least 1 year after lead intake had been discontinued. The outcome measures included tympanometry to assess middle ear function, OAEs to assess cochlear function, and ABRs to assess the auditory nerve and brainstem pathways. There were no significant differences as a function of succimer treatment for any of the tympanometric variables measured. Suprathreshold and threshold distortion product otoacoustic emissions were comparable among the succimer and vehicle groups. However, there was a nonsignificant trend to smaller amplitude distortion products at the highest frequencies assessed (6.4-10.0 kHz). Finally, the auditory evoked response at levels from the auditory nerve to the cerebral cortex did not significantly differ as a function of succimer treatment.

  11. Iron chelation therapy of transfusion-dependent β-thalassemia during pregnancy in the era of novel drugs: is deferasirox toxic?

    Science.gov (United States)

    Diamantidis, Michael D; Neokleous, Nikolaos; Agapidou, Aleka; Vetsiou, Evaggelia; Manafas, Achilles; Fotiou, Paraskevi; Vlachaki, Efthymia

    2016-05-01

    The life expectancy of thalassemic patients has increased, and now approaches that of healthy individuals, thanks to improved treatment regimens. However, pregnancy in women with β-Thalassemia Μajor remains a challenging condition. Recent advances in managing this haemoglobinopathy offer the potential for safe pregnancies with favorable outcome. However, clinical data regarding the use of chelation therapy during pregnancy are limited, and it is unclear whether these agents impose any risk to the developing fetus. Successful pregnancies following unintentional treatment with deferoxamine or deferasirox have rarely been reported. Generally, chelators are not recommended during pregnancy. Regarding the new oral chelators, data on fetotoxicity are lacking. In the present study, we describe the evolution and successful outcome of nine pregnancies in six Greek thalassemic women who received deferasirox inadvertently during early pregnancy, and review the literature regarding fetal anomalies due to chelators. Use of chelation before embarking upon a non-programmed pregnancy remains a difficult and unresolved question. In our study, chelation treatment during pregnancy did not prevent the delivery of healthy children. Nonetheless, the use of deferasirox is contraindicated in pregnant women, based on the product label. Deferasirox should only be used during pregnancy if the potential benefit outweighs the potential fetal risk.

  12. Durable Red Blood Cell Transfusion Independence in a Patient with an MDS/MPN Overlap Syndrome Following Discontinuation of Iron Chelation Therapy

    Directory of Open Access Journals (Sweden)

    Harpreet Kochhar

    2015-01-01

    Full Text Available Background. Hematologic improvement (HI occurs in some patients with acquired anemias and transfusional iron overload receiving iron chelation therapy (ICT but there is little information on transfusion status after stopping chelation. Case Report. A patient with low IPSS risk RARS-T evolved to myelofibrosis developed a regular red blood cell (RBC transfusion requirement. There was no response to a six-month course of study medication or to erythropoietin for three months. At 27 months of transfusion dependence, she started deferasirox and within 6 weeks became RBC transfusion independent, with the hemoglobin normalizing by 10 weeks of chelation. After 12 months of chelation, deferasirox was stopped; she remains RBC transfusion independent with a normal hemoglobin 17 months later. We report the patient’s course in detail and review the literature on HI with chelation. Discussion. There are reports of transfusion independence with ICT, but that transfusion independence may be sustained long term after stopping chelation deserves emphasis. This observation suggests that reduction of iron overload may have a lasting favorable effect on bone marrow failure in at least some patients with acquired anemias.

  13. Vascular-targeted photodynamic therapy with BF2-chelated Tetraaryl-Azadipyrromethene agents: a multi-modality molecular imaging approach to therapeutic assessment.

    LENUS (Irish Health Repository)

    Byrne, A T

    2009-11-03

    Photodynamic therapy (PDT) is a treatment modality for a range of diseases including cancer. The BF(2)-chelated tetraaryl-azadipyrromethenes (ADPMs) are an emerging class of non-porphyrin PDT agent, which have previously shown excellent photochemical and photophysical properties for therapeutic application. Herein, in vivo efficacy and mechanism of action studies have been completed for the lead agent, ADMP06.

  14. Combination therapy of murine mucormycosis or aspergillosis with iron chelation, polyenes, and echinocandins.

    Science.gov (United States)

    Ibrahim, Ashraf S; Gebremariam, Teclegiorgis; Luo, Guanpingsheng; Fu, Yue; French, Samuel W; Edwards, John E; Spellberg, Brad

    2011-04-01

    Liposomal amphotericin B (LAmB) combined wither either micafungin or deferasirox was synergistic in previous murine studies with mucormycosis or aspergillosis. We hypothesized that triple therapy using LAmB, micafungin, and deferasirox could further improve outcomes of mucormycosis or aspergillosis. Triple therapy improved survival and reduced tissue fungal burden of mice with mucormycosis and to a lesser extent with aspergillosis. Continued investigation into the use of triple therapy against mucormycosis and aspergillosis is warranted.

  15. Mercuric oxide poisoning treated with whole-bowel irrigation and chelation therapy.

    Science.gov (United States)

    Ly, Binh T; Williams, Saralyn R; Clark, Richard F

    2002-03-01

    Most reported cases of inorganic mercury poisoning are from mercuric chloride. We report a case of mercuric oxide (HgO) powder ingestion. A 31-year-old man presented to an emergency department after ingestion of approximately 40 g of HgO. Soon after ingestion, he developed nausea, vomiting, and abdominal cramping. Abdominal radiograph revealed densely radiopaque material in the stomach. Gastrointestinal decontamination was accomplished with activated charcoal and whole-bowel irrigation with polyethylene glycol solution (Golytely) for 24 hours until repeat abdominal radiographs no longer demonstrated the substance in the gastrointestinal tract. He was also chelated with British anti-Lewisite for 5 days, followed by succimer for 10 days. He had markedly elevated urine and blood mercury levels after ingestion, but except for a mildly depressed serum bicarbonate (19 mEq/L), his chemistry results remained normal including blood urea nitrogen and creatinine. He had an uncomplicated hospital course and remained asymptomatic at 6 months postingestion. Despite elevated urine and blood mercury levels after ingestion of HgO, our patient did not develop the end-organ toxicity typical of inorganic mercury poisoning.

  16. Chelation Therapy with Oral Solution of Deferiprone in Transfusional Iron-Overloaded Children with Hemoglobinopathies

    Directory of Open Access Journals (Sweden)

    Alexandros Makis

    2013-01-01

    Full Text Available Iron overload in hemoglobinopathies is secondary to blood transfusions, chronic hemolysis, and increased iron absorption and leads to tissue injury requiring the early use of chelating agents. The available agents are parenteral deferoxamine and oral deferiprone and deferasirox. There are limited data on the safety and efficacy of deferiprone at a very young age. The aim of our study was the presentation of data regarding the use of oral solution of deferiprone in 9 children (mean age 6.5, range 2–10 with transfusion dependent hemoglobinopathies (6 beta thalassemia major, 1 thalassemia intermedia, and 2 sickle cell beta thalassemia. The mean duration of treatment was 21.5 months (range 15–31. All children received the oral solution without any problems of compliance. Adverse reactions were temporary abdominal discomfort and diarrhea (1 child, mild neutropenia (1 child that resolved with no need of discontinuation of treatment, and transient arthralgia (1 child that resolved spontaneously. The mean ferritin levels were significantly reduced at the end of 12 months (initial 2440 versus final 1420 μg/L, . This small study shows that oral solution of deferiprone was well tolerated by young children and its use was not associated with major safety concerns. Furthermore, it was effective in decreasing serum ferritin.

  17. Gadolinium(III)-Chelated Silica Nanospheres Integrating Chemotherapy and Photothermal Therapy for Cancer Treatment and Magnetic Resonance Imaging.

    Science.gov (United States)

    Cao, Mingjing; Wang, Pengyang; Kou, Yu; Wang, Jing; Liu, Jing; Li, Yanhui; Li, Jiayang; Wang, Liming; Chen, Chunying

    2015-11-18

    The combination of therapy and diagnosis has been emerging as a promising strategy for cancer treatment. To realize chemotherapy, photothermal therapy, and magnetic resonance imaging (MRI) in one system, we have synthesized a new magnetic nanoparticle (Gd@SiO2-DOX/ICG-PDC) integrating doxorubicin (DOX), indocyanine green (ICG), and gadolinium(III)-chelated silica nanospheres (Gd@SiO2) with a poly(diallyldimethylammonium chloride) (PDC) coating. PDC coating serves as a polymer layer to protect from quick release of drugs from the nanocarriers and increase cellular uptake. The DOX release from Gd@SiO2-DOX/ICG-PDC depends on pH and temperature. The process will be accelerated in the acidic condition than in a neutral pH 7.4. Meanwhile, upon laser irradiation, the photothermal effects promote DOX release and improve the therapeutic efficacy compared to either DOX-loaded Gd@SiO2 or ICG-loaded Gd@SiO2. Moreover, MRI results show that the Gd@SiO2-PDC nanoparticles are safe T1-type MRI contrast agents for imaging. The Gd@SiO2-PDC nanoparticles loaded with DOX and ICG can thus act as a promising theranostic platform for multimodal cancer treatment.

  18. Chelation therapy for the management of diabetic complications: a hypothesis and a proposal for clinical laboratory assessment of metal ion homeostasis in plasma.

    Science.gov (United States)

    Frizzell, Norma; Baynes, John W

    2014-01-01

    In a recent article, we presented the hypothesis that decompartmentalized metal ions are a major contributor to the development of diabetic complications and supported the use of chelation therapy for the treatment of diabetic complications [Nagai R, Murray DB, Metz TO, Baynes JW. Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications. Diabetes 2012;61:549-59]. Evidence in support of this hypothesis included the observation that many drugs used in the treatment of diabetes are chelators, that advanced glycation end product (AGE) inhibitors and AGE breakers lack carbonyl-trapping or AGE-breaker activity but are potent chelators, and that simple copper chelators inhibit vascular pathology in diabetes and aging. In the present article, we extend this hypothesis, proposing the interplay between copper and iron in the development of pathology in diabetes and other chronic age-related diseases, including atherosclerosis and neurodegenerative diseases. We also discuss the need and provide a framework for the development of a clinical laboratory test to assess plasma autoxidative catalytic activity and transition metal homeostasis in vivo.

  19. Role of Oxidative Stress in the Worsening of Neurologic Wilson Disease Following Chelating Therapy.

    Science.gov (United States)

    Kalita, Jayantee; Kumar, Vijay; Ranjan, Abhay; Misra, Usha K

    2015-12-01

    Patients with neurologic Wilson disease (NWD) may worsen on treatment, but there is no study evaluating the role of oxidative stress. We report the role of plasma glutathione (GSH), total antioxidant capacity (TAC) and malondialdehyde (MDA) in the worsening of NWD following treatment. Fifty-one treatment-naïve NWD patients were subjected to detailed clinical evaluation. The severity of NWD was noted, and dystonia was measured by Burke-Fahn-Marsden (BFM) score. Their hematological, serum chemistry, ultrasound abdomen and cranial MRI changes were noted. Plasma GSH, TAC and MDA, serum free copper (Cu) and 24-h urinary Cu were measured at admission and at 3 and 6 months after treatment. The patients were considered worsened if there was one or more grade deterioration in severity scale, >10 % deterioration in BFM score or appearance of new neurologic signs. The median age of the patients was 11 (5-37) years, and 12 were females. Following treatment, 25 patients improved, 12 worsened, and 14 had stationary course. The worsened group at 3 months had lower GSH (1.99 ± 0.17 vs. 2.30 ± 0.30 mg/dl; P = 0.004) and TAC (1.59 ± 0.12 vs. 1.82 ± 0.17 mmol Trolox equivalent/L; P = 0.001) and higher MDA (5.24 ± 0.22 vs. 4.34 ± 0.46 nmol/ml; P < 0.001) levels compared to the improved group. These changes were associated with increased serum free Cu (41.81 ± 3.31 vs. 35.62 ± 6.40 µg/dl; P = 0.02) and 24-h urinary Cu (206.42 ± 41.61 vs. 121.99 ± 23.72 µg/24 h; P < 0.001) in the worsened compared to the improved group. All the patients having worsening were on penicillamine. Worsening following chelating treatment in NWD may be due to oxidative stress which is induced by increased serum free Cu. These results may have future therapeutic implication and needs further study.

  20. Iron Chelation Therapy with Deferasirox Results in Improvement of Liver Enzyme Level in Patients with Iron Overload-Associated Liver Dysfunction

    Science.gov (United States)

    Miura, Yasuo; Matsui, Yusuke; Kaneko, Hitomi; Watanabe, Mitsumasa; Tsudo, Mitsuru

    2010-01-01

    Iron chelation therapy (ICT) has been applied for the patients with iron overload-associated liver dysfunction since it is one of the causes of death in patients with intractable hematological diseases requiring multiple red blood cell transfusions. Recently, deferasirox (DSX), a novel, once-daily oral iron chelator, was demonstrated to have similar efficacy to the conventional continuous infusion of deferoxamine on a decrease in serum ferritin (SF) level in heavily transfused patients. We show three cases of transfusion-mediated iron-overloaded patients with an elevated serum alanine aminotransaminase (ALT). All three patients who received the ICT with DSX showed a decrease in ALT level in association with a decrease in SF level. It is suggested that DSX therapy could be considered to expect the improvement of liver damage for iron-overloaded patients with an abnormal ALT level. PMID:20592762

  1. Iron Chelation Therapy with Deferasirox Results in Improvement of Liver Enzyme Level in Patients with Iron Overload-Associated Liver Dysfunction

    Directory of Open Access Journals (Sweden)

    Yasuo Miura

    2010-01-01

    Full Text Available Iron chelation therapy (ICT has been applied for the patients with iron overload-associated liver dysfunction since it is one of the causes of death in patients with intractable hematological diseases requiring multiple red blood cell transfusions. Recently, deferasirox (DSX, a novel, once-daily oral iron chelator, was demonstrated to have similar efficacy to the conventional continuous infusion of deferoxamine on a decrease in serum ferritin (SF level in heavily transfused patients. We show three cases of transfusion-mediated iron-overloaded patients with an elevated serum alanine aminotransaminase (ALT. All three patients who received the ICT with DSX showed a decrease in ALT level in association with a decrease in SF level. It is suggested that DSX therapy could be considered to expect the improvement of liver damage for iron-overloaded patients with an abnormal ALT level.

  2. Optimising iron chelation therapy with deferasirox for non-transfusion-dependent thalassaemia patients: 1-year results from the THETIS study.

    Science.gov (United States)

    Taher, Ali T; Cappellini, M Domenica; Aydinok, Yesim; Porter, John B; Karakas, Zeynep; Viprakasit, Vip; Siritanaratkul, Noppadol; Kattamis, Antonis; Wang, Candace; Zhu, Zewen; Joaquin, Victor; Uwamahoro, Marie José; Lai, Yong-Rong

    2016-03-01

    Efficacy and safety of iron chelation therapy with deferasirox in iron-overloaded non-transfusion-dependent thalassaemia (NTDT) patients were established in the THALASSA study. THETIS, an open-label, single-arm, multicentre, Phase IV study, added to this evidence by investigating earlier dose escalation by baseline liver iron concentration (LIC) (week 4: escalation according to baseline LIC; week 24: adjustment according to LIC response, maximum 30mg/kg/day). The primary efficacy endpoint was absolute change in LIC from baseline to week 52. 134 iron-overloaded non-transfusion-dependent anaemia patients were enrolled and received deferasirox starting at 10mg/kg/day. Mean actual dose±SD over 1year was 14.70±5.48mg/kg/day. At week 52, mean LIC±SD decreased significantly from 15.13±10.72mg Fe/g dw at baseline to 8.46±6.25mg Fe/g dw (absolute change from baseline, -6.68±7.02mg Fe/g dw [95% CI: -7.91, -5.45]; P<0.0001). Most common drug-related adverse events were gastrointestinal: abdominal discomfort, diarrhoea and nausea (n=6 each). There was one death (pneumonia, not considered drug related). With significant and clinically relevant reductions in iron burden alongside a safety profile similar to that in THALASSA, these data support earlier escalation with higher deferasirox doses in iron-overloaded non-transfusion-dependent anaemia patients.

  3. [Anomalies of the masticatory apparatus in beta-thalassemia. The present status after transfusion and iron-chelating therapy].

    Science.gov (United States)

    Scutellari, P N; Orzincolo, C; Andraghetti, D; Gamberini, M R

    1994-04-01

    Fifty-four homozygous beta-thalassemic patients (26 men and 28 women) aged 7 to 24 years, who had been treated with high transfusion regimen (Hb levels = 9-10 g/dl) and chelation therapy (desferrioxamine, 35-50 mg/kg), underwent clinical and radiographic investigations. This study was aimed at assessing the clinical and radiographic changes in the stomatognathic system (teeth, mandible and maxilla, occlusion relationship and dental bases). All patients underwent orthopantomography and teleradiography of the skull, in the lateral view. Twenty thalassemic patients (13 men and 7 women) of the same age but treated with low transfusion regimes (Hb levels = 5-6 g/dl) were examined as a control group. Our results indicate that: 1) in the control group, osteopenia is the specific lesion of anemia, in both the alveolar process and the mandible, following marrow expansion. Consequently, diastema of incisors and several types of malocclusion follow--i.e., overjet, anterior open-bite and crossbite, nearly all of them associated with II dental and skeletal patterns of Angle's classification. 2) In adequately transfused patients, no lesions are observed in 55% of cases, in both the teeth and the facial skeleton. This means that current treatment methods can prevent bone abnormalities, especially if transfusions begin at birth. Nevertheless, osteopenia of the mandible (31.4%) and dental and/or skeletal malocclusions (40.7%) remain in many cases, because of persistent marrow expansion, which usually follows incorrect treatment. 3) General dental diseases--e.g., caries, paradentosis, gingivitis, etc.--affect both populations with the same incidence.

  4. Reversible lesions in the brain parenchyma in Wilson's disease confirmed by magnetic resonance imaging: earlier administration of chelating therapy can reduce the damage to the brain.

    Science.gov (United States)

    Kozić, Duško B; Petrović, Igor; Svetel, Marina; Pekmezović, Tatjana; Ragaji, Aleksandar; Kostić, Vladimir S

    2014-11-01

    The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson's disease during the long-term chelating therapy using magnetic resonance imaging and a possible significance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson's disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 ± 1.3 years later in 14 patients. Patients were divided into: group A, where chelating therapy was initiated < 24 months from the first symptoms and group B, where the therapy started ≥ 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a significant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions (P = 0.005 and P = 0.024, respectively). If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be expected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity.

  5. Role of iron metabolism genetic determinants in response to chelation therapy in a cohort of β-thalassemia and sickle cell syndromes Italian patients

    Directory of Open Access Journals (Sweden)

    Maria Concetta Renda

    2014-09-01

    Full Text Available In patients with β-thalassemia and sickle cell syndromes there is an important secondary iron overload due to regular blood transfusions and increased duodenal iron absorption. As in genetic hemochromatosis, also the secondary iron storage leads to tissue injury that involves all the major organs: liver, heart, kidney, endocrine glands. At present, in patients with β-thalassemia and sickle cell syndrome, iron chelation therapy is widely used for the treatment of secondary hemochromatosis, to limit the toxic effects of iron overload. In order to maintain the correct homeostasis, several genes are involved in the metabolic pathways of iron, including HFE, FPN (ferroportin and TF (transferrin. In this study we analyzed the genes HFE, FPN and TF, to assess their possible effects on response to therapy with deferasirox and deferiprone, either as monotherapy or in combination therapy in a cohort of patients with β-thalassemia and sickle cell syndromes.

  6. Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes

    Directory of Open Access Journals (Sweden)

    Kontoghiorghe CN

    2016-01-01

    Full Text Available Christina N Kontoghiorghe, George J Kontoghiorghes Postgraduate Research Institute of Science, Technology, Environment and Medicine, Limassol, Cyprus Abstract: The prevalence rate of thalassemia, which is endemic in Southeast Asia, the Middle East, and the Mediterranean, exceeds 100,000 live births per year. There are many genetic variants in thalassemia with different pathological severity, ranging from a mild and asymptomatic anemia to life-threatening clinical effects, requiring lifelong treatment, such as regular transfusions in thalassemia major (TM. Some of the thalassemias are non-transfusion-dependent, including many thalassemia intermedia (TI variants, where iron overload is caused by chronic increase in iron absorption due to ineffective erythropoiesis. Many TI patients receive occasional transfusions. The rate of iron overloading in TI is much slower in comparison to TM patients. Iron toxicity in TI is usually manifested by the age of 30–40 years, and in TM by the age of 10 years. Subcutaneous deferoxamine (DFO, oral deferiprone (L1, and DFO–L1 combinations have been effectively used for more than 20 years for the treatment of iron overload in TM and TI patients, causing a significant reduction in morbidity and mortality. Selected protocols using DFO, L1, and their combination can be designed for personalized chelation therapy in TI, which can effectively and safely remove all the excess toxic iron and prevent cardiac, liver, and other organ damage. Both L1 and DF could also prevent iron absorption. The new oral chelator deferasirox (DFX increases iron excretion and decreases liver iron in TM and TI. There are drawbacks in the use of DFX in TI, such as limitations related to dose, toxicity, and cost, iron load of the patients, and ineffective removal of excess iron from the heart. Furthermore, DFX appears to increase iron and other toxic metal absorption. Future treatments of TI and related iron-loading conditions could involve

  7. Iron chelation therapy with deferasirox in patients with aplastic anemia: a subgroup analysis of 116 patients from the EPIC trial

    DEFF Research Database (Denmark)

    Lee, Jong Wook; Yoon, Sung-Soo; Shen, Zhi Xiang

    2010-01-01

    The prospective 1-year Evaluation of Patients' Iron Chelation with Exjade (EPIC) study enrolled a large cohort of 116 patients with aplastic anemia; the present analyses evaluated the efficacy and safety of deferasirox in this patient population. After 1 year, median serum ferritin decreased...... neutrophil and platelet counts remained stable during treatment, and there were no drug-related cytopenias. This prospective dataset confirms the efficacy and well characterizes the tolerability profile of deferasirox in a large population of patients with aplastic anemia. This study was registered at www...

  8. Overview of chelation recommendations for thalassaemia and sickle cell disease

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    Banu Kaya

    2014-12-01

    Full Text Available The long term consequences of iron toxicity are mostly reversible with effective iron chelation therapy. Recommendations for use of chelation therapy in transfusion dependent thalassaemia (TDT, sickle cell disease (SCD and non transfusion dependent thalassaemia (NTDT continue to evolve as our knowledge and clinical experience increases. Improved chelation options including drug combinations and a better understanding of condition specific factors may help to improve efficiency of chelation regimens and meet the needs of patients more effectively.

  9. Beliefs about chelation among thalassemia patients

    Directory of Open Access Journals (Sweden)

    Trachtenberg Felicia L

    2012-12-01

    Full Text Available Abstract Background Understanding patients’ views about medication is crucial to maximize adherence. Thalassemia is a congenital blood disorder requiring chronic blood transfusions and daily iron chelation therapy. Methods The Beliefs in Medicine Questionnaire (BMQ was used to assess beliefs in chelation in thalassemia patients from North America and London in the Thalassemia Longitudinal Cohort (TLC of the Thalassemia Clinical Research Network (TCRN. Chelation adherence was based on patient report of doses administered out of those prescribed in the last four weeks. Results Of 371 patients (ages 5-58y, mean 24y, 93% were transfused and 92% receiving chelation (26% deferoxamine (DFO; a slow subcutaneous infusion via portable pump, 63% oral, 11% combination. Patients expressed high “necessity” for transfusion (96%, DFO chelation (92% and oral chelation (89%, with lower “concern” about treatment (48%, 39%, 19% respectively. Concern about oral chelation was significantly lower than that of DFO (p Conclusions Despite their requirement for multimodal therapy, thalassemia patients have positive views about medicine, more so than in other disease populations. Patients may benefit from education about the tolerability of chelation and strategies to effectively cope with side effects, both of which might be beneficial in lowering body iron burden. Clinicaltrials.gov identifier NCT00661804

  10. Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with nontransfusion-dependent thalassemia syndromes

    Directory of Open Access Journals (Sweden)

    Taher AT

    2016-12-01

    Full Text Available Ali T Taher,1 John B Porter,2 Antonis Kattamis,3 Vip Viprakasit,4 M Domenica Cappellini51Department of Internal Medicine, American University of Beirut, Beirut, Lebanon; 2Department of Haematology, University College London, London, UK; 3First Department of Pediatrics, University of Athens, Athens, Greece; 4Department of Pediatrics and Thalassemia Center, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 5Department of Internal Medicine, Università di Milano, Ca Granda Foundation IRCCS, Milan, ItalyAs the scientific steering committee for THALASSA (an assessment of Exjade in nontransfusion-dependent thalassemia [NTDT], we read with interest the review by Kontoghiorghe and Kontoghiorghes entitled “Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes” published in January 2016.1 While this review provides a detailed overview of available iron chelators for the treatment of NTDT patients, there remain some factual inaccuracies and misrepresentations of data related to deferasirox. Therefore, we believe that the current article may be misleading to readers of Drug Design, Development and Therapy.Author’s replyGeorge J KontoghiorghesPostgraduate Research Institute of Science, Technology, Environment and Medicine, Limassol, CyprusThere are many murky areas and marketing, legal, ethical, and other conflicts in the pharmaceutical industry, some of which involve physicians and academics. These activities and related ethical issues affect the safety and treatment of millions of patients.1–11 Irregular and sometimes illegal activities for new patented drugs carried out by pharmaceutical companies, such as secrecy agreements with academics/academic institutions, can lead to biased reporting of the results of clinical trials and cover ups or underreporting of toxic side effects, as well as doctor’s bribes

  11. The scientific basis for chelation: animal studies and lead chelation.

    Science.gov (United States)

    Smith, Donald; Strupp, Barbara J

    2013-12-01

    This presentation summarizes several of the rodent and non-human studies that we have conducted to help inform the efficacy and clinical utility of succimer (meso-2,3-dimercaptosuccincinic acid) chelation treatment. We address the following questions: (1) What is the extent of body lead, and in particular brain lead reduction with chelation, and do reductions in blood lead accurately reflect reductions in brain lead? (2) Can succimer treatment alleviate the neurobehavioral impacts of lead poisoning? And (3) does succimer treatment, in the absence of lead poisoning, produce neurobehavioral deficits? Results from our studies in juvenile primates show that succimer treatment is effective at accelerating the elimination of lead from the body, but chelation was only marginally better than the complete cessation of lead exposure alone. Studies in lead-exposed adult primates treated with a single 19-day course of succimer showed that chelation did not measurably reduce brain lead levels compared to vehicle-treated controls. A follow-up study in rodents that underwent one or two 21-day courses of succimer treatment showed that chelation significantly reduced brain lead levels, and that two courses of succimer were significantly more efficacious at reducing brain lead levels than one. In both the primate and rodent studies, reductions in blood lead levels were a relatively poor predictor of reductions in brain lead levels. Our studies in rodents demonstrated that it is possible for succimer chelation therapy to alleviate certain types of lead-induced behavioral/cognitive dysfunction, suggesting that if a succimer treatment protocol that produced a substantial reduction of brain lead levels could be identified for humans, a functional benefit might be derived. Finally, we also found that succimer treatment produced lasting adverse neurobehavioral effects when administered to non-lead-exposed rodents, highlighting the potential risks of administering succimer or other metal-chelating

  12. Iron Chelation and Multiple Sclerosis

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    Kelsey J. Weigel

    2014-01-01

    Full Text Available Histochemical and MRI studies have demonstrated that MS (multiple sclerosis patients have abnormal deposition of iron in both gray and white matter structures. Data is emerging indicating that this iron could partake in pathogenesis by various mechanisms, e.g., promoting the production of reactive oxygen species and enhancing the production of proinflammatory cytokines. Iron chelation therapy could be a viable strategy to block iron-related pathological events or it can confer cellular protection by stabilizing hypoxia inducible factor 1α, a transcription factor that normally responds to hypoxic conditions. Iron chelation has been shown to protect against disease progression and/or limit iron accumulation in some neurological disorders or their experimental models. Data from studies that administered a chelator to animals with experimental autoimmune encephalomyelitis, a model of MS, support the rationale for examining this treatment approach in MS. Preliminary clinical studies have been performed in MS patients using deferoxamine. Although some side effects were observed, the large majority of patients were able to tolerate the arduous administration regimen, i.e., 6–8 h of subcutaneous infusion, and all side effects resolved upon discontinuation of treatment. Importantly, these preliminary studies did not identify a disqualifying event for this experimental approach. More recently developed chelators, deferasirox and deferiprone, are more desirable for possible use in MS given their oral administration, and importantly, deferiprone can cross the blood–brain barrier. However, experiences from other conditions indicate that the potential for adverse events during chelation therapy necessitates close patient monitoring and a carefully considered administration regimen.

  13. Overview of current chelation practices

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    Y. Aydinok

    2011-12-01

    Full Text Available Deferoxamine (DFO is reference standard therapy for transfusional iron overload since the 1980s. Although it is a highly effective iron chelator, the compliance problem to subcutaneous administration of DFO remains as the major problem. The oral chelator Deferiprone (DFP has no marketing licence in North America, however, it has been licensed in India since 1994 and the European Union (EU granted marketing approval for DFP in 1999, specifically for patients with thalassemia major when DFO is inadequate, intolerable or unacceptable. There are still limited data available on the use of DFP in children between 6 and 10 years of age, and no data on DFP use in children under 6 years of age. Subsequently the oral chelator Deferasirox (DFX was approved by FDA and EMA for the treatment of patients with transfusional iron overload -older than 2 years of age- as first line therapy, in 2005 and 2006 respectively. The primary objective of iron chelation is to maintain body iron at safe levels at all times but once iron is accumulated, the objective of iron chelation is to reduce tissue iron to safe levels which is a slow process. The chelation regimen, dose and frequency of administration, of the chelator(s are mainly determined based on body iron burden, presence of myocardial iron and the transfusional iron loading rate. A proper monitoring of chelation is of importance for measuring the response rate to a particular regimen and providing dose adjustments to enhance chelation efficacy and to avoid toxicity. Efficacy of a chelation regimen may exhibit individual variability resulting from factors such as absorbtion and metabolism of the chelator. Tolerability and compliance are also individual variables effecting the response to chelation. Understanding of advantages and limitations of chelators, accurately determining chelation needs of patients with iron overload and designing individualized chelation regimens with less toxicity but optimum efficacy

  14. Current recommendations for chelation for transfusion-dependent thalassemia.

    Science.gov (United States)

    Kwiatkowski, Janet L

    2016-03-01

    Regular red cell transfusions used to treat thalassemia cause iron loading that must be treated with chelation therapy. Morbidity and mortality in thalassemia major are closely linked to the adequacy of chelation. Chelation therapy removes accumulated iron and detoxifies iron, which can prevent and reverse much of the iron-mediated organ injury. Currently, three chelators are commercially available--deferoxamine, deferasirox, and deferiprone--and each can be used as monotherapy or in combination. Close monitoring of hepatic and cardiac iron burden is central to tailoring chelation. Other factors, including properties of the individual chelators, ongoing transfusional iron burden, and patient preference, must be considered. Monotherapy generally is utilized if the iron burden is in an acceptable or near-acceptable range and the dose is adjusted accordingly. Combination chelation often is employed for patients with high iron burden, iron-related organ injury, or where adverse effects of chelators preclude administration of an appropriate chelator dose. The combination of deferoxamine and deferiprone is the best studied, but increasing data are available on the safety and efficacy of newer chelator combinations, including deferasirox with deferoxamine and the oral-only combination of deferasirox with deferiprone. The expanding chelation repertoire should enable better control of iron burden and improved outcomes.

  15. Reversible lesions in the brain parenchyma in Wilson’s disease conifrmed by magnetic resonance imaging:earlier administration of chelating therapy can reduce the damage to the brain

    Institute of Scientific and Technical Information of China (English)

    Duko B Kozi; Igor Petrovi; Marina Svetel; Tatjana Pekmezovi; Aleksandar Ragaji; Vladimir S Kosti

    2014-01-01

    The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson’s disease during the long-term chelating therapy using magnetic resonance imaging and a possible signiifcance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson’s disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 ± 1.3 years later in 14 patients. Patients were divided into: group A, where chelating therapy was initiated < 24 months from the ifrst symp-toms and group B, where the therapy started≥ 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a signiifcant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions (P= 0.005 andP=0.024, respectively). If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be ex-pected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity.

  16. The Chelate Effect Redefined.

    Science.gov (United States)

    da Silva, J. J. R. Frausto

    1983-01-01

    Discusses ambiguities of the accepted definition of the chelate effect, suggesting that it be defined in terms of experimental observation rather than mathematical abstraction. Indicates that the effect depends on free energy change in reaction, ligand basicity, pH of medium, type of chelates formed, and concentration of ligands in solution. (JN)

  17. Tratamento de suporte e quelação de ferro em pacientes com síndromes mielodisplásicas Supportive care, tranfusion and chelation therapy for patients with myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Elizabeth X. Souto

    2006-09-01

    Full Text Available As síndromes mielodisplásicas (SMD são um grupo heterogêneo de distúrbios hematológicos que ocorrem mais freqüentemente em pacientes idosos e que cursa, na maioria dos casos, com anemia crônica dependente de transfusão de hemoderivados. Conseqüentemente, muitos destes pacientes passam a apresentar sobrecarga de ferro, que pode levar a danos teciduais graves. Ambas as terapias, transfusional e de quelação de ferro, quando indicadas, são importantes para manter a sobrevida e a qualidade de vida destes pacientes. A terapia de quelação de ferro está indicada especialmente nos subtipos de SMD com melhor prognóstico e sobrevida longa o suficiente para o desenvolvimento de sobrecarga de ferro com relevância clínica. A terapia de quelação de ferro apresenta algumas limitações relacionadas à necessidade de longo tempo de infusão da deferoxamina, da dificuldade de adesão pelo paciente, bem como da aquisição da bomba de infusão. O uso da deferiprona, que é um quelante oral de ferro, está contra-indicado neste grupo de pacientes, pelo risco de neutropenia e agranulocitose. O deferasirox é um novo quelante oral de ferro em estudo e que poderá, no futuro, ser uma opção adequada para os pacientes com SMD e sobrecarga de ferro. Novos estudos em pacientes com síndromes mielodisplásicas são necessários para melhor estabelecer critérios de diagnóstico da sobrecarga de ferro, bem com da terapia de quelação neste grupo.Myelodysplastic syndromes (MDSs are a heterogeneous group of hematological disorders which are more common in the elderly and related to chronic anemia dependent on blood transfusions. Consequently, many of these patients develop iron overload which may lead to severe injury to tissues. Transfusions and chelation therapy, when indicated, are important for survival and to maintain the quality of life. Chelation therapy is indicated especially for MDS subtypes with a better prognosis and a sufficiently long

  18. Chelating polymeric membranes

    KAUST Repository

    Peinemann, Klaus-Viktor

    2015-01-22

    The present application offers a solution to the current problems associated with recovery and recycling of precious metals from scrap material, discard articles, and other items comprising one or more precious metals. The solution is premised on a microporous chelating polymeric membrane. Embodiments include, but are not limited to, microporous chelating polymeric membranes, device comprising the membranes, and methods of using and making the same.

  19. Tin-117m-labeled stannic (Sn/sup 4 +/) chelate of diethylenetriamine pentaacetic acid (DTPA) for application in diagnosis and therapy

    Science.gov (United States)

    Srivastava, S.C.; Meinken, G.E.; Richards, P.

    1983-08-25

    The radiopharmaceutical reagents of this invention and the class of Tin-117m radiopharmaceuticals are therapeutic and diagnostic agents that incorporate gamma-emitting nuclides that localize in bone after intravenous injection in mammals (mice, rats, dogs, and rabbits). Images reflecting bone structure or function can then be obtained by a scintillation camera that detects the distribution of ionizing radiation emitted by the radioactive agent. Tin-117m-labeled chelates of stannic tin localize almost exclusively in cortical bone. Upon intravenous injection of the reagent, the preferred chelates are phosphonate compounds, preferable, PYP, MDP, EHDP, and DTPA. This class of reagents is therapeutically and diagnostically useful in skeletal scintigraphy and for the radiotherapy of bone tumors and other disorders.

  20. Aluminium, iron, zinc and copper influence the in vitro formation of amyloid fibrils of Abeta42 in a manner which may have consequences for metal chelation therapy in Alzheimer's disease.

    Science.gov (United States)

    House, Emily; Collingwood, Joanna; Khan, Ayesha; Korchazkina, Olga; Berthon, Guy; Exley, Christopher

    2004-06-01

    Metals are found associated with beta-pleated sheets of Abeta42 in vivo and may be involved in their formation. Metal chelation has been proposed as a therapy for Alzheimer's disease on the basis that it may safely dissolve precipitated Abeta peptides. We have followed fibrillisation of Abeta42 in the presence of an additional metal ion (Al(III), Fe(III), Zn(II), Cu(II)) over a period of 32 weeks and we have investigated the dissolution of these aged peptide aggregates in the presence of both desferrioxamine (DFO) and ethylenediaminetetraacetic acid (EDTA). Abeta42 either alone or in the presence of Al(III) or Fe(III) formed beta-pleated sheets of plaque-like amyloids which were dissolved upon incubation with either chelator. Zn(II) inhibited whilst Cu(II) prevented the formation of beta-pleated sheets of Abeta42and neither of these influences were affected by incubation of the aged peptide aggregates with either DFO or EDTA. Freshly prepared solutions of Abeta42 either alone or in the presence of added Al(III) or Fe(III) did not form beta-pleated amyloid in the presence of DFO when incubated for up to 8 weeks. EDTA did not prevent beta-pleated amyloid formation in the same treatments and promoted beta-pleated amyloid formation in the presence of either Zn(II) or Cu(II). The presence of significant concentrations of Al(III) and Fe(III) as contaminants of 'Abeta42 only' preparations suggested that both of these metals were involved in either triggering the formation or stabilising the structure of beta-pleated amyloid. If the formation of such amyloid is critical to the aetiology of AD then the chelation of Al(III) and Fe(III) may prove to be a protective mechanism whilst the chelation of Cu(II) and Zn(II) without also chelating Al(III) and Fe(III) might actually exacerbate the condition.

  1. Terapia quelante oral com deferiprona em pacientes com sobrecarga de ferro Oral iron chelator therapy with deferiprone in patients with overloaded iron

    Directory of Open Access Journals (Sweden)

    Antonio Fabron Jr

    2003-01-01

    Full Text Available Apesar da introdução da quelação parenteral de ferro com desferoxamina há mais de trinta anos, 50% dos pacientes com talassemia major morrem antes dos 35 anos de idade, predominantemente por insuficiência cardíaca secundária a sobrecarga de ferro. Embora a desferrioxamina, possa reduzir ou estabilizar o acúmulo de ferro no corpo, um grande número de pacientes não recebe terapia adequada com este quelante devido principalmente à intolerância a um regime que requer administração parenteral prolongada, cinco a sete dias por semana. Para esses pacientes, a deferiprona, um quelante oralmente ativo, surge com uma alternativa de tratamento para o controle da sobrecarga de ferro. Um grande número de estudos clínicos demonstraram a segurança e eficácia da deferiprona. Estima-se que mais de 6 mil pacientes com sobrecarga de ferro já tenham sido tratados com este quelante, com alguns pacientes tomando a droga por mais de dez anos. A quantidade de ferro excretada induzida pela deferiprona é diretamente influenciada pela dose da droga e pelo grau de sobrecarga de ferro do paciente. Recentemente, demonstrou-se que desferrioxamina e deferiprona exibem capacidades quelantes diversas e que, usados simultaneamente ou numa terapia sequencial, promovem uma excreção de ferro adicional ou sinérgica com rápida redução na carga de ferro do corpo. Pela primeira vez é possível considerar esquemas de quelação individualizados baseados nas necessidades individuais de cada paciente.Despite the introduction of the parenteral iron chelator desferrioxamine more than 30 years ago, 50% of patients with thalassemia major die before the age of 35 years, predominantly due to iron-induced heart failure. Although desferrioxamine can reduce or stabilize the iron load, many patients still do not receive adequate chelation mainly due to its cumbersome mode of administration which impairs the compliance with the regime of repeatedly subcutaneous infusions

  2. The Oral Iron Chelator, Deferasirox, Reverses the Age-Dependent Alterations in Iron and Amyloid-β Homeostasis in Rat Brain: Implications in the Therapy of Alzheimer's Disease.

    Science.gov (United States)

    Banerjee, Priyanjalee; Sahoo, Arghyadip; Anand, Shruti; Bir, Aritri; Chakrabarti, Sasanka

    2016-01-01

    The altered metabolism of iron impacts the brain function in multiple deleterious ways during normal aging as well as in Alzheimer's disease. We have shown in this study that chelatable iron accumulates in the aged rat brain along with overexpression of transferrin receptor 1 (TfR1) and ferritin, accompanied by significant alterations in amyloid-β (Aβ) peptide homeostasis in the aging brain, such as an increased production of the amyloid-β protein precursor, a decreased level of neprilysin, and increased accumulation of Aβ42. When aged rats are given daily the iron chelator, deferasirox, over a period of more than 4 months starting from the 18th month, the age-related accumulation of iron and overexpression of TfR1 and ferritin in the brain are significantly prevented. More interestingly, the chelator treatment also considerably reverses the altered Aβ peptide metabolism in the aging brain implying a significant role of iron in the latter phenomenon. Further, other results indicate that iron accumulation results in oxidative stress and the activation of NF-κB in the aged rat brain, which are also reversed by the deferasirox treatment. The analysis of the results together suggests that iron accumulation and oxidative stress interact at multiple levels that include transcriptional and post-transcriptional mechanisms to bring about changes in the expression levels of TfR1 and ferritin and also alterations in Aβ peptide metabolism in the aging rat brain. The efficacy of deferasirox in preventing age-related changes in iron and Aβ peptide metabolism in the aging brain, as shown here, has obvious therapeutic implications for Alzheimer's disease.

  3. Iron chelating agents for iron overload diseases

    Directory of Open Access Journals (Sweden)

    Guido Crisponi

    2014-09-01

    Full Text Available Although iron is an essential element for life, an excessive amount may become extremely toxic both for its ability to generate reactive oxygen species, and for the lack in humans of regulatory mechanisms for iron excretion. Chelation therapy has been introduced in clinical practice in the seventies of last century to defend thalassemic patients from the effects of iron overload and, in spite of all its limitations, it has dramatically changed both life expectancy and quality of life of patients. It has to be considered that the drugs in clinical use present some disadvantages too, this makes urgent new more suitable chelating agents. The requirements of an iron chelator have been better and better defined over the years and in this paper they will be discussed in detail. As a final point the most interesting ligands studied in the last years will be presented.

  4. Nutritional abrogation of photoimmunosuppression: in vivo investigations.

    Science.gov (United States)

    Pilkington, Suzanne M; Gibbs, Neil K; Friedmann, Peter S; Rhodes, Lesley E

    2014-01-01

    Skin cancer is a major public health concern, and the primary aetiological factor in the majority of skin cancers is ultraviolet radiation (UVR) exposure. UVR not only induces potentially mutagenic DNA damage but also suppresses cell-mediated immunity (CMI), allowing cancerous cells to escape destruction and progress to tumours. A considerable proportion of an individual's annual sun exposure is obtained outside the vacation period when topical and physical measures for photoprotection are irregularly used. Certain nutrients could provide an adjunctive protective role, and evidence is accruing from experimental studies to support their use in abrogation of photoimmunosuppression. Moreover, developments in clinical research methods to evaluate impact of solar-simulated radiation on cutaneous CMI allow the immune protective potential of nutritional agents to be examined in humans in vivo. This article summarises the mediation of CMI and its suppression by UVR, evaluates the methodology for quantitative assessment in vivo, reviews the human studies reported on nutritional abrogation of photoimmunosuppression including recent randomized controlled trials and discusses the mechanisms of photoprotection by the nutrients. This includes, in addition to antioxidants, novel studies of omega-3 polyunsaturated fatty acids and nicotinamide.

  5. Nanoparticle and other metal chelation therapeutics in Alzheimer disease.

    Science.gov (United States)

    Liu, Gang; Garrett, Matthew R; Men, Ping; Zhu, Xiongwei; Perry, George; Smith, Mark A

    2005-09-25

    Current therapies for Alzheimer disease (AD) such as the anticholinesterase inhibitors and the latest NMDA receptor inhibitor, Namenda, provide moderate symptomatic delay at various stages of disease, but do not arrest disease progression or supply meaningful remission. As such, new approaches to disease management are urgently needed. Although the etiology of AD is largely unknown, oxidative damage mediated by metals is likely a significant contributor since metals such as iron, aluminum, zinc, and copper are dysregulated and/or increased in AD brain tissue and create a pro-oxidative environment. This role of metal ion-induced free radical formation in AD makes chelation therapy an attractive means of dampening the oxidative stress burden in neurons. The chelator desferioxamine, FDA approved for iron overload, has shown some benefit in AD, but like many chelators, it has a host of adverse effects and substantial obstacles for tissue-specific targeting. Other chelators are under development and have shown various strengths and weaknesses. In this review, we propose a novel system of chelation therapy through the use of nanoparticles. Nanoparticles conjugated to chelators show a unique ability to cross the blood-brain barrier (BBB), chelate metals, and exit through the BBB with their corresponding complexed metal ions. This method may prove to be a safe and effective means of reducing the metal load in neural tissue thus staving off the harmful effects of oxidative damage and its sequelae.

  6. Bifunctional chelate formers for Tc and Re isotope complexing - preparation, disengagement of conjugated compounds, diagnostic and therapeutical uses. Bifunktionelle Chelatbildner zur Komplexierung von Tc- und Re-Isotopen, Verfahren zu ihrer Herstellung und Darstellung von Konjugaten daraus sowie deren Verwendung in Diagnostik und Therapie

    Energy Technology Data Exchange (ETDEWEB)

    Neumeier, R.; Kramp, W.; Maecke, H.R.

    1991-03-21

    The proposed bifunctional chelate formers have a functional and/or activated group for selective-compound coupling and functional groups for dative bonding of metal ions from carrying groups. The new compounds are used for Tc and Re isotope complexing. The respective conjugated compounds are used in medical diagnostics and therapy.

  7. Deferasirox, an oral chelator in the treatment of iron overload

    OpenAIRE

    I. Portioli

    2013-01-01

    BACKGROUND Deferasirox is a once-daily oral iron chelator developed for treating iron overload complicating long-term transfusion therapy in patients with diseases such as beta-thalassemia and myelodysplastic syndromes. Iron overload can damage the liver, pancreas and the heart. Deferoxamine, the only other drug approved for iron chelation, can prevent these effects but requires parenteral administration. Deferasirox has been approved after a one-year, open-label trial in patients ≥ 2 years o...

  8. Minimal role of metallothionein in decreased chelator efficacy for cadmium.

    Science.gov (United States)

    Waalkes, M P; Watkins, J B; Klaassen, C D

    1983-05-01

    Chelator efficacy in Cd poisoning drops precipitously if therapy is not commenced almost immediately after exposure. Metallothionein (MT), a low-molecular-weight metal-binding protein with high affinity for Cd, may be important for this phenomenon. To more fully assess this role of MT in the acute drop in chelator efficacy following Cd poisoning, rats were injected iv with radioisotopic Cd (1mg/kg as CdCl2; 50 muCi/kg) followed by diethylenetriaminepentaacetic acid (DTPA; 90 mg/kg ip) at various times (0, 15, 30, 60, and 120 min) after Cd. Ther percentage of the Cd dose remaining in major organs 24 hr following Cd was determined. Although DTPA reduced Cd content in the various organs when given immediately after Cd, the chelator was ineffective at all later times. Increases in hepatic and renal MT did not occur until 2 hr after Cd, and did not coincide with the earlier drop in chelator efficacy. Blockade of MT synthesis by actinomycin D treatment (1.25 mg/kg, 1 hr before Cd) failed to prolong the chelators effectiveness. Furthermore, newborn rats have high levels of hepatic MT which had no effect on the time course of chelator effectiveness since DTPA still decreased Cd organ contents if given immediately following Cd but had no effect if given 2 hr after Cd. Therefore, if appears that MT does not have an important role in the acute decrease in efficacy of chelation therapy for Cd poisoning. The quick onset of chelator ineffectiveness may be due to the rapid uptake of Cd into tissues which makes it relatively unavailable of chelation.

  9. Chelated minerals for poultry

    Directory of Open Access Journals (Sweden)

    SL Vieira

    2008-06-01

    Full Text Available Organic minerals have been subject of an increasing number of investigations recently. These compounds can be considered the most significant event regarding commercial forms of minerals targeting animal supplementation in the last decades. Minerals, especially metals, are usually supplemented in poultry feeds using cheap saline sources and have never required a lot of attention in terms of quality. On the other hand, definitions of organic minerals are very broad and frequently lead to confusion when decision-making becomes necessary. Organic minerals include any mineral bound to organic compounds, regardless of the type of existing bond between mineral and organic molecules. Proteins and carbohydrates are the most frequent candidates in organic mineral combinations. Organic fraction size and bond type are not limitations in organic mineral definition; however, essential metals (Cu, Fe, Zn, and Mn can form coordinated bonds, which are stable in intestinal lumen. Metals bound to organic ligands by coordinated bonds can dissociate within animal metabolism whereas real covalent bonds cannot. Chelated minerals are molecules that have a metal bound to an organic ligand through coordinated bonds; but many organic minerals are not chelates or are not even bound through coordinated bonds. Utilization of organic minerals is largely dependent on the ligand; therefore, amino acids and other small molecules with facilitated access to the enterocyte are supposed to be better utilized by animals. Organic minerals with ligands presenting long chains may require digestion prior to absorption. After absorption, organic minerals may present physiological effects, which improve specific metabolic responses, such as the immune response. Many studies have demonstrated the benefits of metal-amino acid chelates on animal metabolism, but the detection positive effects on live performance is less consistent.

  10. Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.

    Science.gov (United States)

    Sankrityayan, Himanshu; Majumdar, Anuradha S

    2016-01-01

    Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 μg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels.

  11. Combination Iron Chelation Therapy with Deferiprone and Deferasirox in Iron-Overloaded Patients with Transfusion-Dependent β-Thalassemia Major

    Science.gov (United States)

    Karami, Hossein; Kosaryan, Mehrnoush; Amree, Arash Hadian; Darvishi-Khezri, Hadi; Mousavi, Masoomeh

    2017-01-01

    There are few papers on the combination therapy of deferiprone (DFP) and deferasirox (DFX) in iron-overloaded patients with transfusion-dependent β-thalassemia major (β-TM). A total of 6 patients with β-TM (5 males and 1 female) with a mean age of 23.8±5.8 years (ranging from 17 to 31) used this treatment regimen. The mean doses of DFP and DFX were 53.9±22.2 and 29.3±6.8 mg/kg/day, respectively. The duration of treatment was 11.5±4.6 months. Their serum ferritin levels were measured to be 2800±1900 and 3400±1600 ng/mL before and after treatment, respectively (p<0.6). Their cardiac magnetic resonance imaging (MRI) T2* values were 16.69±15.35 vs 17.38±5.74 millisecond (ms) before and after treatment, respectively (p < 0.9). Although there was no significant difference between their cardiac MRI T2* values before and after treatment statistically, the values improved after combination therapy with DFP and DFX in most of the patients. Liver MRI T2 * values were changed from 2.12±0.98 to 3.03±1.51 ms after treatment (p < 0.01); Further, their liver T2* values and liver iron concentration (LIC) were improved after treatment. Our study found that cardiac MRI T2* values, liver MRI T2* values, and LIC were improved after combination therapy with DFP and DFX in β-TM patients and that DFP and DFX combination therapy could be used to alleviate cardiac and liver iron loading. PMID:28243431

  12. Comparing potential copper chelation mechanisms in Parkinson's disease protein

    Science.gov (United States)

    Rose, Frisco; Hodak, Miroslav; Bernholc, Jerry

    2011-03-01

    We have implemented the nudged elastic band (NEB) as a guided dynamics framework for our real-space multigrid method of DFT-based quantum simulations. This highly parallel approach resolves a minimum energy pathway (MEP) on the energy hypersurface by relaxing intermediates in a chain-of-states. As an initial application we present an investigation of chelating agents acting on copper ion bound to α -synuclein, whose misfolding is implicated in Parkinson's disease (PD). Copper ions are known to act as highly effective misfolding agents in a-synuclein and are thus an important target in understanding PD. Furthermore, chelation therapy has shown promise in the treatment of Alzheimer's and other neuro-degenerative diseases with similar metal-correlated pathologies. At present, our candidate chelating agents include nicotine, curcumin and clioquinol. We examine their MEP activation barriers in the context of a PD onset mechanism to assess the viability of various chelators for PD remediation.

  13. Macroreticular chelating ion-exchangers.

    Science.gov (United States)

    Hirsch, R F; E Gancher, R; Russo, F R

    1970-06-01

    Two macroreticular chelating ion-exchangers have been prepared and characterized. One contains the iminodiacetate group and the second contains the arsonate group as the ion-exchanging site. The macroreticular resins show selectivities among metal ions similar to those of the commercially available naicroreticular chelating resins. Chromatographie separations on the new resins are rapid and sharp.

  14. 二巯基丁二酸治疗慢性中度铅中毒的实验研究%Effects of chelation therapy with succimer in young rabbits of moderate lead poisoning

    Institute of Scientific and Technical Information of China (English)

    余高妍; 颜崇淮; 余晓刚; 左勇; 邹向宇; 徐健; 吴胜虎; 沈晓明

    2009-01-01

    目的 探讨二巯基丁二酸(又名二巯琥珀酸,DMSA)治疗慢性中度铅中毒幼兔的驱铅效果.方法 24 只离乳(45 d)雄性健康新西兰幼兔,数字表法随机分为治疗组、阳性对照组和阴性对照组,每组8只,经消化道染铅(醋酸铅,每天5 mg/kg) 6周复制中度铅中毒动物模型,然后给予DMSA 驱铅治疗,第1周每天给DMSA 1050 mg/m2 体表面积,然后改为每天700 mg/m2 体表面积连续2周,停药3周,每周采集血液和尿液,12周后杀死并取海马、睾丸、心脏、肝脏、肾脏和脾脏.用原子吸收分光光谱仪测定血铅,电感耦合等离子体质谱仪测尿铅和组织脏器铅,光学显微镜(简称光镜)下观察组织脏器的组织结构.结果 与阳性对照组(PG)相比,DMSA 治疗组(TG)的幼兔展尿铅浓度增加显著,从治疗前的(40.97±1.77)μg/L 显著增加至达到峰值 (1246.96±157.91)μg/L,然后逐步减少,第1周两组相比差异有统计学意义(F=2934.35,P<0.01),三组间相比较差异均具有统计学意义(P值均<0.01);同时血铅水平(blood lead levels,BLLs)在用药后由治疗前的(429.63±10.82)μg/L,锐减到第3周停药时的(238.50±11.82)μg/L,停药后出现一过性反弹,然后再次降低;而PG的BLLs在同时期中呈现缓慢下降过程,到停药3周后为(149.88 4±11.39)μg/L,基本接近于TG的(135.50±7.09)μg/L.TG新西兰兔的组织脏器铅含量显著降低,体重增长明显加快,光镜下观察睾丸和肝脏的病理损伤有一定程度的改善.结论 DMSA 治疗慢性中度铅中毒幼兔,可以快速有效降低血铅和软组织铅,在短时间内减轻铅对组织脏器的毒性作用,使组织脏器的损伤随着机体铅负荷的降低而有所减轻,对铅毒性作用导致的生长发育落后有一定的改善作用.%Objective To explore the effect of chelation therapy with suceimer (DMSA) in male rabbits of moderate lead poisoning during iuvenile stage.Methotis Twenty-four 45-day-old male New Zealand

  15. A Review on Iron Chelators in Treatment of Iron Overload Syndromes

    Science.gov (United States)

    Mobarra, Naser; Shanaki, Mehrnoosh; Ehteram, Hassan; Nasiri, Hajar; Sahmani, Mehdi; Saeidi, Mohsen; Goudarzi, Mehdi; Pourkarim, Hoda; Azad, Mehdi

    2016-01-01

    Iron chelation therapy is used to reduce iron overload development due to its deposition in various organs such as liver and heart after regular transfusion. In this review, different iron chelators implicated in treatment of iron overload in various clinical conditions have been evaluated using more up-to-date studies focusing on these therapeutic agents. Deferoxamine, Deferiprone and Deferasirox are the most important specific US FDA-approved iron chelators. Each of these chelators has their own advantages and disadvantages, various target diseases, levels of deposited iron and clinical symptoms of the afflicted patients which may affect their selection as the best modality. Taken together, in many clinical disorders, choosing a standard chelator does not have an accurate index which requires further clarifications. The aim of this review is to introduce and compare the different iron chelators regarding their advantages and disadvantages, usage dose and specific applications. PMID:27928480

  16. CCCCC pentadentate chelates with planar Möbius aromaticity and unique properties

    Science.gov (United States)

    Zhu, Congqing; Yang, Caixia; Wang, Yongheng; Lin, Gan; Yang, Yuhui; Wang, Xiaoyong; Zhu, Jun; Chen, Xiaoyuan; Lu, Xin; Liu, Gang; Xia, Haiping

    2016-01-01

    The coordinating atoms in polydentate chelates are primarily heteroatoms. We present the first examples of pentadentate chelates with all binding atoms of the chelating agent being carbon atoms, denoted as CCCCC chelates. Having up to five metal-carbon bonds in the equatorial plane has not been previously observed in transition metal chemistry. Density functional theory calculations showed that the planar metallacycle has extended Craig-Möbius aromaticity arising from 12-center–12-electron dπ-pπ π-conjugation. These planar chelates have broad absorption in the ultraviolet-visible–near-infrared region and, thus, notable photothermal performance upon irradiation by an 808-nm laser, indicating that these chelates have potential applications in photothermal therapy. The combination of facile synthesis, high stability, and broad absorption of these complexes could make the polydentate carbon chain a novel building block in coordination chemistry. PMID:27574707

  17. Are we ready to abrogate compulsory vaccinations for children?

    Science.gov (United States)

    Martinelli, Domenico; Tafuri, Silvio; Fortunato, Francesca; Cozza, Vanessa; Germinario, Cinzia A; Prato, Rosa

    2015-01-01

    In Italy, vaccination against diphtheria, tetanus, polio and hepatitis B is compulsory for infants countrywide, except in Veneto region where since 2007 Health Authorities have experimented the suspension of mandatory vaccination. In light of the recent discussion on the potential abrogation in other regions, we explored the opinion of family pediatricians who play a crucial role in promoting immunization programmes in Italy. In November 2009, we interviewed by phone the family pediatricians working in Puglia region using a standardised, ad hoc and piloted questionnaire. Of the 596 contacted, 502 (84.2%) completed the questionnaire (54% female, median age = 52 y). Among the respondents, 72 (14.3%) would agree on the hypothesis of abrogation. This judgment was associated with having a good opinion on the level of awareness of the importance of vaccinations in the general public (OR = 6.6; 95% CI: 3.6-12.1) and having the perception of adequate organization of Vaccination Services in supporting the abrogation (OR = 3.6; 95% CI: 1.7-5.9). Family pediatricians appeared really sceptical about the abrogation of compulsory vaccination that could be hypothesized only increasing public awareness, communication skills and capability of Vaccination Services personnel in offering vaccinations.

  18. Inositol hexa-phosphate: a potential chelating agent for uranium

    Energy Technology Data Exchange (ETDEWEB)

    Cebrian, D.; Tapia, A.; Real, A.; Morcillo, M.A. [Radiobiology Laboratory, Radiation Dosimetry Unit, Department of Environment, CIEMAT, Avda Complutense 22, 28040 Madrid (Spain)

    2007-07-01

    Chelation therapy is an optimal method to reduce the radionuclide-related risks. In the case of uranium incorporation, the treatment of choice is so far i.v infusion of a 1.4% sodium bicarbonate solution, but the efficacy has been proved to be not very high. In this study, we examine the efficacy of some substances: bicarbonate, citrate, diethylenetriamine pentaacetic acid (DTPA), ethidronate (EHBP) and inositol hexa-phosphate (phytic acid) to chelate uranium using a test developed by Braun et al. Different concentrations of phytic acid, an abundant component of plant seeds that is widely distributed in animal cells and tissues in substantial levels, were tested and compared to the same concentrations of sodium citrate, bicarbonate, EHBP and DTPA. The results showed a strong affinity of inositol hexa-phosphate for uranium, suggesting that it could be an effective chelating agent for uranium in vivo. (authors)

  19. Ab initio coordination chemistry for nickel chelation motifs.

    Science.gov (United States)

    Sudan, R Jesu Jaya; Kumari, J Lesitha Jeeva; Sudandiradoss, C

    2015-01-01

    Chelation therapy is one of the most appreciated methods in the treatment of metal induced disease predisposition. Coordination chemistry provides a way to understand metal association in biological structures. In this work we have implemented coordination chemistry to study nickel coordination due to its high impact in industrial usage and thereby health consequences. This paper reports the analysis of nickel coordination from a large dataset of nickel bound structures and sequences. Coordination patterns predicted from the structures are reported in terms of donors, chelate length, coordination number, chelate geometry, structural fold and architecture. The analysis revealed histidine as the most favored residue in nickel coordination. The most common chelates identified were histidine based namely HHH, HDH, HEH and HH spaced at specific intervals. Though a maximum coordination number of 8 was observed, the presence of a single protein donor was noted to be mandatory in nickel coordination. The coordination pattern did not reveal any specific fold, nevertheless we report preferable residue spacing for specific structural architecture. In contrast, the analysis of nickel binding proteins from bacterial and archeal species revealed no common coordination patterns. Nickel binding sequence motifs were noted to be organism specific and protein class specific. As a result we identified about 13 signatures derived from 13 classes of nickel binding proteins. The specifications on nickel coordination presented in this paper will prove beneficial for developing better chelation strategies.

  20. Ab initio coordination chemistry for nickel chelation motifs.

    Directory of Open Access Journals (Sweden)

    R Jesu Jaya Sudan

    Full Text Available Chelation therapy is one of the most appreciated methods in the treatment of metal induced disease predisposition. Coordination chemistry provides a way to understand metal association in biological structures. In this work we have implemented coordination chemistry to study nickel coordination due to its high impact in industrial usage and thereby health consequences. This paper reports the analysis of nickel coordination from a large dataset of nickel bound structures and sequences. Coordination patterns predicted from the structures are reported in terms of donors, chelate length, coordination number, chelate geometry, structural fold and architecture. The analysis revealed histidine as the most favored residue in nickel coordination. The most common chelates identified were histidine based namely HHH, HDH, HEH and HH spaced at specific intervals. Though a maximum coordination number of 8 was observed, the presence of a single protein donor was noted to be mandatory in nickel coordination. The coordination pattern did not reveal any specific fold, nevertheless we report preferable residue spacing for specific structural architecture. In contrast, the analysis of nickel binding proteins from bacterial and archeal species revealed no common coordination patterns. Nickel binding sequence motifs were noted to be organism specific and protein class specific. As a result we identified about 13 signatures derived from 13 classes of nickel binding proteins. The specifications on nickel coordination presented in this paper will prove beneficial for developing better chelation strategies.

  1. Treating Lead Toxicity: Possibilities beyond Synthetic Chelation

    Directory of Open Access Journals (Sweden)

    Shambhavi Tannir

    2013-01-01

    Full Text Available Lead, a ubiquitous metal, is one of the most abundant elements present on earth. Its easy availability and cost effectiveness made it an extremely popular component in the industrial revolution. However, its hazardous health effects were not considered at the time. Over the last few decades, with the adverse effects of lead coming to the forefront, nations across the world have started to recognize and treat lead toxicity. The most reliable and used method until now has been chelation therapy. Recent research has suggested the use of natural products and sources to treat lead poisoning with minimal or no side effects. This review has tried to summarize a few of the natural products/sources being investigated by various groups.

  2. Neurodegenerative diseases and therapeutic strategies using iron chelators.

    Science.gov (United States)

    Ward, Roberta J; Dexter, David T; Crichton, Robert R

    2015-01-01

    This review will summarise the current state of our knowledge concerning the involvement of iron in various neurological diseases and the potential of therapy with iron chelators to retard the progression of the disease. We first discuss briefly the role of metal ions in brain function before outlining the way by which transition metal ions, such as iron and copper, can initiate neurodegeneration through the generation of reactive oxygen and nitrogen species. This results in protein misfolding, amyloid production and formation of insoluble protein aggregates which are contained within inclusion bodies. This will activate microglia leading to neuroinflammation. Neuroinflammation plays an important role in the progression of the neurodegenerative diseases, with activated microglia releasing pro-inflammatory cytokines leading to cellular cell loss. The evidence for metal involvement in Parkinson's and Alzheimer's disease as well as Friedreich's ataxia and multiple sclerosis will be presented. Preliminary results from trials of iron chelation therapy in these neurodegenerative diseases will be reviewed.

  3. Luminescent lanthanide chelates and methods of use

    Science.gov (United States)

    Selvin, Paul R.; Hearst, John

    1997-01-01

    The invention provides lanthanide chelates capable of intense luminescence. The celates comprise a lanthanide chelator covalently joined to a coumarin-like or quinolone-like sensitizer. Exemplary sensitzers include 2- or 4-quinolones, 2- or 4-coumarins, or derivatives thereof e.g. carbostyril 124 (7-amino-4-methyl-2-quinolone), coumarin 120 (7-amino-4-methyl-2-coumarin), coumarin 124 (7-amino-4-(trifluoromethyl)-2-coumarin), aminomethyltrimethylpsoralen, etc. The chelates form high affinity complexes with lanthanides, such as terbium or europium, through chelator groups, such as DTPA. The chelates may be coupled to a wide variety of compounds to create specific labels, probes, diagnostic and/or therapeutic reagents, etc. The chelates find particular use in resonance energy transfer between chelate-lanthanide complexes and another luminescent agent, often a fluorescent non-metal based resonance energy acceptor. The methods provide useful information about the structure, conformation, relative location and/or interactions of macromolecules.

  4. Chelators for investigating zinc metalloneurochemistry.

    Science.gov (United States)

    Radford, Robert J; Lippard, Stephen J

    2013-04-01

    The physiology and pathology of mobile zinc signaling has become an important topic in metalloneurochemistry. To study the action of mobile zinc effectively, specialized tools are required that probe the temporal and positional changes of zinc ions within live tissue and cells. In the present article we describe the design and implementation of selective zinc chelators as antagonists to interrogate the function of mobile zinc, with an emphasis on the pools of vesicular zinc in the terminals of hippocampal mossy fiber buttons.

  5. Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications.

    Science.gov (United States)

    Nagai, Ryoji; Murray, David B; Metz, Thomas O; Baynes, John W

    2012-03-01

    This article outlines evidence that advanced glycation end product (AGE) inhibitors and breakers act primarily as chelators, inhibiting metal-catalyzed oxidation reactions that catalyze AGE formation. We then present evidence that chelation is the most likely mechanism by which ACE inhibitors, angiotensin receptor blockers, and aldose reductase inhibitors inhibit AGE formation in diabetes. Finally, we note several recent studies demonstrating therapeutic benefits of chelators for diabetic cardiovascular and renal disease. We conclude that chronic, low-dose chelation therapy deserves serious consideration as a clinical tool for prevention and treatment of diabetes complications.

  6. Nanoparticle iron chelators: a new therapeutic approach in Alzheimer disease and other neurologic disorders associated with trace metal imbalance.

    Science.gov (United States)

    Liu, Gang; Men, Ping; Harris, Peggy L R; Rolston, Raj K; Perry, George; Smith, Mark A

    2006-10-09

    Accumulating evidence suggests that oxidative stress may be a major etiologic factor in initiating and promoting neurodegeneration in Alzheimer disease. Contributing to this, there is a dyshomeostasis of metal ions in Alzheimer disease with abnormally high levels of redox-active metals, particularly iron, in affected areas of the brain. Although it is unclear whether metal excesses are the sole cause of oxidative stress and neurodegeneration or a by-product of neuronal loss, the finding that metal chelators can partially solubilize amyloid-beta deposits in Alzheimer disease suggests a promising therapeutic role for chelating agents. However, the blood-brain barrier and toxicity of known chelators limit their utility. In this study, we suggest that covalent conjugation of iron chelators with nanoparticles may help overcome the limitations in blood-brain barrier permeability of existing chelation therapy. Using in vitro studies, we have shown that a chelator-nanoparticle system and the chelator-nanoparticle system complexed with iron, when incubated with human plasma, preferentially adsorb apolipoprotein E and apolipoprotein A-I, that would facilitate transport into and out of the brain via mechanisms used for transporting low-density lipoprotein. Our studies suggest a unique approach, utilizing nanoparticles, to transport chelators and chelator-metal complexes in both directions across the blood-brain barrier, thus providing safer and more effective chelation treatment in Alzheimer disease and other neurodegenerative diseases.

  7. Chelation of aluminum by combining deferasirox and deferiprone in rats.

    Science.gov (United States)

    Saljooghi, Amir Shokooh

    2012-09-01

    The hypothesis that two known chelators deferasirox and deferiprone (L1) might be more efficient as combined treatment than as single therapies in removing aluminum from the body was tested in a new acute rat model. Seven-week-old male Wistar rats received chelators: deferasirox (orally [p.o.]), L1 (p.o.) or deferasirox + L1 as 100 or 200 mg/kg dose half an hour after a single intraperitoneal administration of 6 mg Al/kg body weight in the form of chloride. Serum aluminum concentration, urinary aluminum and iron excretions were determined by graphite furnace atomic absorption spectrometry. Both chelators were effective only at the higher dose level. While deferasirox was more effective than L1 in enhancing urinary aluminum excretion, L1 was more effective than deferasirox in enhancing urinary iron excretion. In the combined treatment group, deferasirox did not increase the L1 effect on aluminum and L1 did not increase the effect of deferasirox on iron elimination. Our results support the usefulness of this animal model for preliminary in vivo testing of aluminum chelators. Urinary values were more useful due to the high variability of serum results.

  8. The iron chelator deferasirox protects mice from mucormycosis through iron starvation

    OpenAIRE

    2007-01-01

    Mucormycosis causes mortality in at least 50% of cases despite current first-line therapies. Clinical and animal data indicate that the presence of elevated available serum iron predisposes the host to mucormycosis. Here we demonstrate that deferasirox, an iron chelator recently approved for use in humans by the US FDA, is a highly effective treatment for mucormycosis. Deferasirox effectively chelated iron from Rhizopus oryzae and demonstrated cidal activity in vitro against 28 of 29 clinical...

  9. Clinically approved iron chelators influence zebrafish mortality, hatching morphology and cardiac function.

    Directory of Open Access Journals (Sweden)

    Jasmine L Hamilton

    Full Text Available Iron chelation therapy using iron (III specific chelators such as desferrioxamine (DFO, Desferal, deferasirox (Exjade or ICL-670, and deferiprone (Ferriprox or L1 are the current standard of care for the treatment of iron overload. Although each chelator is capable of promoting some degree of iron excretion, these chelators are also associated with a wide range of well documented toxicities. However, there is currently very limited data available on their effects in developing embryos. In this study, we took advantage of the rapid development and transparency of the zebrafish embryo, Danio rerio to assess and compare the toxicity of iron chelators. All three iron chelators described above were delivered to zebrafish embryos by direct soaking and their effects on mortality, hatching and developmental morphology were monitored for 96 hpf. To determine whether toxicity was specific to embryos, we examined the effects of chelator exposure via intra peritoneal injection on the cardiac function and gene expression in adult zebrafish. Chelators varied significantly in their effects on embryo mortality, hatching and morphology. While none of the embryos or adults exposed to DFO were negatively affected, ICL -treated embryos and adults differed significantly from controls, and L1 exerted toxic effects in embryos alone. ICL-670 significantly increased the mortality of embryos treated with doses of 0.25 mM or higher and also affected embryo morphology, causing curvature of larvae treated with concentrations above 0.5 mM. ICL-670 exposure (10 µL of 0.1 mM injection also significantly increased the heart rate and cardiac output of adult zebrafish. While L1 exposure did not cause toxicity in adults, it did cause morphological defects in embryos at 0.5 mM. This study provides first evidence on iron chelator toxicity in early development and will help to guide our approach on better understanding the mechanism of iron chelator toxicity.

  10. Management of transfusional iron overload – differential properties and efficacy of iron chelating agents

    Directory of Open Access Journals (Sweden)

    Kwiatkowski JL

    2011-09-01

    Full Text Available Janet L Kwiatkowski The Children's Hospital of Philadelphia, Division of Hematology and University of Pennsylvania School of Medicine, Philadelphia, PA, USA Abstract: Regular red cell transfusion therapy ameliorates disease-related morbidity and can be lifesaving in patients with various hematological disorders. Transfusion therapy, however, causes progressive iron loading, which, if untreated, results in endocrinopathies, cardiac arrhythmias and congestive heart failure, hepatic fibrosis, and premature death. Iron chelation therapy is used to prevent iron loading, remove excess accumulated iron, detoxify iron, and reverse some of the iron-related complications. Three chelators have undergone extensive testing to date: deferoxamine, deferasirox, and deferiprone (although the latter drug is not currently licensed for use in North America where it is available only through compassionate use programs and research protocols. These chelators differ in their modes of administration, pharmacokinetics, efficacy with regard to organ-specific iron removal, and adverse-effect profiles. These differential properties influence acceptability, tolerability and adherence to therapy, and, ultimately, the effectiveness of treatment. Chelation therapy, therefore, must be individualized, taking into account patient preferences, toxicities, ongoing transfusional iron intake, and the degree of cardiac and hepatic iron loading. Keywords: transfusion, iron, chelation, magnetic resonance imaging

  11. Carbamoylation abrogates the antioxidant potential of hydrogen sulfide.

    Science.gov (United States)

    Praschberger, Monika; Hermann, Marcela; Laggner, Christian; Jirovetz, Leopold; Exner, Markus; Kapiotis, Stylianos; Gmeiner, Bernhard M K; Laggner, Hilde

    2013-11-01

    Hydrogen sulfide (H2S) has been identified as the third gasotransmitter. Beside its role as signaling molecule in the cardiovascular and nervous system the antioxidant and cyto-protective properties of H2S have gained much attention. In the present study we show that cyanate, an uremic toxin which is found in abundant concentration in sera of patients suffering from chronic kidney disease (CKD), can abrogate the antioxidant and cytoprotective activity of H2S via S-carbamoylation reaction, a reaction that previously has only been shown to have a physiological effect on cysteine groups, but not on H2S. Carbamoylation strongly inhibited the free radical scavenging (ABTS(+·) and alkylperoxyl ROO(·)) properties of H2S. The extent of intracellular ROS formation induced by ROO(·) was diminished by H2S whereas carbamoylation counteracted the protective effect. Reagent HOCl was rapidly inactivated by H2S in contrast to the carbamoylated compound. Protein modification by HOCl was inhibited by H2S but carbamoylation significantly reduced the effect. Thus, S-carbamoylation of low molecular weight thiols by abrogating their antioxidant potential may contribute to the higher oxidative stress observed in CKD.

  12. Application prospect of iron chelator in the prevention and therapy of osteoporosis%铁螯合剂在骨质疏松防治中的应用前景

    Institute of Scientific and Technical Information of China (English)

    赵国阳; 徐又佳

    2015-01-01

    Iron overload may lead to the occurrence and development of osteoporosis, and drug of decreasing i-ron overload may also have clinical potential for osteoporosis patients with iron overload.Currently, the commonly used drugs of decreasing iron are various kinds of iron chelators, which mainly include deferoxamine, deferiprone, and defera-sirox.Here is to summarize the characteristics of three iron chelators, combine with their effects on bone metabolism, and explore their clinical prospect as osteoporosis treatment.%铁过载可导致骨质疏松,降低铁过载的药物有望用于防治伴有铁过载的骨质疏松症。目前临床使用的降低铁过载药物是各种铁鳌合剂,包括去铁胺、去铁酮和地拉罗司。本文总结这3种铁螯合剂临床使用特点,结合其对骨代谢影响实验研究结果,探讨铁鳌合剂作为抗骨质疏松用药的前景。

  13. Role of chelates in treatment of cancer

    Directory of Open Access Journals (Sweden)

    Tripathi Laxmi

    2007-01-01

    Full Text Available Chelates are used in cancer as cytotoxic agent, as radioactive agent in imaging studies and in radioimmunotherapy. Various chelates based on ruthenium, copper, zinc, organocobalt, gold, platinum, palladium, cobalt, nickel and iron are reported as cytotoxic agent. Monoclonal antibodies labeled with radioactive metals such as yttrium-90, indium-111 and iodine-131 are used in radioimmunotherapy. This review is an attempt to compile the use of chelates as cytotoxic drugs and in radioimmunotherapy.

  14. Tumor targeting of radiolabeled antibodies using HYNIC chelate

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Tae Sup; Chung, Wee Sup; Woo, Kwang Sun; Choi, Tae Hyun; Chung, Hye Kyung; Lee, Myung Jin; Kim, So Yeon; Jung, Jae Ho; Choi, Chang Woon; Lim, Sang Moo [KIRAMS, Seoul (Korea, Republic of); Darwati, Siti [National Nuclear Energy Agency, Tangerang (Indonesia)

    2004-07-01

    There is an increasing interest in the use of labeled antibodies for diagnosis of cancers as well as for therapy. Various radiolabeling methods have been used in order to obtain better tumor specific targeting for detection and therapy. It was generally used to tumor targeted immunotherapy and immunodetection that lym-1, mouse monoclonal antibody, was specific binding to surface antigen of Raji. The 3E8 antibody was produced from humanized anti-TAG-72 monoclonal antibody (AKA) by amino acid change in 95-99 residues of heavy chain complementary determinant regions (HCDRs) 3 using phage displayed library technology. In this study, we are investigating the usefulness of HYNIC chelate as a bifunctional chelating agent in radioimmunodetecton of tumor. Two types of antibodies, Lym-1 and 3E8, were used for the conjugation with HYNIC chelate. Lym-1 and 3E8 are specific antibodies to surface antigen of Non-Hogkin's lymphoma and TAG-72 antigen of colorectal carcinoma, respectively. We prepare HYNIC-antibody conjugates, determine radiolabeling yield with {sup 99m}Tc and evaluate tumor targeting in tumor bearing nude mice model.

  15. Hydroxyurea could be a good clinically relevant iron chelator.

    Directory of Open Access Journals (Sweden)

    Khushnooma Italia

    Full Text Available Our previous study showed a reduction in serum ferritin of β-thalassemia patients on hydroxyurea therapy. Here we aimed to evaluate the efficacy of hydroxyurea alone and in combination with most widely used iron chelators like deferiprone and deferasirox for reducing iron from experimentally iron overloaded mice. 70 BALB/c mice received intraperitonial injections of iron-sucrose. The mice were then divided into 8 groups and were orally given hydroxyurea, deferiprone or deferasirox alone and their combinations for 4 months. CBC, serum-ferritin, TBARS, sTfr and hepcidin were evaluated before and after iron overload and subsequently after 4 months of drug therapy. All animals were then killed. Iron staining of the heart and liver tissue was done using Perl's Prussian Blue stain. Dry weight of iron in the heart and liver was determined by atomic absorption spectrometry. Increased serum-ferritin, TBARS, hepcidin and dry weight of iron in the liver and heart showed a significant reduction in groups treated with iron chelators with maximum reduction in the group treated with a combination of deferiprone, deferasirox and hydroxyurea. Thus hydroxyurea proves its role in reducing iron from iron overloaded mice. The iron chelating effect of these drugs can also be increased if given in combination.

  16. MULTIDENTATE TEREPHTHALAMIDATE AND HYDROXYPYRIDONATE LIGANDS: TOWARDS NEW ORALLY ACTIVE CHELATORS

    Energy Technology Data Exchange (ETDEWEB)

    Abergel, Rebecca J.; Raymond, Kenneth N.

    2011-07-13

    The limitations of current therapies for the treatment of iron overload or radioisotope contamination have stimulated efforts to develop new orally bioavailable iron and actinide chelators. Siderophore-inspired tetradentate, hexadentate and octadentate terephthalamidate and hydroxypyridonate ligands were evaluated in vivo as selective and efficacious iron or actinide chelating agents, with several metal loading and ligand assessment procedures, using {sup 59}Fe, {sup 238}Pu, and {sup 241}Am as radioactive tracers. The compounds presented in this study were compared to commercially available therapeutic sequestering agents [deferoxamine (DFO) for iron and diethylenetriaminepentaacetic acid (DPTA) for actinides] and are unrivaled in terms of affinity, selectivity and decorporation efficacy, which attests to the fact that high metal affinity may overcome the low bioavailability properties commonly associated to multidenticity.

  17. Effects of microplusin, a copper-chelating antimicrobial peptide, against Cryptococcus neoformans.

    Science.gov (United States)

    Silva, Fernanda D; Rossi, Diego C P; Martinez, Luis R; Frases, Susana; Fonseca, Fernanda L; Campos, Claudia Barbosa L; Rodrigues, Marcio L; Nosanchuk, Joshua D; Daffre, Sirlei

    2011-11-01

    Microplusin is an antimicrobial peptide isolated from the cattle tick Rhipicephalus (Boophilus) microplus. Its copper-chelating ability is putatively responsible for its bacteriostatic activity against Micrococcus luteus as microplusin inhibits respiration in this species, which is a copper-dependent process. Microplusin is also active against Cryptococcus neoformans (MIC(50) = 0.09 μM), the etiologic agent of cryptococcosis. Here, we show that microplusin is fungistatic to C. neoformans and this inhibitory effect is abrogated by copper supplementation. Notably, microplusin drastically altered the respiratory profile of C. neoformans. In addition, microplusin affects important virulence factors of this fungus. We observed that microplusin completely inhibited fungal melanization, and this effect correlates with the inhibition of the related enzyme laccase. Also, microplusin significantly inhibited the capsule size of C. neoformans. Our studies reveal, for the first time, a copper-chelating antimicrobial peptide that inhibits respiration and growth of C. neoformans and modifies two major virulence factors: melanization and formation of a polysaccharide capsule. These features suggest that microplusin, or other copper-chelation approaches, may be a promising therapeutic for cryptococcosis.

  18. 不同铁螯合剂治疗输血依赖性铁过载的对比研究%A comparative study of different iron chela-tion therapy transfusion dependent iron over-load

    Institute of Scientific and Technical Information of China (English)

    李仙松; 杜娟; 李伟平

    2014-01-01

    目的:对比不同铁螯合剂对贫血患者长期输血治疗后铁过载的驱铁作用及安全性。方法:将24例反复输血的患者在血清铁蛋白(SF)水平相同条件下随机均分为三组,采用不同铁螯合剂去铁治疗,分别检测其在治疗后1个月、2个月、3个月的铁蛋白(SF)水平,并观察其治疗相关不良反应。结果:地拉罗司组在治疗后SF下降最明显,且不良反应最少。结论:地拉罗司治疗输血依赖性铁过载的效果最好,安全性较高,不良反应最少。%AIM:To compare the effects and safety of iron over-load of patients with anemia who received different iron chelators treatment after long-term transfusion.METHODS:Dividing the 24 patients who transfused blood repeatedly into three groups un-der the same condition of serum ferritin (SF)level for iron remov-al treatment with different iron chelators.Then we detected the se-rum ferritin (SF)level after treatment of 1 month,2 months and 3 months respectively,and observed the adverse reactions relative-ly.RESULTS:The group with Deferasirox that the SF level de-creased at most and had minimal adverse reactions after treat-ment.CONCLUSION:The best therapeutic efficacy for iron o-verload of transfusion dependency is Deferasirox which has high safety and minimal adverse reactions.

  19. IL-4 abrogates TH17 cell-mediated inflammation by selective silencing of IL-23 in antigen-presenting cells

    Science.gov (United States)

    Guenova, Emmanuella; Skabytska, Yuliya; Hoetzenecker, Wolfram; Weindl, Günther; Sauer, Karin; Tham, Manuela; Kim, Kyu-Won; Park, Ji-Hyeon; Seo, Ji Hae; Ignatova, Desislava; Cozzio, Antonio; Levesque, Mitchell P.; Volz, Thomas; Köberle, Martin; Kaesler, Susanne; Thomas, Peter; Mailhammer, Reinhard; Ghoreschi, Kamran; Schäkel, Knut; Amarov, Boyko; Eichner, Martin; Schaller, Martin; Clark, Rachael A.; Röcken, Martin; Biedermann, Tilo

    2015-01-01

    Interleukin 4 (IL-4) can suppress delayed-type hypersensitivity reactions (DTHRs), including organ-specific autoimmune diseases in mice and humans. Despite the broadly documented antiinflammatory effect of IL-4, the underlying mode of action remains incompletely understood, as IL-4 also promotes IL-12 production by dendritic cells (DCs) and IFN-γ–producing TH1 cells in vivo. Studying the impact of IL-4 on the polarization of human and mouse DCs, we found that IL-4 exerts opposing effects on the production of either IL-12 or IL-23. While promoting IL-12–producing capacity of DCs, IL-4 completely abrogates IL-23. Bone marrow chimeras proved that IL-4–mediated suppression of DTHRs relies on the signal transducer and activator of transcription 6 (STAT6)-dependent abrogation of IL-23 in antigen-presenting cells. Moreover, IL-4 therapy attenuated DTHRs by STAT6- and activating transcription factor 3 (ATF3)-dependent suppression of the IL-23/TH17 responses despite simultaneous enhancement of IL-12/TH1 responses. As IL-4 therapy also improves psoriasis in humans and suppresses IL-23/TH17 responses without blocking IL-12/TH1, selective IL-4–mediated IL-23/TH17 silencing is promising as treatment against harmful inflammation, while sparing the IL-12–dependent TH1 responses. PMID:25646481

  20. REVIEW ARTICLE:Future of Lead Chelation – Distribution and Treatment

    Directory of Open Access Journals (Sweden)

    Venkatesh Thuppil

    2012-01-01

    Full Text Available Lead is the major environmental toxin resulting in the ill health and deleterious effect on almost all organs in the human body in a slow and effective manner. The best treatment for lead poisoning is chelation therapy which is next only to prevention. The authors describe the disruption of homeostasis of the human body by lead in various tissues like blood, bones, liver, kidneys and brain; and the ability of lead to enter the cell using calcium channels and calcium receptors like Ca++ dependant K+ ion channels, transient receptor potential channels, T-tubules, calmodulin receptors, inositol trisphosphate receptors and ryanodine receptors. We report a few novel chelating agents like ionophores, decadentate ligands, picolinate ligands, octadentate ligand, allicin, thiamine, that show good potential for being used in chelation therapy. Future of leadpoisoning is a challenge to all and it needs to be meticulously studies to have an economic and health approach.

  1. Nanoparticle-chelator conjugates as inhibitors of amyloid-beta aggregation and neurotoxicity: a novel therapeutic approach for Alzheimer disease.

    Science.gov (United States)

    Liu, Gang; Men, Ping; Kudo, Wataru; Perry, George; Smith, Mark A

    2009-05-22

    Oxidative stress and amyloid-beta are considered major etiological and pathological factors in the initiation and promotion of neurodegeneration in Alzheimer disease (AD). Insomuch as causes of such oxidative stress, transition metals, such as iron and copper, which are found in high concentrations in the brains of AD patients and accumulate specifically in the pathological lesions, are viewed as key contributors to the altered redox state. Likewise, the aggregation and toxicity of amyloid-beta is dependent upon transition metals. As such, chelating agents that selectively bind to and remove and/or "redox silence" transition metals have long been considered as attractive therapies for AD. However, the blood-brain barrier and neurotoxicity of many traditional metal chelators has limited their utility in AD or other neurodegenerative disorders. To circumvent this, we previously suggested that nanoparticles conjugated to iron chelators may have the potential to deliver chelators into the brain and overcome such issues as chelator bioavailability and toxic side-effects. In this study, we synthesized a prototype nanoparticle-chelator conjugate (Nano-N2PY) and demonstrated its ability to protect human cortical neurons from amyloid-beta-associated oxidative toxicity. Furthermore, Nano-N2PY nanoparticle-chelator conjugates effectively inhibited amyloid-beta aggregate formation. Overall, this study indicates that Nano-N2PY, or other nanoparticles conjugated to metal chelators, may provide a novel therapeutic strategy for AD and other neurodegenerative diseases associated with excess transition metals.

  2. Questions and Answers on Unapproved Chelation Products

    Science.gov (United States)

    ... of the marketing scheme to convince consumers to purchase unapproved OTC chelation products. These test kits are ... feeds Follow FDA on Twitter Follow FDA on Facebook View FDA videos on YouTube View FDA photos ...

  3. SYNTHESIS AND APPLICATION OF IMINOCARBOXYLIC CHELATING FIBERS

    Institute of Scientific and Technical Information of China (English)

    LiHangqiu; ZhouShaoji

    1997-01-01

    In this paper,fibrous chelating exchangers with-N(CH2COOH)2 group have been prepared for the first time by a weakly basic anion exchange fiber (aminated fiber)as the starting materials.The fibers were quite effective for the adsorption of heavy metal ion such as Cu2+.In addition,IR spectrum of the structure of fibers confirms that it is feasible to prepare iminocarboxylic chelating fiber through direct carboxylation reaction.

  4. Epithelial inactivation of Yy1 abrogates lung branching morphogenesis.

    Science.gov (United States)

    Boucherat, Olivier; Landry-Truchon, Kim; Bérubé-Simard, Félix-Antoine; Houde, Nicolas; Beuret, Laurent; Lezmi, Guillaume; Foulkes, William D; Delacourt, Christophe; Charron, Jean; Jeannotte, Lucie

    2015-09-01

    Yin Yang 1 (YY1) is a multifunctional zinc-finger-containing transcription factor that plays crucial roles in numerous biological processes by selectively activating or repressing transcription, depending upon promoter contextual differences and specific protein interactions. In mice, Yy1 null mutants die early in gestation whereas Yy1 hypomorphs die at birth from lung defects. We studied how the epithelial-specific inactivation of Yy1 impacts on lung development. The Yy1 mutation in lung epithelium resulted in neonatal death due to respiratory failure. It impaired tracheal cartilage formation, altered cell differentiation, abrogated lung branching and caused airway dilation similar to that seen in human congenital cystic lung diseases. The cystic lung phenotype in Yy1 mutants can be partly explained by the reduced expression of Shh, a transcriptional target of YY1, in lung endoderm, and the subsequent derepression of mesenchymal Fgf10 expression. Accordingly, SHH supplementation partially rescued the lung phenotype in vitro. Analysis of human lung tissues revealed decreased YY1 expression in children with pleuropulmonary blastoma (PPB), a rare pediatric lung tumor arising during fetal development and associated with DICER1 mutations. No evidence for a potential genetic interplay between murine Dicer and Yy1 genes during lung morphogenesis was observed. However, the cystic lung phenotype resulting from the epithelial inactivation of Dicer function mimics the Yy1 lung malformations with similar changes in Shh and Fgf10 expression. Together, our data demonstrate the crucial requirement for YY1 in lung morphogenesis and identify Yy1 mutant mice as a potential model for studying the genetic basis of PPB.

  5. Lipoteichoic acid synthesis inhibition in combination with antibiotics abrogates growth of multidrug-resistant Enterococcus faecium.

    Science.gov (United States)

    Paganelli, Fernanda L; van de Kamer, Tim; Brouwer, Ellen C; Leavis, Helen L; Woodford, Neil; Bonten, Marc J M; Willems, Rob J L; Hendrickx, Antoni P A

    2017-03-01

    Enterococcus faecium is a multidrug-resistant (MDR) nosocomial pathogen causing significant morbidity in debilitated patients. New antimicrobials are needed to treat antibiotic-resistant E. faecium infections in hospitalised patients. E. faecium incorporates lipoteichoic acid (LTA) (1,3-polyglycerol-phosphate linked to glycolipid) in its cell wall. The small-molecule inhibitor 1771 [2-oxo-2-(5-phenyl-1,3,4-oxadiazol-2-ylamino)ethyl 2-naphtho[2,1-b]furan-1-ylacetate] specifically blocks the activity of Staphylococcus aureus LtaS synthase, which polymerises 1,3-glycerolphosphate into LTA polymers. Here we characterised the effects of the small-molecule inhibitor 1771 on the growth of E. faecium isolates, alone (28 strains) or in combination with the antibiotics vancomycin, daptomycin, ampicillin, gentamicin or linezolid (15 strains), and on biofilm formation (16 strains). Inhibition of LTA synthesis at the surface of the cell by compound 1771 in combination with current antibiotic therapy abrogates enterococcal growth in vitro but does not affect mature E. faecium biofilms. Targeting LTA synthesis may provide new possibilities to treat MDR E. faecium infections.

  6. Neuroblastoma-targeted nanocarriers improve drug delivery and penetration, delay tumor growth and abrogate metastatic diffusion.

    Science.gov (United States)

    Cossu, Irene; Bottoni, Gianluca; Loi, Monica; Emionite, Laura; Bartolini, Alice; Di Paolo, Daniela; Brignole, Chiara; Piaggio, Francesca; Perri, Patrizia; Sacchi, Angelina; Curnis, Flavio; Gagliani, Maria Cristina; Bruno, Silvia; Marini, Cecilia; Gori, Alessandro; Longhi, Renato; Murgia, Daniele; Sementa, Angela Rita; Cilli, Michele; Tacchetti, Carlo; Corti, Angelo; Sambuceti, Gianmario; Marchiò, Serena; Ponzoni, Mirco; Pastorino, Fabio

    2015-11-01

    Selective tumor targeting is expected to enhance drug delivery and to decrease toxicity, resulting in an improved therapeutic index. We have recently identified the HSYWLRS peptide sequence as a specific ligand for aggressive neuroblastoma, a childhood tumor mostly refractory to current therapies. Here we validated the specific binding of HSYWLRS to neuroblastoma cell suspensions obtained either from cell lines, animal models, or Schwannian-stroma poor, stage IV neuroblastoma patients. Binding of the biotinylated peptide and of HSYWLRS-functionalized fluorescent quantum dots or liposomal nanoparticles was dose-dependent and inhibited by an excess of free peptide. In animal models obtained by the orthotopic implant of either MYCN-amplified or MYCN single copy human neuroblastoma cell lines, treatment with HSYWLRS-targeted, doxorubicin-loaded Stealth Liposomes increased tumor vascular permeability and perfusion, enhancing tumor penetration of the drug. This formulation proved to exert a potent antitumor efficacy, as evaluated by bioluminescence imaging and micro-PET, leading to (i) delay of tumor growth paralleled by decreased tumor glucose consumption, and (ii) abrogation of metastatic spreading, accompanied by absence of systemic toxicity and significant increase in the animal life span. Our findings are functional to the design of targeted nanocarriers with potentiated therapeutic efficacy towards the clinical translation.

  7. CARDIAC FUNCTION AND IRON CHELATION IN THALASSEMIA MAJOR AND INTERMEDIA: A REVIEW OF THE UNDERLYING PATHOPHYSIOLOGY AND APPROACH TO CHELATION MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Athanasios Aessopos

    2009-07-01

    Full Text Available Heart disease is the leading cause of mortality and one of the main causes of morbidity in beta-thalassemia. Patients with homozygous thalassemia may have either a severe phenotype which is usually transfusion dependent or a milder form that is thalassemia intermedia.  The two main factors that determine cardiac disease in homozygous β thalassemia are the high output state that results from chronic tissue hypoxia, hypoxia-induced compensatory reactions and iron overload.  The high output state playing a major role in thalassaemia intermedia and the iron load being more significant in the major form. Arrhythmias, vascular involvement that leads to an increased pulmonary vascular resistance and an increased systemic vascular stiffness and valvular abnormalities also contribute to the cardiac dysfunction in varying degrees according to the severity of the phenotype.  Endocrine abnormalities, infections, renal function and medications can also play a role in the overall cardiac function.  For thalassaemia major, regular and adequate blood transfusions and iron chelation therapy are the mainstays of management. The approach to thalassaemia intermedia, today, is aimed at monitoring for complications and initiating, timely, regular transfusions and/or iron chelation therapy.  Once the patients are on transfusions, then they should be managed in the same way as the thalassaemia major patients.  If cardiac manifestations of dysfunction are present in either form of thalassaemia, high pre transfusion Hb levels need to be maintained in order to reduce cardiac output and appropriate intensive chelation therapy needs to be instituted.  In general recommendations on chelation, today, are usually made according to the Cardiac Magnetic Resonance findings, if available.  With the advances in the latter technology and the ability to tailor chelation therapy according to the MRI findings as well as the availability of three iron chelators, together with

  8. Which psychosocial factors are related to chelation adherence in thalassemia? A systematic review.

    Science.gov (United States)

    Evangeli, Michael; Mughal, Kulsoom; Porter, John B

    2010-06-01

    Good adherence to iron chelation therapy in thalassemia is crucial. Although there is evidence that adherence is related to regimen factors, there has been less emphasis on the relationship between psychosocial (psychological, demographic and social) factors and adherence. We present a systematic review of psychosocial correlates of chelation adherence in thalassemia. Nine studies met the inclusion criteria. Information was extracted regarding the study characteristics and the relationship between psychosocial factors and chelation adherence. Methodological quality was rated. The studies took place in a range of countries, were mostly cross sectional in design, and examined adherence to deferoxamine (DFO) only. Sample sizes ranged from 15 to 1573. A variety of psychosocial variables were examined. Definitions of adherence varied between studies and non adherence rates were also variable (9 to 66%). Older age was consistently associated with lower levels of chelation adherence. There were few other consistent findings. The methodological quality of studies was variable. There is a need for more methodologically sophisticated and theoretically informed studies on psychosocial correlates of chelation adherence. We offer specific suggestions.

  9. Arsenic induced oxidative stress and the role of antioxidant supplementation during chelation: a review.

    Science.gov (United States)

    Flora, S J S; Bhadauria, Smrati; Kannan, G M; Singh, Nutan

    2007-04-01

    Arsenic is a naturally occurring metalloid, ubiquitously present in the environment in both organic and inorganic forms. Arsenic contamination of groundwater in the West Bengal basin in India is unfolding as one of the worst natural geoenvironmental disaster to date. Chronic exposure of humans to high concentration of arsenic in drinking water is associated with skin lesions, peripheral vascular disease, hypertension, Blackfoot disease and high risk of cancer The underlying mechanism of toxicity includes the interaction with the sulphydryl groups and the generation of reactive oxygen species leading to oxidative stress. Chelation therapy with chelating agents like British Anti Lewisite (BAL), sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), meso 2,3 dimercaptosuccinic acid (DMSA) etc., is considered to be the best known treatment against arsenic poisoning. The treatment with these chelating agents however is compromised with certain serious drawbacks/side effects. The studies show that supplementation of antioxidants along with a chelating agent prove to be a better treatment regimen. This review attempts to provide the readers with a comprehensive account of recent developments in the research on arsenic poisoning particularly the role of oxidative stress/free radicals in the toxic manifestation, an update about the recent strategies for the treatment with chelating agents and a possible beneficial role of antioxidants supplementation to achieve the optimum effects.

  10. Synthesis, characterization and in vitro anticancer evaluations of two novel derivatives of deferasirox iron chelator.

    Science.gov (United States)

    Salehi, Samie; Saljooghi, Amir Sh; Shiri, Ali

    2016-06-15

    Iron (Fe) chelation therapy was initially designed to alleviate the toxic effects of excess Fe evident in Fe-overload diseases. However, the novel toxicological properties of some Fe chelator-metal complexes have shifted significant attention to their application in cancer chemotherapy. The present study investigates the new role of deferasirox as an anticancer agent due to its ability to chelate with iron. Because of aminoacids antioxidant effect, deferasirox and its two novel amino acid derivatives have been synthesized through the treatment of deferasirox with DCC as well as glycine or phenylalanine methyl ester. All new compounds have been characterized by elemental analysis, FT-IR NMR and mass spectrometry. Therefore, the cytotoxicity of these compounds was screened for antitumor activity against some cell lines using cisplatin as a comparative standard by MTT assay and Flow cytometry. The impact of iron in the intracellular generation of reactive oxygen species was assessed on HT29 and MDA-MB-231 cells. The potential of the synthesized iron chelators for their efficacy to protect cells against model oxidative injury induced was compared. The reactive oxygen species intracellular fluorescence intensity were measured and the result showed that the reactive oxygen species intensity after iron incubation increased while after chelators incubation the reactive oxygen species intensity were decreased significantly. Besides, the effect of the synthesized compounds on mouse fibroblast cell line (L929) was simultaneously evaluated as control. The pharmacological results showed that deferasirox and its two novel aminoacid derivatives were potent anticancer agents.

  11. Arsenic and lead induced free radical generation and their reversibility following chelation.

    Science.gov (United States)

    Flora, S J S; Flora, G; Saxena, G; Mishra, M

    2007-04-15

    Health hazards caused by heavy metals have become a great concern to the population. Lead and arsenic are one of the most important current global environmental toxicants. Their toxic manifestations are being considered caused primarily due to the imbalance between pro-oxidant and antioxidant homeostasis and also due to a high affinity of these metals for thiol groups on functional proteins. They also interfere with a number of other body functions and are known to affect central nervous system (CNS), hematopoietic system, liver and kidneys and produce serious disorders. They produce both acute and chronic poisoning, of which chronic poisoning is more dangerous as its very difficult to revert back to normal condition after chronic exposure to these insidious metals present in our life. Despite many years of research, we are still far from an effective treatment of chronic plumbism and arsenicosis. Current approved treatment lies in the administration of chelating agents that forms an insoluble complex with the metal and removes it. They have been used clinically as antidotes for treating acute and chronic poisoning. The most widely used chelating agents are calcium disodium ethylenediamine tetra acetic acid (CaNa2EDTA), D-penicillamine and British anti-lewisite (BAL). Meso 2,3 dimercaptosuccinic acid (DMSA), an analogue of BAL, has been tried successfully in animals as well as in humans. But it is unable to remove the metal from intracellular sites. Effective chelation therapy for intoxication by heavy metals depends on whether the chelating agents are able to reach the intracellular site where the heavy metal is firmly bound. One of the important approaches has been the use of combination therapy. This includes use of structurally different chelators or a combination of an adjuvant/ antioxidant/ herbal extracts and a chelator to provide better clinical/ biochemical recovery. A number of other strategies have been suggested to minimize the numerous problems. This

  12. Deferasirox, an oral chelator in the treatment of iron overload

    Directory of Open Access Journals (Sweden)

    I. Portioli

    2013-05-01

    Full Text Available BACKGROUND Deferasirox is a once-daily oral iron chelator developed for treating iron overload complicating long-term transfusion therapy in patients with diseases such as beta-thalassemia and myelodysplastic syndromes. Iron overload can damage the liver, pancreas and the heart. Deferoxamine, the only other drug approved for iron chelation, can prevent these effects but requires parenteral administration. Deferasirox has been approved after a one-year, open-label trial in patients ≥ 2 years old with beta-thalassemia and transfusional emosiderosis randomized to once-daily oral 5, 10, 20, 30 mg/kg/day in comparison of subcutaneous deferoxamine 20-60 mg/mg/kg/day x 5/week. CONCLUSIONS Deferasirox 20-30 mg/kg/day produced reductions in liver iron concentration (LIC similar to those with deferoxamine. Adverse effect of deferasirox (increases of serum creatinine and aminotransferases, including the gastrointestinal ones, are similar but more frequent than those occurring with deferoxamine. Information is lacking on the effects of deferasirox on cardiac iron and cardiac dysfunction which is the most serious complication of transfusional iron overload.

  13. Chelating polymeric beads as potential therapeutics for Wilson's disease.

    Science.gov (United States)

    Mattová, Jana; Poučková, Pavla; Kučka, Jan; Skodová, Michaela; Vetrík, Miroslav; Stěpánek, Petr; Urbánek, Petr; Petřík, Miloš; Nový, Zbyněk; Hrubý, Martin

    2014-10-01

    Wilson's disease is a genetic disorder caused by a malfunction of ATPase 7B that leads to high accumulation of copper in the organism and consequent toxic effects. We propose a gentle therapy to eliminate the excessive copper content with oral administration of insoluble non-resorbable polymer sorbents containing selective chelating groups for copper(II). Polymeric beads with the chelating agents triethylenetetramine, N,N-di(2-pyridylmethyl)amine, and 8-hydroxyquinoline (8HQB) were investigated. In a preliminary copper uptake experiment, we found that 8HQB significantly reduced copper uptake (using copper-64 as a radiotracer) after oral administration in Wistar rats. Furthermore, we measured organ radioactivity in rats to demonstrate that 8HQB radiolabelled with iodine-125 is not absorbed from the gastrointestinal tract after oral administration. Non-resorbability and the blockade of copper uptake were also confirmed with small animal imaging (PET/CT) in mice. In a long-term experiment with Wistar rats fed a diet containing the polymers, we have found that there were no signs of polymer toxicity and the addition of polymers to the diet led to a significant reduction in the copper contents in the kidneys, brains, and livers of the rats. We have shown that polymers containing specific ligands could potentially be novel therapeutics for Wilson's disease.

  14. Using iron chelating agents to enhance dermatological PDT

    Science.gov (United States)

    Curnow, Alison; Dogra, Yuktee; Winyard, Paul; Campbell, Sandra

    2009-06-01

    Topical protoporphyrin IX (PPIX) induced photodynamic therapy (PDT) of basal cell carcinoma (BCC) produces good clinical outcomes with excellent cosmesis as long as the disease remains superficial. Efficacy for nodular BCC however appears inferior to standard treatment unless repeat treatments are performed. Enhancement is therefore required and is possible by employing iron chelating agents to temporarily increase PPIX accumulation above the levels normally obtained using aminolevulinic acid (ALA) or the methyl ester of ALA (MAL) alone. In vitro studies investigated the effect of the novel iron chelator, CP94 on necrotic or apoptotic cell death in cultured human skin fibroblasts and epidermal carcinoma cells incubated with MAL. Furthermore, following a dose escalating safety study conducted with ALA in patients, an additional twelve nodular BCCs were recruited for topical treatment with standard MAL-PDT +/- increasing doses of CP94. Six weeks later following clinical assessment, the whole treatment site was excised for histological analysis. CP94 produced greater cell death in vitro when administered in conjunction with MAL than this porphyrin precursor could produce when administered alone. Clinically, PDT treatment using Metvix + CP94 was a simple and safe modification associated with a trend of reduced tumor thickness with increasing CP94 dose.

  15. Mammalian target of rapamycin inhibitor abrogates abnormal osteoclastogenesis in neurofibromatosis type 1

    Institute of Scientific and Technical Information of China (English)

    LIU Ning; XU Ning; WEI Li-hui; CHAI Guo-lin

    2013-01-01

    Background Neurofibromatosis type 1 (NF1) is the most common genetic syndrome predisposing patients to various tumors due to dysregulation of the Ras signaling pathway.Recent research has shown NF1 patients also suffer a spectrum of bone pathologies.The pathogenesis of NF1 bone diseases is largely unknown.There is no current treatment.By Nf1 heterozygote (Nf1+/-) mice and Nf1 conditional knockout mice,we and other groups demonstrated abnormal osteoblast and osteoclast function due to dysregulation of Ras signaling.However,the specific downstream effector pathways linked to NF1 abnormal osteoblastogenesis and osteoclastogenesis have not been defined.In this study,we investigated the Ras downstream effector related with NF1 bone disease.Methods We used Nf1+/+ and Nf1+/-mice as normal and NF1 models.Bone stromal cells extracted from Nf1+/+ and Nf1+/-mice were induced osteoclasts.The osteoclast cell was stained by tartrate resistant acid phosphatase staining.The osteoclast cell number was counted and the surface area of osteoclast cells was calculated under the microscope.The mRNA of mammalian target of rapamycin (mTOR) was determined by quantitative reverse-transcription-polymerase chain reaction.The presence of ribosomal protein S6 kinase was determined by Western blotting.Results Compared with Nf1+/+ mice,Nf1+/-mice had about 20% more of osteoclast cells.These osteoclast cells werelarger in size with more nuclei.Hyperactive mTOR was detected in Nf1+/-osteoclast cells.Inhibition of mTOR signalingby rapamycin in Nf1+/-osteoclasts abrogated abnormalities in cellular size and number.Conclusion mTOR pathway inhibition may represent a viable therapy for NF1 bone diseases.

  16. Application of iron chelates in hydrodesulphurisation

    NARCIS (Netherlands)

    Wubs, Harm Jan

    1994-01-01

    Several iron chelate based methods for removing hydrogen sulphide from gas streams have been developed over the years. Notwithstanding the number of hydrodesulphurisation plants already in operation, the development of these processes has been more a kind of an art rather than a result of rational p

  17. Recent developments centered on orally active iron chelators

    Directory of Open Access Journals (Sweden)

    Robert Hider

    2014-09-01

    Full Text Available Over the past twenty years there has been a growing interest in the orally active iron chelators, deferiprone and deferasirox, both have been extensively studied. The ability of these compounds to mobilize iron from the heart and endocrine tissue has presented the clinician with some advantages over desferrioxamine, the first therapeutic iron chelator. Other orally active iron chelators are currently under development. The critical features necessary for the design of therapeutically useful orally active iron chelators are presented in this review, together with recent studies devoted to the design of such chelators. This newly emerging range of iron chelators will enable clinicians to apply iron chelation methodology to other disease states and to begin to design personalized chelation regimes.

  18. The iron chelator deferasirox enhances liposomal amphotericin B efficacy in treating murine invasive pulmonary aspergillosis

    Science.gov (United States)

    Ibrahim, Ashraf S.; Gebremariam, Teclegiorgis; French, Samuel W.; Edwards, John E.; Spellberg, Brad

    2010-01-01

    Objectives Increased bone marrow iron levels in patients with haematological malignancies is an independent risk factor for developing invasive pulmonary aspergillosis (IPA), suggesting an important role for iron uptake in the pathogenesis of IPA. We sought to determine the potential for combination therapy with the iron chelator deferasirox + liposomal amphotericin B (LAmB) to improve the outcome of murine IPA compared with LAmB monotherapy. Methods In vitro MIC and minimum fungicidal concentration (MFC) values of the iron chelator, deferasirox, for Aspergillus fumigatus were determined by microdilution assay. In addition, we studied the efficacy of deferasirox alone or combined with LAmB in treating immunocompromised mice infected with A. fumigatus via inhalation. Results Deferasirox was cidal in vitro against A. fumigatus, with an MIC and MFC of 25 and 50 mg/L, respectively. Deferasirox monotherapy modestly prolonged survival of mice with IPA. Combination deferasirox + LAmB therapy synergistically improved survival and reduced lung fungal burden compared with either monotherapy alone. Conclusions Iron chelation therapy with deferasirox alone or in combination with LAmB is effective in treating experimental IPA. Further study of deferasirox is warranted as adjunctive therapy for IPA infections. PMID:19942619

  19. Randomised controlled trials of iron chelators for the treatment of cardiac siderosis in thalassaemia major

    Directory of Open Access Journals (Sweden)

    Arun John Baksi

    2014-09-01

    Full Text Available In conditions requiring repeated blood transfusion or where iron metabolism is abnormal, heart failure may result from accumulation of iron in the heart (cardiac siderosis. Death due to heart failure from cardiac iron overload has accounted for considerable early mortality in β-thalassemia major. The ability to detect iron loading in the heart by cardiovascular magnetic resonance using T2* sequences has created an opportunity to intervene in the natural history of such conditions. However, effective and well tolerated therapy is required to remove iron from the heart. There are currently 3 approved commercially available iron chelators: deferoxamine, deferiprone and deferasirox. We review the high quality randomised controlled trials in this area for iron chelation therapy in the management of cardiac siderosis.

  20. Influence of Chelating Agents on Chromium Fate in Sediment

    Institute of Scientific and Technical Information of China (English)

    WANGXIAOCHANG; SUNJINHE; 等

    1996-01-01

    A laboratory investigation on reaction between chelating agents and chromium was conducted to evaluate the effect of chelating agents on the adsorption and desorption of chromium in sediment.The amount of adsorbed chromium(VI) in sediment decreased slightly by 5%-10% because of addition of chelating agents.Chelating agents inhibited the removal of Cr(Ⅲ)by sediment from solutions and the inhibiting effect was in the order:citric acid>tartaric acid>EDTA,Salicylic acid.No effect of chelating agents on desorption of chromium in sediment was observed.

  1. Chelation: A Fundamental Mechanism of Action of AGE Inhibitors, AGE Breakers, and Other Inhibitors of Diabetes Complications

    Energy Technology Data Exchange (ETDEWEB)

    Nagai, Rhoji; Murray, David B.; Metz, Thomas O.; Baynes, John

    2012-03-01

    Advanced glycation or glycoxidation end-products (AGE) increase in tissue proteins with age, and their rate of accumulation is increased in diabetes, nephropathy and inflammatory diseases. AGE inhibitors include a range of compounds that are proposed to act by trapping carbonyl and dicarbonyl intermediates in AGE formation. However, some among the newer generation of AGE inhibitors lack reactive functional groups that would trap reaction intermediates, indicating an alternative mechanism of action. We propose that AGE inhibitors function primarily as chelators, inhibiting metal-catalyzed oxidation reactions. The AGE-inhibitory activity of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers is also consistent with their chelating activity. Finally, compounds described as AGE breakers, or their hydrolysis products, also have strong chelating activity, suggesting that these compounds also act through their chelating activity. We conclude that chelation is the common, and perhaps the primary, mechanism of action of AGE inhibitors and breakers, and that chronic, mild chelation therapy should prove useful in treatment of diabetes and age-related diseases characterized by oxidative stress, inflammation and increased chemical modification of tissue proteins by advanced glycoxidation and lipoxidation end-products.

  2. Federal regulation of unapproved chelation products.

    Science.gov (United States)

    Lee, Charles E

    2013-12-01

    Chelation products can be helpful in the treatment of metal poisoning. However, many unapproved products with unproven effectiveness and safety are marketed to consumers, frequently via the internet. This paper describes the primary responsibility of the Health Fraud and Consumer Outreach Branch of the United States Food and Drug Administration to identify and address health fraud products. Efforts to prevent direct and indirect hazards to the population's health through regulatory actions are described.

  3. Determinants of mitotic catastrophe on abrogation of the G2 DNA damage checkpoint by UCN-01.

    Science.gov (United States)

    On, Kin Fan; Chen, Yue; Ma, Hoi Tang; Chow, Jeremy P H; Poon, Randy Y C

    2011-05-01

    Genotoxic stress such as ionizing radiation halts entry into mitosis by activation of the G(2) DNA damage checkpoint. The CHK1 inhibitor 7-hydroxystaurosporine (UCN-01) can bypass the checkpoint and induce unscheduled mitosis in irradiated cells. Precisely, how cells behave following checkpoint abrogation remains to be defined. In this study, we tracked the fates of individual cells after checkpoint abrogation, focusing in particular on whether they undergo mitotic catastrophe. Surprisingly, while a subset of UCN-01-treated cells were immediately eliminated during the first mitosis after checkpoint abrogation, about half remained viable and progressed into G(1). Both the delay of mitotic entry and the level of mitotic catastrophe were dependent on the dose of radiation. Although the level of mitotic catastrophe was specific for different cell lines, it could be promoted by extending the mitosis. In supporting this idea, weakening of the spindle-assembly checkpoint, by either depleting MAD2 or overexpressing the MAD2-binding protein p31(comet), suppressed mitotic catastrophe. Conversely, delaying of mitotic exit by depleting either p31(comet) or CDC20 tipped the balance toward mitotic catastrophe. These results underscore the interplay between the level of DNA damage and the effectiveness of the spindle-assembly checkpoint in determining whether checkpoint-abrogated cells are eliminated during mitosis.

  4. Enhancement and abrogation : modifications of host immune status influence IL-2 and LAK cell immunotherapy

    NARCIS (Netherlands)

    E.P. Steller (Erick)

    1988-01-01

    textabstractThis thesis will discuss the role immune cells and the host immune system can play in enhancement and abrogation of this novel immunotherapy with interleukin 2 and lymphokine-activated killer cells. Chapter 3 and 4 will discuss the scoring methods in this intraperitoneal cancer and immun

  5. Chelation-induced ototoxicity in thalassemic patients: Role of distortion-product otoacoustic emissions and various management parameters

    Directory of Open Access Journals (Sweden)

    Vikram Bhardwaj

    2016-01-01

    Full Text Available Context and Aims: A limited number of studies have been conducted for the assessment of hearing loss in thalassemic patients on regular chelation therapy and even fewer studies were conducted using otoacoustic emissions (OAEs. The present study was conducted to assess the prevalence of ototoxicity in multiple transfused thalassemic patients on regular iron chelation therapy (with desferrioxamine [DFO] and deferasirox, to compare the efficacy of OAEs (distortion-product OAEs [DPOAEs] with that of pure tone audiometry (PTA for hearing assessment and to correlate ototoxicity with age, mean hemoglobin (Hb, serum ferritin levels, dose and duration of chelation therapy, and therapeutic index Settings and Design: This was a prospective, observational study conducted in a tertiary care hospital. Subjects and Methods: Thirty thalassemic patients undergoing regular iron chelation therapy with DFO and deferasirox were included in this prospective study. Hearing assessment was done using otoscopy, tympanometry, PTA, and DPOAEs between January 1, 2010, and June 30, 2010. Follow-up studies were conducted after 12 months of chelation therapy using the same tests. Patients with and without ototoxicity were compared with respect to age, mean Hb, serum ferritin levels, dose and duration of chelation therapy, and therapeutic index. Statistical Analysis Used: Statistical analysis was carried out using the Student's t-test for normally distributed data and Pearson Chi-square test for categorical data. For nonparametric variables, Mann–Whitney and Wilcoxon tests were applied. Results: Using DPOAEs, 36% of patients were detected having a hearing deficit at the start of the study which increased to 46% at the end of study, whereas using PTA, the detection of hearing loss was 10% and 23%, respectively. DPOAE analysis showed a statistically significant decrease in the signal to noise ratio after 1 year of therapy at 4000 Hz, 5714 Hz, and 8000 Hz with maximum number of

  6. Novel Terbium Chelate Doped Fluorescent Silica Nanoparticles

    Institute of Scientific and Technical Information of China (English)

    Ning Qiaoyu; Meng Jianxin; Wang Haiming; Liu Yingliang; Man Shiqing

    2006-01-01

    Novel terbium chelate doped silica fluorescent nanoparticles were prepared and characterized.The preparation was carried out in water-in-oil (W/O) microemulsion containing monomer precursor (pAB-DTPAA-APTEOS), Triton X-100, n-hexanol, and cyclohexane by controlling copolymerization of tetraethyl orthosilicate and 3-aminopropyl-triethyloxysilane.The nanoparticles are spherical and uniform in size, about 30 nm in diameter, strongly fluorescent, and highly stable.The amino groups directly introduced to the surface of the nanoparticles using APTEOS during preparation made the surface modification and bioconjugation of the nanoparticles easier.The nanoparticles are expected as an efficient time-resolved luminescence biological label.

  7. The use of chelating agents in clinical toxicology and environmental medicine; Einsatz von Chelatbildnern in der Klinischen Toxikologie und Umweltmedizin

    Energy Technology Data Exchange (ETDEWEB)

    Felgenhauer, N.; Zilker, T. [Technische Univ. Muenchen (Germany). Inst. fuer Pharmakologie und Toxikologie

    2000-07-01

    Nowadays DMPS and DMSA have displaced dimercaprol and CaNa{sub 2}EDTA as the most important agents for chelating therapy. DMPS and DMSA appear effective, safe, specific and simple to administer and have become absolutely indispensable to the treatment of acute metal poisoning. However, in chronic metal poisonings, as they are discussed in Environmental Medicine today, there are no data available, which justify the use of these chelating agents or any other chelating therapy. Indication, dosing schedule, form of application, duration, safety and clinical benefit of chelating therapy are not sufficiently investigated in chronic metal poisoning. Also the use of the so-called DMPS challenge test to estimate the amalgam related body burden of mercury reveals no further information that the mercury excretion in 24 h-urine without application of DMPS. (orig.) [German] Heute verfuegen wir mit dem DMPS und dem DMSA ueber zwei effektive, gut vertraegliche, realtiv spezifische und leicht zu verabreichende Antidote, die fuer die Behandlung akuter Metallvergiftungen unverzichtbar geworden sind. Bei chronischen Metallvergiftungen wie sie in der Umweltmedizin diskutiert werden, ist der Einsatz dieser Chelatbildner aufgrund der heute vorliegenden Datenlage jedoch nicht zu rechtfertigen. Indikation, Dosierung, Applikationsform, Dauer, Sicherheit und klinischer Benefit einer Chelattherapie sind bei chronischen Metallvergiftungen noch nicht ausreichend untersucht. Auch bringt der Mobilisationstest mit DMPS zur Beurteilung einer amalgambedingten Hg-Belastung keinen wesentlichen Erkenntnisgewinn gegenueber der spontanen Hg-Ausscheidung im 24-Stunden-Urin. (orig.)

  8. Progress on Study of Luminescence of Rare Earth Organic Chelates

    Institute of Scientific and Technical Information of China (English)

    杨燕生; 安保礼; 龚孟濂; 史华红; 雷衡毅; 孟建新

    2002-01-01

    Based on the investigation of the luminescence of a series of rare earth organic chelates, some relationships between luminescence and the structure of the chelates were proposed: the intensity of sensitized luminescence of central lanthanide ions(Ln3+) in a rare earth organic chelate depends on (1)the suitability of the energy gap between the excited triplet energy level of the ligands and the lowest excited energy level of Ln3+ ions; (2)the rigidity and planarity of the structure of the chelate molecule; (3)the existence of a suitable secondary ligand which may increase rigidity and the stability of the chelate molecule; and (4) the existence of a suitable π-conjugated system in the chelate molecule. According to the above relationships, 25 novel organic ligands were designed and synthesized, and their lanthanide chelates were prepared. Investigation of the photoluminescence for the new chelates shows that some of the chelates are strongly luminescent, and are applied to fluoroimmunoassay for determination of human immunoglobulin(IgG), to preparation of fluorescent plastics, and to determination of growth hormone for plants. Two novel spectroscopy-probe techniques for structure of coordination compounds and biological molecules were proposed and developed based on vibronic spectroscopy of Tb3+ complexes and fluorescence of Ce3+.

  9. Metal regeneration of iron chelates in nitric oxide scrubbing

    Science.gov (United States)

    Chang, S.G.; Littlejohn, D.; Shi, Y.

    1997-08-19

    The present invention relates to a process of using metal particles to reduce NO to NH{sub 3}. More specifically, the invention concerns an improved process to regenerate iron (II) (CHELATE) by reduction of iron (II) (CHELATE) (NO) complex, which process comprises: (a) contacting an aqueous solution containing iron (II) (CHELATE) (NO) with metal particles at between about 20 and 90 C to reduce NO present, produce ammonia or an ammonium ion, and produce free iron (II) (CHELATE) at a pH of between about 3 and 8. The process is useful to remove NO from flue gas and reduce pollution. 34 figs.

  10. Ascorbate status modulates reticuloendothelial iron stores and response to deferasirox iron chelation in ascorbate-deficient rats

    DEFF Research Database (Denmark)

    Brewer, Casey; Otto-Duessel, Maya; Lykkesfeldt, Jens

    2012-01-01

    Iron chelation is essential to patients on chronic blood transfusions to prevent toxicity from iron overload and remove excess iron. Deferasirox (DFX) is the most commonly used iron chelator in the United States; however, some patients are relatively refractory to DFX therapy. We postulated...... that vitamin C supplementation would improve the availability of transfusional iron to DFX treatment by promoting iron's redox cycling, increasing its soluble ferrous form and promoting its release from reticuloendothelial cells. Osteogenic dystrophy rats (n = 54) were given iron dextran injections for 10...... 12 weeks of sham chelation. Most importantly, ascorbate supplementation at 2250 ppm improved DFX efficiency, allowing DFX to remove 21% more hepatic iron than ascorbate supplementation with 900 ppm or 150 ppm (p vitamin C status modulates the release of iron from...

  11. Design of intrahepatocyte copper(I) chelators as drug candidates for Wilson's disease.

    Science.gov (United States)

    Gateau, Christelle; Delangle, Pascale

    2014-05-01

    Wilson's disease is an autosomal recessive disease caused by mutations on the ATP7B gene found on chromosome 13. Since the corresponding ATPase is in charge of copper (Cu) distribution and excretion in the liver, its malfunctioning leads to Cu overload. This short review deals with treatments of this rare disease, which aim at decreasing Cu toxicity and are, therefore, based on chelation therapy. The drugs used since the 1950s are described first, then a novel approach developed in our laboratory is presented. Since the liver is the main organ of Cu distribution in the body, we targeted the pool of intracellular Cu in hepatocytes. This Cu pool is in the +1 oxidation state, and therefore soft sulfur ligands inspired from binding sites found in metallothioneins were developed. Their targeting to the hepatocytes by functionalization with ligands of the asialoglycoprotein receptor led to their cellular incorporation and intracellular Cu chelation.

  12. L-carnitine, a diet component and organic cation transporter OCTN ligand, displays immunosuppressive properties and abrogates intestinal inflammation.

    Science.gov (United States)

    Fortin, G; Yurchenko, K; Collette, C; Rubio, M; Villani, A-C; Bitton, A; Sarfati, M; Franchimont, D

    2009-04-01

    Allele variants in the L-carnitine (LCAR) transporters OCTN1 (SLC22A4, 1672 C --> T) and OCTN2 (SLC22A5, -207 G --> C) have been implicated in susceptibility to Crohn's disease (CD). LCAR is consumed in the diet and transported actively from the intestinal lumen via the organic cation transporter OCTN2. While recognized mainly for its role in fatty acid metabolism, several lines of evidence suggest that LCAR may also display immunosuppressive properties. This study sought to investigate the immunomodulatory capacity of LCAR on antigen-presenting cell (APC) and CD4+ T cell function by examining cytokine production and the expression of activation markers in LCAR-supplemented and deficient cell culture systems. The therapeutic efficacy of its systemic administration was then evaluated during the establishment of colonic inflammation in vivo. LCAR treatment significantly inhibited both APC and CD4+ T cell function, as assessed by the expression of classical activation markers, proliferation and cytokine production. Carnitine deficiency resulted in the hyperactivation of CD4+ T cells and enhanced cytokine production. In vivo, protection from trinitrobenzene sulphonic acid colitis was observed in LCAR-treated mice and was attributed to the abrogation of both innate [interleukin (IL)-1beta and IL-6 production] and adaptive (T cell proliferation in draining lymph nodes) immune responses. LCAR therapy may therefore represent a novel alternative therapeutic strategy and highlights the role of diet in CD.

  13. Chelation Treatment for Autism Spectrum Disorders: A Systematic Review

    Science.gov (United States)

    Davis, Tonya N.; O'Reilly, Mark; Kang, Soyeon; Lang, Russell; Rispoli, Mandy; Sigafoos, Jeff; Lancioni, Giulio; Copeland, Daelynn; Attai, Shanna; Mulloy, Austin

    2013-01-01

    Chelation treatment is used to eliminate specific metals from the body, such as mercury. It has been hypothesized that mercury poisoning may be a factor in autism and data suggest that perhaps 7% of individuals with autism spectrum disorder (ASD) have received chelation treatment. It would therefore seem timely to review studies investigating the…

  14. Potentials and drawbacks of chelate-enhanced phytoremediation of soils

    NARCIS (Netherlands)

    Römkens, P.F.A.M.; Bouwman, L.A.; Japenga, J.; Draaisma, C.

    2002-01-01

    Chelate-enhanced phytoremediation has been proposed as an effective tool for the extraction of heavy metals from soils by plants. However, side-effects related to the addition of chelates, e.g. metal leaching and effects on soil micro-organisms, were usually neglected. Therefore, greenhouse and lysi

  15. Is copper chelation an effective anti-angiogenic strategy for cancer treatment?

    Science.gov (United States)

    Antoniades, V; Sioga, A; Dietrich, E M; Meditskou, S; Ekonomou, L; Antoniades, K

    2013-12-01

    Angiogenesis and the acquisition of an angiogenic phenotype is important for cancer cell proliferation. Copper in an essential trace element that participates in many enzymatic complexes like the cytochrome c, superoxide dismutase and lysyl oxidase and it is involved in processes, like embryogenesis, growth, angiogenesis and carcinogenesis. In particular, its involvement in carcinogenesis was described for the first time in oral submucous fibrosis, where fibroblasts produce large amounts of collagen in the presence of copper. Copper's action in carcinogenesis is two-fold: (1) it participates in reactions with an increased redox potential that result in the production of oxidative products and oxidative stress. Through this mechanism, copper may cause DNA mutations in the nucleus and mitochondria or alterations to membrane phospholipids, (2) it participates in angiogenesis even in the absence of angiogenic molecules, as it was reported for the first time in rabbit cornea models with copolymer pellets charged with PGE1. Copper chelation regimens like penicillamine and tetrathiomolybdate are being described in the literature as having anti-angiogenic, anti-fibrotic and anti-inflammatory actions. Animal models of brain cancer that evaluated the anti-angiogenic properties of copper, have proven evidence of the reduction of tumor's microvascular supply, tumor volume and vascular permeability after plasma copper levels reduction. Interestingly, plasma copper levels reduction was shown to suppress micrometastases generation in mice models of breast cancer. We hypothesize that copper chelation therapy: increases oxidative stress in cancer cells to a level that does not allow survival because of the reduction of anti-oxidative enzymes production. It may also result in inhibition of angiogenesis and of the initiation of the angiogenic switch, because copper normally enhances endothelial cell migration and proliferation, improves binding of growth factors to endothelial cells

  16. Quantitative measurement of metal chelation by fourier transform infrared spectroscopy

    Directory of Open Access Journals (Sweden)

    Monika E. Miller

    2015-12-01

    Full Text Available Nutritionally important minerals are more readily absorbed by living systems when complexed with organic acids, resulting in higher consumer demand and premium prices for these products. These chelated metals are produced by reaction of metal oxides and acids in aqueous solution. However, unreacted dry blends are sometimes misrepresented as metal chelates, when in reality they are only simple mixtures of the reactants typically used to synthesize them. This practice has increased interest in developing analytical methods that are capable of measuring the extent of metal chelation for quality control and regulatory compliance. We describe a novel method to rapidly measure the percent chelation of citric and malic acids with calcium, magnesium, and zinc. Utilization of attenuated total reflectance (FTIR-ATR provides for the direct, rapid measurement of solid samples. The inclusion of an internal standard allows independent determination of either free or chelated acids from integrated areas in a single spectrum.

  17. Luminescence of a conjugated polymer containing europium (III) chelate

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Hao; Xie, Fang, E-mail: xiefang4498@126.com

    2013-12-15

    A europium (III) chelate has been incorporated in a conjugated polymer, poly-[2,2′-bipyridine-5,5′-diyl-(2,5-dihexyl-1,4-phenylene)]. From the absorbance and emission spectra measurement and using the Judd–Ofelt theory, an efficient energy transfer between the conjugated polymer and the europium (III) chelate has been confirmed. The luminescence lifetime of Eu{sup 3+} ion in the conjugated polymer is 0.352 ms and the emission cross section of this material is 3.11×10{sup −21} cm{sup 2}. -- Highlights: • A europium chelate has been incorporated in a conjugated polymer. • Energy transfer in the conjugated polymer containing europium chelate is efficient. • The conjugated polymer containing europium chelate is a promising optical material.

  18. Chelating ionic liquids for reversible zinc electrochemistry.

    Science.gov (United States)

    Kar, Mega; Winther-Jensen, Bjorn; Forsyth, Maria; MacFarlane, Douglas R

    2013-05-21

    Advanced, high energy-density, metal-air rechargeable batteries, such as zinc-air, are of intense international interest due to their important role in energy storage applications such as electric and hybrid vehicles, and to their ability to deal with the intermittency of renewable energy sources such as solar and wind. Ionic liquids offer a number of ideal thermal and physical properties as potential electrolytes in such large-scale energy storage applications. We describe here the synthesis and characterisation of a family of novel "chelating" ILs designed to chelate and solubilize the zinc ions to create electrolytes for this type of battery. These are based on quaternary alkoxy alkyl ammonium cations of varying oligo-ether side chains and anions such as p-toluene sulfonate, bis(trifluoromethylsulfonyl)amide and dicyanoamides. This work shows that increasing the ether chain length in the cation from two to four oxygens can increase the ionic conductivity and reduce the melting point from 67 °C to 15 °C for the tosylate system. Changing the anion also plays a significant role in the nature of the zinc deposition electrochemistry. We show that zinc can be reversibly deposited from [N(222(20201))][NTf2] and [N(222(202020201))][NTf2] beginning at -1.4 V and -1.7 V vs. SHE, respectively, but not in the case of tosylate based ILs. This indicates that the [NTf2] is a weaker coordinating anion with the zinc cation, compared to the tosylate anion, allowing the coordination of the ether chain to dominate the behavior of the deposition and stripping of zinc ions.

  19. Relationship between conformational flexibility and chelate cooperativity.

    Science.gov (United States)

    Misuraca, M Cristina; Grecu, Tudor; Freixa, Zoraida; Garavini, Valentina; Hunter, Christopher A; van Leeuwen, Piet W N M; Segarra-Maset, M Dolores; Turega, Simon M

    2011-04-15

    A family of four biscarbamates (AA) and four bisphenols (DD) were synthesized, and H-bonding interactions between all AA•DD combinations were characterized using (1)H NMR titrations in carbon tetrachloride. A chemical double mutant cycle analysis shows that there are no secondary electrostatic interactions or allosteric cooperativity in these systems, and the system therefore provides an ideal platform for investigating the relationship between chemical structure and chelate cooperativity. Effective molarities (EMs) were measured for 12 different systems, where the number of rotors in the chains connecting the two H-bond sites was varied from 5 to 20. The association constants vary by less than an order of magnitude for all 12 complexes, and the variation in EM is remarkably small (0.1-0.9 M). The results provide a relationship between EM and the number of rotors in the connecting chains (r): EM ≈ 10r(-3/2). The value of 10 M is the upper limit for the value of EM for a noncovalent intramolecular interaction. Introduction of rotors reduces the value of EM from this maximum in accord with a random walk analysis of the encounter probability of the chain ends (r(-3/2)). Noncovalent EMs never reach the very high values observed for covalent processes, which places limitations on the magnitudes of the effects that one is likely to achieve through the use of chelate cooperativity in supramolecular assembly and catalysis. On the other hand, the decrease in EM due to the introduction of conformational flexibility is less dramatic than one might expect based on the behavior of covalent systems, which limits the losses in binding affinity caused by poor preorganization of the interaction sites.

  20. Curcumin inhibits growth of Saccharomyces cerevisiae through iron chelation.

    Science.gov (United States)

    Minear, Steven; O'Donnell, Allyson F; Ballew, Anna; Giaever, Guri; Nislow, Corey; Stearns, Tim; Cyert, Martha S

    2011-11-01

    Curcumin, a polyphenol derived from turmeric, is an ancient therapeutic used in India for centuries to treat a wide array of ailments. Interest in curcumin has increased recently, with ongoing clinical trials exploring curcumin as an anticancer therapy and as a protectant against neurodegenerative diseases. In vitro, curcumin chelates metal ions. However, although diverse physiological effects have been documented for this compound, curcumin's mechanism of action on mammalian cells remains unclear. This study uses yeast as a model eukaryotic system to dissect the biological activity of curcumin. We found that yeast mutants lacking genes required for iron and copper homeostasis are hypersensitive to curcumin and that iron supplementation rescues this sensitivity. Curcumin penetrates yeast cells, concentrates in the endoplasmic reticulum (ER) membranes, and reduces the intracellular iron pool. Curcumin-treated, iron-starved cultures are enriched in unbudded cells, suggesting that the G(1) phase of the cell cycle is lengthened. A delay in cell cycle progression could, in part, explain the antitumorigenic properties associated with curcumin. We also demonstrate that curcumin causes a growth lag in cultured human cells that is remediated by the addition of exogenous iron. These findings suggest that curcumin-induced iron starvation is conserved from yeast to humans and underlies curcumin's medicinal properties.

  1. Fixation kinetics of chelated and non-chelated zinc in semi-arid alkaline soils: application to zinc management

    Science.gov (United States)

    Udeigwe, Theophilus K.; Eichmann, Madeleine; Menkiti, Matthew C.

    2016-07-01

    This study was designed to examine the fixation pattern and kinetics of zinc (Zn) in chelated (ethylenediaminetetraacetic acid, EDTA) and non-chelated mixed micronutrient systems of semi-arid alkaline soils from the Southern High Plains, USA. Soils were characterized for a suite of chemical and physical properties and data obtained from extraction experiments fitted to various kinetic models. About 30 % more plant-available Zn was fixed in the non-chelated system within the first 14 days with only about 18 % difference observed between the two systems by day 90, suggesting that the effectiveness of the chelated compounds tended to decrease over time. The strengths of the relationships of change in available Zn with respect to other micronutrients (copper, iron, and manganese) were higher and more significant in the non-chelated system (average R2 of 0.83), compared to the chelated (average R2 of 0.42). Fixation of plant-available Zn was best described by the power-function model (R2 = 0.94, SE = 0.076) in the non-chelated system, and was poorly described by all the models examined in the chelated system. Reaction rate constants and relationships generated from this study can serve as important tools for micronutrient management and for future micronutrient modeling studies on these soils and other semi-arid regions of the world.

  2. DNA nuclease activity of Rev-coupled transition metal chelates.

    Science.gov (United States)

    Joyner, Jeff C; Keuper, Kevin D; Cowan, J A

    2012-06-07

    Artificial nucleases containing Rev-coupled metal chelates based on combinations of the transition metals Fe(2+), Co(2+), Ni(2+), and Cu(2+) and the chelators DOTA, DTPA, EDTA, NTA, tripeptide GGH, and tetrapeptide KGHK have been tested for DNA nuclease activity. Originally designed to target reactive transition metal chelates (M-chelates) to the HIV-1 Rev response element mRNA, attachment to the arginine-rich Rev peptide also increases DNA-binding affinity for the attached M-chelates. Apparent K(D) values ranging from 1.7 to 3.6 µM base pairs for binding of supercoiled pUC19 plasmid DNA by Ni-chelate-Rev complexes were observed, as a result of electrostatic attraction between the positively-charged Rev peptide and negatively-charged DNA. Attachment of M-chelates to the Rev peptide resulted in enhancements of DNA nuclease activity ranging from 1-fold (no enhancement) to at least 13-fold (for Cu-DTPA-Rev), for the rate of DNA nicking, with second order rate constants for conversion of DNA(supercoiled) to DNA(nicked) up to 6 × 10(6) M(-1) min(-1), and for conversion of DNA(nicked) to DNA(linear) up to 1 × 10(5) M(-1) min(-1). Freifelder-Trumbo analysis and the ratios of linearization and nicking rate constants (k(lin)/k(nick)) revealed concerted mechanisms for nicking and subsequent linearization of plasmid DNA for all of the Rev-coupled M-chelates, consistent with higher DNA residency times for the Rev-coupled M-chelates. Observed rates for Rev-coupled M-chelates were less skewed by differing DNA-binding affinities than for M-chelates lacking Rev, as a result of the narrow range of DNA-binding affinities observed, and therefore relationships between DNA nuclease activity and other catalyst properties, such as coordination unsaturation, the ability to consume ascorbic acid and generate diffusible radicals, and the identity of the metal center, are now clearly illustrated in light of the similar DNA-binding affinities of all M-chelate-Rev complexes. This work

  3. Succimer chelation normalizes reactivity to reward omission and errors in lead-exposed rats.

    Science.gov (United States)

    Beaudin, Stéphane A; Stangle, Diane E; Smith, Donald R; Levitsky, David A; Strupp, Barbara J

    2007-01-01

    This study evaluated the efficacy of a 3-week course of succimer treatment to alleviate behavioral deficits in rats exposed to lead (Pb) for the first 4 weeks of life. A 3 x 2 factorial design was used: three levels of lead exposure (No Pb, Moderate, and High Pb) and two levels of chelation (succimer or vehicle). Behavioral testing was conducted following chelation therapy, from 2 to 9 months of age; this report presents the results of two of the administered tasks: (1) a conditional olfactory discrimination task (baseline task), and (2) a conditional olfactory discrimination task with periodic reward omission on some correct trials (RO task). In the RO task, the performance disruption produced by committing an error on the previous trial was significantly greater for both unchelated lead-exposed groups than for controls. The High Pb rats were also more sensitive to reward omission than controls, providing converging evidence for impaired regulation of arousal or emotion. Importantly, succimer treatment was effective in normalizing the heightened reactivity of the lead-exposed animals to both errors and reward omission. In addition, non-lead-exposed rats that were treated with succimer tended to be more affected by a prior error than controls in their latency to respond on post-error trials. In sum, these findings provide new evidence that succimer chelation can significantly lessen the lasting neurobehavioral dysfunction produced by early lead exposure, but also suggest that there may be risks of administering the drug to individuals without elevated blood lead levels.

  4. A New Synthesis of TE2A-a Potential Bifunctional Chelator for {sup 64}Cu

    Energy Technology Data Exchange (ETDEWEB)

    Pandya, Darpan N.; Kwak, Won Jung; Park, Jeong Chan; Gawande, Manoj B.; Yoo, Jeong Soo [Kyungpook National University, Daegu (Korea, Republic of); Kim, Jung Young; An, Gwang Il [Molecular Imaging Research Center, Seoul (Korea, Republic of); Ryu, Eun Kyoung [Korea Basic Science Institute, Chungbuk (Korea, Republic of)

    2010-09-15

    The development of a new bifunctional chelator, which holds radio metals strongly in living systems, is a prerequisite for the successful application of disease-specific biomolecules to medical diagnosis and therapy. Recently, TE2A was reported to make kinetically more stable Cu({Pi}) complexes than TETA. Herein, we report a new synthetic route to TE2A and explore its potential as a bifunctional chelator. TE2A was synthesized using the regioselective alkylation of benzyl bromoacetate and successive de protection of the methylene bridge and benzyl group. Salt-free TE2A was radiolabeled with {sup 64}Cu and micro PET imaging was performed to follow the clearance pattern of the {sup 64}Cu-TE2A complex. TE2A was conjugated with cyclic RGD peptide and the TE2A-c(RGDyK) conjugate was radiolabeled with {sup 64}Cu. TE2A was prepared in salt-free form cyclam in an overall yield of 74%. The micro PET images showed that {sup 64}Cu-TE2A is excreted rapidly from the body by the kidney and liver. TE2A was successfully conjugated with c(RGDyK) peptide through on carboxylate group and the TE2A-c(RGDyK) conjugate was radiolabeled with {sup 64}Cu in 94% yield within 30 min. TE2A can be used by itself as a bifunctional chelator without any further structural modification.

  5. Is aceruloplasminemia treatable? Combining iron chelation and fresh-frozen plasma treatment.

    Science.gov (United States)

    Poli, L; Alberici, A; Buzzi, P; Marchina, E; Lanari, A; Arosio, C; Ciccone, A; Semeraro, F; Gasparotti, R; Padovani, A; Borroni, Barbara

    2017-02-01

    We report the case of a patient with hereditary ceruloplasmin deficiency due to a novel gene mutation in ceruloplasmin gene (CP), treated with fresh frozen plasma (FFP) and iron chelation therapy. A 59-year-old man with a past history of diabetes was admitted to our department due to progressive gait difficulties and cognitive impairment. Neurological examination revealed a moderate cognitive decline, with mild extrapyramidal symptoms, ataxia, and myoclonus. Brain T2-weighted MR imaging showed bilateral basal ganglia hypointensity with diffuse iron deposition. Increased serum ferritin, low serum copper concentration, undetectable ceruloplasmin, and normal urinary copper excretion were found. The genetic analysis of the CP (OMIM #604290) reported compound heterozygosity for two mutations, namely c.848G > A and c.2689_2690delCT. Treatment with FFP (500 mL i.v./once a week) and administration of iron chelator (Deferoxamine 1000 mg i.v/die for 5 days, followed by Deferiprone 500 mg/die per os) were undertaken. At the 6-month follow-up, clinical improvement of gait instability, trunk ataxia, and myoclonus was observed; brain MRI scan showed no further progression of basal ganglia T2 hypointensity. This case report suggests that the early initiation of combined treatment with FFP and iron chelation may be useful to reduce the accumulation of iron in the central nervous system and to improve the neurological symptoms.

  6. Chelation: Harnessing and Enhancing Heavy Metal Detoxification—A Review

    Directory of Open Access Journals (Sweden)

    Margaret E. Sears

    2013-01-01

    Full Text Available Toxic metals such as arsenic, cadmium, lead, and mercury are ubiquitous, have no beneficial role in human homeostasis, and contribute to noncommunicable chronic diseases. While novel drug targets for chronic disease are eagerly sought, potentially helpful agents that aid in detoxification of toxic elements, chelators, have largely been restricted to overt acute poisoning. Chelation, that is multiple coordination bonds between organic molecules and metals, is very common in the body and at the heart of enzymes with a metal cofactor such as copper or zinc. Peptides glutathione and metallothionein chelate both essential and toxic elements as they are sequestered, transported, and excreted. Enhancing natural chelation detoxification pathways, as well as use of pharmaceutical chelators against heavy metals are reviewed. Historical adverse outcomes with chelators, lessons learned in the art of using them, and successes using chelation to ameliorate renal, cardiovascular, and neurological conditions highlight the need for renewed attention to simple, safe, inexpensive interventions that offer potential to stem the tide of debilitating, expensive chronic disease.

  7. Affinity purification of copper chelating peptides from chickpea protein hydrolysates.

    Science.gov (United States)

    Megías, Cristina; Pedroche, Justo; Yust, Maria M; Girón-Calle, Julio; Alaiz, Manuel; Millan, Francisco; Vioque, Javier

    2007-05-16

    Chickpea protein hydrolysates obtained with alcalase and flavourzyme were used for purification of copper chelating peptides by affinity chromatography using copper immobilized on solid supports. The chelating activity of purified peptides was indirectly measured by the inhibition of beta-carotene oxidation in the presence of copper. Two protein hydrolysates, obtained after 10 and 100 min of hydrolysis, were the most inhibitory of beta-carotene oxidation. Purified copper chelating peptides from these protein hydrolysates contained 19.7 and 35.1% histidine, respectively, in comparison to 2.7 and 2.6% in the protein hydrolysates. Chelating peptides from hydrolysate obtained after 10 min of hydrolysis were the most antioxidative being 8.3 times more antioxidative than the hydrolysate, while chelating peptides purified from protein hydrolysate obtained after 100 min were 3.1 times more antioxidative than its hydrolysate. However, the histidine content was higher in peptides derived from the 100 min hydrolysate (19.7 against 35.1% in 10 min hydrolysate), indicating that this amino acid is not the only factor involved in the antioxidative activity, and other factors such as peptide size or amino acid sequence are also determinant. This manuscript shows that affinity chromatography is a useful procedure for purification of copper chelating peptides. This method can be extended to other metals of interest in nutrition, such as calcium, iron, or zinc. Purified chelating peptides, in addition to their antioxidative properties, may also be useful in food mineral fortification for increasing the bioavailability of these metals.

  8. Effects of Iron Chelators on the Formation and Development of Aspergillus fumigatus Biofilm.

    Science.gov (United States)

    Nazik, Hasan; Penner, John C; Ferreira, Jose A; Haagensen, Janus A J; Cohen, Kevin; Spormann, Alfred M; Martinez, Marife; Chen, Vicky; Hsu, Joe L; Clemons, Karl V; Stevens, David A

    2015-10-01

    Iron acquisition is crucial for the growth of Aspergillus fumigatus. A. fumigatus biofilm formation occurs in vitro and in vivo and is associated with physiological changes. In this study, we assessed the effects of Fe chelators on biofilm formation and development. Deferiprone (DFP), deferasirox (DFS), and deferoxamine (DFM) were tested for MIC against a reference isolate via a broth macrodilution method. The metabolic effects (assessed by XTT [2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt]) on biofilm formation by conidia were studied upon exposure to DFP, DFM, DFP plus FeCl3, or FeCl3 alone. A preformed biofilm was exposed to DFP with or without FeCl3. The DFP and DFS MIC50 against planktonic A. fumigatus was 1,250 μM, and XTT gave the same result. DFM showed no planktonic inhibition at concentrations of ≤2,500 μM. By XTT testing, DFM concentrations of biofilms forming in A. fumigatus or preformed biofilms (P biofilm formation (P Biofilm formation with 625 μM DFP plus any concentration of FeCl3 was lower than that in the controls (P biofilms, DFP in the range of ≥625 to 1,250 μM was inhibitory compared to the controls (P biofilm formation (P biofilm increased with 2,500 μM FeCl3 only (P biofilms of A. fumigatus clinical isolates to DFP were noted. In conclusion, iron stimulates biofilm formation and preformed biofilms. Chelators can inhibit or enhance biofilms. Chelation may be a potential therapy for A. fumigatus, but we show here that chelators must be chosen carefully. Individual isolate susceptibility assessments may be needed.

  9. Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib.

    Science.gov (United States)

    Yamamoto, Naoki; Yamasaki, Takahiro; Takami, Taro; Uchida, Koichi; Fujisawa, Koichi; Matsumoto, Toshihiko; Saeki, Issei; Terai, Shuji; Sakaida, Isao

    2016-05-01

    Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient l-amino acid-defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC.

  10. Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib

    Science.gov (United States)

    Yamamoto, Naoki; Yamasaki, Takahiro; Takami, Taro; Uchida, Koichi; Fujisawa, Koichi; Matsumoto, Toshihiko; Saeki, Issei; Terai, Shuji; Sakaida, Isao

    2016-01-01

    Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient l-amino acid-defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC. PMID:27257345

  11. Combinatorial treatment using targeted MEK and SRC inhibitors synergistically abrogates tumor cell growth and induces mesenchymal-epithelial transition in non-small-cell lung carcinoma.

    Science.gov (United States)

    Chua, Kian Ngiap; Kong, Li Ren; Sim, Wen Jing; Ng, Hsien Chun; Ong, Weijie Richard; Thiery, Jean Paul; Huynh, Hung; Goh, Boon Cher

    2015-10-01

    Oncogenesis in non-small cell lung cancer (NSCLC) is regulated by a complex signal transduction network. Single-agent targeted therapy fails frequently due to treatment insensitivity and acquired resistance. In this study, we demonstrate that co-inhibition of the MAPK and SRC pathways using a PD0325901 and Saracatinib kinase inhibitor combination can abrogate tumor growth in NSCLC. PD0325901/Saracatinib at 0.25:1 combination was screened against a panel of 28 NSCLC cell lines and 68% of cell lines were found to be sensitive (IC50 cell migration and matrigel invasion. The co-inhibition of MAPK and SRC induced strong G1/G0 cell cycle arrest in the NSCLC lines, inhibited anchorage independent growth and delayed tumor growth in H460 and H358 mouse xenografts. These data provide rationale for further investigating the combination of MAPK and SRC pathway inhibitors in advanced stage NSCLC.

  12. STUDY ON THERMAL DECOMPOSITION KINETICS OF URUSHIOL METAL CHELATE POLYMERS

    Institute of Scientific and Technical Information of China (English)

    HU Binghuan; CHEN Riyao; LIN Jinhuo; CHEN Wending

    1994-01-01

    The thermal decomposition kinetics of urushiol-Cu, urushiol-Nd and urushiol-Ti chelate polymers has been studied by non-isothermal thermogravimetry. The results suggest that the thermal decomposition kinetics of three chelate polymers are all of first order. Their average activation energy values of the thermal decomposition calculated by Ozawa-(Ⅰ) method are 110.79,136.98 and 163.64 kJ mol-1respectively,which increase linearly with the metal valence of the metal chelate polymers

  13. Synthetic Lubricating Oil Greases Containing Metal Chelates of Schiff Bases

    Science.gov (United States)

    1992-09-15

    greases comprising the addition to said greases of effective amounts of a chelated Schiff base derived from the condensation of approximately stoichiometic amounts of at least one aldehyde and a polyamine.

  14. Development of Multi-Functional Chelators Based on Sarcophagine Cages

    Directory of Open Access Journals (Sweden)

    Shuanglong Liu

    2014-04-01

    Full Text Available A new class of multifunctionalized sarcophagine derivatives was synthesized for 64Cu chelation. The platform developed in this study could have broad applications in 64Cu-radiopharmaceuticals.

  15. Metal chelate process to remove pollutants from fluids

    Science.gov (United States)

    Chang, Shih-Ger T.

    1994-01-01

    The present invention relates to improved methods using an organic iron chelate to remove pollutants from fluids, such as flue gas. Specifically, the present invention relates to a process to remove NO.sub.x and optionally SO.sub.2 from a fluid using a metal ion (Fe.sup.2+) chelate wherein the ligand is a dimercapto compound wherein the --SH groups are attached to adjacent carbon atoms (HS--C--C--SH) or (SH--C--CCSH) and contain a polar functional group so that the ligand of DMC chelate is water soluble. Alternatively, the DMC' is covalently attached to a water insoluble substrate such as a polymer or resin, e.g., polystyrene. The chelate is regenerated using electroreduction or a chemical additive. The dimercapto compound bonded to a water insoluble substrate is also useful to lower the concentration or remove hazardous metal ions from an aqueous solution.

  16. A Brief Review of Chelators for Radiolabeling Oligomers

    Directory of Open Access Journals (Sweden)

    Yuxia Liu

    2010-05-01

    Full Text Available The chemical modification of oligomers such as DNA, PNA, MORF, LNA to attach radionuclides for nuclear imaging and radiotherapy applications has become a field rich in innovation as older methods are improved and new methods are introduced. This review intends to provide a brief overview of several chelators currently in use for the labeling of oligomers with metallic radionuclides such as 99mTc, 111In and 188Re. While DNA and its analogs have been radiolabeled with important radionuclides of nonmetals such as 32P, 35S, 14C, 18F and 125I, the labeling methods for these isotopes involve covalent chemistry that is quite distinct from the coordinate-covalent chelation chemistry described herein. In this review, we provide a summary of the several chelators that have been covalently conjugated to oligomers for the purpose of radiolabeling with metallic radionuclides by chelation and including details on the conjugation, the choice of radionuclides and labeling methods.

  17. Metal chelate process to remove pollutants from fluids

    Science.gov (United States)

    Chang, S.G.T.

    1994-12-06

    The present invention relates to improved methods using an organic iron chelate to remove pollutants from fluids, such as flue gas. Specifically, the present invention relates to a process to remove NO[sub x] and optionally SO[sub 2] from a fluid using a metal ion (Fe[sup 2+]) chelate wherein the ligand is a dimercapto compound wherein the --SH groups are attached to adjacent carbon atoms (HS--C--C--SH) or (SH--C--CCSH) and contain a polar functional group so that the ligand of DMC chelate is water soluble. Alternatively, the DMC is covalently attached to a water insoluble substrate such as a polymer or resin, e.g., polystyrene. The chelate is regenerated using electroreduction or a chemical additive. The dimercapto compound bonded to a water insoluble substrate is also useful to lower the concentration or remove hazardous metal ions from an aqueous solution. 26 figures.

  18. The culture of referendum in Albania: Technical and theoritecal reflections on the abrogative referendum

    Directory of Open Access Journals (Sweden)

    Valbona Pajo Bala

    2014-01-01

    Full Text Available The aim of this paper is to analyse the Albanian constitutional and legal framework on referenda, in general, focusing special attention to the abrogative referenda of a law or part thereof. Given the absence of any concrete case of an abrogative referenda held in Albania, which does not creates very much room for discussion in that regard, the paper, through a comparative approach on the referenda culture in other european states, aims at offering to the reader a more complete view on the mechanisms and guarantees enjoyed by voters and the effective way of their use, in order to give life to the direct democracy, but without replacing the representative one. In addition, part of the analyses will be the powers of the Constitutional Court for the ex ante constitutional review of the issue subject to a referendum, the review of constitutionality of the referndum and of its results. In this context, the paper will focus on the constitutional case-law as a tool for increasing the referenda culture and shaping the constitional order, as well as a source of standards and values. Another objective of the paper is to open a discussion on the need for the reception of referenda-related standards elaborated in those European countries, where the culture of helding a referenda and the case-law on the regard is enriched and may serve as a qualitative basis for further reference.

  19. Tyrosine phosphorylation of Munc18c on residue 521 abrogates binding to Syntaxin 4

    Directory of Open Access Journals (Sweden)

    Bryant Nia J

    2011-05-01

    Full Text Available Abstract Background Insulin stimulates exocytosis of GLUT4 from an intracellular store to the cell surface of fat and muscle cells. Fusion of GLUT4-containing vesicles with the plasma membrane requires the SNARE proteins Syntaxin 4, VAMP2 and the regulatory Sec1/Munc18 protein, Munc18c. Syntaxin 4 and Munc18c form a complex that is disrupted upon insulin treatment of adipocytes. Munc18c is tyrosine phosphorylated in response to insulin in these cells. Here, we directly test the hypothesis that tyrosine phosphorylation of Munc18c is responsible for the observed insulin-dependent abrogation of binding between Munc18c and Syntaxin 4. Results We show that Munc18c is directly phosphorylated by recombinant insulin receptor tyrosine kinase in vitro. Using pull-down assays, we show that phosphorylation abrogates binding of Munc18c to both Syntaxin 4 and the v-SNARE VAMP2, as does the introduction of a phosphomimetic mutation into Munc18c (Y521E. Conclusion Our data indicate that insulin-stimulated tyrosine phosphorylation of Munc18c impairs the ability of Munc18c to bind its cognate SNARE proteins, and may therefore represent a regulatory step in GLUT4 traffic.

  20. Chelated Ruthenium Catalysts for Z-Selective Olefin Metathesis

    Science.gov (United States)

    Endo, Koji; Grubbs, Robert H.

    2011-01-01

    We report the development of ruthenium-based metathesis catalysts with chelating N-heterocyclic carbene (NHC) ligands which catalyze highly Z-selective olefin metathesis. A very simple and convenient synthetic procedure of such a catalyst has been developed. An intramolecular C-H bond activation of the NHC ligand, which is promoted by anion ligand substitution, forms the appropriate chelate for stereo- controlled olefin metathesis. PMID:21563826

  1. Iron Chelation Adherence to Deferoxamine and Deferasirox in Thalassemia

    OpenAIRE

    Trachtenberg, Felicia; Vichinsky, Elliott; Haines, Dru; Pakbaz, Zahra; Mednick, Lauren; Sobota, Amy; Kwiatkowski, Janet; Thompson, Alexis A.; Porter, John; Coates, Thomas; Giardina, Patricia J.; Olivieri, Nancy; Yamashita, Robert; Neufeld, Ellis J.

    2011-01-01

    The Thalassemia Clinical Research Network collected adherence information from 79 patients on deferoxamine and 186 on deferasirox from 2007 to 2009. Chelation adherence was defined as percent of doses administered in the last 4 weeks (patient report) out of those prescribed (chart review). Chelation history since 2002 was available for 97 patients currently on deferoxamine and 217 on deferasirox, with crude estimates of adherence from chart review. Self-reported adherence to both deferoxamine...

  2. The effect of iron loading and iron chelation on the innate immune response and subclinical organ injury during human endotoxemia: a randomized trial

    NARCIS (Netherlands)

    Eijk, L.T.G.J. van; Heemskerk, S.; Pluijm, R.W. van der; Wijk, S.M. van; Peters, W.H.M.; Hoeven, J.G. van der; Kox, M.; Swinkels, D.W.; Pickkers, P.

    2014-01-01

    In this double-blind randomized placebo-controlled trial involving 30 healthy male volunteers we investigated the acute effects of iron loading (single dose of 1.25 mg/kg iron sucrose) and iron chelation therapy (single dose of 30 mg/kg deferasirox) on iron parameters, oxidative stress, the innate i

  3. The efficacy of iron chelator regimes in reducing cardiac and hepatic iron in patients with thalassaemia major: a clinical observational study

    Directory of Open Access Journals (Sweden)

    Berdoussi Eleni

    2009-06-01

    Full Text Available Abstract Background Available iron chelation regimes in thalassaemia may achieve different changes in cardiac and hepatic iron as assessed by MR. The aim of this study was to assess the efficacy of four available iron chelator regimes in 232 thalassaemia major patients by assessing the rate of change in repeated measurements of cardiac and hepatic MR. Results For the heart, deferiprone and the combination of deferiprone and deferoxamine significantly reduced cardiac iron at all levels of iron loading. As patients were on deferasirox for a shorter time, a second analysis ("Initial interval analysis" assessing the change between the first two recorded MR results for both cardiac and hepatic iron (minimum interval 12 months was made. Combination therapy achieved the most rapid fall in cardiac iron load at all levels and deferiprone alone was significantly effective with moderate and mild iron load. In the liver, deferasirox effected significant falls in iron load and combination therapy resulted in the most rapid decline. Conclusion With the knowledge of the efficacy of the different available regimes and the specific iron load in the heart and the liver, appropriate tailoring of chelation therapy should allow clearance of iron. Combination therapy is best in reducing both cardiac and hepatic iron, while monotherapy with deferiprone or deferasirox are effective in the heart and liver respectively. The outcomes of this study may be useful to physicians as to the chelation they should prescribe according to the levels of iron load found in the heart and liver by MR.

  4. Iron Chelation Adherence to Deferoxamine and Deferasirox in Thalassemia

    Science.gov (United States)

    Trachtenberg, Felicia; Vichinsky, Elliott; Haines, Dru; Pakbaz, Zahra; Mednick, Lauren; Sobota, Amy; Kwiatkowski, Janet; Thompson, Alexis A.; Porter, John; Coates, Thomas; Giardina, Patricia J.; Olivieri, Nancy; Yamashita, Robert; Neufeld, Ellis J.

    2015-01-01

    The Thalassemia Clinical Research Network collected adherence information from 79 patients on deferoxamine and 186 on deferasirox from 2007 to 2009. Chelation adherence was defined as percent of doses administered in the last 4 weeks (patient report) out of those prescribed (chart review). Chelation history since 2002 was available for 97 patients currently on deferoxamine and 217 on deferasirox, with crude estimates of adherence from chart review. Self-reported adherence to both deferoxamine and deferasirox were quite high, with slightly higher adherence to the oral chelator (97 vs. 92%). Ninety percent of patients on deferasirox reported at least 90% adherence, compared with 75% of patients on deferoxamine. Adherence to both chelators was highest in children, followed by adolescents and older adults. Predictors of lower deferoxamine adherence were smoking in the past year, problems sticking themselves (adults only), problems wearing their pump, and fewer transfusions in the past year. Predictors of lower deferasirox adherence were bodily pain and depression. Switching chelators resulted in increased adherence, regardless of the direction of the switch, although switching from deferoxamine to deferasirox was far more common. As adherence to deferoxamine is higher than previously reported, it appears beneficial for patients to have a choice in chelators. PMID:21523808

  5. Extraction of metals using supercritical fluid and chelate forming legand

    Science.gov (United States)

    Wai, Chien M.; Laintz, Kenneth E.

    1998-01-01

    A method of extracting metalloid and metal species from a solid or liquid material by exposing the material to a supercritical fluid solvent containing a chelating agent is described. The chelating agent forms chelates that are soluble in the supercritical fluid to allow removal of the species from the material. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is a fluorinated .beta.-diketone. In especially preferred embodiments the extraction solvent is supercritical carbon dioxide, and the chelating agent comprises a fluorinated .beta.-diketone and a trialkyl phosphate, or a fluorinated .beta.-diketone and a trialkylphosphine oxide. Although a trialkyl phosphate can extract lanthanides and actinides from acidic solutions, a binary mixture comprising a fluorinated .beta.-diketone and a trialkyl phosphate or a trialkylphosphine oxide tends to enhance the extraction efficiencies for actinides and lanthanides. The method provides an environmentally benign process for removing contaminants from industrial waste without using acids or biologically harmful solvents. The method is particularly useful for extracting actinides and lanthanides from acidic solutions. The chelate and supercritical fluid can be regenerated, and the contaminant species recovered, to provide an economic, efficient process.

  6. Extraction of metals using supercritical fluid and chelate forming ligand

    Science.gov (United States)

    Wai, C.M.; Laintz, K.E.

    1998-03-24

    A method of extracting metalloid and metal species from a solid or liquid material by exposing the material to a supercritical fluid solvent containing a chelating agent is described. The chelating agent forms chelates that are soluble in the supercritical fluid to allow removal of the species from the material. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is a fluorinated {beta}-diketone. In especially preferred embodiments the extraction solvent is supercritical carbon dioxide, and the chelating agent comprises a fluorinated {beta}-diketone and a trialkyl phosphate, or a fluorinated {beta}-diketone and a trialkylphosphine oxide. Although a trialkyl phosphate can extract lanthanides and actinides from acidic solutions, a binary mixture comprising a fluorinated {beta}-diketone and a trialkyl phosphate or a trialkylphosphine oxide tends to enhance the extraction efficiencies for actinides and lanthanides. The method provides an environmentally benign process for removing contaminants from industrial waste without using acids or biologically harmful solvents. The method is particularly useful for extracting actinides and lanthanides from acidic solutions. The chelate and supercritical fluid can be regenerated, and the contaminant species recovered, to provide an economic, efficient process. 7 figs.

  7. Iron chelation adherence to deferoxamine and deferasirox in thalassemia.

    Science.gov (United States)

    Trachtenberg, Felicia; Vichinsky, Elliott; Haines, Dru; Pakbaz, Zahra; Mednick, Lauren; Sobota, Amy; Kwiatkowski, Janet; Thompson, Alexis A; Porter, John; Coates, Thomas; Giardina, Patricia J; Olivieri, Nancy; Yamashita, Robert; Neufeld, Ellis J

    2011-05-01

    The Thalassemia Clinical Research Network collected adherence information from 79 patients on deferoxamine and 186 on deferasirox from 2007 to 2009. Chelation adherence was defined as percent of doses administered in the last 4 weeks (patient report) out of those prescribed(chart review). Chelation history since 2002 was available for 97 patients currently on deferoxamine and 217 on deferasirox, with crude estimates of adherence from chart review. Self-reported adherence to both deferoxamine and deferasirox were quite high, with slightly higher adherence to the oral chelator (97 vs. 92%). Ninety percent of patients on deferasirox reported at least 90% adherence, compared with 75% of patients on deferoxamine. Adherence to both chelators was highest in children, followed by adolescents and older adults.Predictors of lower deferoxamine adherence were smoking in the past year, problems sticking themselves (adults only), problems wearing their pump, and fewer transfusions in the past year. Predictors of lower deferasirox adherence were bodily pain and depression. Switching chelators resulted in increased adherence, regardless of the direction of the switch, although switching from deferoxamine to deferasirox was far more common. As adherence to deferoxamine is higher than previously reported, it appears beneficial for patients to have a choice in chelators.

  8. THE STUDIES ON CHELATING FIBER V.ADSORPTION BEHAVIOR OF Au3+ ONTO CHELATING FIBER CONTAINING AMIDOXIME GROUPS

    Institute of Scientific and Technical Information of China (English)

    LINWeiping; LUYun; 等

    1992-01-01

    The adsorption behavior of ionic gold onto chelating fiber containing amidoxime groups was investigated. The chelating fiber presents high adsorption capacity for ionic gold Au3+(up to 626mg/g,when the content of amidoxime group reaches 7.59mmol/g),and possesses the ability to reduce the Au3+ into metallic gold,In the redox process,the amidoxime group is oxidized into carboxyl group.

  9. Immunosuppression abrogates resistance of young rabbits to Rabbit Haemorrhagic Disease (RHD).

    Science.gov (United States)

    Marques, Raquel M; Teixeira, Luzia; Aguas, Artur P; Ribeiro, Joana C; Costa-e-Silva, António; Ferreira, Paula G

    2014-02-04

    Rabbit Haemorrhagic Disease (RHD) is caused by a calicivirus (RHDV) that kills 90% of infected adult European rabbits within 3 days. Remarkably, young rabbits are resistant to RHD. We induced immunosuppression in young rabbits by treatment with methylprednisolone acetate (MPA) and challenged the animals with RHDV by intramuscular injection. All of these young rabbits died within 3 days of infection due to fulminant hepatitis, presenting a large number of RHDV-positive dead or apoptotic hepatocytes, and a significant seric increase in cytokines, features that are similar to those of naïve adult rabbits infected by RHDV. We conclude that MPA-induced immunosuppression abrogates the resistance of young rabbits to RHD, indicating that there are differences in the innate immune system between young and adult rabbits that contribute to their distinct resistance/susceptibility to RHDV infection.

  10. HCV NS5A abrogates p53 protein function by interfering with p53-DNA binding

    Institute of Scientific and Technical Information of China (English)

    Guo-Zhong Gong; Yong-Fang Jiang; Yan He; Li-Ying Lai; Ying-Hua Zhu; Xian-Shi Su

    2004-01-01

    AIM: To evaluate the inhibition effect of HCV NS5A on p53 transactivation on p21 promoter and explore its possible mechanism for influencing p53 function.METHODS: p53 function of transactivation on p21 promoter was studied with a luciferase reporter system in which the luciferase gene is driven by p21 promoter, and the p53-DNA binding ability was observed with the use of electrophoretic mobility-shift assay (EMSA). Lipofectin mediated p53 or HCV NS5A expression vectors were used to transfect hepatoma cell lines to observe whether HCV NS5A could abrogate the binding ability of p53 to its specific DNA sequence and p53 transactivation on p21 promoter.Western blot experiment was used for detection of HCV NS5A and p53 proteins expression.RESULTS: Relative luciferase activity driven by p21 promoter increased significantly in the presence of endogenous p53 protein. Compared to the control group, exogenous p53 protein also stimulated p21 promoter driven luciferase gene expression in a dose-dependent way. HCV NS5A protein gradually inhibited both endogenous and exogenous p53 transactivation on p21 promoter with increase of the dose of HCV NS5A expression plasmid. By the experiment of EMSA, we could find p53 binding to its specific DNA sequence and, when co-transfected with increased dose of HCV NS5A expression vector, the p53 binding affinity to its DNA gradually decreased and finally disappeared. Between the Huh 7 cells transfected with p53 expression vector alone or co-transfected with HCV NS5A expression vector, there was no difference in the p53 protein expression.CONCLUSION: HCV NS5A inhibits p53 transactivation on p21 promoter through abrogating p53 binding affinity to its specific DNA sequence. It does not affect p53 protein expression.

  11. Side effects of Deferasirox Iron Chelation in Patients with Beta Thalassemia Major or Intermedia

    Directory of Open Access Journals (Sweden)

    Murtadha Al-Khabori

    2013-03-01

    Full Text Available Objectives: Chelating agents remain the mainstay in reducing the iron burden and extending patient survival in homozygous beta-thalassemia but adverse and toxic effects may increase with the institution and long term use of this essential therapy. This study aimed to estimate the incidence of deferasirox (DFX side effects in patients with thalassemia major or intermedia.Methods: A retrospective study of 72 patients (mean age: 20.3±0.9 yrs; 36 male, 36 female with thalassemia major or intermedia treated at Sultan Qaboos University Hospital, Oman, was performed to assess the incidence of side effects related to deferasirox over a mean of 16.7 month follow-up period.Results: Six patients experienced rashes and 6 had gastro-intestinal upset. DFX was discontinued in 18 patients for the following reasons: persistent progressive rise(s in serum creatinine (7 patients; 40% mean serum creatinine rise from baseline, feeling unwell (2, severe diarrhea (1, pregnancy (1, death unrelated to chelator (2 and rise in serum transaminases (2. Three patients were reverted to desferoxamine and deferiprone combination therapy as DFX was no longer biochemically effective after 18 months of therapy. There was no correlation between baseline serum ferritin and serum creatinine or a rise in serum creatinine. Cardiac MRI T2* did not change with DFX therapy. However, there was an improvement in liver MRI T2* (p=0.013.Conclusion: Renal side effects related to deferasirox appear to be higher than those reported in published clinical trials. Further larger studies are required to confirm these findings.

  12. Side effects of Deferasirox Iron Chelation in Patients with Beta Thalassemia Major or Intermedia

    Science.gov (United States)

    Al-Khabori, Murtadha; Bhandari, Sunil; Al-Huneini, Mohammed; Al-Farsi, Khalil; Panjwani, Vinodh; Daar, Shahina

    2013-01-01

    Objectives Chelating agents remain the mainstay in reducing the iron burden and extending patient survival in homozygous beta-thalassemia but adverse and toxic effects may increase with the institution and long term use of this essential therapy. This study aimed to estimate the incidence of deferasirox (DFX) side effects in patients with thalassemia major or intermedia. Methods A retrospective study of 72 patients (mean age: 20.3±0.9 yrs; 36 male, 36 female) with thalassemia major or intermedia treated at Sultan Qaboos University Hospital, Oman, was performed to assess the incidence of side effects related to deferasirox over a mean of 16.7 month follow-up period. Results Six patients experienced rashes and 6 had gastro-intestinal upset. DFX was discontinued in 18 patients for the following reasons: persistent progressive rise(s) in serum creatinine (7 patients; 40% mean serum creatinine rise from baseline), feeling unwell (2), severe diarrhea (1), pregnancy (1), death unrelated to chelator (2) and rise in serum transaminases (2). Three patients were reverted to desferoxamine and deferiprone combination therapy as DFX was no longer biochemically effective after 18 months of therapy. There was no correlation between baseline serum ferritin and serum creatinine or a rise in serum creatinine. Cardiac MRI T2* did not change with DFX therapy. However, there was an improvement in liver MRI T2* (p=0.013). Conclusion Renal side effects related to deferasirox appear to be higher than those reported in published clinical trials. Further larger studies are required to confirm these findings. PMID:23599881

  13. Mercury exposure: evaluation and intervention the inappropriate use of chelating agents in the diagnosis and treatment of putative mercury poisoning.

    Science.gov (United States)

    Risher, John F; Amler, Sherlita N

    2005-08-01

    Public awareness of the potential for mercury to cause health problems has increased dramatically in the last 15 years. It is now widely recognized that significant exposure to all forms of mercury (elemental/metallic and both inorganic and organic compounds) can result in a variety of adverse health effects, including neurological, renal, respiratory, immune, dermatologic, reproductive, and developmental sequellae. And while the various media have made the general population cognizant of the need to avoid unnecessary exposure to this naturally occurring element, there has also evolved a growing tendency to attribute unexplainable neurologic, as well as other, signs and symptoms to mercury, whether or not significant exposure to mercury has actually occurred. For the physician, making a diagnosis of mercury intoxication can be difficult, because many of the clinical signs and symptoms of mercury exposure can also be attributed to any number of causes, including undiagnosed neurological diseases, pharmacotherapy, vitamin or mineral deficiencies, and psychological stress. The physician must be able to recognize the clinical manifestations of mercury intoxication, and understand the importance of biological markers in making a definitive diagnosis of mercury poisoning. In a desire to treat the patient complaining of symptoms similar to some that can be caused by mercury, a growing number of physicians, particularly those in alternative medicine fields, result to chelation to "rid" the body of the mercury, believed to be the cause of the ailments. And although the use of chelation is increasing, controlled studies showing that this procedure actually improves outcome are lacking. If chelation therapy is considered to be indicated, the attending physician should communicate the risks of chelation to the patient before beginning treatment with metal-chelating drugs.

  14. Engineering an antibody with picomolar affinity to DOTA chelates of multiple radionuclides for pretargeted radioimmunotherapy and imaging

    Energy Technology Data Exchange (ETDEWEB)

    Orcutt, Kelly Davis; Slusarczyk, Adrian L. [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Cieslewicz, Maryelise [Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Ruiz-Yi, Benjamin [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Bhushan, Kumar R. [Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Frangioni, John V. [Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Wittrup, K. Dane, E-mail: wittrup@mit.ed [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

    2011-02-15

    Introduction: In pretargeted radioimmunotherapy (PRIT), a bifunctional antibody is administered and allowed to pre-localize to tumor cells. Subsequently, a chelated radionuclide is administered and captured by cell-bound antibody while unbound hapten clears rapidly from the body. We aim to engineer high-affinity binders to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelates for use in PRIT applications. Methods: We mathematically modeled antibody and hapten pharmacokinetics to analyze hapten tumor retention as a function of hapten binding affinity. Motivated by model predictions, we used directed evolution and yeast surface display to affinity mature the 2D12.5 antibody to DOTA, reformatted as a single chain variable fragment (scFv). Results: Modeling predicts that for high antigen density and saturating bsAb dose, a hapten-binding affinity of 100 pM is needed for near-maximal hapten retention. We affinity matured 2D12.5 with an initial binding constant of about 10 nM to DOTA-yttrium chelates. Affinity maturation resulted in a 1000-fold affinity improvement to biotinylated DOTA-yttrium, yielding an 8.2{+-}1.9 picomolar binder. The high-affinity scFv binds DOTA complexes of lutetium and gadolinium with similar picomolar affinity and indium chelates with low nanomolar affinity. When engineered into a bispecific antibody construct targeting carcinoembryonic antigen, pretargeted high-affinity scFv results in significantly higher tumor retention of a {sup 111}In-DOTA hapten compared to pretargeted wild-type scFv in a xenograft mouse model. Conclusions: We have engineered a versatile, high-affinity, DOTA-chelate-binding scFv. We anticipate it will prove useful in developing pretargeted imaging and therapy protocols to exploit the potential of a variety of radiometals.

  15. Supercritical Fluid Extraction of Metal Chelate: A Review.

    Science.gov (United States)

    Ding, Xin; Liu, Qinli; Hou, Xiongpo; Fang, Tao

    2017-03-04

    Supercritical fluid extraction (SFE), as a new green extraction technology, has been used in extracting various metal species. The solubilities of chelating agents and corresponding metal chelates are the key factors which influence the efficiency of SFE. Other main properties of them such as stability and selectivity are also reviewed. The extraction mechanisms of mainly used chelating agents are explained by typical examples in this paper. This is the important aspect of SFE of metal ions. Moreover, the extraction efficiencies of metal species also depend on other factors such as temperature, pressure, extraction time and matrix effect. The two main complexation methods namely in-situ and on-line chelating SFE are described in detail. As an efficient chelating agent, tributyl phosphate-nitric acid (TBP-HNO3) complex attracts much attention. The SFE of metal ions, lanthanides and actinides as well as organometallic compounds are also summarized. With the proper selection of ligands, high efficient extraction of metal species can be obtained. As an efficient sample analysis method, supercritical fluid chromatography (SFC) is introduced in this paper. Recently, the extraction method combining ionic liquids (ILs) with supercritical fluid has been becoming a novel technology for treating metal ions. The kinetics related to SFE of metal species is discussed with some specific examples.

  16. Preparation and Properties of Iminodiacetic Acid Chelate Fiber

    Directory of Open Access Journals (Sweden)

    QIAN Jin-xin

    2016-07-01

    Full Text Available The iminodiacetic acid chelate fiber(IDACF which has a property of selective adsorption, was fabricated by amination and carboxylation using chloramethylated polypropylene grafted styrene fiber as raw material. Orthogonal experiment was adopted to study the effect of temperature, time, liquor ratio and the amount of chloroacetic acid on carboxylation reaction. The maximum adsorption capacity of iminodiacetic acid chelate fiber to Cu2+ is 65.54mg·g-1, which is 10.52 times of that of Fe3+. Elementary analysis(EA, Fourier transform infrared spectrum(FT-IR, scanning electron microscopy(SEM and thermogrametry(TG were used to characterize the structure and the properties of the iminodiacetic acid chelate fiber. The results show that iminodiacetic acid has been transformed to the raw fiber successfully after amination and carboxymethylation, and IDACF has good thermal stability.

  17. Albumin microspheres labeled with Ga-67 by chelation: concise communication.

    Science.gov (United States)

    Hnatowich, D J; Schlegel, P

    1981-07-01

    Albumin microspheres have been synthesized eith EDTA and DTPA chelating groups covalently bound to their surface. The microspheres may be labeled with Ga-67 at high yield (97 +/- 2%) by transcomplexation from a 0.1 M Ga-67 acetate solution. With EDTA microspheres the resulting label dissociates only slightly after no detectable dissociation over this period. By contrast, microspheres without chelating groups lose their label virtually completely under these conditions. Following intravenous administration of sized Ga-67 DTPA microspheres in mice, about (84 +/- 16)% of the activity localizes in the lungs at 5 min, with (60 +/- 7)% remaining after 2 hr. Since labeling is by chelation, the microspheres may also be tagged with other metallic radionuclides

  18. Synthesis and Characteristics of A Novel Heavy Metal Ions Chelator

    Institute of Scientific and Technical Information of China (English)

    LIU Zhuannian; SONG Yejing; HAN Xiaogang

    2012-01-01

    Polyacrylamide-urea-sulfanilamide(PUS) was prepared as a novel heavy metal ions chelator and successfully used to simultaneously remove heavy metals from wastewater effluents.The effects of reaction parameters (sodium hydroxide,material ratio,temprature and contact time) were monitored to specify the best synthesis conditions.PUS was chemically characterized by means of infrared spectroscopy (FTIR) and ultraviolet-visible (UV-Vis).The simultaneous chelation performance of PUS towards selected heavy metals ions,Ni2+,Cu2+,Pb2+,Zn2+,Cd2+ was discussed,showing that Ni2+,Cu2+,Pb2+,Zn2+ could be better chelated.It is indicated that the synthesized PUS is a potential remediation material when used for the treatment of wastewater containing metal ions.

  19. Chelation of heavy metals by potassium butyl dithiophosphate

    Institute of Scientific and Technical Information of China (English)

    Ying Xu; Zhigang Xie; Lu Xue

    2011-01-01

    Potassium butyl dithiophosphate (PBD) was developed and introduced as a new chelating agent for heavy metal removal.The synthesized PBD were characterized by IR and NMR.The effects of pH, chelating agent dosage, and other heavy metal ions on the performance of PBD in Cd2+ removal from water are investigated.Experimental results showed that the chelating agent could be used to treat acidic heavy metal wastewater.The Cd2+ removal was not affected by solution pH value within the range of 2 to 6.The Cd2+ removal rate could reach over 99%.Therefore, the deficiency of the precipitation process using hydroxide under alkaline condition can be overcome.Without the need for pH adjustment, the method could save on costs.If Cd2+ co-exists with Pb2+ and Cu2+, the affinity of the chelating agent with these three heavy metal ions was in the order of: Cu2+ > Pb2+ > Cd2+.Through PBD chelating precipitation,all the contents of Pb2+, Cd2+, and Cu2+ in wastewater met the standard levels through a one-step treatment.The one-step treatment process was superior to the process (sectional treatment is required) of precipitation with hydroxide.When the pH was between 3 and 11, the amount of leached chelated Cd2+ was much lower than that obtained by precipitation with hydroxide.Therefore, the risk of environmental pollution could be further reduced.

  20. Chelation in metal intoxication—Principles and paradigms

    DEFF Research Database (Denmark)

    Aaseth, Jan; Skaug, Marit Aralt; Cao, Yang;

    2015-01-01

    of heavy metal poisoning, and available as capsules for oral use. In copper overload, DMSA appears to be a potent antidote, although d-penicillamine is still widely used. In the chelation of iron, the thiols are inefficient, since iron has higher affinity for ligands with nitrogen and oxygen, but the new...... oral iron antidotes deferiprone and desferasirox have entered into the clinical arena. Comparisons of these agents and deferoxamine infusions are in progress. General principles for research and development of new chelators are briefly outlined in this review...

  1. Tetrandrine: A Potent Abrogator of G2 Checkpoint Function in Tumor Cells and Its Mechanism

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To assess the ability of tetrandrine (Tet) to enhance the sensitivity to irradiation and its mechanism in cell lines of human breast cancer p53-mutant MCF-7/ADR, p53-wild-type MCF-7 and human colon carcinoma p53-mutant HT-29 as well as in C26 colorectal carcinoma-bearing BALB/c mice. Methods MCF-7/ADR, HT-29 and MCF-7 cells were exposed to irradiation in the absence or presence of tetrandrine. The effect of Tet on the cytotoxicity of X-irradiation in these three cells was determined and the effect of tetrandrine on cell cycle arrest induced by irradiation in its absence or presence was studied by flow cytometry, Moreover, mitotic index measurement determined mitosis of cells to enter mitosis. Western blotting was employed to detect cyclin B1 and Cdc2 proteins in extracts from irradiated or non-irradiated cells of MCF-7/ADR, HT-29 and MCF-7 treated with tetrandrine at various concentrations. Tumor growth delay assay was conducted to determine the radio-sensitization of tetrandrine in vivo. Results Clonogenic assay showed that tetrandrine markedly enhanced the lethal effect of X-rays on p53-mutant MCF-7/ADR and HT-29 cells and the sensitization enhancement ratio (SER) of tetrandrine was 1.51 and 1.63, but its SER was only 1.1 in p53-wt MCF-7 cells. Irradiated p53-mutant MCF-7/ADR and HT-29 cells were only arrested in G2/M phase while MCF-7 cells were arrested in G1 and G2/M phases. Radiation-induced G2 phase arrests were abrogated by tetrandrine in a concentration-dependent manner in MCF-7/ADR and HT-29 cells,whereas redistribution within MCF-7 cell cycle changed slightly. The proportion of cells in M phase increased from 1.3% to 14.7% in MCF-7/ADR cells, and from 1.5% to 13.2% in HT-29 cells, but 2.4% to 7.1% in MCF-7 cells. Furthermore, the levels of cyclin B 1 and Cdc2 expression decreased after X-irradiation in MCF-7/ADR and HT-29 cells, and the mitotic index was also lower. Tet could reverse the decrease and induce the irradiated cells to enter mitosis

  2. Herpesvirus telomerase RNA (vTR with a mutated template sequence abrogates herpesvirus-induced lymphomagenesis.

    Directory of Open Access Journals (Sweden)

    Benedikt B Kaufer

    2011-10-01

    Full Text Available Telomerase reverse transcriptase (TERT and telomerase RNA (TR represent the enzymatically active components of telomerase. In the complex, TR provides the template for the addition of telomeric repeats to telomeres, a protective structure at the end of linear chromosomes. Human TR with a mutation in the template region has been previously shown to inhibit proliferation of cancer cells in vitro. In this report, we examined the effects of a mutation in the template of a virus encoded TR (vTR on herpesvirus-induced tumorigenesis in vivo. For this purpose, we used the oncogenic avian herpesvirus Marek's disease virus (MDV as a natural virus-host model for lymphomagenesis. We generated recombinant MDV in which the vTR template sequence was mutated from AATCCCAATC to ATATATATAT (vAU5 by two-step Red-mediated mutagenesis. Recombinant viruses harboring the template mutation replicated with kinetics comparable to parental and revertant viruses in vitro. However, mutation of the vTR template sequence completely abrogated virus-induced tumor formation in vivo, although the virus was able to undergo low-level lytic replication. To confirm that the absence of tumors was dependent on the presence of mutant vTR in the telomerase complex, a second mutation was introduced in vAU5 that targeted the P6.1 stem loop, a conserved region essential for vTR-TERT interaction. Absence of vTR-AU5 from the telomerase complex restored virus-induced lymphoma formation. To test if the attenuated vAU5 could be used as an effective vaccine against MDV, we performed vaccination-challenge studies and determined that vaccination with vAU5 completely protected chickens from lethal challenge with highly virulent MDV. Taken together, our results demonstrate 1 that mutation of the vTR template sequence can completely abrogate virus-induced tumorigenesis, likely by the inhibition of cancer cell proliferation, and 2 that this strategy could be used to generate novel vaccine candidates

  3. Cationic albumin-conjugated chelating agent as a novel brain drug delivery system in neurodegeneration.

    Science.gov (United States)

    Kamalinia, Golnaz; Khodagholi, Fariba; Shaerzadeh, Fatemeh; Tavssolian, Faranak; Chaharband, Farkhondeh; Atyabi, Fatemeh; Sharifzadeh, Mohammad; Amini, Mohsen; Dinarvand, Rassoul

    2015-11-01

    The critical role of metal ions and in particular iron in oxidative stress and protein aggregation offers chelation therapy as a sensible pharmaceutical strategy in oxidative stress-induced neuronal damages. In this research, we conjugated an iron-chelating agent, deferasirox, to cationized human serum albumin molecules in order to develop a novel brain delivery system for the management of neurodegenerative disorders due to the significant role of oxidative stress-induced neuronal injury in such diseases. Cationized albumin is known to be able to transport to brain tissue via adsorptive-mediated transcytosis. The developed structures were molecularly characterized, and their conjugation ratio was determined. PC12 cell line was utilized to evaluate the neuroprotective features of these newly developed molecules in the presence of hydrogen peroxide neuronal damage and to identify the mechanisms behind the observed neuronal protection including apoptotic and autophagic pathways. Furthermore, a rat model of Alzheimer's disease was utilized to evaluate the impact of conjugated structures in vivo. Data analysis revealed that the conjugated species were able to hinder apoptotic cell death while enhancing autophagic process. The developed conjugated species were also able to attenuate amyloid beta-induced learning deficits when administered peripherally.

  4. Abrogation of CC chemokine receptor 9 ameliorates ventricular remodeling in mice after myocardial infarction.

    Science.gov (United States)

    Huang, Yan; Wang, Dandan; Wang, Xin; Zhang, Yijie; Liu, Tao; Chen, Yuting; Tang, Yanhong; Wang, Teng; Hu, Dan; Huang, Congxin

    2016-01-01

    CC chemokine receptor 9 (CCR9), which is a unique receptor for CC chemokine ligand (CCL25), is mainly expressed on lymphocytes, dendritic cells (DCs) and monocytes/macrophages. CCR9 mediates the chemotaxis of inflammatory cells and participates in the pathological progression of inflammatory diseases. However, the role of CCR9 in the pathological process of myocardial infarction (MI) remains unexplored; inflammation plays a key role in this process. Here, we used CCR9 knockout mice to determine the functional significance of CCR9 in regulating post-MI cardiac remodeling and its underlying mechanism. MI was induced by surgical ligation of the left anterior descending coronary artery in CCR9 knockout mice and their CCR9+/+ littermates. Our results showed that the CCR9 expression levels were up-regulated in the hearts of the MI mice. Abrogation of CCR9 improved the post-MI survival rate and left ventricular (LV) dysfunction and decreased the infarct size. In addition, the CCR9 knockout mice exhibited attenuated inflammation, apoptosis, structural and electrical remodeling compared with the CCR9+/+ MI mice. Mechanistically, CCR9 mainly regulated the pathological response by interfering with the NF-κB and MAPK signaling pathways. In conclusion, the data reveal that CCR9 serves as a novel modulator of pathological progression following MI through NF-κB and MAPK signaling.

  5. Telomerase expression abrogates rapamycin-induced irreversible growth arrest of uterine fibroid smooth muscle cells.

    Science.gov (United States)

    Suo, Guangli; Sadarangani, Anil; Tang, Wingchung; Cowan, Bryan D; Wang, Jean Y J

    2014-09-01

    Uterine fibroids are the most common solid tumors found in women of reproductive age. It has been reported that deregulation of the mammalian target of rapamycin (mTOR) pathway plays an important role in the etiology of leiomyoma. Here, we investigated the effect of rapamycin, an inhibitor of mTORC1, on the growth of primary fibroid smooth muscle cells (fSMCs) and human telomerase reverse transcriptase (hTERT)-transduced and immortalized fSMCs. With the primary fSMCs, a 24-hour treatment with rapamycin was sufficient to trigger a growth arrest that was not reversible upon drug removal. By contrast, the growth inhibitory effect of rapamycin on the hTERT-transduced fSMCs was readily reversible, as these cells resumed proliferation upon the withdrawal of the drug. These results suggest that rapamycin-induced irreversible growth arrest of fSMCs is dependent on the senescence barrier that is abrogated by the ectopic expression of telomerase.

  6. Secoisolariciresinol diglucoside abrogates oxidative stress-induced damage in cardiac iron overload condition.

    Directory of Open Access Journals (Sweden)

    Stephanie Puukila

    Full Text Available Cardiac iron overload is directly associated with cardiac dysfunction and can ultimately lead to heart failure. This study examined the effect of secoisolariciresinol diglucoside (SDG, a component of flaxseed, on iron overload induced cardiac damage by evaluating oxidative stress, inflammation and apoptosis in H9c2 cardiomyocytes. Cells were incubated with 50 μ5M iron for 24 hours and/or a 24 hour pre-treatment of 500 μ M SDG. Cardiac iron overload resulted in increased oxidative stress and gene expression of the inflammatory mediators tumor necrosis factor-α, interleukin-10 and interferon γ, as well as matrix metalloproteinases-2 and -9. Increased apoptosis was evident by increased active caspase 3/7 activity and increased protein expression of Forkhead box O3a, caspase 3 and Bax. Cardiac iron overload also resulted in increased protein expression of p70S6 Kinase 1 and decreased expression of AMP-activated protein kinase. Pre-treatment with SDG abrogated the iron-induced increases in oxidative stress, inflammation and apoptosis, as well as the increased p70S6 Kinase 1 and decreased AMP-activated protein kinase expression. The decrease in superoxide dismutase activity by iron treatment was prevented by pre-treatment with SDG in the presence of iron. Based on these findings we conclude that SDG was cytoprotective in an in vitro model of iron overload induced redox-inflammatory damage, suggesting a novel potential role for SDG in cardiac iron overload.

  7. Upregulation of neurovascular communication through filamin abrogation promotes ectopic periventricular neurogenesis

    Science.gov (United States)

    Houlihan, Shauna L; Lanctot, Alison A; Guo, Yan; Feng, Yuanyi

    2016-01-01

    Neuronal fate-restricted intermediate progenitors (IPs) are derived from the multipotent radial glia (RGs) and serve as the direct precursors for cerebral cortical neurons, but factors that control their neurogenic plasticity remain elusive. Here we report that IPs’ neuron production is enhanced by abrogating filamin function, leading to the generation of periventricular neurons independent of normal neocortical neurogenesis and neuronal migration. Loss of Flna in neural progenitor cells (NPCs) led RGs to undergo changes resembling epithelial-mesenchymal transition (EMT) along with exuberant angiogenesis that together changed the microenvironment and increased neurogenesis of IPs. We show that by collaborating with β-arrestin, Flna maintains the homeostatic signaling between the vasculature and NPCs, and loss of this function results in escalated Vegfa and Igf2 signaling, which exacerbates both EMT and angiogenesis to further potentiate IPs’ neurogenesis. These results suggest that the neurogenic potential of IPs may be boosted in vivo by manipulating Flna-mediated neurovascular communication. DOI: http://dx.doi.org/10.7554/eLife.17823.001 PMID:27664421

  8. Abrogation of plasminogen activator inhibitor-1-vitronectin interaction ameliorates acute kidney injury in murine endotoxemia.

    Directory of Open Access Journals (Sweden)

    Kamlesh K Gupta

    Full Text Available Sepsis-induced acute kidney injury (AKI contributes to the high mortality and morbidity in patients. Although the pathogenesis of AKI during sepsis is poorly understood, it is well accepted that plasminogen activator inhibitor-1 (PAI-1 and vitronectin (Vn are involved in AKI. However, the functional cooperation between PAI-1 and Vn in septic AKI has not been completely elucidated. To address this issue, mice were utilized lacking either PAI-1 (PAI-1-/- or expressing a PAI-1-mutant (PAI-1R101A/Q123K in which the interaction between PAI-1 and Vn is abrogated, while other functions of PAI-1 are retained. It was found that both PAI-1-/- and PAI-1R101A/Q123K mice are associated with decreased renal dysfunction, apoptosis, inflammation, and ERK activation as compared to wild-type (WT mice after LPS challenge. Also, PAI-1-/- mice showed attenuated fibrin deposition in the kidneys. Furthermore, a lack of PAI-1 or PAI-1-Vn interaction was found to be associated with an increase in activated Protein C (aPC in plasma. These results demonstrate that PAI-1, through its interaction with Vn, exerts multiple deleterious mechanisms to induce AKI. Therefore, targeting of the PAI-1-Vn interaction in kidney represents an appealing therapeutic strategy for the treatment of septic AKI by not only altering the fibrinolytic capacity but also regulating PC activity.

  9. Niacinamide abrogates the organ dysfunction and acute lung injury caused by endotoxin.

    Science.gov (United States)

    Kao, Shang-Jyh; Liu, Demeral David; Su, Chain-Fa; Chen, Hsing I

    2007-09-01

    Poly (ADP-ribose) synthabse (PARS) or polymerase (PARP) is a cytotoxic enzyme causing cellular damage. Niacinamide inhibits PARS or PARP. The present experiment tests the effects of niacinamide (NCA) on organ dysfunction and acute lung injury (ALI) following lipopolysaccharide (LPS). LPS was administered to anesthetized rats and to isolated rat lungs. In anesthetized rats, LPS caused systemic hypotension and increased biochemical factors, nitrate/nitrite (NOx), methyl guanidine (MG), tumor necrosis factoralpha (TNFalpha), and interleukin-1beta (IL-1beta). In isolated lungs, LPS increased lung weight (LW) to body weight ratio, LW gain, protein and dye tracer leakage, and capillary permeability. The insult also increased NOx, MG, TNFalpha, and IL-1beta in lung perfusate, while decreased adenosine triphosphate (ATP) content with an increase in PARP activity in lung tissue. Pathological examination revealed pulmonary edema with inflammatory cell infiltration. These changes were abrogated by posttreatment (30 min after LPS) with NCA. Following LPS, the inducible NO synthase (iNOS) mRNA expression was increased. NCA reduced the iNOS expression. Niacinamide exerts protective effects on the organ dysfunction and ALI caused by endotoxin. The mechanisms may be mediated through the inhibition on the PARP activity, iNOS expression and the subsequent suppression of NO, free radicals, and proinflammatory cytokines with restoration of ATP.

  10. Effector T Cells Abrogate Stroma-Mediated Chemoresistance in Ovarian Cancer.

    Science.gov (United States)

    Wang, Weimin; Kryczek, Ilona; Dostál, Lubomír; Lin, Heng; Tan, Lijun; Zhao, Lili; Lu, Fujia; Wei, Shuang; Maj, Tomasz; Peng, Dongjun; He, Gong; Vatan, Linda; Szeliga, Wojciech; Kuick, Rork; Kotarski, Jan; Tarkowski, Rafał; Dou, Yali; Rattan, Ramandeep; Munkarah, Adnan; Liu, J Rebecca; Zou, Weiping

    2016-05-19

    Effector T cells and fibroblasts are major components in the tumor microenvironment. The means through which these cellular interactions affect chemoresistance is unclear. Here, we show that fibroblasts diminish nuclear accumulation of platinum in ovarian cancer cells, resulting in resistance to platinum-based chemotherapy. We demonstrate that glutathione and cysteine released by fibroblasts contribute to this resistance. CD8(+) T cells abolish the resistance by altering glutathione and cystine metabolism in fibroblasts. CD8(+) T-cell-derived interferon (IFN)γ controls fibroblast glutathione and cysteine through upregulation of gamma-glutamyltransferases and transcriptional repression of system xc(-) cystine and glutamate antiporter via the JAK/STAT1 pathway. The presence of stromal fibroblasts and CD8(+) T cells is negatively and positively associated with ovarian cancer patient survival, respectively. Thus, our work uncovers a mode of action for effector T cells: they abrogate stromal-mediated chemoresistance. Capitalizing upon the interplay between chemotherapy and immunotherapy holds high potential for cancer treatment.

  11. Galangin Abrogates Ovalbumin-Induced Airway Inflammation via Negative Regulation of NF-κB

    Directory of Open Access Journals (Sweden)

    Wang-Jian Zha

    2013-01-01

    Full Text Available Persistent activation of nuclear factor κB (NF-κB has been associated with the development of asthma. Galangin, the active pharmacological ingredient from Alpinia galanga, is reported to have a variety of anti-inflammatory properties in vitro via negative regulation of NF-κB. This study aimed to investigate whether galangin can abrogate ovalbumin- (OVA- induced airway inflammation by negative regulation of NF-κB. BALB/c mice sensitized and challenged with OVA developed airway hyperresponsiveness (AHR and inflammation. Galangin dose dependently inhibited OVA-induced increases in total cell counts, eosinophil counts, and interleukin-(IL- 4, IL-5, and IL-13 levels in bronchoalveolar lavage fluid, and reduced serum level of OVA-specific IgE. Galangin also attenuated AHR, reduced eosinophil infiltration and goblet cell hyperplasia, and reduced expression of inducible nitric oxide synthase and vascular cell adhesion protein-1 (VCAM-1 levels in lung tissue. Additionally, galangin blocked inhibitor of κB degradation, phosphorylation of the p65 subunit of NF-κB, and p65 nuclear translocation from lung tissues of OVA-sensitized mice. Similarly, in normal human airway smooth muscle cells, galangin blocked tumor necrosis factor-α induced p65 nuclear translocation and expression of monocyte chemoattractant protein-1, eotaxin, CXCL10, and VCAM-1. These results suggest that galangin can attenuate ovalbumin-induced airway inflammation by inhibiting the NF-κB pathway.

  12. Laccase Immobilization by Chelated Metal Ion Coordination Chemistry

    Directory of Open Access Journals (Sweden)

    Qingqing Wang

    2014-09-01

    Full Text Available In this work, amidoxime polyacrylonitrile (AOPAN nanofibrous membrane was prepared by a reaction between PAN nanofibers and hydroxylamine hydrochloride. The AOPAN nanofibrous membranes were used for four metal ions (Fe3+, Cu2+, Ni2+, Cd2+ chelation under different conditions. Further, the competition of different metal ions coordinating with AOPAN nanofibrous membrane was also studied. The AOPAN chelated with individual metal ion (Fe3+, Cu2+, Ni2+, Cd2+ and also the four mixed metal ions were further used for laccase (Lac immobilization. Compared with free laccase, the immobilized laccase showed better resistance to pH and temperature changes as well as improved storage stability. Among the four individual metal ion chelated membranes, the stability of the immobilized enzymes generally followed the order as Fe–AOPAN–Lac > Cu–AOPAN–Lac > Ni–AOPAN–Lac > Cd–AOPAN–Lac. In addition, the immobilized enzyme on the carrier of AOPAN chelated with four mixed metal ions showed the best properties.

  13. Iron chelator daphnetin against Pneumocystis carinii in vitro

    Institute of Scientific and Technical Information of China (English)

    叶彬; 郑玉强; 武卫华; 张静

    2004-01-01

    Background Although there are several drugs and drug combinations for the treatment of Pneumocystis carinii (P. carinii) pneumonia, all drugs have the toxicity as well as low efficacy. Iron chelators have been proposed as a source of new drugs for combating these infections. We hypothesized that iron chelators would suppress the growth of P. carinii by deprivation of the nutritional iron required for growth. In this study, a short-term axenic culture system of P. carinii was established. Daphnetin (7,8-dihydroxycoumarin), a known iron chelator, was demonstrated to exhibit in vitro activity against P. carinii in this system. Methods P. carinii organisms were obtained from the lungs of immunosuppressed rats. The culture system consisted of Iscove Dulbecco Eagle's Minimum Essential Medium (IMDM), supplemented with S-adenosyl-L-methionine, N-acetylglucosamine, putrescine, L-cysteine, L-glutamine, 2-mercaptoethanol, and fetal bovine serum, and was maintained at 37℃, in 5% CO2, 95% O2, at the optimal pH of 8.0. The culture system was used to assess the effect of daphnetin on the proliferation of P. carinii organisms. The ultrastructures of the treated organisms were observed by transmission electron microscopy.Conclusions Daphnetin can suppress the growth of P. carinii in vitro. The efficacy of daphnetin in suppressing the the growth of P. carinii in vitro is related to its ability to chelate iron.

  14. Encapsulation and retention of chelated-copper inside hydrophobic nanoparticles

    DEFF Research Database (Denmark)

    Hervella, Pablo; Ortiz, Elisa Parra; Needham, David

    2016-01-01

    ) Chelate copper into the octaethyl porphyrin; (3) Encapsulate OEP-Cu in nanoparticles: the encapsulation efficiency of copper into liquid nanoparticles (LNP), solid nanoparticles (SNP) and phospholipid liposomes (PL) was evaluated by UV-Vis and atomic absorption spectroscopy; (4) Retain the encapsulated...

  15. Iron chelating active packaging: Influence of competing ions and pH value on effectiveness of soluble and immobilized hydroxamate chelators.

    Science.gov (United States)

    Ogiwara, Yoshiko; Roman, Maxine J; Decker, Eric A; Goddard, Julie M

    2016-04-01

    Many packaged foods utilize synthetic chelators (e.g. ethylenediaminetetraacetic acid, EDTA) to inhibit iron-promoted oxidation or microbial growth which would result in quality loss. To address consumer demands for all natural products, we have previously developed a non-migratory iron chelating active packaging material by covalent immobilization of polyhydroxamate and demonstrated its efficacy in delaying lipid oxidation. Herein, we demonstrate the ability of this hydroxamate-functionalized iron chelating active packaging to retain iron chelating capacity; even in the presence of competing ions common in food. Both immobilized and soluble hydroxamate chelators retained iron chelating capacity in the presence of calcium, magnesium, and sodium competing ions, although at pH 5.0 the presence of calcium reduced immobilized hydroxamate iron chelation. A strong correlation was found between colorimetric and mass spectral analysis of iron chelation by the chelating packaging material. Such chelating active packaging may support reducing additive use in product formulations, while retaining quality and shelf life.

  16. Examining the fixation kinetics of chelated and non-chelated copper and the applications to micronutrient management in semiarid alkaline soils

    Science.gov (United States)

    Udeigwe, T. K.; Eichmann, M. B.; Menkiti, M. C.; Kusi, N. Y. O.

    2016-02-01

    This study examined and compared the fixation and fixation kinetics of copper (Cu) in chelated (ethylene diamine tetraacetic acid, EDTA) and non-chelated mixed systems of micronutrients in the semiarid soils of the Southern High Plains, USA, using findings from Cu extraction studies and kinetic models. Approximately, 22 % more Cu was fixed in the non-chelated system compared to the chelated within the first 14 days with only 7 % difference between the two systems by day 90. Findings suggest a decrease in the effectiveness of chelated micronutrients over time, highlighting the significance of timing even when chelated micronutrients are used. The strengths of the relationship of change in available Cu with respect to other micronutrients (iron (Fe), manganese (Mn), and zinc (Zn)) were higher in the non-chelated system (R2: 0.68-0.94), compared to the chelated (R2: 0.42-0.81), with slopes of 0.40 (Cu-Fe), 0.31 (Cu-Mn), and 1.04 (Cu-Zn) in the non-chelated system and 0.26 (Cu-Fe), 0.22 (Cu-Mn), and 0.90 (Cu-Zn) in the chelated system. Reduction in the amount of available Cu was best described by the power function model (R2 = 0.91, SE = 0.081) in the non-chelated system and second-order model (R2 = 0.95, SE = 0.010) in the chelated system. The applications generated from this study could be used as tools for improved micronutrient management and also provide baseline data for future work in other semiarid/arid alkaline soils of the world. Findings are also more applicable to field settings, an improvement over related previous studies.

  17. Targeting ILK and {beta}4 integrin abrogates the invasive potential of ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yoon Pyo; Kim, Baek Gil [BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Gao, Ming-Qing; Kang, Suki [Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cho, Nam Hoon, E-mail: cho1988@yuhs.ac [BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer The potential of targeting ILK and integrins for highly aggressive ovarian cancer. Black-Right-Pointing-Pointer Unanticipated synergistic effect for the combination of ILK/{beta}4 integrin. Black-Right-Pointing-Pointer Combination of ILK/{beta}4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. Black-Right-Pointing-Pointer Targeting of {beta}4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of {beta}1 and {beta}4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of {beta}1 and {beta}4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of {beta}4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of {beta}4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting {beta}4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.

  18. Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Ahad, Amjid [Lipid Metabolism Laboratory, Department of Biochemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Ganai, Ajaz Ahmad [Department of Biotechnology, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Mujeeb, Mohd [Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Siddiqui, Waseem Ahmad, E-mail: was.sid121@gmail.com [Lipid Metabolism Laboratory, Department of Biochemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India)

    2014-08-15

    Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16 weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-kB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway. - Highlights: • Chrysin reduced renal oxidative stress and inflammation in diabetic rats. • Chrysin reduced serum levels of pro-inflammatory in diabetic rats. • Chrysin exhibited renal protective effect by suppressing the TNF-α pathway.

  19. Enteric-coated tablet of risedronate sodium in combination with phytic acid, a natural chelating agent, for improved oral bioavailability.

    Science.gov (United States)

    Kim, Jeong S; Jang, Sun W; Son, Miwon; Kim, Byoung M; Kang, Myung J

    2016-01-20

    The oral bioavailability (BA) of risedronate sodium (RS), an antiresorptive agent, is less than 1% due to its low membrane permeability as well as the formation of non-absorbable complexes with multivalent cations such as calcium ion (Ca(2+)) in the gastrointestinal tract. In the present study, to increase oral BA of the bisphosphonate, a novel enteric-coated tablet (ECT) dosage form of RS in combination with phytic acid (IP6), a natural chelating agent recognized as safe, was formulated. The chelating behavior of IP6 against Ca(2+), including a stability constant for complex formulation was characterized using the continuous variation method. Subsequently, in vitro dissolution profile and in vivo pharmacokinetic profile of the novel ECT were evaluated comparatively with that of the marketed product (Altevia, Sanofi, US), an ECT containing ethylenediaminetetraacetic acid (EDTA) as a chelating agent, in beagle dogs. The logarithm of stability constant for Ca(2+)-IP6 complex, an equilibrium constant approximating the strength of the interaction between two chemicals to form complex, was 19.05, which was 3.9-fold (p<0.05) and 1.7-fold (p<0.05) higher than those of Ca(2+)-RS and Ca(2+)-EDTA complexes. The release profile of RS from both enteric-coated dosage forms was equivalent, regardless of the type of chelating agent. An in vivo absorption study in beagle dogs revealed that the maximum plasma concentration and area under the curve of RS after oral administration of IP6-containing ECT were approximately 7.9- (p<0.05) and 5.0-fold (p<0.05) higher than those of the marketed product at the same dose (35mg as RS). Therefore, our study demonstrates the potential usefulness of the ECT system in combination with IP6 for an oral therapy with the bisphosphonate for improved BA.

  20. EGFR-targeted plasmonic magnetic nanoparticles suppress lung tumor growth by abrogating G2/M cell-cycle arrest and inducing DNA damage

    Science.gov (United States)

    Kuroda, Shinji; Tam, Justina; Roth, Jack A; Sokolov, Konstantin; Ramesh, Rajagopal

    2014-01-01

    Background We have previously demonstrated the epidermal growth factor receptor (EGFR)-targeted hybrid plasmonic magnetic nanoparticles (225-NP) produce a therapeutic effect in human lung cancer cell lines in vitro. In the present study, we investigated the molecular mechanism of 225-NP-mediated antitumor activity both in vitro and in vivo using the EGFR-mutant HCC827 cell line. Methods The growth inhibitory effect of 225-NP on lung tumor cells was determined by cell viability and cell-cycle analysis. Protein expression related to autophagy, apoptosis, and DNA-damage were determined by Western blotting and immunofluorescence. An in vivo efficacy study was conducted using a human lung tumor xenograft mouse model. Results The 225-NP treatment markedly reduced tumor cell viability at 72 hours compared with the cell viability in control treatment groups. Cell-cycle analysis showed the percentage of cells in the G2/M phase was reduced when treated with 225-NP, with a concomitant increase in the number of cells in Sub-G1 phase, indicative of cell death. Western blotting showed LC3B and PARP cleavage, indicating 225-NP-treatment activated both autophagy- and apoptosis-mediated cell death. The 225-NP strongly induced γH2AX and phosphorylated histone H3, markers indicative of DNA damage and mitosis, respectively. Additionally, significant γH2AX foci formation was observed in 225-NP-treated cells compared with control treatment groups, suggesting 225-NP induced cell death by triggering DNA damage. The 225-NP-mediated DNA damage involved abrogation of the G2/M checkpoint by inhibiting BRCA1, Chk1, and phospho-Cdc2/CDK1 protein expression. In vivo therapy studies showed 225-NP treatment reduced EGFR phosphorylation, increased γH2AX foci, and induced tumor cell apoptosis, resulting in suppression of tumor growth. Conclusion The 225-NP treatment induces DNA damage and abrogates G2/M phase of the cell cycle, leading to cellular apoptosis and suppression of lung tumor growth

  1. EGFR-targeted plasmonic magnetic nanoparticles suppress lung tumor growth by abrogating G2/M cell-cycle arrest and inducing DNA damage

    Directory of Open Access Journals (Sweden)

    Kuroda S

    2014-08-01

    G2/M checkpoint by inhibiting BRCA1, Chk1, and phospho-Cdc2/CDK1 protein expression. In vivo therapy studies showed 225-NP treatment reduced EGFR phosphorylation, increased γH2AX foci, and induced tumor cell apoptosis, resulting in suppression of tumor growth. Conclusion: The 225-NP treatment induces DNA damage and abrogates G2/M phase of the cell cycle, leading to cellular apoptosis and suppression of lung tumor growth both in vitro and in vivo. Our findings provide a rationale for combining 225-NP with other DNA-damaging agents for achieving enhanced anticancer activity. Keywords: lung cancer, epidermal growth factor receptor, autophagy

  2. Lanthanides caged by the organic chelates; structural properties.

    Science.gov (United States)

    Smentek, Lidia

    2011-04-13

    The structure, in particular symmetry, geometry and morphology of organic chelates coordinated with the lanthanide ions are analyzed in the present review. This is the first part of a complete presentation of a theoretical description of the properties of systems, which are widely used in technology, but most of all, in molecular biology and medicine. The discussion is focused on the symmetry and geometry of the cages, since these features play a dominant role in the spectroscopic activity of the lanthanides caged by organic chelates. At the same time, the spectroscopic properties require more formal presentation in the language of Racah algebra, and deserve a separate analysis. In addition to the parent systems of DOTA, DOTP, EDTMP and CDTMP presented here, their modifications by various antennas are analyzed. The conclusions that have a strong impact upon the theory of the energy transfer and the sensitized luminescence of these systems are based on the results of numerical density functional theory calculations.

  3. Removal of cadmium from fish sauce using chelate resin.

    Science.gov (United States)

    Sasaki, Tetsuya; Araki, Ryohei; Michihata, Toshihide; Kozawa, Miyuki; Tokuda, Koji; Koyanagi, Takashi; Enomoto, Toshiki

    2015-04-15

    Fish sauce that is prepared from squid organs contains cadmium (Cd), which may be present at hazardous concentrations. Cd molecules are predominantly protein bound in freshly manufactured fish sauce, but are present in a liberated form in air-exposed fish sauce. In the present study, we developed a new method for removing both Cd forms from fish sauce using chelate resin and a previously reported tannin treatment. Sixteen-fold decreases in Cd concentrations were observed (0.78-0.05 mg/100 mL) following the removal of liberated Cd using chelate resin treatment, and the removal of protein-bound Cd using tannin treatment. Major nutritional components of fish sauce were maintained, including free amino acids and peptides, and angiotensin I-converting enzyme inhibitory and antioxidant activities.

  4. Flue gas desulfurization/denitrification using metal-chelate additives

    Science.gov (United States)

    Harkness, John B. L.; Doctor, Richard D.; Wingender, Ronald J.

    1986-01-01

    A method of simultaneously removing SO.sub.2 and NO from oxygen-containing flue gases resulting from the combustion of carbonaceous material by contacting the flue gas with an aqueous scrubber solution containing an aqueous sulfur dioxide sorbent and an active metal chelating agent which promotes a reaction between dissolved SO.sub.2 and dissolved NO to form hydroxylamine N-sulfonates. The hydroxylamine sulfonates are then separated from the scrubber solution which is recycled.

  5. Mineral Levels in Thalassaemia Major Patients Using Different Iron Chelators.

    Science.gov (United States)

    Genc, Gizem Esra; Ozturk, Zeynep; Gumuslu, Saadet; Kupesiz, Alphan

    2016-03-01

    The goal of the present study was to determine the levels of minerals in chronically transfused thalassaemic patients living in Antalya, Turkey and to determine mineral levels in groups using different iron chelators. Three iron chelators deferoxamine, deferiprone and deferasirox have been used to remove iron from patients' tissues. There were contradictory results in the literature about minerals including selenium, zinc, copper, and magnesium in thalassaemia major patients. Blood samples from the 60 thalassaemia major patients (the deferoxamine group, n = 19; the deferiprone group, n = 20 and the deferasirox group, n = 21) and the controls (n = 20) were collected. Levels of selenium, zinc, copper, magnesium, and iron were measured, and all of them except iron showed no significant difference between the controls and the patients regardless of chelator type. Serum copper levels in the deferasirox group were lower than those in the control and deferoxamine groups, and serum magnesium levels in the deferasirox group were higher than those in the control, deferoxamine and deferiprone groups. Iron levels in the patient groups were higher than those in the control group, and iron levels showed a significant correlation with selenium and magnesium levels. Different values of minerals in thalassaemia major patients may be the result of different dietary intake, chelator type, or regional differences in where patients live. That is why minerals may be measured in thalassaemia major patients at intervals, and deficient minerals should be replaced. Being careful about levels of copper and magnesium in thalassaemia major patients using deferasirox seems to be beneficial.

  6. Decontamination of process equipment using recyclable chelating solvent

    Energy Technology Data Exchange (ETDEWEB)

    Jevec, J.; Lenore, C.; Ulbricht, S. [Babcock & Wilcox, Co., R& DD, Alliance, OH (United States)

    1995-10-01

    The Department of Energy (DOE) is now faced with the task of meeting decontamination and decommissioning obligations at numerous facilities by the year 2019. Due to the tremendous volume of material involved, innovative decontamination technologies are being sought that can reduce the volumes of contaminated waste materials and secondary wastes requiring disposal. This report describes the results of the performance testing of chelates and solvents for the dissolution of uranium.

  7. 驱铜治疗对肝豆状核变性患者脑组织磁共振波谱的影响%Brain 1H-MRS study on the effects of copper chelation therapy on WD patients

    Institute of Scientific and Technical Information of China (English)

    吴舒梅; 杨任民; 胡文彬; 韩咏竹; 胡纪源; 王训; 李凯; 王共强; 吴君霞; 苏增锋

    2015-01-01

    目的:观察肝豆状核变性(wilson disease, WD)患者脑组织氢质子磁共振波谱(1H-MRS)的改变及患者在驱铜治疗前后脑组织1H-MRS的变化情况,为WD的评价预后提供参考。方法选择39例WD患者,分为非脑型组18例;脑型疗前组及短期治疗组均为21例,其中长期治疗组20例。分别利用1.5T超导磁共振诊断仪对患者进行1H-MRS单体素信号采集,在驱铜治疗后再次检测,比较治疗前后各指标的变化。20例均无血缘关系的健康志愿者作为对照组。结果患者的年龄、性别与对照组有可比性。39例WD患者左侧壳核、尾状核头部NAA/Cr较丘脑部位明显降低(P0.05);长期治疗组左侧壳核、丘脑部位NAA/Cr及NAA/Cho的均值较脑型疗前组明显升高(P0.05). The mean of NAA/Cr and NAA/Cho in the left putamen and basal ganglion was much higher in long-term treatment group than in brain type group(P<0.01 or P<0.05). The mean of Cho/Cr in the left head of caudate nucleus were much higher after treatment compared with prior-treatment group(P<0.05). The mean of NAA/Cr in the left putamen, head of the left caudate nucleus and basal ganglion in all groups was negatively correlated with course of the disease. Conclusion There are significant differences in brain metabolism among different type of WD. The long-term but not short-term copper chelation significantly improves brain metabolism. NAA/Cr may be used as a non-invasive indicator to examine the efficacy of treatment.

  8. Copper and Zinc Chelation as a Treatment of Alzheimer's Disease

    Science.gov (United States)

    Hodak, Miroslav; Bernholc, Jerry

    2014-03-01

    Alzheimer's disease (AD) is a neurodegenerative disorder affecting millions of people in the U.S. The cause of the disease remains unknown, but amyloid- β (A β), a short peptide, is considered causal its pathogenesis. At cellular level, AD is characterized by deposits mainly composed of A β that also contain elevated levels of transition metals ions. Targeting metals is a promising new strategy for AD treatment, which uses moderately strong metal chelators to sequester them from A β or the environment. PBT2 is a chelating compound that has been the most promising in clinical trials. In our work, we use computer simulations to investigate complexes of a close analog of PBT2 with Cu2+ and Zn2+ ions. The calculations employ KS/FD DFT method, which combines Kohn-Sham DFT with the frozen-density DFT to achieve efficient description of explicit solvent beyond the first solvation shell. Our work is based on recent experiments and examines both 1:1 and 2:1 chelator-metal stochiometries detected experimentally. The results show that copper attaches more strongly than zinc, find that 1:1 complexes involve water in the first coordination shell and determine which one of several possible 2:1 geometries is the most preferable.

  9. Elucidating Interactions between DMSO and Chelate-Based Ionic Liquids.

    Science.gov (United States)

    Chen, Hang; Wang, Xinyu; Yao, Jia; Chen, Kexian; Guo, Yan; Zhang, Pengfei; Li, Haoran

    2015-12-21

    The C-D bond stretching vibrations of deuterated dimethyl sulfoxide ([D6 ]DMSO) and the C2 -H bond stretching vibrations of 1,1,1,5,5,5-hexafluoropentane-2,4-dione (hfac) ligand in anion are chosen as probes to elucidate the solvent-solute interaction between chelate-based ionic liquids (ILs) and DMSO by vibrational spectroscopic studies. The indirect effect from the interaction of the adjacent S=O functional group of DMSO with the cation [C10 mim](+) and anion [Mn(hfac)3 ](-) of the ILs leads to the blue-shift of the C-D stretching vibrations of DMSO. The C2 -H bond stretching vibrations in hfac ligand is closely related to the ionic hydrogen bond strength between the cation and anion of chelate-based ILs. EPR studies reveal that the crystal field of the central metal is kept when the chelate-based ILs are in different microstructure environment in the solution.

  10. Examining the fixation kinetics of chelated and non-chelated copper micronutrient and the applications to micronutrient management in semi-arid alkaline soils

    Science.gov (United States)

    Udeigwe, T. K.; Eichmann, M. B.; Menkiti, M. C.

    2015-10-01

    The relationship between the deficiency of a nutrient in plants and its total concentration in the soil is complex. This study examined and compared the fixation and fixation kinetics of copper (Cu) in chelated (Ethylene diamine tetraacetic acid, EDTA) and non-chelated mixed systems of micronutrients in the semi-arid soils of the Southern High Plains, US using findings from Cu extraction studies and kinetic models. Approximately, 22 % more Cu was fixed in the non-chelated system within the first 14 days with only 7 % difference between the two systems by day 90. Findings suggest a decrease in the effectiveness of chelated micronutrient over time, highlighting the significance of timing even when chelated micronutrients are applied. The strengths of the relationship of change in available Cu with respect to other micronutrients [iron (Fe), manganese (Mn), and zinc (Zn)] were higher in the non-chelated system (R2: 0.68-0.94), compared to the chelated (R2: 0.42-0.81) with slopes of 0.40 (Cu-Fe), 0.31 (Cu-Mn), and 1.04 (Cu-Zn) in the non-chelated system and 0.26 (Cu-Fe), 0.22 (Cu-Mn), and 0.90 (Cu-Zn) in the chelated. Reduction in the amount of available Cu was best described by the power function model (R2 = 0.91, SE = 0.081) in the non-chelated system and second order model (R2 = 0.95, SE = 0.010) in the chelated system. The applications generated from this study could be used as tools for improved micronutrient management and also provide baseline data for future work in other semi-arid/arid alkaline soils of the world. Findings are also more applicable to field settings, an improvement over related previous studies.

  11. Genistein abrogates G2 arrest induced by curcumin in p53 deficient T47D cells

    Directory of Open Access Journals (Sweden)

    Astuti Puji

    2012-11-01

    Full Text Available Abstract Background The high cost and low level of cancer survival urge the finding of new drugs having better mechanisms. There is a high trend of patients to be “back to nature” and use natural products as an alternative way to cure cancer. The fact is that some of available anticancer drugs are originated from plants, such as taxane, vincristine, vinblastine, pacitaxel. Curcumin (diferuloylmethane, a dietary pigment present in Curcuma longa rizhome is reported to induce cell cycle arrest in some cell lines. Other study reported that genistein isolated from Glycine max seed inhibited phosphorylation of cdk1, gene involved during G2/M transition and thus could function as G2 checkpoint abrogator. The inhibition of cdk1 phosphorylation is one of alternative strategy which could selectively kill cancer cells and potentially be combined with DNA damaging agent such as curcumin. Methods T47D cell line was treated with different concentrations of curcumin and genistein, alone or in combination; added together or with interval time. Flow Cytometry and MTT assay were used to evaluate cell cycle distribution and viability, respectively. The presence of apoptotic cells was determined using acridine orange-ethidium bromide staining. Results In this study curcumin induced G2 arrest on p53 deficient T47D cells at the concentration of 10 μM. Increasing concentration up to 30 μM increased the number of cell death. Whilst genistein alone at low concentration (≤10 μM induced cell proliferation, addition of genistein (20 μM 16 h after curcumin resulted in more cell death (89%, 34% higher than that administered at the same time (56%. The combination treatment resulted in apoptotic cell death. Combining curcumin with high dose of genistein (50 μM induced necrotic cells. Conclusions Genistein increased the death of curcumin treated T47D cells. Appropriate timing of administration and concentration of genistein determine the outcome of

  12. Natural Mutations in Streptococcus agalactiae Resulting in Abrogation of β Antigen Production.

    Science.gov (United States)

    Vasilyeva, Anastasia; Santos Sanches, Ilda; Florindo, Carlos; Dmitriev, Alexander

    2015-01-01

    Streptococcus agalactiae genome encodes 21 two-component systems (TCS) and a variety of regulatory proteins in order to control gene expression. One of the TCS, BgrRS, comprising the BgrR DNA-binding regulatory protein and BgrS sensor histidine kinase, was discovered within a putative virulence island. BgrRS influences cell metabolism and positively control the expression of bac gene, coding for β antigen at transcriptional level. Inactivation of bgrR abrogated bac gene expression and increased virulence properties of S. agalactiae. In this study, a total of 140 strains were screened for the presence of bac gene, and the TCS bgrR and bgrS genes. A total of 53 strains carried the bac, bgrR and bgrS genes. Most of them (48 strains) expressed β antigen, while five strains did not express β antigen. Three strains, in which bac gene sequence was intact, while bgrR and/or bgrS genes had mutations, and expression of β antigen was absent, were complemented with a constructed plasmid pBgrRS(P) encoding functionally active bgrR and bgrS gene alleles. This procedure restored expression of β antigen indicating the crucial regulatory role of TCS BgrRS. The complemented strain A49V/BgrRS demonstrated attenuated virulence in intraperitoneal mice model of S. agalactiae infection compared to parental strain A49V. In conclusion we showed that disruption of β antigen expression is associated with: i) insertion of ISSa4 upstream the bac gene just after the ribosomal binding site; ii) point mutation G342A resulting a stop codon TGA within the bac gene and a truncated form of β antigen; iii) single deletion (G) in position 439 of the bgrR gene resulting in a frameshift and the loss of DNA-binding domain of the BgrR protein, and iv) single base substitutions in bgrR and bgrS genes causing single amino acid substitutions in BgrR (Arg187Lys) and BgrS (Arg252Gln). The fact that BgrRS negatively controls virulent properties of S. agalactiae gives a novel clue for understanding of S

  13. Silibinin ameliorates arsenic induced nephrotoxicity by abrogation of oxidative stress, inflammation and apoptosis in rats.

    Science.gov (United States)

    Prabu, S Milton; Muthumani, M

    2012-12-01

    Arsenic (As) is an environmental and industrial pollutant that affects various organs in human and experimental animals. Silibinin is a naturally occurring plant bioflavonoid found in the milk thistle of Silybum marianum, which has been reported to have a wide range of pharmacological properties. A body of evidence has accumulated implicating the free radical generation with subsequent oxidative stress in the biochemical and molecular mechanisms of As toxicity. Since kidney is the critical target organ of chronic As toxicity, we carried out this study to investigate the effects of silibinin on As-induced toxicity in the kidney of rats. In experimental rats, oral administration of sodium arsenite [NaAsO(2), 5 mg/(kg day)] for 4 weeks significantly induced renal damage which was evident from the increased levels of serum urea, uric acid, creatinine with a significant (p rats. Co-administration of silibinin (75 mg/kg day) along with As resulted in a reversal of As-induced biochemical changes in kidney accompanied by a significant decrease in lipid peroxidation and an increase in the level of renal antioxidant defense system. The histopathological and immunohistochemical studies in the kidney of rats also shows that silibinin (75 mg/kg day) markedly reduced the toxicity of As and preserved the normal histological architecture of the renal tissue, inhibited the caspase-3 mediated tubular cell apoptosis and decreased the NADPH oxidase, iNOS and NF-κB over expression by As and upregulated the Nrf2 expression in the renal tissue. The present study suggests that the nephroprotective potential of silibinin in As toxicity might be due to its antioxidant and metal chelating properties, which could be useful for achieving optimum effects in As-induced renal damage.

  14. A mathematical model to elucidate brain tumor abrogation by immunotherapy with T11 target structure.

    Directory of Open Access Journals (Sweden)

    Sandip Banerjee

    Full Text Available T11 Target structure (T11TS, a membrane glycoprotein isolated from sheep erythrocytes, reverses the immune suppressed state of brain tumor induced animals by boosting the functional status of the immune cells. This study aims at aiding in the design of more efficacious brain tumor therapies with T11 target structure. We propose a mathematical model for brain tumor (glioma and the immune system interactions, which aims in designing efficacious brain tumor therapy. The model encompasses considerations of the interactive dynamics of glioma cells, macrophages, cytotoxic T-lymphocytes (CD8(+ T-cells, TGF-β, IFN-γ and the T11TS. The system undergoes sensitivity analysis, that determines which state variables are sensitive to the given parameters and the parameters are estimated from the published data. Computer simulations were used for model verification and validation, which highlight the importance of T11 target structure in brain tumor therapy.

  15. Livin abrogates apoptosis of SPC-A1 cell by regulating JNKI signaling pathway.

    Science.gov (United States)

    Chen, Yu-Sheng; Li, Hong-Ru; Lin, Ming; Chen, Gang; Xie, Bao-Song; Xu, Neng-Luan; Lin, Li-Fang

    2010-06-01

    Livin, a novel member of inhibitors of apoptosis protein, is highly expressed in tumor tissues. It is a potential target in tumor therapy. Silencing its gene expression has been found to promote tumor cell apoptosis or increase tumor sensitivity to therapies. This paper studied the effect of livin anti-apoptotic activity and examined its molecular mechanisms. In the study, higher levels of cell apoptosis were measured by FACS in the experiment group with livin expression silenced than that in controls (P SPC-A1 by activating JNK1 signaling pathway and inhibiting caspase-3 activation.

  16. Biodegradable gadolinium-chelated cationic poly(urethane amide) copolymers for gene transfection and magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Xiaolong [Department of Radiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065 (China); Wang, Gangmin [Department of Urology, Huashan Hospital, Fudan University, Shanghai 200040 (China); Shi, Ting [The Institute for Translational Nanomedicine, Shanghai East Hospital, Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Shanghai 200092 (China); Shao, Zhihong [Department of Radiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065 (China); Zhao, Peng; Shi, Donglu [The Institute for Translational Nanomedicine, Shanghai East Hospital, Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Shanghai 200092 (China); Ren, Jie [Institute of Nano and Biopolymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai 201804 (China); Lin, Chao, E-mail: chaolin@tongji.edu.cn [The Institute for Translational Nanomedicine, Shanghai East Hospital, Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Shanghai 200092 (China); Wang, Peijun, E-mail: tjpjwang@sina.com [Department of Radiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065 (China)

    2016-08-01

    Theranostic nano-polyplexes containing gene and imaging agents hold a great promise for tumor diagnosis and therapy. In this work, we develop a group of new gadolinium (Gd)-chelated cationic poly(urethane amide)s for gene delivery and T{sub 1}-weighted magnetic resonance (MR) imaging. Cationic poly(urethane amide)s (denoted as CPUAs) having multiple disulfide bonds, urethane and amide linkages were synthesized by stepwise polycondensation reaction between 1,4-bis(3-aminopropyl)piperazine and a mixture of di(4-nitrophenyl)-2, 2′-dithiodiethanocarbonate (DTDE-PNC) and diethylenetriaminepentaacetic acid (DTPA) dianhydride at varied molar ratios. Then, Gd-chelated CPUAs (denoted as GdCPUAs) were produced by chelating Gd(III) ions with DTPA residues of CPUAs. These GdCPUAs could condense gene into nanosized and positively-charged polyplexes in a physiological condition and, however, liberated gene in an intracellular reductive environment. In vitro transfection experiments revealed that the GdCPUA at a DTDE-PNC/DTPA residue molar ratio of 85/15 induced the highest transfection efficiency in different cancer cells. This efficiency was higher than that yielded with 25 kDa branched polyethylenimine as a positive control. GdCPUAs and their polyplexes exhibited low cytotoxicity when an optimal transfection activity was detected. Moreover, GdCPUAs may serve as contrast agents for T{sub 1}-weighted magnetic resonance imaging. The results of this work indicate that biodegradable Gd-chelated cationic poly(urethane amide) copolymers have high potential for tumor theranostics. - Highlights: • Novel cationic gadolinium-chelated poly(urethane amide)s (GdCPUAs) are prepared. • GdCPUAs can induce a high transfection efficacy in different cancer cells. • GdCPUAs reveal good cyto-compatibility against cancer cells. • GdCPUAs may be applied as T{sub 1}-contrast agents for magnetic resonance imaging. • GdCPUAs hold high potential for cancer theranostics.

  17. Deferasirox as adjunctive therapy for mucormycosis.

    NARCIS (Netherlands)

    Donnelly, J.P.; Lahav, M.

    2012-01-01

    Mucormycosis can be devastating and, as yet, there are no ideal therapies available. Observations that iron chelation may be a useful adjunct to antifungal treatment encouraged Spellberg et al. (J Antimicrob Chemother 2012; 715-22) to undertake a trial of deferasirox combined with liposomal amphoter

  18. EFFICACY AND SAFETY OF DEFERASIROX WHEN COMPARED TO D EFERIPRONE AS ORAL IRON CHELATING AGENT : A RANDOMIZED CONTROL TRIAL

    Directory of Open Access Journals (Sweden)

    Sanjeeva

    2015-03-01

    Full Text Available BACKGROUND : Thalassemia is one of the most common inherited hemoglobinopathy seen in southern India. With regular blood transfusion, these children live longer but associated morbidity due to iron overload impairs the quality of life. We studied the efficacy and safety of new oral iron chelator, deferasirox, compared with deferiprone which was used for long time. MATERIAL AND METHODS : We cond ucted a prospective randomised control study, between January 2011 to June 2012 at thalassemia day care centre of Indira Gandhi I nstitute of C hild H ealth, Bengaluru. The children who were diagnosed as Thalassemia and receiving regular blood transfusion wit h serum ferritin levels more than 1000ng/ml and not receiving any chelation therapy were included in the study. These children were randomly divided into two groups as group 1 and group 2 by computer generated randomization. The children included in g roup 1 received Deferasirox and group 2 received Deferiprone as chelation therapy. The dosage of deferasirox was 20mg/kg/day once daily and that of deferiprone 75 mg/kg/day in three divided daily doses. The primary study outcome was to measure and compare the d ecrease in serum ferritin levels between the two study groups. The secondary outcome measures were to compare the side effect profiles among the two groups. RESULTS : We included 41 thalessemic children and 19 of them were included in group 1 (Deferasirox and 22 children in Group 2 (Deferiprone. At the end of study period of 18 months three children in group II discontinued therapy due to side effects, hence the remaining 19 were available for final analysis in group 2 whereas no drop outs in the group 1. During the study period, the serum ferritin decreased from 3261±2613ng/dl to 1586±766 ng/dl in group 1 as compared in group 2 from 4109±3153 ng/dl to 1743±1138 ng/dl (fig 2. This was also not statistically significant. In group 2, 68% of the children expe rienced adverse effect as compared

  19. Ferritin iron minerals are chelator targets, antioxidants, and coated, dietary iron.

    Science.gov (United States)

    Theil, Elizabeth C

    2010-08-01

    Cellular ferritin is central for iron balance during transfusions therapies; serum ferritin is a small fraction of body ferritin, albeit a convenient reporter. Iron overload induces extra ferritin protein synthesis but the protein is overfilled with the extra iron that damages ferritin, with conversion to toxic hemosiderin. Three new approaches that manipulate ferritin to address excess iron, hemosiderin, and associated oxidative damage in Cooley's Anemia and other iron overload conditions are faster removal of ferritin iron with chelators guided to ferritin gated pores by peptides; more ferritin protein synthesis using ferritin mRNA activators, by metal complexes that target mRNA 3D structures; and determining if endocytotic absorption of iron from legumes, which is mostly ferritin, is regulated during iron overload to prevent excess iron entry while providing protein. More of a focus on ferritin features, including protein cage structure, iron mineral, regulatable mRNA, and specific gut absorption properties, will achieve the three novel experimental goals for managing iron homeostasis with transfusion therapies.

  20. Preparation of Polysulfone-supported Phosphoramidic Acid Type Chelate Membrane and Its Sorption Properties for Ag+

    Institute of Scientific and Technical Information of China (English)

    WANG Bing; CUI Yong-fang; DU Qi-yun; PEI Guang-ling

    2002-01-01

    A blending chelate filter membrane with high chelate capacity for Ag+ has been prepared by blending of phosphoramidic acid resin and polysulfone. The major parameters influencing structure of the chelate filter membranes such as the blending ratio, phosphoramidic acid resin grain size and temperature of casting solution have been studied. The relationship among the chelate amount of Ag+, pH value, Ag+ concentration and phosphoramidic acid resin grain diameter were examined. The chelate filter membrane had a capacity of1438μg/cm2 for Ag+ under appropriate conditions.Sorption isotherm of Ag + could be expressed with the Freundlich sorption model. The dynamic chelate experiments proved that the sorption and desorption of membranes could be realized simultaneously for Ag+.

  1. Zinc chelation reduces hippocampal neurogenesis after pilocarpine-induced seizure.

    Directory of Open Access Journals (Sweden)

    Jin Hee Kim

    Full Text Available Several studies have shown that epileptic seizures increase hippocampal neurogenesis in the adult. However, the mechanism underlying increased neurogenesis after seizures remains largely unknown. Neurogenesis occurs in the subgranular zone (SGZ of the hippocampus in the adult brain, although an understanding of why it actively occurs in this region has remained elusive. A high level of vesicular zinc is localized in the presynaptic terminals of the SGZ. Previously, we demonstrated that a possible correlation may exist between synaptic zinc localization and high rates of neurogenesis in this area after hypoglycemia. Using a lithium-pilocarpine model, we tested our hypothesis that zinc plays a key role in modulating hippocampal neurogenesis after seizure. Then, we injected the zinc chelator, clioquinol (CQ, 30 mg/kg, into the intraperitoneal space to reduce brain zinc availability. Neuronal death was detected with Fluoro Jade-B and NeuN staining to determine whether CQ has neuroprotective effects after seizure. The total number of degenerating and live neurons was similar in vehicle and in CQ treated rats at 1 week after seizure. Neurogenesis was evaluated using BrdU, Ki67 and doublecortin (DCX immunostaining 1 week after seizure. The number of BrdU, Ki67 and DCX positive cell was increased after seizure. However, the number of BrdU, Ki67 and DCX positive cells was significantly decreased by CQ treatment. Intracellular zinc chelator, N,N,N0,N-Tetrakis (2-pyridylmethyl ethylenediamine (TPEN, also reduced seizure-induced neurogenesis in the hippocampus. The present study shows that zinc chelation does not prevent neurodegeneration but does reduce seizure-induced progenitor cell proliferation and neurogenesis. Therefore, this study suggests that zinc has an essential role for modulating hippocampal neurogenesis after seizure.

  2. Complexation and Antimicrobial Studies of Some Divalent Metal Chelates

    Directory of Open Access Journals (Sweden)

    Suparna Ghosh

    2010-01-01

    Full Text Available Metal chelates of Ni(II and Cu(II with the ligand 5-acetamido-1,3,4-thiadiazole-2-sulphonamide have been synthesized. The isolated compounds have been characterized by elemental analysis, molar conductivity, magnetic moment, electronic and IR spectral studies. The analytical data reflects the metal to ligand stoichiometry to be 1: 2. The conductivity data of the complexes also suggests their non-electrolytic nature. The stability constants and free energy change for the complexes have been calculated.. Ligand and their complexes have been screened for their biological activity and the data show good activity of these complexes and ligands.

  3. Synthesis and Adsorption Properties of Polystyrene-supported Chelating Resins Containing Heterocyclic Functional Groups

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    A series of new chelating resins with incorporating heterocyclic functional groups:pyridine, thiadizole, benzothizole into macroporous chloromethylated polystyrene were synthesized via hydrophilic spacer arm of polyethylene glycol co ntaining sulfur. These chelating resins were found to show high adsorption capacities for Ag+, Hg2+, Au3+ and Pd2+, and the presence of spacer arm can enhance adsorption ability due to increase the hydrophilicity of the chelating resins.

  4. Alkenes as Chelating Groups in Diastereoselective Additions of Organometallics to Ketones.

    Science.gov (United States)

    Raffier, Ludovic; Gutierrez, Osvaldo; Stanton, Gretchen R; Kozlowski, Marisa C; Walsh, Patrick J

    2014-10-13

    Alkenes have been discovered to be chelating groups to Zn(II), enforcing highly stereoselective additions of organozincs to β,γ-unsaturated ketones. (1)H NMR studies and DFT calculations provide support for this surprising chelation mode. The results expand the range of coordinating groups for chelation-controlled carbonyl additions from heteroatom Lewis bases to simple C-C double bonds, broadening the 60 year old paradigm.

  5. Performance of Nonmigratory Iron Chelating Active Packaging Materials in Viscous Model Food Systems.

    Science.gov (United States)

    Roman, Maxine J; Decker, Eric A; Goddard, Julie M

    2015-09-01

    Many packaged food products undergo quality deterioration due to iron promoted oxidative reactions. Recently, we have developed a nonmigratory iron chelating active packaging material that represents a novel approach to inhibit oxidation of foods while addressing consumer demands for "cleanˮ labels. A challenge to the field of nonmigratory active packaging is ensuring that surface-immobilized active agents retain activity in a true food system despite diffusional limitations. Yet, the relationship between food viscosity and nonmigratory active packaging activity retention has never been characterized. The objective of this study was to investigate the influence of food viscosity on iron chelation by a nonmigratory iron chelating active packaging material. Methyl cellulose was added to aqueous buffered iron solutions to yield model systems with viscosities ranging from ∼1 to ∼10(5)  mPa·s, representing viscosities ranging from beverage to mayonnaise. Iron chelation was quantified by material-bound iron content using colorimetry and inductively coupled plasma-optical emission spectrometry (ICP-OES).  Maximum iron chelation was reached in solutions up to viscosity ∼10(2)  mPa·s. In more viscous solutions (up to ∼10(4)  mPa·s), there was a significant decrease in iron chelating capacity (P influence of different food hydrocolloids on the performance of nonmigratory iron chelating active packaging was characterized. Methyl cellulose and carrageenan did not compete with the material for specific iron chelation (P > 0.05). Materials retained 32% to 45% chelating capacity when in contact with competitively chelating hydrocolloids guar gum, locust bean gum, and xanthan gum. This work demonstrates the potential application of nonmigratory iron chelating active packaging in liquid and semi-liquid foods to allow for the removal of synthetic chelators, while maintaining food quality.

  6. N-Acetyl-Cysteine as Effective and Safe Chelating Agent in Metal-on-Metal Hip-Implanted Patients: Two Cases

    Directory of Open Access Journals (Sweden)

    Andrea Giampreti

    2016-01-01

    Full Text Available Systemic toxicity associated with cobalt (Co and chromium (Cr containing metal hip alloy may result in neuropathy, cardiomyopathy, and hypothyroidism. However clinical management concerning chelating therapy is still debated in literature. Here are described two metal-on-metal hip-implanted patients in which N-acetyl-cysteine decreased elevated blood metal levels. A 67-year-old male who underwent Co/Cr hip implant in September 2009 referred to our Poison Control Centre for persisting elevated Co/Cr blood levels (from March 2012 to November 2014. After receiving oral high-dose N-acetyl-cysteine, Co/Cr blood concentrations dropped by 86% and 87% of the prechelation levels, respectively, and persisted at these latter concentrations during the following 6 months of follow-up. An 81-year-old female who underwent Co/Cr hip implant in January 2007 referred to our Centre for detection of high Co and Cr blood levels in June 2012. No hip revision was indicated. After a therapy with oral high-dose N-acetyl-cysteine Co/Cr blood concentrations decreased of 45% and 24% of the prechelation levels. Chelating agents reported in hip-implanted patients (EDTA, DMPS, and BAL are described in few cases. N-acetyl-cysteine may provide chelating sites for metals and in our cases reduced Co and Cr blood levels and resulted well tolerable.

  7. Induction of intrinsic and extrinsic apoptosis through oxidative stress in drug-resistant cancer by a newly synthesized Schiff base copper chelate.

    Science.gov (United States)

    Banerjee, Kaushik; Basu, Soumya; Das, Satyajit; Sinha, Abhinaba; Biswas, Manas Kumar; Choudhuri, Soumitra Kumar

    2016-01-01

    Multidrug resistance (MDR) in cancer represents a variety of strategies employed by tumor cells to evade the beneficial cytotoxic effects of structurally different anticancer drugs and thus confers impediments to the successful treatment of cancers. Efflux of drugs by MDR protein-1, functional P-glycoprotein and elevated level of reduced glutathione confer resistance to cell death or apoptosis and thus provide a possible therapeutic target for overcoming MDR in cancer. Previously, we reported that a Schiff base ligand, potassium-N-(2-hydroxy 3-methoxy-benzaldehyde)-alaninate (PHMBA) overcomes MDR in both in vivo and in vitro by targeting intrinsic apoptotic/necrotic pathway through induction of reactive oxygen species (ROS). The present study describes the synthesis and spectroscopic characterization of a copper chelate of Schiff base, viz., copper (II)-N-(2-hydroxy-3-methoxy-benzaldehyde)-alaninate (CuPHMBA) and the underlying mechanism of cell death induced by CuPHMBA in vitro. CuPHMBA kills both the drug-resistant and sensitive cell types irrespective of their drug resistance phenotype. The cell death induced by CuPHMBA follows apoptotic pathway and moreover, the cell death is associated with intrinsic mitochondrial and extrinsic receptor-mediated pathways. Oxidative stress plays a pivotal role in the process as proved by the fact that antioxidant enzyme; polyethylene glycol conjugated-catalase completely blocked CuPHMBA-induced ROS generation and abrogated cell death. To summarize, the present work provides a compelling rationale for the future clinical use of CuPHMBA, a redox active copper chelate in the treatment of cancer patients, irrespective of their drug-resistance status.

  8. Effect of metal chelators on the oxidative stability of model wine.

    Science.gov (United States)

    Kreitman, Gal Y; Cantu, Annegret; Waterhouse, Andrew L; Elias, Ryan J

    2013-10-02

    Oxidation is a major problem with respect to wine quality, and winemakers have few tools at their disposal to control it. In this study, the effect of exogenous Fe(II) (bipyridine; Ferrozine) and Fe(III) chelators (ethylenediaminetetraacetic acid, EDTA; phytic acid) on nonenzymatic wine oxidation was examined. The ability of these chelators to affect the formation of 1-hydroxyethyl radicals (1-HER) and acetaldehyde was measured using a spin trapping technique with electron paramagnetic resonance (EPR) and by HPLC-PDA, respectively. The chelators were then investigated for their ability to prevent the oxidative loss of an important aroma-active thiol, 3-mercaptohexan-1-ol (3MH). The Fe(II)-specific chelators were more effective than the Fe(III) chelators with respect to 1-HER inhibition during the early stages of oxidation and significantly reduced oxidation markers compared to a control during the study. However, although the addition of Fe(III) chelators was less effective or even showed an initial pro-oxidant activity, the Fe(III) chelators proved to be more effective antioxidants compared to Fe(II) chelators after 8 days of accelerated oxidation. In addition, it is shown for the first time that Fe(II) and Fe(III) chelators can significantly inhibit the oxidative loss of 3MH in model wine.

  9. TGF-β1 induced epithelial to mesenchymal transition (EMT in human bronchial epithelial cells is enhanced by IL-1β but not abrogated by corticosteroids

    Directory of Open Access Journals (Sweden)

    Zuraw Bruce L

    2009-10-01

    Full Text Available Abstract Background Chronic persistent asthma is characterized by ongoing airway inflammation and airway remodeling. The processes leading to airway remodeling are poorly understood, and there is increasing evidence that even aggressive anti-inflammatory therapy does not completely prevent this process. We sought to investigate whether TGFβ1 stimulates bronchial epithelial cells to undergo transition to a mesenchymal phenotype, and whether this transition can be abrogated by corticosteroid treatment or enhanced by the pro-inflammatory cytokine IL-1β. Methods BEAS-2B and primary normal human bronchial epithelial cells were stimulated with TGFβ1 and expression of epithelial and mesenchymal markers assessed by quantitative real-time PCR, immunoblotting, immunofluorescence microscopy and zymography. In some cases the epithelial cells were also incubated with corticosteroids or IL-1β. Results were analyzed using non-parametric statistical tests. Results Treatment of BEAS-2B or primary human bronchial epithelial cells with TGFβ1 significantly reduced the expression level of the epithelial adherence junction protein E-cadherin. TGFβ1 then markedly induced mesenchymal marker proteins such as collagen I, tenascin C, fibronectin and α-smooth muscle actin mRNA in a dose dependant manner. The process of mesenchymal transition was accompanied by a morphological change towards a more spindle shaped fibroblast cell type with a more motile and invasive phenotype. Corticosteroid pre-treatment did not significantly alter the TGFβ1 induced transition but IL-1β enhanced the transition. Conclusion Our results indicate, that TGFβ1 can induce mesenchymal transition in the bronchial epithelial cell line and primary cells. Since asthma has been strongly associated with increased expression of TGFβ1 in the airway, epithelial to mesenchymal transition may contribute to the contractile and fibrotic remodeling process that accompanies chronic asthma.

  10. Abrogating phosphorylation of eIF4B is required for EGFR and mTOR inhibitor synergy in triple-negative breast cancer.

    Science.gov (United States)

    Madden, Julie M; Mueller, Kelly L; Bollig-Fischer, Aliccia; Stemmer, Paul; Mattingly, Raymond R; Boerner, Julie L

    2014-09-01

    Triple-negative breast cancer (TNBC) patients suffer from a highly malignant and aggressive disease. They have a high rate of relapse and often develop resistance to standard chemotherapy. Many TNBCs have elevated epidermal growth factor receptor (EGFR) but are resistant to EGFR inhibitors as monotherapy. In this study, we sought to find a combination therapy that could sensitize TNBC to EGFR inhibitors. Phospho-mass spectrometry was performed on the TNBC cell line, BT20, treated with 0.5 μM gefitinib. Immunoblotting measured protein levels and phosphorylation. Colony formation and growth assays analyzed the treatment on cell proliferation, while MTT assays determined the synergistic effect of inhibitor combination. A Dual-Luciferase reporter gene plasmid measured translation. All statistical analysis was done on CalucuSyn and GraphPad Prism using ANOVAs. Phospho-proteomics identified the mTOR pathway to be of interest in EGFR inhibitor resistance. In our studies, combining gefitinib and temsirolimus decreased cell growth and survival in a synergistic manner. Our data identified eIF4B, as a potentially key fragile point in EGFR and mTOR inhibitor synergy. Decreased eIF4B phosphorylation correlated with drops in growth, viability, clonogenic survival, and cap-dependent translation. Taken together, these data suggest EGFR and mTOR inhibitors abrogate growth, viability, and survival via disruption of eIF4B phosphorylation leading to decreased translation in TNBC cell lines. Further, including an mTOR inhibitor along with an EGFR inhibitor in TNBC with increased EGFR expression should be further explored. Additionally, translational regulation may play an important role in regulating EGFR and mTOR inhibitor synergy and warrant further investigation.

  11. Dietary chlorophyllin abrogates TGFβ signaling to modulate the hallmark capabilities of cancer in an animal model of forestomach carcinogenesis.

    Science.gov (United States)

    Thiyagarajan, Paranthaman; Kavitha, Krishnamurthy; Thautam, Avaneesh; Dixit, Madhulika; Nagini, Siddavaram

    2014-07-01

    Transforming growth factor (TGF) β signaling pathway plays a central role in the regulation of a wide range of cellular processes involved in the acquisition of the malignant phenotype. The objective of the present study was to examine the effect of chlorophyllin, a semisynthetic derivative of chlorophyll on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)--induced rat forestomach carcinogenesis based on the modulation of TGFβ signaling and the downstream target genes associated with cell proliferation, apoptosis evasion, angiogenesis, invasion, and metastasis. We determined the effect of dietary chlorophyllin on TGFβ signaling and the downstream events-cell proliferation, apoptosis evasion, angiogenesis, invasion, and metastasis by semiquantitative and quantitative reverse transcription (RT)-PCR, Western blot, and immunohistochemical analyses. We further validated the inhibition of TGFβ signaling by chlorophyllin by performing molecular docking studies. We found that dietary supplementation of chlorophyllin at 4-mg/kg bw inhibits the development of MNNG-induced forestomach carcinomas by downregulating the expression of TGFβ RI, TGFβ RII, and Smad 2 and 4 and upregulating Smad 7, thereby abrogating canonical TGFβ signaling. Docking interactions also confirmed the inhibition of TGFβ signaling by chlorophyllin via inactivating TGFβ RI. Furthermore, attenuation of TGFβ signaling by chlorophyllin also blocked cell proliferation, angiogenesis, invasion, and metastasis, and induced mitochondria-mediated cell death. Dietary chlorophyllin that simultaneously abrogates TGFβ signaling pathway and the key hallmark events of cancer appear to be an ideal candidate for cancer chemoprevention.

  12. Radiosensitization of metformin in pancreatic cancer cells via abrogating the G2 checkpoint and inhibiting DNA damage repair.

    Science.gov (United States)

    Wang, Zheng; Lai, Song-Tao; Ma, Ning-Yi; Deng, Yun; Liu, Yong; Wei, Dong-Ping; Zhao, Jian-Dong; Jiang, Guo-Liang

    2015-12-01

    Recent evidences have demonstrated the potential of metformin as a novel agent for cancer prevention and treatment. Here, we investigated its ability of radiosensitization and the underlying mechanisms in human pancreatic cancer cells. In this study, we found that metformin at 5 mM concentration enhanced the radiosensitivity of MIA PaCa-2 and PANC-1 cells, with sensitization enhancement ratios of 1.39 and 1.27, respectively. Mechanistically, metformin caused abrogation of the G2 checkpoint and increase of mitotic catastrophe, associated with suppression of Wee1 kinase and in turn CDK1 Tyr15 phosphorylation. Furthermore, metformin inhibited both expression and irradiation-induced foci formation of Rad51, a key player in homologous recombination repair, ultimately leading to persistent DNA damage, as reflected by γ-H2AX and 53BP1 signaling. Finally, metformin-mediated AMPK/mTOR/p70S6K was identified as a possible upstream pathway controlling translational regulation of Wee1 and Rad51. Our data suggest that metformin radiosensitizes pancreatic cancer cells in vitro via abrogation of the G2 checkpoint and inhibition of DNA damage repair. However, the in vivo study is needed to further confirm the findings from the in vitro study.

  13. Multivalent chelators for spatially and temporally controlled protein functionalization.

    Science.gov (United States)

    You, Changjiang; Piehler, Jacob

    2014-05-01

    Site-specific protein modification-e.g. for immobilization or labelling-is a key prerequisite for numerous bioanalytical applications. Although modification by use of short peptide tags is particularly attractive, efficient and bio-orthogonal systems are still lacking. Here, we review the application of multivalent chelators (MCH) for high-affinity yet reversible recognition of oligohistidine (His)-tagged proteins. MCH are based on multiple nitrilotriacetic acid (NTA) moieties grafted on to molecular scaffolds suitable for conjugation to surfaces, probes or other biomolecules. Reversible interaction with the His-tag is mediated via transition metal ions chelated by the NTA moieties. The small size and biochemical compatibility of these recognition units and the possibility of rapid dissociation of the interaction with His-tagged proteins despite sub-nanomolar binding affinity, enable distinct and versatile handling and modification of recombinant proteins. In this review, we briefly introduce the key principles and features of MCH-His-tag interactions and recapitulate the broad spectrum of bioanalytical applications with a focus on quantitative protein interaction analysis on micro or nano-patterned solid surfaces and specific protein labelling in living cells.

  14. Selective separation of indium by iminodiacetic acid chelating resin

    Directory of Open Access Journals (Sweden)

    M. C. B. Fortes

    2007-06-01

    Full Text Available Indium can be recovered by treating residues, flue dusts, slags, and metallic intermediates in zinc smelting. This paper investigates the adsorption characteristics of indium and iron on an iminodiacetic acid chelating resin, Amberlite®IRC748 (Rohm and Haas Co.-USA. High concentrations of iron are always present in the aqueous feed solution of indium recovery. In addition, the chemical behaviour of iron in adsorptive systems is similar to that of indium. The metal concentrations in the aqueous solution were based on typical indium sulfate leach liquor obtained from zinc hydrometallurgical processing in a Brazilian plant. The ionic adsorption experiments were carried out by the continuous column method. Amberlite®IRC748 resin had a high affinity for indium under acidic conditions. Indium ions adsorbed onto the polymeric resin were eluted with a 0.5mol/dm³ sulphuric acid solution passed through the resin bed in the column. 99.5% pure indium sulfate aqueous solution was obtained using the iminodiacetic acid chelating resin Amberlite®IRC748.

  15. Magnetic memory effect in chelated zero valent iron nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, N., E-mail: nilotpal@vit.ac.in [School of Advanced Sciences, VIT University, Vellore 632014, Tamilnadu (India); Mandal, B.K.; Mohan Kumar, K. [School of Advanced Sciences, VIT University, Vellore 632014, Tamilnadu (India)

    2012-11-15

    We report the study of nonequilibrium magnetic behavior of air stable zero valent iron nanoparticles synthesized in presence of N-cetyl-N,N,N-trimethyl ammonium bromide chelating agent. X-ray photoelectron spectroscopy study has suggested the presence of iron oxides on nZVI surfaces. Zero-field-cooled and field-cooled magnetization measurements have been carried out at 20-300 K and 100 Oe. For field-cooled measurements with 1 h stops at 200, 100 and 50 K when compared with the warming cycle, we found the signature of magnetic memory effect. A study of magnetic relaxation at the same temperatures shows the existence of two relaxation times. - Highlights: Black-Right-Pointing-Pointer Zero valent iron nanoparticles are synthesized with CTAB chelating agent. Black-Right-Pointing-Pointer X-ray photoelectron spectroscopy study has shown the presence of iron oxide. Black-Right-Pointing-Pointer Magnetization measurement has displayed signature of magnetic memory. Black-Right-Pointing-Pointer Magnetization measurement with time suggested presence of 2 relaxation times.

  16. Functional characterization of the chloroplast ferric chelate oxidoreductase enzyme.

    Science.gov (United States)

    Solti, Adám; Müller, Brigitta; Czech, Viktória; Sárvári, Éva; Fodor, Ferenc

    2014-05-01

    Iron (Fe) has an essential role in the biosynthesis of chlorophylls and redox cofactors, and thus chloroplast iron uptake is a process of special importance. The chloroplast ferric chelate oxidoreductase (cFRO) has a crucial role in this process but it is poorly characterized. To study the localization and mechanism of action of cFRO, sugar beet (Beta vulgaris cv Orbis) chloroplast envelope fractions were isolated by gradient ultracentrifugation, and their purity was tested by western blotting against different marker proteins. The ferric chelate reductase (FCR) activity of envelope fractions was studied in the presence of NAD(P)H (reductants) and FAD coenzymes. Reduction of Fe(III)-ethylenediaminetetraacetic acid was monitored spectrophotometrically by the Fe(II)-bathophenanthroline disulfonate complex formation. FCR activity, that is production of free Fe(II) for Fe uptake, showed biphasic saturation kinetics, and was clearly associated only to chloroplast inner envelope (cIE) vesicles. The reaction rate was > 2.5 times higher with NADPH than with NADH, which indicates the natural coenzyme preference of cFRO activity and its dependence on photosynthesis. FCR activity of cIE vesicles isolated from Fe-deficient plants also showed clear biphasic kinetics, where the KM of the low affinity component was elevated, and thus this component was down-regulated.

  17. Selective separation of indium by iminodiacetic acid chelating resin

    Energy Technology Data Exchange (ETDEWEB)

    Fortes, M.C.B.; Benedetto, J.S. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Martins, A.H. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Engenharia Metalurgica e de Materiais]. E-mail: ahmartin@demet.ufmg.br

    2007-04-15

    - Indium can be recovered by treating residues, flue dusts, slags, and metallic intermediates in zinc smelting. This paper investigates the adsorption characteristics of indium and iron on an iminodiacetic acid chelating resin, Amberlite{sup R} IRC748 (Rohm and Haas Co.-USA). High concentrations of iron are always present in the aqueous feed solution of indium recovery. In addition, the chemical behaviour of iron in adsorptive systems is similar to that of indium. The metal concentrations in the aqueous solution were based on typical indium sulfate leach liquor obtained from zinc hydrometallurgical processing in a Brazilian plant. The ionic adsorption experiments were carried out by the continuous column method. Amberlite{sup R} IRC748 resin had a high affinity for indium under acidic conditions. Indium ions adsorbed onto the polymeric resin were eluted with a 0.5 mol/dm{sup 3} sulphuric acid solution passed through the resin bed in the column. 99.5% pure indium sulfate aqueous solution was obtained using the iminodiacetic acid chelating resin Amberlite{sup R} IRC748. (author)

  18. Investigation of a potential macromolecular MRI contrast agent prepared from PPI (G = 2, polypropyleneimine, generation 2) dendrimer bifunctional chelates

    Science.gov (United States)

    Wang, Jianxin Steven

    The long-term objective is to develop magnetic resonance (MR) contrast agents that actively and passively target tumors for diagnosis and therapy. Many diagnostic imaging techniques for cancer lack specificity. A dendrimer based magnetic resonance imaging contrast agent has been developed with large proton relaxation enhancements and high molecular relaxivities. A new type of linear dendrimer based MRI contrast agent that is built from the polypropyleneimine and polyamidoamine dendrimers in which free amines have been conjugated to the chelate DTPA, which further formed the complex with Gadolinium (Gd) was studied. The specific research goals were to test the hypothesis that a linear chelate with macromolecular agents can be used in vitro and in vivo. This work successfully examined the adequacy and viability of the application for this agent in vitro and in vivo. A small animal whole body counter was designed and constructed to allow us to monitor biodistribution and kinetic mechanisms using a radioisotope labeled complex. The procedures of metal labeling, separation and purification have been established from this work. A biodistribution study has been performed using radioisotope induced organ/tissue counting and gamma camera imaging. The ratio of percentage of injected dose per gram organ/tissue for kidney and liver is 3.71 from whole body counter and 3.77 from the gamma camera. The results suggested that retention of Gd (III) is too high and a more kinetically stable chelate should be developed. The pharmacokinetic was evaluated in the whole animal model with the whole body clearance, and a kinetics model was developed. The pharmacokinetic results showed a bi-exponential decay in the animal model with two component excretion constants 1.43e(-5) and 0.0038511, which give half-lives of 3 hours and 33.6 days, respectively. Magnetic resonance imaging of this complex resulted in a 52% contrast enhancement in the rat kidney following the agents' administration in

  19. Histone deacetylase inhibitors promote glioma cell death by G2 checkpoint abrogation leading to mitotic catastrophe.

    Science.gov (United States)

    Cornago, M; Garcia-Alberich, C; Blasco-Angulo, N; Vall-Llaura, N; Nager, M; Herreros, J; Comella, J X; Sanchis, D; Llovera, M

    2014-10-02

    Glioblastoma multiforme is resistant to conventional anti-tumoral treatments due to its infiltrative nature and capability of relapse; therefore, research efforts focus on characterizing gliomagenesis and identifying molecular targets useful on therapy. New therapeutic strategies are being tested in patients, such as Histone deacetylase inhibitors (HDACi) either alone or in combination with other therapies. Here two HDACi included in clinical trials have been tested, suberanilohydroxamic acid (SAHA) and valproic acid (VPA), to characterize their effects on glioma cell growth in vitro and to determine the molecular changes that promote cancer cell death. We found that both HDACi reduce glioma cell viability, proliferation and clonogenicity. They have multiple effects, such as inducing the production of reactive oxygen species (ROS) and activating the mitochondrial apoptotic pathway, nevertheless cell death is not prevented by the pan-caspase inhibitor Q-VD-OPh. Importantly, we found that HDACi alter cell cycle progression by decreasing the expression of G2 checkpoint kinases Wee1 and checkpoint kinase 1 (Chk1). In addition, HDACi reduce the expression of proteins involved in DNA repair (Rad51), mitotic spindle formation (TPX2) and chromosome segregation (Survivin) in glioma cells and in human glioblastoma multiforme primary cultures. Therefore, HDACi treatment causes glioma cell entry into mitosis before DNA damage could be repaired and to the formation of an aberrant mitotic spindle that results in glioma cell death through mitotic catastrophe-induced apoptosis.

  20. Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: linker effects on the relaxivity.

    Science.gov (United States)

    Ferreira, Miguel F; Gonçalves, Janaina; Mousavi, Bibimaryam; Prata, Maria I M; Rodrigues, Sérgio P J; Calle, Daniel; López-Larrubia, Pilar; Cerdan, Sebastian; Rodrigues, Tiago B; Ferreira, Paula M; Helm, Lothar; Martins, José A; Geraldes, Carlos F G C

    2015-03-07

    The relaxivity displayed by Gd(3+) chelates immobilized onto gold nanoparticles is the result of the complex interplay between the nanoparticle size, the water exchange rate and the chelate structure. In this work we study the effect of the length of ω-thioalkyl linkers, anchoring fast water exchanging Gd(3+) chelates onto gold nanoparticles, on the relaxivity of the immobilized chelates. Gold nanoparticles functionalized with Gd(3+) chelates of mercaptoundecanoyl and lipoyl amide conjugates of the DO3A-N-(α-amino)propionate chelator were prepared and studied as potential CA for MRI. High relaxivities per chelate, of the order of magnitude 28-38 mM(-1) s(-1) (30 MHz, 25 °C), were attained thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. Fast local rotational motions of the immobilized chelates around connecting linkers (internal flexibility) still limit the attainable relaxivity. The degree of internal flexibility of the immobilized chelates seems not to be correlated with the length of the connecting linkers. Biodistribution and MRI studies in mice suggest that the in vivo behavior of the gold nanoparticles was determined mainly by size. Small nanoparticles (HD = 3.9 nm) undergo fast renal clearance and avoidance of the RES organs while larger nanoparticles (HD = 4.8 nm) undergo predominantly hepatobiliary excretion. High relaxivities, allied to chelate and nanoparticle stability and fast renal clearance in vivo suggest that functionalized gold nanoparticles hold great potential for further investigation as MRI contrast agents. This study contributes to a better understanding of the effect of linker length on the relaxivity of gold nanoparticles functionalized with Gd(3+) complexes. It is a relevant contribution towards "design rules" for nanostructures functionalized with Gd(3+) chelates as Contrast Agents for MRI and multimodal imaging.

  1. Uranyl binary and ternary chelates of tenoxicam. Synthesis, spectroscopic and thermal characterization of ternary chelates of tenoxicam and alanine with transition metals

    Science.gov (United States)

    El-Gamel, Nadia E. A.

    2007-11-01

    Ternary Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and UO 2(II) chelates with tenoxicam (Ten) drug (H 2L 1) and dl-alanine (Ala) (HL 2) and also the binary UO 2(II) chelate with Ten were studied. The structures of the chelates were elucidated using elemental, molar conductance, magnetic moment, IR, diffused reflectance and thermal analyses. UO 2(II) binary chelate was isolated in 1:2 ratio with the formula [UO 2(H 2L) 2](NO 3) 2. The ternary chelates were isolated in 1:1:1 (M:H 2L 1:L 2) ratios and have the general formulae [M(H 2L 1)(L 2)(Cl) n(H 2O) m]· yH 2O (M = Fe(III) ( n = 2, m = 0, y = 2), Co(II) ( n = 1, m = 1, y = 2) and Ni(II) ( n = 1, m = 1, y = 3)); [M(H 2L 1)(L 2)](X) z· yH 2O (M = Cu(II) (X = AcO, z = 1, y = 0), Zn(II) (X = AcO, z = 1, y = 3) and UO 2(II) (X = NO 3, z = 1, y = 2)). IR spectra reveal that Ten behaves as a neutral bidentate ligand coordinated to the metal ions via the pyridine-N and carbonyl-O groups, while Ala behaves as a uninegatively bidentate ligand coordinated to the metal ions via the deprotonated carboxylate-O and amino-N. The magnetic and reflectance spectral data confirm that all the chelates have octahedral geometry except Cu(II) and Zn(II) chelates have tetrahedral structures. Thermal decomposition of the chelates was discussed in relation to structure and different thermodynamic parameters of the decomposition stages were evaluated.

  2. THE SYNTHESIS OF URUSHIOL TITANIUM CHELATE POLYMERS AND THEIR STRUCTURAL CHARACTERISTICS

    Institute of Scientific and Technical Information of China (English)

    HU Binghuan; CHEN Wending; LIN Jinhuo

    1993-01-01

    The synthetic method and structural characteristics of urushiol-titanium chelates (UT) and urushiol-titanium chelate polymer for anticorrosive coatings have been studied.Two kinds of coating films made from UT polymer show excellent physico-mechanical properties and possess good chemical resistance to strong acids and alkalis, many kinds of salt solutions and organic solvents,stable at high temperature.

  3. Enhancement of 5-aminolevulinic acid-based fluorescence detection of side population-defined glioma stem cells by iron chelation

    Science.gov (United States)

    Wang, Wenqian; Tabu, Kouichi; Hagiya, Yuichiro; Sugiyama, Yuta; Kokubu, Yasuhiro; Murota, Yoshitaka; Ogura, Shun-ichiro; Taga, Tetsuya

    2017-01-01

    Cancer stem cells (CSCs) are dominantly responsible for tumor progression and chemo/radio-resistance, resulting in tumor recurrence. 5-aminolevulinic acid (ALA) is metabolized to fluorescent protoporphyrin IX (PpIX) specifically in tumor cells, and therefore clinically used as a reagent for photodynamic diagnosis (PDD) and therapy (PDT) of cancers including gliomas. However, it remains to be clarified whether this method could be effective for CSC detection. Here, using flow cytometry-based analysis, we show that side population (SP)-defined C6 glioma CSCs (GSCs) displayed much less 5-ALA-derived PpIX fluorescence than non-GSCs. Among the C6 GSCs, cells with ultralow PpIX fluorescence exhibited dramatically higher tumorigenicity when transplanted into the immune-deficient mouse brain. We further demonstrated that the low PpIX accumulation in the C6 GSCs was enhanced by deferoxamine (DFO)-mediated iron chelation, not by reserpine-mediated inhibition of PpIX-effluxing ABCG2. Finally, we found that the expression level of the gene for heme oxygenase-1 (HO-1), a heme degradation enzyme, was high in C6 GSCs, which was further up-regulated when treated with 5-ALA. Our results provide important new insights into 5-ALA-based PDD of gliomas, particularly photodetection of SP-defined GSCs by iron chelation based on their ALA-PpIX-Heme metabolism. PMID:28169355

  4. Combined Iron Chelator and Antioxidant Exerted Greater Efficacy on Cardioprotection Than Monotherapy in Iron-Overloaded Rats.

    Directory of Open Access Journals (Sweden)

    Suwakon Wongjaikam

    Full Text Available Iron chelators are used to treat iron overload cardiomyopathy patients. However, a direct comparison of the benefits of three common iron chelators (deferoxamine (DFO, deferiprone (DFP and deferasirox (DFX or an antioxidant (N-acetyl cysteine (NAC with a combined DFP and NAC treatments on left ventricular (LV function with iron overload has not been investigated.Male Wistar rats were fed with either a normal diet or a high iron diet (HFe group for 4 months. After 2 months, the HFe-fed rats were divided into 6 groups to receive either: a vehicle, DFO (25 mg/kg/day, DFP (75 mg/kg/day, DFX (20 mg/kg/day, NAC (100 mg/kg/day or the combined DFP and NAC for 2 months. Our results demonstrated that HFe rats had increased plasma non-transferrin bound iron (NTBI, malondialdehyde (MDA, cardiac iron and MDA levels and cardiac mitochondrial dysfunction, leading to LV dysfunction. Although DFO, DFP, DFX or NAC improved these parameters, leading to improved LV function, the combined DFP and NAC therapy caused greater improvement, leading to more extensively improved LV function.The combined DFP and NAC treatment had greater efficacy than monotherapy in cardioprotection through the reduction of cardiac iron deposition and improved cardiac mitochondrial function in iron-overloaded rats.

  5. A NOVEL METAL CHELATE AFFINITY ADSORBENT FOR PROTEIN UPTAKE

    Institute of Scientific and Technical Information of China (English)

    WANGYongjian; BAIShu; 等

    2001-01-01

    In this article,a spherical chitosan gel crosslinked by epichlorohydrin was prepared.It was then loaded with copper ions to produce a metal chelate affinity adsorbent for protein.The uptake of bovine serum albumin(BSA)by the affinity adsorbent was investigated.and the adsorption capacity for BSA as high as 40mg/g-wet beads was observed.The adsorption equilibrium data was well correlated by the Langmuir equation.The adsorption was considerably affected by pH.In additio.The amount of BSA adsorbed onto the beads decreased with the increasing of aqueous phase ionic strength,so adsorbed BAS can be desorbed by adjusting pH orionic strength of the solution.

  6. Synthesis and characterization of dihexyldithiocarbamate as a chelating agent in extraction of gold(III)

    Science.gov (United States)

    Fatimah, Soja Siti; Bahti, Husein H.; Hastiawan, Iwan; Permanasari, Anna

    2016-02-01

    The use of dialkyldithiocarbamates as chelating agents of transition metals have been developing for decades. Many chelating agents have been synthesized and used in the extraction of the metals. Studies on particular aspects of extraction of the metals, such as the effect of increasing hydrophobicity of chelating agents on the effectiveness of the extraction, have been done. However, despite the many studies on the synthesis and applications of this type of chelating agents, interests in the aspect of molecular structure of the synthesized ligands and of their complexes, have been limited. This study aimed at synthesizing and characterizing dihexylthiocarbamate, and using the ligand for the extraction of gold III). Characterization of the ligand and of its metal complex were done by using elemental analysis, DTG, and spectroscopic methods to include NMR, (1H, and 13C), FTIR, and MS-ESI. Data on the synthesis, characterization, and the application of the ligand as a chelating agent are presented.

  7. Synthesis and characterization of dihexyldithiocarbamate as a chelating agent in extraction of gold(III)

    Energy Technology Data Exchange (ETDEWEB)

    Fatimah, Soja Siti, E-mail: soja-sf@upi.edu [Departemen Pendidikan Kimia, Universitas Pendidikan Indonesia, Jl. Dr. Setiabudhi No. 229, Bandung 40154 (Indonesia); Department of Chemistry, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Jl. Raya Bandung-Sumedang, Km. 21, Jatinangor (Indonesia); Bahti, Husein H.; Hastiawan, Iwan [Department of Chemistry, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Jl. Raya Bandung-Sumedang, Km. 21, Jatinangor (Indonesia); Permanasari, Anna [Departemen Pendidikan Kimia, Universitas Pendidikan Indonesia, Jl. Dr. Setiabudhi No. 229, Bandung 40154 (Indonesia)

    2016-02-08

    The use of dialkyldithiocarbamates as chelating agents of transition metals have been developing for decades. Many chelating agents have been synthesized and used in the extraction of the metals. Studies on particular aspects of extraction of the metals, such as the effect of increasing hydrophobicity of chelating agents on the effectiveness of the extraction, have been done. However, despite the many studies on the synthesis and applications of this type of chelating agents, interests in the aspect of molecular structure of the synthesized ligands and of their complexes, have been limited. This study aimed at synthesizing and characterizing dihexylthiocarbamate, and using the ligand for the extraction of gold III). Characterization of the ligand and of its metal complex were done by using elemental analysis, DTG, and spectroscopic methods to include NMR, ({sup 1}H, and {sup 13}C), FTIR, and MS-ESI. Data on the synthesis, characterization, and the application of the ligand as a chelating agent are presented.

  8. Design and synthesis of zinc-selective chelators for extracellular applications.

    Science.gov (United States)

    Kawabata, Eri; Kikuchi, Kazuya; Urano, Yasuteru; Kojima, Hirotatsu; Odani, Akira; Nagano, Tetsuo

    2005-01-26

    Zinc (Zn2+) is found in every cell in human bodies. A few millimolar of free Zn2+ exists in the vesicles of presynaptic neurons in the mammalian brain and is released by synaptic activity or depolarization, modulating the function of certain ion channels and receptors. Although various chemical tools for measuring Zn2+ in biological samples, such as fluorescent probes for Zn2+, have been developed, Zn2+-selective chelators have room to be improved. Research on Zn2+ signals in the brain has traditionally employed several chelators, which have several shortcomings for biological applications. Here we report the design, synthesis, and properties of new membrane-impermeable chelators selective for Zn2+ and describe biological applications in hippocampal slices. As a result, our newly designed chelator revealed the first biological implication that presynaptic Zn2+ can be released in the CA1 region. This confirms the utility of these new chelatotrs as extracellular Zn2+ chelators for biological applications.

  9. Effects of Zinc Chelators on Aflatoxin Production in Aspergillus parasiticus

    Science.gov (United States)

    Wee, Josephine; Day, Devin M.; Linz, John E.

    2016-01-01

    Zinc concentrations strongly influence aflatoxin accumulation in laboratory media and in food and feed crops. The presence of zinc stimulates aflatoxin production, and the absence of zinc impedes toxin production. Initial studies that suggested a link between zinc and aflatoxin biosynthesis were presented in the 1970s. In the present study, we utilized two zinc chelators, N,N,N′,N′-tetrakis (2-pyridylmethyl) ethane-1,2-diamine (TPEN) and 2,3-dimercapto-1-propanesulfonic acid (DMPS) to explore the effect of zinc limitation on aflatoxin synthesis in Aspergillus parasiticus. TPEN but not DMPS decreased aflatoxin biosynthesis up to six-fold depending on whether A. parasiticus was grown on rich or minimal medium. Although we observed significant inhibition of aflatoxin production by TPEN, no detectable changes were observed in expression levels of the aflatoxin pathway gene ver-1 and the zinc binuclear cluster transcription factor, AflR. Treatment of growing A. parasiticus solid culture with a fluorescent zinc probe demonstrated an increase in intracellular zinc levels assessed by increases in fluorescent intensity of cultures treated with TPEN compared to controls. These data suggest that TPEN binds to cytoplasmic zinc therefore limiting fungal access to zinc. To investigate the efficacy of TPEN on food and feed crops, we found that TPEN effectively decreases aflatoxin accumulation on peanut medium but not in a sunflower seeds-derived medium. From an application perspective, these data provide the basis for biological differences that exist in the efficacy of different zinc chelators in various food and feed crops frequently contaminated by aflatoxin. PMID:27271668

  10. Beryllium Chelation by Dicarboxylic Acids in Aqueous Solution.

    Science.gov (United States)

    Schmidt, Michael; Bauer, Andreas; Schmidbaur, Hubert

    1997-05-07

    Maleic and phthalic acids are found to react with Be(OH)(2), generated in situ from BeSO(4)(aq) and Ba(OH)(2)(aq), in aqueous solution at pH 3.0 or 4.4, respectively (25 degrees C), to give solutions containing the complexes (H(2)O)(2)Be[(OOCCH)(2)] (1) and (H(2)O)(2)Be[(OOC)(2)C(6)H(4)] (3). The products can be isolated in high yield and identified by microanalytical data. With 2 equiv of the dicarboxylic acids and the pH adjusted to 5.5 and 5.9, respectively, by addition of ammonia, the bis-chelate complexes [(NH(4))(+)](2){[Be[(OOCCH)(2)](2)}(2)(-) (2) and [(NH(4))(+)](2){Be[(OOC)(2)C(6)H(4)](2)}(2)(-) (4) are obtained, which can also be isolated. The compounds show distinct (9)Be, (1)H, and (13)C resonances in their NMR spectra in aqueous solutions. Layering of an aqueous solution of compound 4 with acetone at ambient temperature leads to the precipitation of single crystals suitable for an X-ray structure determination. This salt (5) was found to contain the bis-chelated dianion {Be[(OOC)(2)C(6)H(4)](2)}(2)(-) with the beryllium atom in the spiro center of two seven-membered rings and an overall geometry approaching closely C(2) symmetry. These anions are associated with two crystallographically independent but structurally similar counterions [MeC(O)CH(2)CMe(2)NH(3)](+), which are the product of a condensation reaction of the ammonium cation with the acetone solvent. In the crystal the ammonium hydrogen atoms of the cations form N-H.O hydrogen bonds with the oxo functions of the dianion.

  11. Mechanistic basis for overcoming platinum resistance using copper chelating agents.

    Science.gov (United States)

    Liang, Zheng D; Long, Yan; Tsai, Wen-Bin; Fu, Siqing; Kurzrock, Razelle; Gagea-Iurascu, Mihai; Zhang, Fan; Chen, Helen H W; Hennessy, Bryan T; Mills, Gordon B; Savaraj, Niramol; Kuo, Macus Tien

    2012-11-01

    Platinum-based antitumor agents are widely used in cancer chemotherapy. Drug resistance is a major obstacle to the successful use of these agents because once drug resistance develops, other effective treatment options are limited. Recently, we conducted a clinical trial using a copper-lowering agent to overcome platinum drug resistance in ovarian cancer patients and the preliminary results are encouraging. In supporting this clinical study, using three pairs of cisplatin (cDDP)-resistant cell lines and two ovarian cancer cell lines derived from patients who had failed in platinum-based chemotherapy, we showed that cDDP resistance associated with reduced expression of the high-affinity copper transporter (hCtr1), which is also a cDDP transporter, can be preferentially resensitized by copper-lowering agents because of enhanced hCtr1 expression, as compared with their drug-sensitive counterparts. Such a preferential induction of hCtr1 expression in cDDP-resistant variants by copper chelation can be explained by the mammalian copper homeostasis regulatory mechanism. Enhanced cell-killing efficacy by a copper-lowering agent was also observed in animal xenografts bearing cDDP-resistant cells. Finally, by analyzing a public gene expression dataset, we found that ovarian cancer patients with elevated levels of hCtr1 in their tumors, but not ATP7A and ATP7B, had more favorable outcomes after platinum drug treatment than those expressing low hCtr1 levels. This study reveals the mechanistic basis for using copper chelation to overcome cDDP resistance in clinical investigations.

  12. Synthesis, Characterization, and in Vitro Evaluation of a New TSPO-Selective Bifunctional Chelate Ligand.

    Science.gov (United States)

    Denora, Nunzio; Margiotta, Nicola; Laquintana, Valentino; Lopedota, Angela; Cutrignelli, Annalisa; Losacco, Maurizio; Franco, Massimo; Natile, Giovanni

    2014-06-12

    The 18-kDa translocator protein (TSPO) is overexpressed in many types of cancers and is also abundant in activated microglial cells occurring in inflammatory neurodegenerative diseases. Thus, TSPO has become an extremely attractive subcellular target not only for imaging disease states overexpressing this protein, but also for a selective mitochondrial drug delivery. In this work we report the synthesis, the characterization, and the in vitro evaluation of a new TSPO-selective ligand, 2-(8-(2-(bis(pyridin-2-yl)methyl)amino)acetamido)-2-(4-chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-N,N-dipropylacetamide (CB256), which fulfils the requirements for a bifunctional chelate approach. The goal was to provide a new TSPO ligand that could be used further to prepare coordination complexes of a metallo drug to be used in diagnosis and therapy. However, the ligand itself proved to be a potent tumor cell growth inhibitor and DNA double-strand breaker.

  13. Biomolecule conjugation strategy using novel water-soluble phosphine-based chelating agents

    Science.gov (United States)

    Katti, Kattesh V.; Gali, Hariprasad; Volkert, Wynn A.

    2004-08-24

    This invention describes a novel strategy to produce phosphine-functionalized biomolecules (e.g. peptides or proteins) for potential use in the design and development of site-specific radiopharmaceuticals for diagnosis or therapy of specific cancers. Hydrophilic alkyl phosphines, in general, tend to be oxidatively unstable. Therefore, incorporation of such phosphine functionalities on peptide (and other biomolecule) backbones, without oxidizing the P.sup.III centers, is difficult. In this context this discovery reports on a new technology by which phosphines, in the form of bifunctional chelating agents, can be directly incorporated on biomolecular backbones using manual synthetic or solid phase peptide synthesis methodologies. The superior ligating abilities of phosphine ligands, with various diagnostically (e.g. TC-99m) or therapeutically (e.g. Re186/188, Rh-105, Au-199) useful radiometals, coupled with the findings that the resulting complexes demonstrate high in vivo stability makes this approach useful in the development of radiolabeled biomolecules for applications in the design of tumor-specific radiopharmaceuticals.

  14. Curcumin Inhibits Growth of Saccharomyces cerevisiae through Iron Chelation ▿ ††

    Science.gov (United States)

    Minear, Steven; O'Donnell, Allyson F.; Ballew, Anna; Giaever, Guri; Nislow, Corey; Stearns, Tim; Cyert, Martha S.

    2011-01-01

    Curcumin, a polyphenol derived from turmeric, is an ancient therapeutic used in India for centuries to treat a wide array of ailments. Interest in curcumin has increased recently, with ongoing clinical trials exploring curcumin as an anticancer therapy and as a protectant against neurodegenerative diseases. In vitro, curcumin chelates metal ions. However, although diverse physiological effects have been documented for this compound, curcumin's mechanism of action on mammalian cells remains unclear. This study uses yeast as a model eukaryotic system to dissect the biological activity of curcumin. We found that yeast mutants lacking genes required for iron and copper homeostasis are hypersensitive to curcumin and that iron supplementation rescues this sensitivity. Curcumin penetrates yeast cells, concentrates in the endoplasmic reticulum (ER) membranes, and reduces the intracellular iron pool. Curcumin-treated, iron-starved cultures are enriched in unbudded cells, suggesting that the G1 phase of the cell cycle is lengthened. A delay in cell cycle progression could, in part, explain the antitumorigenic properties associated with curcumin. We also demonstrate that curcumin causes a growth lag in cultured human cells that is remediated by the addition of exogenous iron. These findings suggest that curcumin-induced iron starvation is conserved from yeast to humans and underlies curcumin's medicinal properties. PMID:21908599

  15. Intestinal microbiota shifts towards elevated commensal Escherichia coli loads abrogate colonization resistance against Campylobacter jejuni in mice.

    Directory of Open Access Journals (Sweden)

    Lea-Maxie Haag

    Full Text Available BACKGROUND: The zoonotic pathogen Campylobacter jejuni is a leading cause of bacterial foodborne enterocolitis in humans worldwide. The understanding of immunopathology underlying human campylobacteriosis is hampered by the fact that mice display strong colonization resistance against the pathogen due to their host specific gut microbiota composition. METHODOLOGY/PRINCIPAL FINDINGS: Since the microbiota composition changes significantly during intestinal inflammation we dissected factors contributing to colonization resistance against C. jejuni in murine ileitis, colitis and in infant mice. In contrast to healthy animals C. jejuni could stably colonize mice suffering from intestinal inflammation. Strikingly, in mice with Toxoplasma gondii-induced acute ileitis, C. jejuni disseminated to mesenteric lymphnodes, spleen, liver, kidney, and blood. In infant mice C. jejuni infection induced enterocolitis. Mice suffering from intestinal inflammation and C. jejuni susceptible infant mice displayed characteristical microbiota shifts dominated by increased numbers of commensal Escherichia coli. To further dissect the pivotal role of those distinct microbiota shifts in abrogating colonization resistance, we investigated C. jejuni infection in healthy adult mice in which the microbiota was artificially modified by feeding live commensal E. coli. Strikingly, in animals harboring supra-physiological intestinal E. coli loads, colonization resistance was significantly diminished and C. jejuni infection induced enterocolitis mimicking key features of human campylobacteriosis. CONCLUSION/SIGNIFICANCE: Murine colonization resistance against C. jejuni is abrogated by changes in the microbiota composition towards elevated E. coli loads during intestinal inflammation as well as in infant mice. Intestinal inflammation and microbiota shifts thus represent potential risk factors for C. jejuni infection. Corresponding interplays between C. jejuni and microbiota might

  16. Peroxisome proliferator-activated receptor-gamma abrogates Smad-dependent collagen stimulation by targeting the p300 transcriptional coactivator.

    Science.gov (United States)

    Ghosh, Asish K; Bhattacharyya, Swati; Wei, Jun; Kim, Suyeon; Barak, Yaacov; Mori, Yasuji; Varga, John

    2009-09-01

    Ligands of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) abrogate the stimulation of collagen gene transcription induced by transforming growth factor-beta (TGF-beta). Here, we delineate the mechanisms underlying this important novel physiological function for PPAR-gamma in connective tissue homeostasis. First, we demonstrated that antagonistic regulation of TGF-beta activity by PPAR-gamma ligands involves cellular PPAR-gamma, since 15-deoxy-Delta12,14-prostaglandin J(2) (15d-PGJ(2)) failed to block TGF-beta-induced responses in either primary cultures of PPAR-gamma-null murine embryonic fibroblasts, or in normal human skin fibroblasts with RNAi-mediated knockdown of PPAR-gamma. Next, we examined the molecular basis underlying the abrogation of TGF-beta signaling by PPAR-gamma in normal human fibroblasts in culture. The results demonstrated that Smad-dependent transcriptional responses were blocked by PPAR-gamma without preventing Smad2/3 activation. In contrast, the interaction between activated Smad2/3 and the transcriptional coactivator and histone acetyltransferase p300 induced by TGF-beta, and the accumulation of p300 on consensus Smad-binding DNA sequences and histone H4 hyperacetylation at the COL1A2 locus, were all prevented by PPAR-gamma. Wild-type p300, but not a mutant form of p300 lacking functional histone acetyltransferase, was able to restore TGF-beta-induced stimulation of COL1A2 in the presence of PPAR-gamma ligands. Collectively, these results indicate that PPAR-gamma blocked Smad-mediated transcriptional responses by preventing p300 recruitment and histone H4 hyperacetylation, resulting in the inhibition of TGF-beta-induced collagen gene expression. Pharmacological activation of PPAR-gamma thus may represent a novel therapeutic approach to target p300-dependent TGF-beta profibrotic responses such as stimulation of collagen gene expression.

  17. Artonin E and Structural Analogs from Artocarpus Species Abrogates Estrogen Receptor Signaling in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Imaobong Etti

    2016-06-01

    Full Text Available The increasing rate of mortality ensued from breast cancer has encouraged research into safer and efficient therapy. The human Estrogen receptor α has been implicated in the majority of reported breast cancer cases. Molecular docking employing Glide, Schrodinger suite 2015, was used to study the binding affinities of small molecules from the Artocarpus species after their drug-like properties were ascertained. The structure of the ligand-binding domain of human Estrogen receptor α was retrieved from Protein Data Bank while the structures of compounds were collected from PubChem database. The binding interactions of the studied compounds were reported as well as their glide scores. The best glide scored ligand, was Artonin E with a score of −12.72 Kcal when compared to other studied phytomolecules and it evoked growth inhibition of an estrogen receptor positive breast cancer cells in submicromolar concentration (3.8–6.9 µM in comparison to a reference standard Tamoxifen (18.9–24.1 µM within the tested time point (24–72 h. The studied ligands, which had good interactions with the target receptor, were also drug-like when compared with 95% of orally available drugs with the exception of Artoelastin, whose predicted physicochemical properties rendered it less drug-like. The in silico physicochemical properties, docking interactions and growth inhibition of the best glide scorer are indications of the anti-breast cancer relevance of the studied molecules.

  18. Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation

    DEFF Research Database (Denmark)

    Connolly, Brian M; Choi, Eun Young; Gårdsvoll, Henrik;

    2010-01-01

    the interaction between endogenous uPA and uPAR is selectively abrogated, whereas other functions of both the protease and its receptor are retained. Specifically, we introduced 4 amino acid substitutions into the growth factor domain (GFD) of uPA that abrogate uPAR binding while preserving the overall structure...... of the domain. Analysis of Plau(GFDhu/GFDhu) mice revealed an unanticipated role of the uPA-uPAR interaction in suppressing inflammation secondary to fibrin deposition. In contrast, leukocyte recruitment and tissue regeneration were unaffected by the loss of uPA binding to uPAR. This study identifies...

  19. MR imaging of lung ventilation with aerosolized Gadolinium-chelates; MR-Bildgebung der Lungenventilation mittels aerosolierter Gadolinium-Chelate

    Energy Technology Data Exchange (ETDEWEB)

    Haage, P.; Karaagac, S.; Spuentrup, E.; Guenther, R.W. [RWTH Aachen (Germany). Klinik fuer Radiologische Diagnostik; Adam, G. [Universitaetsklinikum Hamburg-Eppendorf (Germany). Abt. fuer Diagnostische und Interventionelle Radiologie

    2003-02-01

    Purpose: To evaluate the feasibility of magnetic resonance assessment of human lung ventilation with aerosolized Gd-chelates in healthy volunteers. Materials and Methods: Five healthy adults (mean age 37 years) were studied with a 1.5 T unit. The volunteers were instructed to inhale the aerosol through an airtight facial mask for 10 minutes. The aerosol was generated with a jet-type small particle nebulizer with attached heater. Ventilation imaging was performed using a respiration-gated dynamic T{sub 1}-weighted turbo spin echo sequence (T{sub R}=199 ms, T{sub E}=8.5 ms, 12 signal averages, slice thickness 10 mm). Pulmonary signal intensity changes were calculated before and after nebulization. Results: The investigation was successfully carried out in all volunteers. An acute or delayed allergic reaction to the aerosolized contrast medium was not observed. In 4 of 5 experiments (80%), a homogeneous signal intensity increase was readily visualized with an average signal increase of 35% after 10 minutes; in one experiment, the aerosol distribution was slightly heterogeneous. (orig.) [German] Ziel: Bestimmung der Durchfuehrbarkeit einer kernspintomographischen Darstellung der Lungenventilation mittels aerosolierter Gd-Chelate bei gesunden Probanden. Methoden: 5 Probanden (Durchschnittsalter 37 Jahre) wurden in einem 1,5T System untersucht. Die Probanden atmeten spontan aerosoliertes Gd-DTPA ueber eine Atemmaske fuer eine Dauer von 10 Minuten. Das Kontrastmittel-Aerosol wurde ueber einen leistungsfaehigen druckluftbetriebenen Vernebler generiert. Die Illustration der Ventilation erfolgte mit einer atemgegateten dynamischen T{sub 1}-gewichteten Turbo-Spin-Echosequenz. Zur Quantitifizerung der Lungenventilation wurden die Signalintensitaeten im Lungengewebe vor und nach Verneblung berechnet. Ergebnisse: Alle Untersuchungen wurden komplikationslos durchgefuehrt und beendet. Eine akute oder verzoegerte Kontrastmittelreaktion wurde nicht beobachtet. In 4 von 5

  20. Removal of Fe3+ and Zn2+ from plasma metalloproteins by iron chelating therapeutics depicted with SEC-ICP-AES.

    Science.gov (United States)

    Sooriyaarachchi, Melani; Gailer, Jürgen

    2010-08-28

    The iron chelation therapy drugs desferrioxamine B (DFO) and deferiprone (DFP) are used to treat iron overload patients, but not much is known about their adverse effects on other essential metals in vivo. After the addition of a clinically relevant dose of DFP or an equimolar dose of DFO to human plasma in vitro, the mixtures were analyzed by size exclusion chromatography (SEC) coupled to an inductively coupled plasma atomic emission spectrometer (ICP-AES). Simultaneous detection of the emission lines of copper, iron and zinc allowed the visualization of changes that these drugs exerted at the metalloprotein level. After the addition of DFP, a metalloprotein level. Thus, SEC-ICP-AES emerges as a useful analytical tool to visualize health-relevant bioinorganic chemistry-related reactions of medicinal drugs in blood plasma in vitro.

  1. Synthesis and characterization of tricarbonyl-Re/Tc(I chelate probes targeting the G protein-coupled estrogen receptor GPER/GPR30.

    Directory of Open Access Journals (Sweden)

    Ritwik Burai

    Full Text Available The discovery of the G protein-coupled estrogen receptor GPER (also GPR30 and the resulting development of selective chemical probes have revealed new aspects of estrogen receptor biology. The potential clinical relevance of this receptor has been suggested from numerous studies that have identified GPER expression in breast, endometrial, ovarian and other cancers. Thus GPER can be considered a candidate biomarker and target for non-invasive imaging and therapy. We have designed and synthesized a series of organometallic tricarbonyl-rhenium complexes conjugated to a GPER-selective small molecule derived from tetrahydro-3H-cyclopenta[c]quinoline. The activity and selectivity of these chelates in GPER-mediated signaling pathways were evaluated. These results demonstrate that GPER targeting characteristics depend strongly on the structure of the chelate and linkage. Ethanone conjugates functioned as agonists, a 1,2,3-triazole spacer yielded an antagonist, and derivatives with increased steric volume exhibited decreased activities. Promising GPER selectivity was observed, as none of the complexes interacted with the nuclear estrogen receptors. Radiolabeling with technetium-99m in aqueous media was efficient and gave radioligands with high radiochemical yields and purity. These chelates have favorable physicochemical properties, show excellent stability in biologically relevant media, exhibit receptor specificity and are promising candidates for continuing development as diagnostic imaging agents targeting GPER expression in cancer.

  2. LONGITUDINAL STUDY ON LIVER FUNCTIONS IN PATIENTS WITH THALASSEMIA MAJOR BEFORE AND AFTER DEFERASIROX (DFX) THERAPY

    OpenAIRE

    Ashraf Tawfik Soliman; Mohamed Yassin; Fawzia AlYafei; Lolwa Al-Naimi; Noora Almarri; Aml Sabt; Vincenzo De Sanctis

    2014-01-01

    With regular blood transfusion and iron chelation therapy, most patients with thalassemia major (BTM) now survive beyond the third decade of life . Liver disease is becoming an important cause of morbidity and mortality in these patients. Chronic hepatitis and/or severe iron overload are important causes of liver pathology. Iron chelation with desferrioxamine (Desferal)  reduces excessive body iron, but its efficacy is limited by poor compliance and dose related toxicity. The recent use of De...

  3. Longitudinal Study on Liver Functions in Patients with Thalassemia Major before and after Deferasirox (DFX) Therapy

    OpenAIRE

    SOLIMAN, Ashraf; Yassin, Mohamed; Al Yafei, Fawzia; Al-Naimi, Lolwa; Almarri, Noora; Sabt, Aml; De Sanctis, Vincenzo

    2014-01-01

    By performing regular blood transfusion and iron chelation therapy, most patients with beta thalassemia major (BTM) now survive beyond the third decade of life. Liver disease is becoming an important cause of morbidity and mortality in these patients. Chronic hepatitis and/or severe iron overload are both important causes of liver pathology. Iron chelation with desferrioxamine (DFO) reduces excessive body iron, but its efficacy is limited by poor compliance and dose related toxicity. The rece...

  4. Iron chelators can protect against oxidative stress through ferryl heme reduction.

    Science.gov (United States)

    Reeder, Brandon J; Hider, Robert C; Wilson, Michael T

    2008-02-01

    Iron chelators such as desferrioxamine have been shown to ameliorate oxidative damage in vivo. The mechanism of this therapeutic action under non-iron-overload conditions is, however, complex, as desferrioxamine has properties that can impact on oxidative damage independent of its capacity to act as an iron chelator. Desferrioxamine can act as a reducing agent to remove cytotoxic ferryl myoglobin and hemoglobin and has recently been shown to prevent the formation of a highly cytotoxic heme-to-protein cross-linked derivative of myoglobin. In this study we have examined the effects of a wide range of iron chelators, including the clinically used hydroxypyridinone CP20 (deferriprone), on the stability of ferryl myoglobin and on the formation of heme-to-protein cross-linking. We show that all hydroxypyridinones, as well as many other iron chelators, are efficient reducing agents of ferryl myoglobin. These compounds are also effective at preventing the formation of cytotoxic derivatives of myoglobin such as heme-to-protein cross-linking. These results show that the use of iron chelators in vivo may ameliorate oxidative damage under conditions of non-iron overload by at least two mechanisms. The antioxidant effects of chelators in vivo cannot, therefore, be attributed solely to iron chelation.

  5. Function of the iron-binding chelator produced by Coriolus versicolor in lignin biodegradation

    Institute of Scientific and Technical Information of China (English)

    WANG Lu; YAN WenChao; CHEN JiaChuan; HUANG Feng; GAO PeiJi

    2008-01-01

    An ultrafiltered low-molecular-weight preparation of chelating compounds was isolated from a wood-containing culture of the white-rot basidiomycete Coriolus versicolor. This preparation could chelate Fe3+ and reduce Fe3+ to Fe2+, demonstrating that the substance may serve as a ferric chelator,oxygen-reducing agent, and redox-cycling molecule, which would include functioning as the electron transport carrier in Fenton reaction. Lignin was treated with the iron-binding chelator and the changes in structure were investigated by 1H-NMR, 13C-NMR, difference spectrum caused by ionization under alkaline conditions and nitrobenzene oxidation. The results indicated that the iron-binding chelator could destroy the β-O-4 bonds in etherified lignin units and insert phenolic hydroxyl groups. The low-molecular-weight chelator secreted by C. versicolor resulted in new phenolic substructures in the lignin polymer, making it susceptible to attack by laccase or manganese peroxidase. Thus, the synergic action of the iron-binding chelator and the lignocellulolytic enzymes made the substrate more accessible to degradation.

  6. Chelating capture and magnetic removal of non-magnetic heavy metal substances from soil

    Science.gov (United States)

    Fan, Liren; Song, Jiqing; Bai, Wenbo; Wang, Shengping; Zeng, Ming; Li, Xiaoming; Zhou, Yang; Li, Haifeng; Lu, Haiwei

    2016-02-01

    A soil remediation method based on magnetic beneficiation is reported. A new magnetic solid chelator powder, FS@IDA (core-shell Fe3O4@SiO2 nanoparticles coated with iminodiacetic acid chelators), was used as a reactive magnetic carrier to selectively capture non-magnetic heavy metals in soil by chelation and removal by magnetic separation. FS@IDA was prepared via inorganic-organic and organic synthesis reactions that generated chelating groups on the surface of magnetic, multi-core, core-shell Fe3O4@SiO2 (FS) nanoparticles. These reactions used a silane coupling agent and sodium chloroacetate. The results show that FS@IDA could chelate the heavy metal component of Cd, Zn, Pb, Cu and Ni carbonates, lead sulfate and lead chloride in water-insoluble salt systems. The resulting FS@IDA-Cd and FS@IDA-Pb chelates could be magnetically separated, resulting in removal rates of approximately 84.9% and 72.2% for Cd and Pb, respectively. FS@IDA could not remove the residual heavy metals and those bound to organic matter in the soil. FS@IDA did not significantly alter the chemical composition of the soil, and it allowed for fast chelating capture, simple magnetic separation and facilitated heavy metal elution. FS@IDA could also be easily prepared and reprocessed.

  7. Recovery Properties of Polysulfone Hollow Fiber Chelating Membrane Modified with Thiourea for Mercury ( Ⅱ )

    Institute of Scientific and Technical Information of China (English)

    WANG Bing; XIAO Feng; HUANG Lei

    2007-01-01

    The adsorption isotherms of the polysulfone hollow fiber chelating membrane modified with thiourea as chelating groups for Hg2+ were determined. The effects of mobile phase conditions and the operating parameters on removal performance of the chelating membrane for Hg2+ were also investigated. The recovery of Hg2+ decreased at low pH and the optimum range of pH was from 6 to 7. The feed concentration effected on recovery of Hg2+ at the specified loading amount of Hg2+. The Hg2+ could be removed from different concentration feed solution by chelating membrane. The increase of feed flow rate led to slight decrease of recovery of Hg2+ at the specified loading amount of Hg2+. The chelating membrane could be operated at height feed flow rate and a large-scale removal of Hg2+ could be realized. With the increase of load amount, Hg2+ recovery decreased, but the saturation degree of chelating membrane increased. According to required recovery of Hg2+ and the saturation degree of chelating membrane, the optimum loading amount of Hg2+ should be selected in the actual removal of Hg2+.

  8. Generation, Fractionation, and Characterization of Iron-Chelating Protein Hydrolysate from Palm Kernel Cake Proteins.

    Science.gov (United States)

    Zarei, Mohammad; Ghanbari, Rahele; Tajabadi, Naser; Abdul-Hamid, Azizah; Bakar, Fatimah Abu; Saari, Nazamid

    2016-02-01

    Palm kernel cake protein was hydrolyzed with different proteases namely papain, bromelain, subtilisin, flavourzyme, trypsin, chymotrypsin, and pepsin to generate different protein hydrolysates. Peptide content and iron-chelating activity of each hydrolysate were evaluated using O-phthaldialdehyde-based spectrophotometric method and ferrozine-based colorimetric assay, respectively. The results revealed a positive correlation between peptide contents and iron-chelating activities of the protein hydrolysates. Protein hydrolysate generated by papain exhibited the highest peptide content of 10.5 mM and highest iron-chelating activity of 64.8% compared with the other hydrolysates. Profiling of the papain-generated hydrolysate by reverse phase high performance liquid chromatography fractionation indicated a direct association between peptide content and iron-chelating activity in most of the fractions. Further fractionation using isoelectric focusing also revealed that protein hydrolysate with basic and neutral isoelectric point (pI) had the highest iron-chelating activity, although a few fractions in the acidic range also exhibited good metal chelating potential. After identification and synthesis of papain-generated peptides, GGIF and YLLLK showed among the highest iron-chelating activities of 56% and 53%, whereas their IC50 were 1.4 and 0.2 μM, respectively.

  9. Function of the iron-binding chelator produced by Coriolus versicolor in lignin biodegradation

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    An ultrafiltered low-molecular-weight preparation of chelating compounds was isolated from a wood-containing culture of the white-rot basidiomycete Coriolus versicolor. This preparation could chelate Fe3+ and reduce Fe3+ to Fe2+, demonstrating that the substance may serve as a ferric chelator, oxygen-reducing agent, and redox-cycling molecule, which would include functioning as the electron transport carrier in Fenton reaction. Lignin was treated with the iron-binding chelator and the changes in structure were investigated by 1H-NMR, 13C-NMR, difference spectrum caused by ionization under alkaline conditions and nitrobenzene oxidation. The results indicated that the iron-binding chelator could destroy the β-O-4 bonds in etherified lignin units and insert phenolic hydroxyl groups. The low-molecular-weight chelator secreted by C. versicolor resulted in new phenolic substructures in the lignin polymer, making it susceptible to attack by laccase or manganese peroxidase. Thus, the synergic action of the iron-binding chelator and the lignocellulolytic enzymes made the substrate more acces- sible to degradation.

  10. Deferasirox is a powerful NF-κB inhibitor in myelodysplastic cells and in leukemia cell lines acting independently from cell iron deprivation by chelation and reactive oxygen species scavenging

    Science.gov (United States)

    Messa, Emanuela; Carturan, Sonia; Maffè, Chiara; Pautasso, Marisa; Bracco, Enrico; Roetto, Antonella; Messa, Francesca; Arruga, Francesca; Defilippi, Ilaria; Rosso, Valentina; Zanone, Chiara; Rotolo, Antonia; Greco, Elisabetta; Pellegrino, Rosa M.; Alberti, Daniele; Saglio, Giuseppe; Cilloni, Daniela

    2010-01-01

    Background Usefulness of iron chelation therapy in myelodysplastic patients is still under debate but many authors suggest its possible role in improving survival of low-risk myelodysplastic patients. Several reports have described an unexpected effect of iron chelators, such as an improvement in hemoglobin levels, in patients affected by myelodysplastic syndromes. Furthermore, the novel chelator deferasirox induces a similar improvement more rapidly. Nuclear factor-κB is a key regulator of many cellular processes and its impaired activity has been described in different myeloid malignancies including myelodysplastic syndromes. Design and Methods We evaluated deferasirox activity on nuclear factor-κB in myelodysplastic syndromes as a possible mechanism involved in hemoglobin improvement during in vivo treatment. Forty peripheral blood samples collected from myelodysplastic syndrome patients were incubated with 50 μM deferasirox for 18h. Results Nuclear factor-κB activity dramatically decreased in samples showing high basal activity as well as in cell lines, whereas no similar behavior was observed with other iron chelators despite a similar reduction in reactive oxygen species levels. Additionally, ferric hydroxyquinoline incubation did not decrease deferasirox activity in K562 cells suggesting the mechanism of action of the drug is independent from cell iron deprivation by chelation. Finally, incubation with both etoposide and deferasirox induced an increase in K562 apoptotic rate. Conclusions Nuclear factor-κB inhibition by deferasirox is not seen from other chelators and is iron and reactive oxygen species scavenging independent. This could explain the hemoglobin improvement after in vivo treatment, such that our hypothesis needs to be validated in further prospective studies. PMID:20534700

  11. Neuroprotective Effect of a New 7,8-Dihydroxycoumarin-Based Fe(2+)/Cu(2+) Chelator in Cell and Animal Models of Parkinson's Disease.

    Science.gov (United States)

    Aguirre, Pabla; García-Beltrán, Olimpo; Tapia, Victoria; Muñoz, Yorka; Cassels, Bruce K; Núñez, Marco T

    2017-01-18

    Disturbed iron homeostasis, often coupled to mitochondrial dysfunction, plays an important role in the progression of common neurodegenerative diseases such as Parkinson's disease (PD). Recent studies have underlined the relevance of iron chelation therapy for the treatment of these diseases. Here we describe the synthesis, chemical, and biological characterization of the multifunctional chelator 7,8-dihydroxy-4-((methylamino)methyl)-2H-chromen-2-one (DHC12). Metal selectivity of DHC12 was Cu(2+) ∼ Fe(2+) > Zn(2+) > Fe(3+). No binding capacity was detected for Hg(2+), Co(2+), Ca(2+), Mn(2+), Mg(2+), Ni(2+), Pb(2+), or Cd(2+). DHC12 accessed cells colocalizing with Mitotracker Orange, an indication of mitochondrial targeting. In addition, DHC12 chelated mitochondrial and cytoplasmic labile iron. Upon mitochondrial complex I inhibition, DHC12 protected plasma membrane and mitochondria against lipid peroxidation, as detected by the reduced formation of 4-hydroxynonenal adducts and oxidation of C11-BODIPY(581/591). DHC12 also blocked the decrease in mitochondrial membrane potential, detected by tetramethylrhodamine distribution. DHC12 inhibited MAO-A and MAO-B activity. Oral administration of DHC12 to mice (0.25 mg/kg body weight) protected substantia nigra pars compacta (SNpc) neurons against MPTP-induced death. Taken together, our results support the concept that DHC12 is a mitochondrial-targeted neuroprotective iron-copper chelator and MAO-B inhibitor with potent antioxidant and mitochondria protective activities. Oral administration of low doses of DHC12 is a promising therapeutic strategy for the treatment of diseases with a mitochondrial iron accumulation component, such as PD.

  12. Study of Anti-Fatigue Effect in Rats of Ferrous Chelates Including Hairtail Protein Hydrolysates

    Science.gov (United States)

    Huang, Saibo; Lin, Huimin; Deng, Shang-gui

    2015-01-01

    The ability of ferrous chelates including hairtail protein hydrolysates to prevent and reduce fatigue was studied in rats. After hydrolysis of hairtail surimi with papain, the hairtail protein hydrolysates (HPH) were separated into three groups by range of relative molecular weight using ultrafiltration membrane separation. Hairtail proteins were then chelated with ferrous ions, and the antioxidant activity, the amino acid composition and chelation rate of the three kinds of ferrous chelates including hairtail protein hydrolysates (Fe-HPH) were determined. Among the three groups, the Fe-HPH chelate showing the best conditions was selected for the anti-fatigue animal experiment. For it, experimental rats were randomly divided into seven groups. Group A was designated as the negative control group given distilled water. Group B, the positive control group, was given glutathione. Groups C, D and E were designated as the Fe-HPH chelate treatment groups and given low, medium, and high doses, respectively. Group F was designated as HPH hydrolysate treatment group, and Group G was designated as FeCl2 treatment group. The different diets were orally administered to rats for 20 days. After that time, rats were subjected to forced swimming training after 1 h of gavage. Rats given Fe-FPH chelate had higher haemoglobin regeneration efficiency (HRE), longer exhaustive swimming time and higher SOD activity. Additionally, Fe-FPH chelate was found to significantly decrease the malondialdehyde content, visibly enhance the GSH-Px activity in liver and reduce blood lactic acid of rats. Fe-HPH chelate revealed an anti-fatigue effect, similar to or better than the positive control substance and superior to HPH or Fe when provided alone. PMID:26633476

  13. Isomerism in benzyl-DOTA derived bifunctional chelators: implications for molecular imaging.

    Science.gov (United States)

    Payne, Katherine M; Woods, Mark

    2015-02-18

    The bifunctional chelator IB-DOTA has found use in a range of biomedical applications given its ability to chelate many metal ions, but in particular the lanthanide(III) ions. Gd(3+) in particular is of interest in the development of new molecular imaging agents for MRI and is highly suitable for chelation by IB-DOTA. Given the long-term instability of the aryl isothiocyanate functional group we have used the more stable nitro derivative (NB-DOTA) to conduct a follow-up study of some of our previous work on the coordination chemistry of chelates of these BFCs. Using a combination of NMR and HPLC to study the Eu(3+) and Yb(3+) chelates of NB-DOTA, we have demonstrated that this ligand will produce two discrete regioisomeric chelates at the point at which the metal ion is introduced into the BFC. These regioisomers are defined by the position of the benzylic substituent on the macrocyclic ring: adopting an equatorial position either at the corner or the side of the [3333] ring conformation. These regioisomers are incapable of interconversion and are distinct, separate structures with different SAP/TSAP ratios. The side isomer exhibits an increased population of the TSAP isomer, pointing to more rapid water exchange kinetics in this regioisomer. This has potential ramifications for the use of these two regioisomers of Gd(3+)-BFC chelates in MRI applications. We have also found that, remarkably, there is little or no freedom of rotation about the first single bond extending from the macrocyclic ring to the benzylic substituent. Since this is the linkage through which the chelate is conjugated to the remainder of the molecular imaging probe, this result implies that there may be reduced local rotation of the Gd(3+) chelate within a molecular imaging probe. This implies that this type of BFC could exhibit higher relaxivities than other types of BFC.

  14. Study of Anti-Fatigue Effect in Rats of Ferrous Chelates Including Hairtail Protein Hydrolysates

    Directory of Open Access Journals (Sweden)

    Saibo Huang

    2015-12-01

    Full Text Available The ability of ferrous chelates including hairtail protein hydrolysates to prevent and reduce fatigue was studied in rats. After hydrolysis of hairtail surimi with papain, the hairtail protein hydrolysates (HPH were separated into three groups by range of relative molecular weight using ultrafiltration membrane separation. Hairtail proteins were then chelated with ferrous ions, and the antioxidant activity, the amino acid composition and chelation rate of the three kinds of ferrous chelates including hairtail protein hydrolysates (Fe-HPH were determined. Among the three groups, the Fe-HPH chelate showing the best conditions was selected for the anti-fatigue animal experiment. For it, experimental rats were randomly divided into seven groups. Group A was designated as the negative control group given distilled water. Group B, the positive control group, was given glutathione. Groups C, D and E were designated as the Fe-HPH chelate treatment groups and given low, medium, and high doses, respectively. Group F was designated as HPH hydrolysate treatment group, and Group G was designated as FeCl2 treatment group. The different diets were orally administered to rats for 20 days. After that time, rats were subjected to forced swimming training after 1 h of gavage. Rats given Fe-FPH chelate had higher haemoglobin regeneration efficiency (HRE, longer exhaustive swimming time and higher SOD activity. Additionally, Fe-FPH chelate was found to significantly decrease the malondialdehyde content, visibly enhance the GSH-Px activity in liver and reduce blood lactic acid of rats. Fe-HPH chelate revealed an anti-fatigue effect, similar to or better than the positive control substance and superior to HPH or Fe when provided alone.

  15. Abrogation of Chk1-mediated S/G2 checkpoint by UCN-01 enhances ara-C-induced cytotoxicity in human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Rong-guang SHAO; Chun-Xia CAO; Yves POMMIER

    2004-01-01

    AIM: To investigate whether 7-hydroxystaurosporine (UCN-01) affects cell cycle progression in arabinosylcytosine (ara-C) treated human colon carcinoma HT-29 cells. METHODS: Cytotoxicity, DNA synthesis, cell cycle distribution,protein level, and kinase activity were determined by clonogenic assay, flow cytometry, DNA synthesis assay,immunoblotting, and kinase assays, respectively. RESULTS: UCN-01 abrogated an S/G2-phase checkpoint in HT29 cells treated with ara-C. When UCN-01 was added after treatment with ara-C, the rate of recovery of DNA synthesis was enhanced and colony-forming ability diminished. Thus, premature recovery of DNA synthesis was associated with increased cytotoxicity. Measurements of cyclin A and B protein levels, Cdk2 and Cdc2 kinase activities, Cdc25C phosphorylation, and Chkl kinase activity were consistent with UCN-01-induced abrogation of the S/G2-phase checkpoint in ara-C treated cells. CONCLUSION: The abrogation of the S/G2 checkpoint may be due to inhibition of Chkl kinase by UCN-01. The enhanced cytotoxicity produced when UCN-01 was combined with ara-C suggested a rationale for the use of this drug combination for tumors that might be susceptible to cell cycle checkpoint abrogation.

  16. Chelate effects in sulfate binding by amide/urea-based ligands.

    Science.gov (United States)

    Jia, Chuandong; Wang, Qi-Qiang; Begum, Rowshan Ara; Day, Victor W; Bowman-James, Kristin

    2015-07-01

    The influence of chelate and mini-chelate effects on sulfate binding was explored for six amide-, amide/amine-, urea-, and urea/amine-based ligands. Two of the urea-based hosts were selective for SO4(2-) in water-mixed DMSO-d6 systems. Results indicated that the mini-chelate effect provided by a single urea group with two NH binding sites appears to provide enhanced binding over two amide groups. Furthermore, additional urea binding sites incorporated into the host framework appeared to overcome to some extent competing hydration effects with increasing water content.

  17. The Effect of Chelating Copolymer Additive on the Yttrium Iron Garnet Nanoparticle Formation

    Institute of Scientific and Technical Information of China (English)

    Wang; Cheng-chien

    2007-01-01

    1 Results Yttrium iron garnet (YIG) is a well-known ferromagnetic garnet material and has widely used in electronic devices[1].A new acrylic chelating polymer was developed to act as the additive of the preparation of YIG precursor in our previous study[2].The sintering temperature of YIG nanocrystal obtained by this YIG precursor (ACP) was magnificently descended from 1 000 to 600 ℃.In this study,we were further to study the effect of amount of chelating polymer and the compositions of chelating polyme...

  18. A membrane-specific tyrosinase chelate: the mitotic regulator?

    Science.gov (United States)

    Kharasch, J A

    1987-06-01

    Cancer's random, reversible, unstable transitions to "normal" structures imply their functional relation. Similar random, continuous, reversible oncogene "mutational transformation" also lacks a consistent hybrid. Positing cancer's "mutationally altered genotype" leads to medically foreign causes, qualities, inducers, suppressors, immune proteins, and viruses. Its random variation, however, opposes the functionally discrete, ordered, stable, irreversible hybrid variation and single-valued transforms of molecular genetics. There, "causal mutational operators" remain unspecified; only consistent single-valued DNA base and amino acid change, as "transform operand", are made explicit. A mitotically "blocked" (normal) and "unblocked" (malignant) stem cell "phenotype", operationally constructed from microscopic data, is therefore viewed within the homeostatic context of open-system enzyme-regulatory equilibrium. This functional, stochastic field distribution between "structurally bound" and "freely dividing" stem cell number discloses their putative regulatory mitotic-blocking factor. A tyrosinase complex, interacting by Cu2+-Fe2+ chelation with a proline hydroxylase divisional enzyme near stem cell ribosomes, maintains steady-state mitotic equilibrium. Based upon familiar medical, biochemical, and energy principles this confronts cancer's pigmentary-depigmentary signs, glycolytic metabolism, elevated serum tyrosinase, defective collagen production, exposed membrane binding sites, and tyrosine's recent growth control role.

  19. mer and fac isomerism in tris chelate diimine metal complexes.

    Science.gov (United States)

    Dabb, Serin L; Fletcher, Nicholas C

    2015-03-14

    In this perspective, we highlight the issue of meridional (mer) and facial (fac) orientation of asymmetrical diimines in tris-chelate transition metal complexes. Diimine ligands have long been the workhorse of coordination chemistry, and whilst there are now good strategies to isolate materials where the inherent metal centered chirality is under almost complete control, and systematic methodologies to isolate heteroleptic complexes, the conceptually simple geometrical isomerism has not been widely investigated. In systems where the two donor atoms are significantly different in terms of the σ-donor and π-accepting ability, the fac isomer is likely to be the thermodynamic product. For the diimine complexes with two trigonal planar nitrogen atoms there is much more subtlety to the system, and external factors such as the solvent, lattice packing and the various steric considerations play a delicate role in determining the observed and isolable product. In this article we discuss the possibilities to control the isomeric ratio in labile systems, consider the opportunities to separate inert complexes and discuss the observed differences in their spectroscopic properties. Finally we report on the ligand orientation in supramolecular systems where facial coordination leads to simple regular structures such as helicates and tetrahedra, but the ability of the ligand system to adopt a mer orientation enables self-assembled structures of considerable beauty and complexity.

  20. New method to estimate stability of chelate complexes

    CERN Document Server

    Grigoriev, F V; Romanov, A N; Kondakova, O A; Sulimov, V B

    2009-01-01

    A new method allowing calculation of the stability of chelate complexes with Mg2+ ion in water have been developed. The method is based on two-stage scheme for the complex formation. The first stage is the ligand transfer from an arbitrary point of the solution to the second solvation shell of the Mg2+ ion. At this stage the ligand is considered as a charged or neutral rigid body. The second stage takes into account disruption of coordinate bonds between Mg2+ and water molecules from the first solvation shell and formation of the bonds between the ligand and the Mg2+ ion. This effect is considered using the quantum chemical modeling. It has been revealed that the main contribution to the free energy of the complex formation is caused by the disruption/formation of the coordinate bonds between Mg2+, water molecules and the ligand. Another important contribution to the complex formation energy is change of electrostatic interactions in water solvent upon the ligand binding with Mg2+ ion. For all complexes under...

  1. Preventive therapy of experimental colitis with selected iron chelators and anti-oxidants

    Directory of Open Access Journals (Sweden)

    Mohsen Minaiyan

    2012-01-01

    Conclusions: Maltol with the highest test dose was capable to protect against experimentally induced colitis. Kojic acid and vitamin E were not effective in this animal model of colon inflammation. More detailed studies are warranted to explore the mechanisms involved in anti-colitic property of maltol and to explain ineffectiveness of kojic acid and vitamin E.

  2. [15]aneN4S: Synthesis, Thermodynamic Studies and Potential Applications in Chelation Therapy

    Directory of Open Access Journals (Sweden)

    Nuno Torres

    2014-01-01

    Full Text Available The purpose of this work was to synthesize and characterize the thiatetraaza macrocycle 1-thia-4,7,10,13-tetraazacyclopentadecane ([15]aneN4S. Its acid-base behaviour was studied by potentiometry at 25 °C and ionic strength 0.10 M in KNO3. The protonation sequence of this ligand was investigated by 1H-NMR titration that also allowed the determination of protonation constants in D2O. Binding studies of [15]aneN4S with Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Hg2+ and Pb2+ metal ions were further performed under the same experimental conditions. The results demonstrated that this compound has a higher selectivity and thermodynamic stability for Hg2+ and Cu2+, followed by Ni2+. The UV-visible-near IR spectroscopies and magnetic moment data for the Co(II and Ni(II complexes indicated a tetragonal distorted coordination geometry for both metal centres. The value of magnetic moment and the X-band EPR spectra of the Cu(II complex are consistent with a distorted square pyramidal geometry.

  3. Proton therapy

    Science.gov (United States)

    Proton beam therapy; Cancer - proton therapy; Radiation therapy - proton therapy; Prostate cancer - proton therapy ... that use x-rays to destroy cancer cells, proton therapy uses a beam of special particles called ...

  4. Nonionic metal-chelating surfactants mediated solvent-free thermo-induced separation of uranyl

    Energy Technology Data Exchange (ETDEWEB)

    Larpent, Ch.; Prevost, S. [Versailles-St-Quentin Univ., Institut Lavoisier, UMR-CNRS 8180, 78 - Versailles (France); Prevost, S.; Zemb, Th.; Testard, F. [CEA Saclay, Dept. de Recherche sur l' Etat Condense, les Atomes et les Molecules (DSM/DRECAM/SCM/LIONS), 91 - Gif sur Yvette (France); Berthon, L. [CEA Valrho, Site de Marcoule, Dept. Radiochimie et Procedes (DEN/DRCP/SCPS/LCSE), 30 (France)

    2007-08-15

    Thermo-responsive metal-chelating surfactants permit the solvent-free, cloud point extraction of uranyl nitrate and afford a real molecular economy compared to conventional separation techniques. (authors)

  5. Click-to-Chelate: Development of Technetium and Rhenium-Tricarbonyl Labeled Radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Thomas L. Mindt

    2013-03-01

    Full Text Available The Click-to-Chelate approach is a highly efficient strategy for the radiolabeling of molecules of medicinal interest with technetium and rhenium-tricarbonyl cores. Reaction of azide-functionalized molecules with alkyne prochelators by the Cu(I-catalyzed azide-alkyne cycloaddition (CuAAC; click reaction enables the simultaneous synthesis and conjugation of tridentate chelating systems for the stable complexation of the radiometals. In many cases, the functionalization of (biomolecules with the ligand system and radiolabeling can be achieved by convenient one-pot procedures. Since its first report in 2006, Click-to-Chelate has been applied to the development of numerous novel radiotracers with promising potential for translation into the clinic. This review summarizes the use of the Click-to-Chelate approach in radiopharmaceutical sciences and provides a perspective for future applications.

  6. Absorption of nitric oxide into aqueous solutions of ferrous chelates accompanied by instantaneous reaction

    NARCIS (Netherlands)

    Demmink, J.F; vanGils, I.C.F.; Beenackers, A.A C M

    1997-01-01

    The absorption of nitric oxide (NO) into aqueous solutions of ferrous chelates of nitrilotriacetic acid (NTA), ethylene diaminetetraacetic acid (EDTA), hydroxyethylenediaminetriacetic acid (HEDTA), and diethylenetriaminepentaacetic acid (DTPA) was studied in a stirred cell reactor. Experimental cond

  7. CATALYTIC HYDROGENATION OF ACRYLATE ASMMETRIC Dd(Ⅱ)—CHELATING RESINS CONTAINING AMINO ACID LIGANDS

    Institute of Scientific and Technical Information of China (English)

    Wangying; WangHongzuo; 等

    1995-01-01

    The catalytic hydrogenation of palladium chelating resins containing chiral amino acid ligands based on lower crosslinked poly(chloroethyl acrylate) and some effects on the rate of hydrogenation were studied.

  8. Bifunctional chelates of RH-105 and AU199 as potential radiotherapeutic agents

    Energy Technology Data Exchange (ETDEWEB)

    Droege, P.

    1997-03-01

    Research is presented on new bifunctional chelating ligand systems with stability on the macroscopic and radiochemical levels. The synthesis of the following complexes are described: rhodium 105, palladium 109, and gold 198.

  9. Bifunctional chelating agent for the design and development of site specific radiopharmaceuticals and biomolecule conjugation strategy

    Science.gov (United States)

    Katti, Kattesh V.; Prabhu, Kandikere R.; Gali, Hariprasad; Pillarsetty, Nagavara Kishore; Volkert, Wynn A.

    2003-10-21

    There is provided a method of labeling a biomolecule with a transition metal or radiometal in a site specific manner to produce a diagnostic or therapeutic pharmaceutical compound by synthesizing a P.sub.2 N.sub.2 -bifunctional chelating agent intermediate, complexing the intermediate with a radio metal or a transition metal, and covalently linking the resulting metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. Also provided is a method of synthesizing the --PR.sub.2 containing biomolecules by synthesizing a P.sub.2 N.sub.2 -bifunctional chelating agent intermediate, complexing the intermediate with a radiometal or a transition metal, and covalently linking the resulting radio metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. There is provided a therapeutic or diagnostic agent comprising a --PR.sub.2 containing biomolecule.

  10. Mutations Abrogating VP35 Interaction with Double-Stranded RNA Render Ebola Virus Avirulent in Guinea Pigs

    Energy Technology Data Exchange (ETDEWEB)

    Prins, Kathleen C.; Delpeut, Sebastien; Leung, Daisy W.; Reynard, Olivier; Volchkova, Valentina A.; Reid, St. Patrick; Ramanan, Parameshwaran; Cárdenas, Washington B.; Amarasinghe, Gaya K.; Volchkov, Viktor E.; Basler, Christopher F. (CNRS-INSERM); (Mount Sinai Hospital); (LB-Ecuador); (Iowa State)

    2010-10-11

    Ebola virus (EBOV) protein VP35 is a double-stranded RNA (dsRNA) binding inhibitor of host interferon (IFN)-{alpha}/{beta} responses that also functions as a viral polymerase cofactor. Recent structural studies identified key features, including a central basic patch, required for VP35 dsRNA binding activity. To address the functional significance of these VP35 structural features for EBOV replication and pathogenesis, two point mutations, K319A/R322A, that abrogate VP35 dsRNA binding activity and severely impair its suppression of IFN-{alpha}/{beta} production were identified. Solution nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography reveal minimal structural perturbations in the K319A/R322A VP35 double mutant and suggest that loss of basic charge leads to altered function. Recombinant EBOVs encoding the mutant VP35 exhibit, relative to wild-type VP35 viruses, minimal growth attenuation in IFN-defective Vero cells but severe impairment in IFN-competent cells. In guinea pigs, the VP35 mutant virus revealed a complete loss of virulence. Strikingly, the VP35 mutant virus effectively immunized animals against subsequent wild-type EBOV challenge. These in vivo studies, using recombinant EBOV viruses, combined with the accompanying biochemical and structural analyses directly correlate VP35 dsRNA binding and IFN inhibition functions with viral pathogenesis. Moreover, these studies provide a framework for the development of antivirals targeting this critical EBOV virulence factor.

  11. An exon 53 frameshift mutation in CUBN abrogates cubam function and causes Imerslund-Gräsbeck syndrome in dogs.

    Science.gov (United States)

    Fyfe, John C; Hemker, Shelby L; Venta, Patrick J; Fitzgerald, Caitlin A; Outerbridge, Catherine A; Myers, Sherry L; Giger, Urs

    2013-08-01

    Cobalamin malabsorption accompanied by selective proteinuria is an autosomal recessive disorder known as Imerslund-Gräsbeck syndrome in humans and was previously described in dogs due to amnionless (AMN) mutations. The resultant vitamin B12 deficiency causes dyshematopoiesis, lethargy, failure to thrive, and life-threatening metabolic disruption in the juvenile period. We studied 3 kindreds of border collies with cobalamin malabsorption and mapped the disease locus in affected dogs to a 2.9Mb region of homozygosity on canine chromosome 2. The region included CUBN, the locus encoding cubilin, a peripheral membrane protein that in concert with AMN forms the functional intrinsic factor-cobalamin receptor expressed in ileum and a multi-ligand receptor in renal proximal tubules. Cobalamin malabsorption and proteinuria comprising CUBN ligands were demonstrated by radiolabeled cobalamin uptake studies and SDS-PAGE, respectively. CUBN mRNA and protein expression were reduced ~10 fold and ~20 fold, respectively, in both ileum and kidney of affected dogs. DNA sequencing demonstrated a single base deletion in exon 53 predicting a translational frameshift and early termination codon likely triggering nonsense mediated mRNA decay. The mutant allele segregated with the disease in the border collie kindred. The border collie disorder indicates that a CUBN mutation far C-terminal from the intrinsic factor-cobalamin binding site can abrogate receptor expression and cause Imerslund-Gräsbeck syndrome.

  12. Inhibition of MARCH5 ubiquitin ligase abrogates MCL1-dependent resistance to BH3 mimetics via NOXA.

    Science.gov (United States)

    Subramanian, Aishwarya; Andronache, Adrian; Li, Yao-Cheng; Wade, Mark

    2016-03-29

    BH3 mimetic compounds induce tumor cell death through targeted inhibition of anti-apoptotic BCL2 proteins. Resistance to one such compound, ABT-737, is due to increased levels of anti-apoptotic MCL1. Using chemical and genetic approaches, we show that resistance to ABT-737 is abrogated by inhibition of the mitochondrial RING E3 ligase, MARCH5. Mechanistically, this is due to increased expression of pro-apoptotic BCL2 family member, NOXA, and is associated with MARCH5 regulation of MCL1 ubiquitylation and stability in a NOXA-dependent manner. MARCH5 expression contributed to an 8-gene signature that correlates with sensitivity to the preclinical BH3 mimetic, navitoclax. Furthermore, we observed a synthetic lethal interaction between MCL1 and MARCH5 in MCL1-dependent breast cancer cells. Our data uncover a novel level at which the BCL2 family is regulated; furthermore, they suggest targeting MARCH5-dependent signaling will be an effective strategy for treatment of BH3 mimetic-resistant tumors, even in the presence of high MCL1.

  13. CD40-signalling abrogates induction of RORγt+ Treg cells by intestinal CD103+ DCs and causes fatal colitis

    Science.gov (United States)

    Barthels, Christian; Ogrinc, Ana; Steyer, Verena; Meier, Stefanie; Simon, Ferdinand; Wimmer, Maria; Blutke, Andreas; Straub, Tobias; Zimber-Strobl, Ursula; Lutgens, Esther; Marconi, Peggy; Ohnmacht, Caspar; Garzetti, Debora; Stecher, Bärbel; Brocker, Thomas

    2017-01-01

    Immune homeostasis in intestinal tissues depends on the generation of regulatory T (Treg) cells. CD103+ dendritic cells (DCs) acquire microbiota-derived material from the gut lumen for transport to draining lymph nodes and generation of receptor-related orphan γt+ (RORγt+) Helios−-induced Treg (iTreg) cells. Here we show CD40-signalling as a microbe-independent signal that can induce migration of CD103+ DCs from the lamina propria (LP) to the mesenteric lymph nodes. Transgenic mice with constitutive CD11c-specific CD40-signalling have reduced numbers of CD103+ DCs in LP and a low frequency of RORγt+Helios− iTreg cells, exacerbated inflammatory Th1/Th17 responses, high titres of microbiota-specific immunoglobulins, dysbiosis and fatal colitis, but no pathology is detected in other tissues. Our data demonstrate a CD40-dependent mechanism capable of abrogating iTreg cell induction by DCs, and suggest that the CD40L/CD40-signalling axis might be able to intervene in the generation of new iTreg cells in order to counter-regulate immune suppression to enhance immunity. PMID:28276457

  14. ORGANIC CHELATING REAGENT ON REDOX ADSORPTION OF ACTIVATED CARBON FIBER TOWARDS Au3+

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Organic chelating reagent influences upon the redox adsorption of activated carbon fibertowards Au3- were systematically investigated. The experimental results indicated that the presenceof organic chelating reagent on activated carbon fiber strongly affects adsorption capacity ofactivated carbon fiber towards Au3+. The reduction-adsorption amount of Au3+ increased three timesby the presence of 8-quinolinol. Furthermore, The reduction-adsorption amount of Au3+ depended onthe pH value of adsorption and temperature.

  15. Synthesis, Characterization and Chelating Properties of 4-Butyrylsemicarbazone-1-phenyl-3-methyl-2-pyrazolin-5-one

    Directory of Open Access Journals (Sweden)

    J. D. Patel

    2010-01-01

    Full Text Available 4-Butyrylsemicarbazone-1-phenyl-3-methyl-2-pyrazolin-5-one (BUMP-SC was prepared and its metal chelates of Cu2+, Ni2+, Co2+, Mn2+, Fe2+, Fe3+, Cr3+, UO2 and OV were prepared. The ligands and its chelates were characterized by elemental analysis, metal:ligand (M:L stoichiometry, IR-electronic spectral studies and magnetic properties. The compounds also were screened for their antimicrobial activity.

  16. Role of the Symmetry of Multipoint Hydrogen Bonding on Chelate Cooperativity in Supramolecular Macrocyclization Processes.

    Science.gov (United States)

    Montoro-García, Carlos; Camacho-García, Jorge; López-Pérez, Ana M; Mayoral, María J; Bilbao, Nerea; González-Rodríguez, David

    2016-01-01

    Herein, we analyze the intrinsic chelate effect that multipoint H-bonding patterns exert on the overall energy of dinucleoside cyclic systems. Our results indicate that the chelate effect is regulated by the symmetry of the H-bonding pattern, and that the effective molarity is reduced by about three orders of magnitude when going from the unsymmetric ADD-DAA or DDA-AAD patterns to the symmetric DAD-ADA pattern.

  17. The Role of Chelation in the Treatment of Arsenic and Mercury Poisoning

    OpenAIRE

    Kosnett, Michael J

    2013-01-01

    Chelation for heavy metal intoxication began more than 70 years ago with the development of British anti-lewisite (BAL; dimercaprol) in wartime Britain as a potential antidote the arsenical warfare agent lewisite (dichloro[2-chlorovinyl]arsine). DMPS (unithiol) and DMSA (succimer), dithiol water-soluble analogs of BAL, were developed in the Soviet Union and China in the late 1950s. These three agents have remained the mainstay of chelation treatment of arsenic and mercury intoxication for mor...

  18. Reversible retinopathy associated with oral deferasirox therapy

    OpenAIRE

    Walia, Harpreet S.; Yan, Jiong

    2013-01-01

    A 17-year-old girl with a history of sickle cell anaemia undergoing chronic blood transfusions and iron-chelation therapy presented for multiple ophthalmic examinations. During treatment with deferoxamine, her examination remained stable but 2 years after changing to deferasirox she presented with decreased visual acuity and only mild funduscopic changes. Marked electrophysiological abnormalities were also evident. After cessation of deferasirox, her visual acuity improved and electrophysiolo...

  19. Optimization of chelators to enhance uranium uptake from tailings for phytoremediation.

    Science.gov (United States)

    Jagetiya, Bhagawatilal; Sharma, Anubha

    2013-04-01

    A greenhouse experiment was set up to investigate the ability of citric acid (CA), oxalic acid (OA), nitrilotriacetic acid (NTA) and EDTA for phytoremediation of uranium tailings by Indian mustard [Brassica juncea (L.) Czern. et Coss]. Uranium tailings were collected from Umra mining region and mixed with 75% of garden soil which yielded a 25:75 mixture. Prepared pots were divided into four sets and treated with following different concentrations - 0.1, 0.5, 2.5 and 12.5 mmol kg(-1) soil additions for each of the four chelators. Control pots which were not treated with chelators. Experiments were conducted in completely randomized block design with triplicates. The optimum concentrations of these chelators were found on the basis of biomass production, tolerance and accumulation potential. The data collected were expressed statistically. EDTA produced maximum growth depression whereas, minimum occurred in the case of NTA. Maximum U uptake (3.5-fold) in the roots occurred at 2.5 mmol of CA, while NTA proved to be the weakest for the same purpose. Severe toxicity in the form of reduced growth and plant death was recorded at 12.5 mmol of each chelator. Minimum growth inhibition produced by chelators occurred in NTA which was followed by OA, moderate in CA and maximum was traced in EDTA applications. Chelator strengthened U uptake in the present study follows the order: CA>EDTA>OA>NTA.

  20. The role of chelation in the treatment of arsenic and mercury poisoning.

    Science.gov (United States)

    Kosnett, Michael J

    2013-12-01

    Chelation for heavy metal intoxication began more than 70 years ago with the development of British anti-lewisite (BAL; dimercaprol) in wartime Britain as a potential antidote the arsenical warfare agent lewisite (dichloro[2-chlorovinyl]arsine). DMPS (unithiol) and DMSA (succimer), dithiol water-soluble analogs of BAL, were developed in the Soviet Union and China in the late 1950s. These three agents have remained the mainstay of chelation treatment of arsenic and mercury intoxication for more than half a century. Animal experiments and in some instances human data indicate that the dithiol chelators enhance arsenic and mercury excretion. Controlled animal experiments support a therapeutic role for these chelators in the prompt treatment of acute poisoning by arsenic and inorganic mercury salts. Treatment should be initiated as rapidly as possible (within minutes to a few hours), as efficacy declines or disappears as the time interval between metal exposure and onset of chelation increases. DMPS and DMSA, which have a higher therapeutic index than BAL and do not redistribute arsenic or mercury to the brain, offer advantages in clinical practice. Although chelation following chronic exposure to inorganic arsenic and inorganic mercury may accelerate metal excretion and diminish metal burden in some organs, potential therapeutic efficacy in terms of decreased morbidity and mortality is largely unestablished in cases of chronic metal intoxication.

  1. Hydroxypyri(mi)dine-based chelators as antidotes of toxicity due to aluminum and actinides.

    Science.gov (United States)

    Santos, M A; Esteves, M A; Chaves, S

    2012-01-01

    This review is focused on recent developments on hydroxypyri(mi)dines, as aluminum and actinide chelating agents to combat the toxicity due to accumulations of these metal ions in human body resulting from excessive metal exposure. After a brief update revision of the most common processes of aluminum (Al) exposure, as well as the associated toxicities and pathologies, we will focus on the current available Al chelators and future perspective as potential antidotes of Al toxicity. Due to the similarity between Al and Fe, a major emphasis is given to the hydroxypyridinone and hydroxypyrimidinone chelators, since they are analogues of the current iron chelators in clinical use (DFP and DFO). This review includes issues such as molecular design strategies and corresponding effects on the associated physico-chemical properties, lipo-hydrophilic balance, toxicity, in vivo bioassays and current clinical applications. The hydroxypyri(mi)dine chelators are also suitable for other hard metal ions, such as the radiotoxic actinides, and so a brief review is included on the applications of these chelators in actinides scavenging.

  2. Donor-Appended N,C-Chelate Organoboron Compounds: Influence of Donor Strength on Photochromic Behaviour.

    Science.gov (United States)

    Mellerup, Soren K; Yuan, Kang; Nguyen, Carmen; Lu, Zheng-Hong; Wang, Suning

    2016-08-22

    Recently, four-coordinated N,C-chelate organoboron compounds have been found to show many interesting photochemical transformations depending on the nature of their chelating framework. As such, the effect of substitution on the chelate ligand has been well-established and understood, but the impact of the aryl groups attached to the boron atom remains less clear. To investigate the effect of enhanced charge-transfer character, a series of new N,C-chelate organoboron compounds with donor-functionalized aryl groups have been synthesized and characterized using NMR, UV/Vis, and electrochemical methods. These compounds were found to possess bright and tunable charge-transfer luminescence which is dependent on the donor strength of the amino substituent. In addition, some of these compounds undergo photochromic switching, producing dark isomers of various colors. This work establishes that donor-functionalization of the aryl groups in N,C-chelate boron compounds is an effective strategy for tuning both the photophysical and photochemical properties of such systems. The new findings also help elucidate the influence of electronic structure on the photoreactivity of N,C-chelate organoboron compounds which appears to be as important as steric crowding around the boron atom.

  3. Effects of micronutrients deficiency and inoculation with arbuscular mycorrhizal fungi on chelator exudation by tomato root

    Directory of Open Access Journals (Sweden)

    E. Shirmohammadi

    2010-12-01

    Full Text Available Arbuscular mycorrhizal fungi (AMF can affect their host plants growth through nutrient uptake enhancement. Determination of chelators (siderophores and phytosiderophores in root leachates is of importance in order to account for the effects of AMF on nutrient uptake by plants. In this study, tomato plants were inoculated with either Glomus intraradices or Glomus etunicatum or left un-inoculated as non-mycorrhizal control, in pots containing sterile and acid washed perlite. Rorison’s nutrient solution harbouring three levels of Fe, Mn, Zn and Cu (full strength, half strength and without micronutrients was applied to the pots during three month- growth period. Root leachates were collected and total chelator concentration was quantified by titration with DTPA. Plant roots showed lower mycorrhizal colonization in this condition. The amounts of chelators produced by roots were significantly different in AMF species. In plants inoculated with G. intraradices, the highest chelator production occurred in the absence of micronutrients and in its half strength as well, but the micronutrient levels had no significant effect on chelator production in plants inoculated with G. etunicatum. In the absence of micronutrients, chelator production was higher in G.intraradices inoculated plants compared to the G. etunicatum ones.

  4. Antidiabetic effect of glucosaminic acid-cobalt (II chelate in streptozotocin-induced diabetes in mice

    Directory of Open Access Journals (Sweden)

    Talba T

    2011-04-01

    Full Text Available Tahirou Talba1, Xia Wen Shui1, Qinyuan Cheng1,2, Xin Tian21Key Laboratory of Food Processing Technology, 2School of Medicine and Pharmaceutics, Jiangnan University, Wuxi, Jiangsu, People's Republic of ChinaBackground: The purpose of this study was to assess the in vivo ability of glucosaminic acid-cobalt (II chelate to reduce glycemia.Methods: Different concentrations of chelate solution were administrated to mice with diabetes induced by streptozotocin. Daily oral administration of chelate solution 0.4 mL at various concentrations (0.32–0.4 g/mL led to reduction in water intake by the diabetic mice after 5 days of treatment, with a subsequent reduction in glucose levels observed 2 weeks later. Daily food intake was related to both chelate concentration as well as glycemia reduction. The food intake of mice treated with glucosaminic acid-cobalt (II chelate solution was 1.5-fold that of untreated mice.Keywords: glucosaminic acid, cobalt, chelate, streptozotocin, glycemia reduction

  5. Predicting the kinetics of chelating agents in man from animal data

    Energy Technology Data Exchange (ETDEWEB)

    Durbin, P.W.; Schmidt, C.T. (Lawrence Berkeley Lab., CA (USA))

    1989-01-01

    Published data were collected on clearance of 82Br, 24Na, inulin, and the ligands CaNa2-EDTA and CaNa3-DTPA from plasma of rats, dogs, and adult men. Data were restructured to a common base and reanalyzed using a two-compartment open-system kinetic model with an outlet from plasma to urinary excretion or from interstitial fluid to deposition in tissues. This was used to obtain transfer rates, distribution volumes, renal clearance, tracer content of interstitial fluid, and cumulative urinary excretion. The validity of the approach was demonstrated by good agreement of the calculated distribution volumes and renal clearances of the selected tracers with published values obtained by other analytical methods. The values of the parameters of the plasma curves and the transfer rates for EDTA and DTPA in the animals were combined with physiological data to evaluate the kinetic parameters of those substances in man. The human kinetic parameters of the ligands predicted from rat or dog data differed, on the average, from the values calculated from human data by +/- 13 and +/- 38%, respectively. The effective concentration of EDTA or DTPA in body fluids from time of injection to complete excretion and the mean concentration for the first 360 min after injection was calculated to be about four times greater in man than in rats and 3.5 times greater than in dogs for equimolar amounts injected. Based on the pharmacokinetics of DTPA, chelation therapy immediately after an actinide accident involving inhalation or extensive skin damage will be more efficient and more effective if a fraction of the standard clinical ZnNa3-DTPA dosage is administered every few hours instead of as a single daily injection.

  6. Zinc glycine chelate absorption characteristics in Sprague Dawley rat.

    Science.gov (United States)

    Yue, M; Fang, S L; Zhuo, Z; Li, D D; Feng, J

    2015-06-01

    This study was conducted to investigate absorption characteristics of zinc glycine chelate (Zn-Gly) by evaluating tissues zinc status and the expression of zinc transporters in rats. A total of 24 male rats were randomly allocated to three treatments and administered either saline or 35 mg Zn/kg body weight from zinc sulphate (ZnSO4 ) or Zn-Gly by feeding tube separately. Four rats per group were slaughtered and tissues were collected at 2 and 6 h after gavage respectively. Our data showed that Zn-Gly did more effectively in increasing (p < 0.05) serum zinc levels, and the activities of serum and liver alkaline phosphatase (ALP) and liver Cu/Zn superoxide dismutase (Cu/Zn SOD) at 2 and 6 h. By 2 h after the zinc load, the mRNA and protein abundance of intestinal metallothionein1 (MT1) and zinc transporter SLC30A1 (ZnT1) were higher (p < 0.05), and zinc transporter SLC39A4 (Zip4) lower (p < 0.05) in ZnSO4 compared to other groups. Zinc transporter SLC39A5 (Zip5) mRNA expression was not zinc responsive, but Zip5 protein abundance was remarkably (p < 0.05) increased in ZnSO4 2 h later. Overall, our results indicated that in short-term periods, Zn-Gly was more effective in improving body zinc status than ZnSO4 , and ZnSO4 did more efficiently on the regulation of zinc transporters in small intestine.

  7. Sobrecarga e quelação de ferro na anemia falciforme Iron overload and iron chelation in sickle cell disease

    Directory of Open Access Journals (Sweden)

    Rodolfo D. Cançado

    2007-09-01

    regimens have been of the highest priority in the last years.In this review, the most important advances in iron-chelating therapy are described, particularly the analysis of the two orally active iron chelators: deferiprone and the novel oral chelator deferasirox.

  8. Plasma membrane Toll-like receptor activation increases bacterial uptake but abrogates endosomal Lactobacillus acidophilus induction of interferon-β.

    Science.gov (United States)

    Boye, Louise; Welsby, Iain; Lund, Lisbeth Drozd; Goriely, Stanislas; Frøkiaer, Hanne

    2016-11-01

    Lactobacillus acidophilus induces a potent interferon-β (IFN-β) response in dendritic cells (DCs) by a Toll-like receptor 2 (TLR2) -dependent mechanism, in turn leading to strong interleukin-12 (IL-12) production. In the present study, we investigated the involvement of different types of endocytosis in the L. acidophilus-induced IFN-β and IL-12 responses and how TLR2 or TLR4 ligation by lipopolysaccharide and Pam3/4CSK4 influenced endocytosis of L. acidophilus and the induced IFN-β and IL-12 production. Lactobacillus acidophilus was endocytosed by constitutive macropinocytosis taking place in the immature cells as well as by spleen tyrosine kinase (Syk) -dependent phagocytosis but without involvement of plasma membrane TLR2. Stimulation with TLR2 or TLR4 ligands increased macropinocytosis in a Syk-independent manner. As a consequence, incubation of DCs with TLR ligands before incubation with L. acidophilus enhanced the uptake of the bacteria. However, in these experimental conditions, induction of IFN-β and IL-12 was strongly inhibited. As L. acidophilus-induced IFN-β depends on endocytosis and endosomal degradation before signalling and as TLR stimulation from the plasma membrane leading to increased macropinocytosis abrogates IFN-β induction we conclude that plasma membrane TLR stimulation leading to increased macropinocytosis decreases endosomal induction of IFN-β and speculate that this is due to competition between compartments for molecules involved in the signal pathways. In summary, endosomal signalling by L. acidophilus that leads to IFN-β and IL-12 production is inhibited by TLR stimulation from the plasma membrane.

  9. Combined inhibition of p38 and Akt signaling pathways abrogates cyclosporine A-mediated pathogenesis of aggressive skin SCCs

    Energy Technology Data Exchange (ETDEWEB)

    Arumugam, Aadithya; Walsh, Stephanie B.; Xu, Jianmin; Afaq, Farrukh [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019 (United States); Elmets, Craig A. [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019 (United States); Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019 (United States); Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer p38 and Akt are the crucial molecular targets in the pathogenesis of SCCs in OTRs. Black-Right-Pointing-Pointer Combined inhibition of these targets diminished tumor growth by 90%. Black-Right-Pointing-Pointer Inhibition of these targets act through downregulating mTOR signaling pathway. -- Abstract: Non-melanoma skin cancers (NMSCs) are the most common neoplasm in organ transplant recipients (OTRs). These cancers are more invasive and metastatic as compared to those developed in normal cohorts. Previously, we have shown that immunosuppressive drug, cyclosporine A (CsA) directly alters tumor phenotype of cutaneous squamous cell carcinomas (SCCs) by activating TGF-{beta} and TAK1/TAB1 signaling pathways. Here, we identified novel molecular targets for the therapeutic intervention of these SCCs. We observed that combined blockade of Akt and p38 kinases-dependent signaling pathways in CsA-promoted human epidermoid carcinoma A431 xenograft tumors abrogated their growth by more than 90%. This diminution in tumor growth was accompanied by a significant decrease in proliferation and an increase in apoptosis. The residual tumors following the combined treatment with Akt inhibitor triciribine and p38 inhibitors SB-203580 showed significantly diminished expression of phosphorylated Akt and p38 and these tumors were less invasive and highly differentiated. Diminished tumor invasiveness was associated with the reduced epithelial-mesenchymal transition as ascertained by the enhanced E-cadherin and reduced vimentin and N-cadherin expression. Consistently, these tumors also manifested reduced MMP-2/9. The decreased p-Akt expression was accompanied by a significant reduction in p-mTOR. These data provide first important combinatorial pharmacological approach to block the pathogenesis of CsA-induced highly aggressive cutaneous neoplasm in OTRs.

  10. Oral delivery of Brucella spp. recombinant protein U-Omp16 abrogates the IgE-mediated milk allergy

    Science.gov (United States)

    Smaldini, Paola Lorena; Ibañez, Andrés Esteban; Fossati, Carlos Alberto; Cassataro, Juliana; Docena, Guillermo Horacio

    2014-01-01

    Food allergies are increasingly common disorders and no therapeutic strategies are yet approved. The unlipidated Omp16 (U-Omp16) is the outer membrane protein of 16 kDa from B. abortus and possesses a mucosal adjuvant property. In this study, we aimed to examine the U-Omp16 capacity to abrogate an allergen-specific Th2 immune response when it is administered as an oral adjuvant in a mouse model of food allergy.   Balb/c mice were sensitized with cholera toxin and cow’s milk proteins (CMP) by gavage and simultaneously treated with U-Omp16 and CMP. Oral challenge with CMP was performed to evaluate the allergic status of mice. Symptoms, local (small bowel cytokine and transcription factor gene expression) and systemic (specific isotypes and spleen cell-secreted cytokines) parameters, and skin tests were done to evaluate the immune response. We found that the oral administration of U-Omp16 with CMP during sensitization dampened the allergic symptoms, with negativization of immediate skin test and increased skin DTH response. Serum specific IgE and IL-5 were inhibited and a Th1 response was promoted (specific IgG2a antibodies and CMP-induced IFN-γ secretion). We found at the mucosal site an inhibition of the gene expression corresponding to IL-13 and Gata-3, with an induction of IFN-γ and T-bet. These results indicated that the oral administration of U-Omp16 significantly controlled the allergic response in sensitized mice with a shift of the balance of Th1- and Th2-T cells toward Th1 predominance. These findings suggest that U-Omp16 may be useful as a Th1-directing adjuvant in an oral vaccine. PMID:25424811

  11. Hepatitis C virus core protein abrogates the DDX3 function that enhances IPS-1-mediated IFN-beta induction.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Oshiumi

    Full Text Available The DEAD box helicase DDX3 assembles IPS-1 (also called Cardif, MAVS, or VISA in non-infected human cells where minimal amounts of the RIG-I-like receptor (RLR protein are expressed. DDX3 C-terminal regions directly bind the IPS-1 CARD-like domain as well as the N-terminal hepatitis C virus (HCV core protein. DDX3 physically binds viral RNA to form IPS-1-containing spots, that are visible by confocal microscopy. HCV polyU/UC induced IPS-1-mediated interferon (IFN-beta promoter activation, which was augmented by co-transfected DDX3. DDX3 spots localized near the lipid droplets (LDs where HCV particles were generated. Here, we report that HCV core protein interferes with DDX3-enhanced IPS-1 signaling in HEK293 cells and in hepatocyte Oc cells. Unlike the DEAD box helicases RIG-I and MDA5, DDX3 was constitutively expressed and colocalized with IPS-1 around mitochondria. In hepatocytes (O cells with the HCV replicon, however, DDX3/IPS-1-enhanced IFN-beta-induction was largely abrogated even when DDX3 was co-expressed. DDX3 spots barely merged with IPS-1, and partly assembled in the HCV core protein located near the LD in O cells, though in some O cells IPS-1 was diminished or disseminated apart from mitochondria. Expression of DDX3 in replicon-negative or core-less replicon-positive cells failed to cause complex formation or LD association. HCV core protein and DDX3 partially colocalized only in replicon-expressing cells. Since the HCV core protein has been reported to promote HCV replication through binding to DDX3, the core protein appears to switch DDX3 from an IFN-inducing mode to an HCV-replication mode. The results enable us to conclude that HCV infection is promoted by modulating the dual function of DDX3.

  12. Hepatitis C virus core protein abrogates the DDX3 function that enhances IPS-1-mediated IFN-beta induction.

    Science.gov (United States)

    Oshiumi, Hiroyuki; Ikeda, Masanori; Matsumoto, Misako; Watanabe, Ayako; Takeuchi, Osamu; Akira, Shizuo; Kato, Nobuyuki; Shimotohno, Kunitada; Seya, Tsukasa

    2010-12-08

    The DEAD box helicase DDX3 assembles IPS-1 (also called Cardif, MAVS, or VISA) in non-infected human cells where minimal amounts of the RIG-I-like receptor (RLR) protein are expressed. DDX3 C-terminal regions directly bind the IPS-1 CARD-like domain as well as the N-terminal hepatitis C virus (HCV) core protein. DDX3 physically binds viral RNA to form IPS-1-containing spots, that are visible by confocal microscopy. HCV polyU/UC induced IPS-1-mediated interferon (IFN)-beta promoter activation, which was augmented by co-transfected DDX3. DDX3 spots localized near the lipid droplets (LDs) where HCV particles were generated. Here, we report that HCV core protein interferes with DDX3-enhanced IPS-1 signaling in HEK293 cells and in hepatocyte Oc cells. Unlike the DEAD box helicases RIG-I and MDA5, DDX3 was constitutively expressed and colocalized with IPS-1 around mitochondria. In hepatocytes (O cells) with the HCV replicon, however, DDX3/IPS-1-enhanced IFN-beta-induction was largely abrogated even when DDX3 was co-expressed. DDX3 spots barely merged with IPS-1, and partly assembled in the HCV core protein located near the LD in O cells, though in some O cells IPS-1 was diminished or disseminated apart from mitochondria. Expression of DDX3 in replicon-negative or core-less replicon-positive cells failed to cause complex formation or LD association. HCV core protein and DDX3 partially colocalized only in replicon-expressing cells. Since the HCV core protein has been reported to promote HCV replication through binding to DDX3, the core protein appears to switch DDX3 from an IFN-inducing mode to an HCV-replication mode. The results enable us to conclude that HCV infection is promoted by modulating the dual function of DDX3.

  13. Antioxidants Abrogate Alpha-Tocopherylquinone-Mediated Down-Regulation of the Androgen Receptor in Androgen-Responsive Prostate Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Alexandra M Fajardo

    Full Text Available Tocopherylquinone (TQ, the oxidation product of alpha-tocopherol (AT, is a bioactive molecule with distinct properties from AT. In this study, AT and TQ are investigated for their comparative effects on growth and androgenic activity in prostate cancer cells. TQ potently inhibited the growth of androgen-responsive prostate cancer cell lines (e.g., LAPC4 and LNCaP cells, whereas the growth of androgen-independent prostate cancer cells (e.g., DU145 cells was not affected by TQ. Due to the growth inhibitory effects induced by TQ on androgen-responsive cells, the anti-androgenic properties of TQ were examined. TQ inhibited the androgen-induced activation of an androgen-responsive reporter and inhibited the release of prostate specific antigen from LNCaP cells. TQ pretreatment was also found to inhibit AR activation as measured using the Multifunctional Androgen Receptor Screening assay. Furthermore, TQ decreased androgen-responsive gene expression, including TM4SF1, KLK2, and PSA over 5-fold, whereas AT did not affect the expression of androgen-responsive genes. Of importance, the antiandrogenic effects of TQ on prostate cancer cells were found to result from androgen receptor protein down-regulation produced by TQ that was not observed with AT treatment. Moreover, none of the androgenic endpoints assessed were affected by AT. The down-regulation of androgen receptor protein by TQ was abrogated by co-treatment with antioxidants. Overall, the biological actions of TQ were found to be distinct from AT, where TQ was found to be a potent inhibitor of cell growth and androgenic activity in androgen-responsive prostate cancer cells.

  14. A combination of an anti-SLAMF6 antibody and ibrutinib efficiently abrogates expansion of chronic lymphocytic leukemia cells

    Science.gov (United States)

    Yigit, Burcu; Halibozek, Peter J.; Chen, Shih-Shih; O'Keeffe, Michael S.; Arnason, Jon; Avigan, David; Gattei, Valter; Bhan, Atul; Cen, Osman; Longnecker, Richard; Chiorazzi, Nicholas; Wang, Ninghai; Engel, Pablo; Terhorst, Cox

    2016-01-01

    The signaling lymphocyte activation molecule family [SLAMF] of cell surface receptors partakes in both the development of several immunocyte lineages and innate and adaptive immune responses in humans and mice. For instance, the homophilic molecule SLAMF6 (CD352) is in part involved in natural killer T cell development, but also modulates T follicular helper cell and germinal B cell interactions. Here we report that upon transplantation of a well-defined aggressive murine B220+CD5+ Chronic Lymphocytic Leukemia (CLL) cell clone, TCL1-192, into SCID mice one injection of a monoclonal antibody directed against SLAMF6 (αSlamf6) abrogates tumor progression in the spleen, bone marrow and blood. Similarly, progression of a murine B cell lymphoma, LMP2A/λMyc, was also eliminated by αSlamf6. But, surprisingly, αSLAMF6 neither eliminated TCL1-192 nor LMP2A/λMyc cells, which resided in the peritoneal cavity or omentum. This appeared to be dependent upon the tumor environment, which affected the frequency of sub-populations of the TCL1-192 clone or the inability of peritoneal macrophages to induce Antibody Dependent Cellular Cytotoxicity (ADCC). However, co-administering αSlamf6 with the Bruton tyrosine kinase (Btk) inhibitor, ibrutinib, synergized to efficiently eliminate the tumor cells in the spleen, bone marrow, liver and the peritoneal cavity. Because an anti-human SLAMF6 mAb efficiently killed human CLL cells in vitro and in vivo, we propose that a combination of αSlamf6 with ibrutinib should be considered as a novel therapeutic approach for CLL and other B cell tumors. PMID:27029059

  15. Comparison of bifunctional chelates for {sup 64}Cu antibody imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Cara L.; Crisp, Sarah; Bensimon, Corinne [MDS Nordion, Vancouver, BC (Canada); Yapp, Donald T.T.; Ng, Sylvia S.W. [British Columbia Cancer Agency Research Centre, Vancouver, BC (Canada); University of British Columba, The Faculty of Pharmaceutical Sciences, Vancouver, BC (Canada); Sutherland, Brent W. [British Columbia Cancer Agency Research Centre, Vancouver, BC (Canada); Gleave, Martin [Prostate Centre at Vancouver General Hospital, Vancouver, BC (Canada); Jurek, Paul; Kiefer, Garry E. [Macrocyclics Inc., Dallas, TX (United States)

    2010-11-15

    Improved bifunctional chelates (BFCs) are needed to facilitate efficient {sup 64}Cu radiolabeling of monoclonal antibodies (mAbs) under mild conditions and to yield stable, target-specific agents. The utility of two novel BFCs, 1-Oxa-4,7,10-triazacyclododecane-5-S-(4-isothiocyanatobenzyl)-4,7,10-triacetic acid (p-SCN-Bn-Oxo-DO3A) and 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-4-S-(4-isothiocyanatobenzyl)-3,6,9-triacetic acid (p-SCN-Bn-PCTA), for mAb imaging with {sup 64}Cu were compared to the commonly used S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (p-SCN-Bn-DOTA). The BFCs were conjugated to trastuzumab, which targets the HER2/neu receptor. {sup 64}Cu radiolabeling of the conjugates was optimized. Receptor binding was analyzed using flow cytometry and radioassays. Finally, PET imaging and biodistribution studies were done in mice bearing either HER2/neu-positive or HER2/neu-negative tumors. {sup 64}Cu-Oxo-DO3A- and PCTA-trastuzumab were prepared at room temperature in >95% radiochemical yield (RCY) in <30 min, compared to only 88% RCY after 2 h for the preparation of {sup 64}Cu-DOTA-trastuzumab under the same conditions. Cell studies confirmed that the immunoreactivity of the mAb was retained for each of the bioconjugates. In vivo studies showed that {sup 64}Cu-Oxo-DO3A- and PCTA-trastuzumab had higher uptake than the {sup 64}Cu-DOTA-trastuzumab at 24 h in HER2/neu-positive tumors, resulting in higher tumor to background ratios and better tumor images. By 40 h all three of the {sup 64}Cu-BFC-trastuzumab conjugates allowed for clear visualization of the HER2/neu-positive tumors but not the negative control tumor. The antibody conjugates of PCTA and Oxo-DO3A were shown to have superior {sup 64}Cu radiolabeling efficiency and stability compared to the analogous DOTA conjugate. In addition, {sup 64}Cu-PCTA and Oxo-DO3A antibody conjugates may facilitate earlier imaging with greater target to background ratios than

  16. N-acetylcysteine protects rats with chronic renal failure from gadolinium-chelate nephrotoxicity.

    Directory of Open Access Journals (Sweden)

    Leonardo Victor Barbosa Pereira

    Full Text Available The aim of this study was to evaluate the effect of Gd-chelate on renal function, iron parameters and oxidative stress in rats with CRF and a possible protective effect of the antioxidant N-Acetylcysteine (NAC. Male Wistar rats were submitted to 5/6 nephrectomy (Nx to induced CRF. An ionic-cyclic Gd (Gadoterate Meglumine was administrated (1.5 mM/KgBW, intravenously 21 days after Nx. Clearance studies were performed in 4 groups of anesthetized animals 48 hours following Gd- chelate administration: 1--Nx (n = 7; 2--Nx+NAC (n = 6; 3--Nx+Gd (n = 7; 4--Nx+NAC+Gd (4.8 g/L in drinking water, initiated 2 days before Gd-chelate administration and maintained during 4 days (n = 6. This group was compared with a control. We measured glomerular filtration rate, GFR (inulin clearance, ml/min/kg BW, proteinuria (mg/24 hs, serum iron (µg/dL; serum ferritin (ng/mL; transferrin saturation (%, TIBC (µg/dL and TBARS (nmles/ml. Normal rats treated with the same dose of Gd-chelate presented similar GFR and proteinuria when compared with normal controls, indicating that at this dose Gd-chelate is not nephrotoxic to normal rats. Gd-chelate administration to Nx-rats results in a decrease of GFR and increased proteinuria associated with a decrease in TIBC, elevation of ferritin serum levels, transferrin oversaturation and plasmatic TBARS compared with Nx-rats. The prophylactic treatment with NAC reversed the decrease in GFR and the increase in proteinuria and all alterations in iron parameters and TBARS induced by Gd-chelate. NAC administration to Nx rat did not modify the inulin clearance and iron kinetics, indicating that the ameliorating effect of NAC was specific to Gd-chelate. These results suggest that NAC can prevent Gd-chelate nephrotoxicity in patients with chronic renal failure.

  17. Reversible adsorption of catalase onto Fe(3+) chelated poly(AAm-GMA)-IDA cryogels.

    Science.gov (United States)

    Aktaş Uygun, Deniz; Uygun, Murat; Akgöl, Sinan; Denizli, Adil

    2015-05-01

    In this presented study, poly(acrylamide-glycidyl methacrylate) [poly(AAm-GMA)] cryogels were synthesized by cryopolymerization technique at sub-zero temperature. Prepared cryogels were then functionalized with iminodiacetic acid (IDA) and chelated with Fe(3+) ions in order produce the metal chelate affinity matrix. Synthesized cryogels were characterized with FTIR, ESEM and EDX analysis, and it was found that the cryogel had sponge like structure with interconnected pores and their pore diameter was about 200 μm. Fe(3+) chelated poly(AAm-GMA)-IDA cryogels were used for the adsorption of catalase and optimum adsorption conditions were determined by varying the medium pH, initial catalase concentration, temperature and ionic strength. Maximum catalase adsorption onto Fe(3+) chelated poly(AAm-GMA)-IDA cryogel was found to be 12.99 mg/g cryogel at 25 °C, by using pH 5.0 acetate buffer. Adsorbed catalase was removed from the cryogel by using 1.0M of NaCl solution and desorption yield was found to be 96%. Additionally, reusability profile of the Fe(3+) chelated poly(AAm-GMA)-IDA cryogel was also investigated and it was found that, adsorption capacity of the cryogels didn't decrease significantly at the end of the 40 reuses. Catalase activity studies were also tested and it was demonstrated that desorbed catalase retained 70% of its initial activity.

  18. Preparation of amine group-containing chelating fiber for thorough removal of mercury ions.

    Science.gov (United States)

    Ma, Nianfang; Yang, Ying; Chen, Shuixia; Zhang, Qikun

    2009-11-15

    An aminated chelating fiber (AF) with high adsorption capacity for mercury ions was prepared by grafting copolymerization of acrylonitrile onto polypropylene fiber, followed by aminating with chelating molecule diethylenetriamine. Effects of reaction conditions such as temperature, reaction time, bath ratio and dosage of catalyst on the grafting yield were studied. Chemical structure, tensile strength and thermal stability of AF were characterized. The adsorption performances for mercury were evaluated by batch adsorption experiments and kinetic experiments. The results show that AF is effective for the removal of mercury over a wide range of pH. The chelating fiber also shows much higher adsorption capacities for mercury, the equilibrium adsorption amount could be as high as 657.9 mg/g for mercury. The high adsorption capacity of Hg(2+) on AF is resulted from the strong chelating interaction between amine groups and mercury ions. Two amine groups coordinate with one mercury ion could be speculated from the adsorption capacity and amine group content on AF. The kinetic adsorption results indicate that the adsorption rates of AF for mercury are very rapid. Furthermore, the residual concentration was less than 1 microg/L with feed concentration of mercury below 1mg/L, which can meet the criterion of drinking water, which indicates that the chelating fiber prepared in this study could be applied to low-level Hg contaminated drinking water purification.

  19. Iron Chelation Inhibits Osteoclastic Differentiation In Vitro and in Tg2576 Mouse Model of Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Jun-Peng Guo

    Full Text Available Patients of Alzheimer's disease (AD frequently have lower bone mineral density and higher rate of hip fracture. Tg2576, a well characterized AD animal model that ubiquitously express Swedish mutant amyloid precursor protein (APPswe, displays not only AD-relevant neuropathology, but also age-dependent bone deficits. However, the underlying mechanisms remain poorly understood. As APP is implicated as a regulator of iron export, and the metal chelation is considered as a potential therapeutic strategy for AD, we examined iron chelation's effect on the osteoporotic deficit in Tg2576 mice. Remarkably, in vivo treatment with iron chelator, clinoquinol (CQ, increased both trabecular and cortical bone-mass, selectively in Tg2576, but not wild type (WT mice. Further in vitro studies showed that low concentrations of CQ as well as deferoxamine (DFO, another iron chelator, selectively inhibited osteoclast (OC differentiation, without an obvious effect on osteoblast (OB differentiation. Intriguingly, both CQ and DFO's inhibitory effect on OC was more potent in bone marrow macrophages (BMMs from Tg2576 mice than that of wild type controls. The reduction of intracellular iron levels in BMMs by CQ was also more dramatic in APPswe-expressing BMMs. Taken together, these results demonstrate a potent inhibition on OC formation and activation in APPswe-expressing BMMs by iron chelation, and reveal a potential therapeutic value of CQ in treating AD-associated osteoporotic deficits.

  20. Chapter 5 - Development of iron chelator-nanoparticle conjugates as potential therapeutic agents for Alzheimer disease.

    Science.gov (United States)

    Liu, Gang; Men, Ping; Perry, George; Smith, Mark A

    2009-01-01

    Oxidative stress is known to play a key role in the initiation and promotion of the neurodegeneration that characterizes the pathogenesis of Alzheimer disease (AD). An accumulation of redox active transition metals, including iron and copper, is likely a major generator of reactive oxidative species and other free radicals and is thought to induce a detrimental cycle of oxidative stress, amyloid-beta aggregation, and neurodegeneration. As such, metal chelators may provide an alternative therapeutic approach to sequester redox active metals and prevent the onslaught of oxidative damage. Unfortunately, however, metal chelation approaches are currently limited in their potential, since many cannot readily pass the blood-brain barrier (BBB), due to their hydrophilicity, and many are neurotoxic at high concentrations. To circumvent such issues, here we describe the development of iron chelator-nanoparticle conjugation that allows delivery of target chelator to the brain in the absence of neurotoxicity. Such nanoparticle delivery of iron chelators will likely provide a highly advantageous mode of attack on the oxidative stress that plagues AD as well as other conditions characterized by excess metal accumulation.

  1. Iron Chelation Inhibits Osteoclastic Differentiation In Vitro and in Tg2576 Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Guo, Jun-Peng; Pan, Jin-Xiu; Xiong, Lei; Xia, Wen-Fang; Cui, Shun; Xiong, Wen-Cheng

    2015-01-01

    Patients of Alzheimer's disease (AD) frequently have lower bone mineral density and higher rate of hip fracture. Tg2576, a well characterized AD animal model that ubiquitously express Swedish mutant amyloid precursor protein (APPswe), displays not only AD-relevant neuropathology, but also age-dependent bone deficits. However, the underlying mechanisms remain poorly understood. As APP is implicated as a regulator of iron export, and the metal chelation is considered as a potential therapeutic strategy for AD, we examined iron chelation's effect on the osteoporotic deficit in Tg2576 mice. Remarkably, in vivo treatment with iron chelator, clinoquinol (CQ), increased both trabecular and cortical bone-mass, selectively in Tg2576, but not wild type (WT) mice. Further in vitro studies showed that low concentrations of CQ as well as deferoxamine (DFO), another iron chelator, selectively inhibited osteoclast (OC) differentiation, without an obvious effect on osteoblast (OB) differentiation. Intriguingly, both CQ and DFO's inhibitory effect on OC was more potent in bone marrow macrophages (BMMs) from Tg2576 mice than that of wild type controls. The reduction of intracellular iron levels in BMMs by CQ was also more dramatic in APPswe-expressing BMMs. Taken together, these results demonstrate a potent inhibition on OC formation and activation in APPswe-expressing BMMs by iron chelation, and reveal a potential therapeutic value of CQ in treating AD-associated osteoporotic deficits.

  2. Intracellular reduction/activation of a disulfide switch in thiosemicarbazone iron chelators

    Science.gov (United States)

    Akam, Eman A.; Chang, Tsuhen M.; Astashkin, Andrei V.

    2014-01-01

    Iron scavengers (chelators) offer therapeutic opportunities in anticancer drug design by targeting the increased demand for iron in cancer cells as compared to normal cells. Prochelation approaches are expected to avoid systemic iron depletion as chelators are liberated under specific intracellular conditions. In the strategy described herein, a disulfide linkage is employed as a redox-directed switch within the binding unit of an antiproliferative thiosemicarbazone prochelator, which is activated for iron coordination following reduction to the thiolate chelator. In glutathione redox buffer, this reduction event occurs at physiological concentrations and half-cell potentials. Consistent with concurrent reduction and activation, higher intracellular thiol concentrations increase cell susceptibility to prochelator toxicity in cultured cancer cells. The reduction of the disulfide switch and intracellular iron chelation are confirmed in cell-based assays using calcein as a fluorescent probe for paramagnetic ions. The resulting low-spin Fe(III) complex is identified in intact Jurkat cells by EPR spectroscopy measurements, which also document a decreased concentration of active ribonucleotide reductase following exposure to the prochelator. Cell viability and fluorescence-based assays show that the iron complex presents low cytotoxicity and does not participate in intracellular redox chemistry, indicating that this antiproliferative chelation strategy does not rely on the generation of reactive oxygen species. PMID:25100578

  3. Increased Uptake of Chelated Copper Ions by Lolium perenne Attributed to Amplified Membrane and Endodermal Damage

    Directory of Open Access Journals (Sweden)

    Anthea Johnson

    2015-10-01

    Full Text Available The contributions of mechanisms by which chelators influence metal translocation to plant shoot tissues are analyzed using a combination of numerical modelling and physical experiments. The model distinguishes between apoplastic and symplastic pathways of water and solute movement. It also includes the barrier effects of the endodermis and plasma membrane. Simulations are used to assess transport pathways for free and chelated metals, identifying mechanisms involved in chelate-enhanced phytoextraction. Hypothesized transport mechanisms and parameters specific to amendment treatments are estimated, with simulated results compared to experimental data. Parameter values for each amendment treatment are estimated based on literature and experimental values, and used for model calibration and simulation of amendment influences on solute transport pathways and mechanisms. Modeling indicates that chelation alters the pathways for Cu transport. For free ions, Cu transport to leaf tissue can be described using purely apoplastic or transcellular pathways. For strong chelators (ethylenediaminetetraacetic acid (EDTA and diethylenetriaminepentaacetic acid (DTPA, transport by the purely apoplastic pathway is insufficient to represent measured Cu transport to leaf tissue. Consistent with experimental observations, increased membrane permeability is required for simulating translocation in EDTA and DTPA treatments. Increasing the membrane permeability is key to enhancing phytoextraction efficiency.

  4. Increased Uptake of Chelated Copper Ions by Lolium perenne Attributed to Amplified Membrane and Endodermal Damage.

    Science.gov (United States)

    Johnson, Anthea; Singhal, Naresh

    2015-10-23

    The contributions of mechanisms by which chelators influence metal translocation to plant shoot tissues are analyzed using a combination of numerical modelling and physical experiments. The model distinguishes between apoplastic and symplastic pathways of water and solute movement. It also includes the barrier effects of the endodermis and plasma membrane. Simulations are used to assess transport pathways for free and chelated metals, identifying mechanisms involved in chelate-enhanced phytoextraction. Hypothesized transport mechanisms and parameters specific to amendment treatments are estimated, with simulated results compared to experimental data. Parameter values for each amendment treatment are estimated based on literature and experimental values, and used for model calibration and simulation of amendment influences on solute transport pathways and mechanisms. Modeling indicates that chelation alters the pathways for Cu transport. For free ions, Cu transport to leaf tissue can be described using purely apoplastic or transcellular pathways. For strong chelators (ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA)), transport by the purely apoplastic pathway is insufficient to represent measured Cu transport to leaf tissue. Consistent with experimental observations, increased membrane permeability is required for simulating translocation in EDTA and DTPA treatments. Increasing the membrane permeability is key to enhancing phytoextraction efficiency.

  5. Mechanism and efficiency of cell death of type II photosensitizers: effect of zinc chelation.

    Science.gov (United States)

    Pavani, Christiane; Iamamoto, Yassuko; Baptista, Maurício S

    2012-01-01

    A series of meso-substituted tetra-cationic porphyrins, which have methyl and octyl substituents, was studied in order to understand the effect of zinc chelation and photosensitizer subcellular localization in the mechanism of cell death. Zinc chelation does not change the photophysical properties of the photosensitizers (all molecules studied are type II photosensitizers) but affects considerably the interaction of the porphyrins with membranes, reducing mitochondrial accumulation. The total amount of intracellular reactive species induced by treating cells with photosensitizer and light is similar for zinc-chelated and free-base porphyrins that have the same alkyl substituent. Zinc-chelated porphyrins, which are poorly accumulated in mitochondria, show higher efficiency of cell death with features of apoptosis (higher MTT response compared with trypan blue staining, specific acridine orange/ethidium bromide staining, loss of mitochondrial transmembrane potential, stronger cytochrome c release and larger sub-G1 cell population), whereas nonchelated porphyrins, which are considerably more concentrated in mitochondria, triggered mainly necrotic cell death. We hypothesized that zinc-chelation protects the photoinduced properties of the porphyrins in the mitochondrial environment.

  6. Synthesis, characterization and cyclic voltammetric study of copper(II) and nickel(II) polymer chelates.

    Science.gov (United States)

    Azmeera, Venkanna; Rastogi, Pankaj Kumar; Adhikary, Pubali; Ganesan, Vellaichamy; Krishnamoorthi, S

    2014-09-22

    Graft copolymers based on dextran (Dx) and 2-acrylamido-2-methyl-1-propane sulphonic acid (AMPS) were synthesized by free radical initiated solution polymerization technique using ceric ammonium nitrate as initiator. These graft copolymers were used to prepare Cu(II) and Ni(II) chelates by reactions with Cu(II) and Ni(II) metal ions respectively. Graft copolymer and metal chelates were characterized by elemental analysis, intrinsic viscosity, FT-IR, scanning electron microscopy (SEM), atomic force microscopy (AFM), thermogravimetric analysis (TGA) and powder X-ray diffraction (XRD). Elemental analysis, intrinsic viscosity and FT-IR studies revealed the incorporation of metal ions to form metal chelates. SEM studies showed the change in morphology due to metal incorporation. From AFM studies it was observed that there was increase in Root mean square (RMS) roughness values in case of metal complexes. Metal chelates were observed to be thermally more stable than graft copolymer from TGA. UV-vis spectroscopy study revealed increase in absorbance values and cyclic voltammetric (CV) studies showed more than tenfold increase in redox current due to formation of Cu(II) and Ni(II) metal chelates. The binding constants of each complex determined by using UV-visible spectroscopy revealed that Cu(II) has more binding ability than Ni(II).

  7. Study of Competitive Chelating Reaction between Lanthanum and Tribromoarsenazo in the Medium of Weak Acid by Capillary Zone Electrophoresis

    Institute of Scientific and Technical Information of China (English)

    胡涌刚; 周培疆; 邓延倬; 程介克

    2003-01-01

    Two kinds of metal chelates of rare earth elements reacted with tribrimoarsenazo formed under the condition of critic acid were observed by simultaneous technique of capillary electrophoresisphotothermal interference spectrometry. The tendency of the conversion between these chelates as functions of the mole ratio of the reagent and the metal, pH value and the elapsing time was investigated. Kinetic equation of competitive chelating reaction between the TBA-La (Ⅲ) and La (Ⅲ) -critic acid were established. It was found that the competitive chelating reaction follows secondorder kinetics, for this second-order reaction, k=5.55 L·mol-1·S-1.

  8. Thumbnail Sketches: EDTA-Type Chelating Agents in Everyday Consumer Products: Some Medicinal and Personal Care Products.

    Science.gov (United States)

    Hart, J. Roger

    1984-01-01

    Discusses various ethylenediaminetetraacetate (EDTA)-type chelating agents found in ophthalmic products, personal care products, and disinfectants. Also discusses the properties and action of these EDTA agents. (JN)

  9. The hexadentate hydroxypyridinonate TREN-(Me-3,2-HOPO) is a more orally active iron chelator than its bidentate analogue.

    Science.gov (United States)

    Yokel, R A; Fredenburg, A M; Durbin, P W; Xu, J; Rayens, M K; Raymond, K N

    2000-04-01

    Bidentate hydroxypyridinone chelators effectively complex and facilitate excretion of trivalent iron. To test the hypothesis that hexadentate chelators are more effective than bidentate chelators at low concentrations, urinary and biliary Fe excretions were determined in Fe-loaded rats before and after administration of a bidentate chelator, Pr-(Me-3,2-HOPO), or its hexadentate analogue, TREN-(Me-3,2-HOPO). The bidentate chelator slightly increased biliary Fe excretion in Fe-loaded rats after IV (90 micromol/kg) and PO (90 or 270 micromol/kg) administration, but chelation efficiency did not exceed 1%. The hexadentate chelator markedly increased biliary Fe excretion, achieving overall chelation efficiencies of 14% after IV administration of 30 micromol/kg and 8 or 3% after PO (30 or 90 micromol/kg) administration. The hexadentate chelator was significantly more effective than the bidentate chelator after IV injection and oral dosing. In chelator-treated Fe-loaded or saline-injected rats, >90% of the excreted Fe was in the bile. Oral TREN-(Me-3,2-HOPO), given to non-Fe-loaded rats, did not appreciably change Fe output, indicating that there was little Fe depletion in the absence of Fe overload. These results support the hypothesis that greater Fe chelation efficiency can be achieved with hexadentate than with bidentate chelators at lower, and presumably safer, concentrations. The results also demonstrate that TREN-(Me-3, 2-HOPO) is a promising, orally effective, Fe chelator.

  10. Abrogation of E-cadherin-mediated cellular aggregation allows proliferation of pluripotent mouse embryonic stem cells in shake flask bioreactors.

    Directory of Open Access Journals (Sweden)

    Lisa Mohamet

    Full Text Available BACKGROUND: A fundamental requirement for the exploitation of embryonic stem (ES cells in regenerative medicine is the ability to reproducibly derive sufficient numbers of cells of a consistent quality in a cost-effective manner. However, undifferentiated ES cells are not ideally suited to suspension culture due to the formation of cellular aggregates, ultimately limiting scalability. Significant advances have been made in recent years in the culture of ES cells, including automated adherent culture and suspension microcarrier or embryoid body bioreactor culture. However, each of these methods exhibits specific disadvantages, such as high cost, additional downstream processes or reduced cell doubling times. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that abrogation of the cell surface protein E-cadherin, using either gene knockout (Ecad-/- or the neutralising antibody DECMA-1 (EcadAb, allows culture of mouse ES cells as a near-single cell suspension in scalable shake flask culture over prolonged periods without additional media supplements. Both Ecad-/- and EcadAb ES cells exhibited adaptation phases in suspension culture, with optimal doubling times of 7.3 h±0.9 and 15.6 h±4.7 respectively and mean-fold increase in viable cell number of 95.1±2.0 and 16±0.9-fold over 48 h. EcadAb ES cells propagated as a dispersed cell suspension for 15 d maintained expression of pluripotent markers, exhibited a normal karyotype and high viability. Subsequent differentiation of EcadAb ES cells resulted in expression of transcripts and proteins associated with the three primary germ layers. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration of the culture of pluripotent ES cells as a near-single cell suspension in a manual fed-batch shake flask bioreactor and represents a significant improvement on current ES cell culture techniques. Whilst this proof-of-principle method would be useful for the culture of human ES and iPS cells, further steps are

  11. Synthesis and Preparation of Polysulfone Hollow Fiber Chelating Membrane Modified with Thiourea

    Institute of Scientific and Technical Information of China (English)

    WANG Bing; HUANG Lei; XIAO Feng

    2006-01-01

    Several kinds of chloromethyl polysulfones (CMPF) with different chlorinity and reactive groups were synthesized by Friedel-crafts reaction, which could be utilized as reactively matrix membrane materials. The CMPF hollow matrix membranes were prepared with phase inversion by utilization of CMPF/additive/DMAC casting solution and CMPF as membrane materials. It was found that the effects of additive content, bore liquid and dry spinning distance on the structure of CMPF hollow fiber matrix membrane were different. A high qualified polysulfone hollow fiber chelating membrane modified with thiourea as chelating groups was prepared using CMPF as membrane matrix materials,through the reaction between thiourea and CMPF hollow fiber matrix membrane to afford the methyl iso-thiourium polysulfone. The experimental results showed that thermal drawing could increase the mechanical properties of matrix membrane, and the thermal treatment could increase the homogeneity and stability of the structure of polysulfone hollow fiber chelating membrane modified with thiourea.

  12. Inhibitor Ranking Through QM based Chelation Calculations for Virtual Screening of HIV-1 RNase H inhibition

    DEFF Research Database (Denmark)

    Poongavanam, Vasanthanathan; Svendsen, Casper Steinmann; Kongsted, Jacob

    2014-01-01

    . Furthermore, full protein fragment molecular orbital (FMO) calculations were conducted and subsequently analysed for individual residue stabilization/destabilization energy contributions to the overall binding affinity in order to better understand the true and false predictions. After a successful assessment......Quantum mechanical (QM) calculations have been used to predict the binding affinity of a set of ligands towards HIV-1 RT associated RNase H (RNH). The QM based chelation calculations show improved binding affinity prediction for the inhibitors compared to using an empirical scoring function...... of the methods based on the use of a training set of molecules, QM based chelation calculations were used as filter in virtual screening of compounds in the ZINC database. By this, we find, compared to regular docking, QM based chelation calculations to significantly reduce the large number of false positives...

  13. Separation of metal chelates and organometallic compounds by SFC and SFE/GC.

    Science.gov (United States)

    Wai, C M; Wang, S

    2000-07-05

    Supercritical fluid chromatography (SFC) combines the high diffusion coefficients of gas chromatography (GC) and the solubility properties of liquid chromatography (LC). SFC generally requires lower temperatures for chromatographic separations and thus is more suitable for analyzing thermally labile compounds including a number of metal chelates and organometallic compounds. SFC also allows interfacing between supercritical fluid extraction (SFE) and chromatographic analysis of metal-containing compounds. A large number of metal chelates and organometallic compounds can be separated by SFC. This article summarizes SFC separation of various chelates of transition metals, heavy metals, lanthanides and actinides as well as organometallic compounds of lead, mercury, and tin reported in the recent literature. This article also discusses SFC detection systems and the determination of solubility of organometallic compounds by SFC.

  14. Synthesis and Characterization of 2-Decyl-DTPA and Its Gd(Ⅲ) Chelate

    Institute of Scientific and Technical Information of China (English)

    FENG Zhi-ming; LI Feng; CHEN Rong; ZHU Xiao-juan; LI Xiao-ru

    2004-01-01

    The present paper covers the synthesis and the characterization of ligand 2-decyl-3, 6, 9-tris(carboxymethyl)-3,6,9-triazaundecan-1,11-dioic acid, H5L, and its Gd(Ⅲ) chelate. The protonation constants for H5L(lgKHi=10.90, 8.50, 4.55, 2.92, 2.20) and the stability constant for GdL2- (lgKGdL2-=22.80) were determined by means of potentiometric titration. They are similar to the corresponding values of DTPA and Gd-DTPA, respectively. The results obtained show that the basicity of the ligand and the stability constant of its Gd(Ⅲ) chelate are not obviously altered after the introduction of a linear chain decyl group into the terminal acetic acid residue of DTPA. The Gd(Ⅲ) chelate may be a potential contrast agent with liver-specificity for magnetic resonance imaging(MRI).

  15. Critical evaluation of treatment strategies involving adsorption and chelation for wastewater containing copper, zinc and cyanide

    Energy Technology Data Exchange (ETDEWEB)

    Bose, P.; Bose, M.A.; Kumar, S. [Indian Inst. of Technology, Kanpur (India). Dept Civil Engineering, Environmental Engineering & Management Programme

    2002-11-01

    Industrial wastewater containing heavy metals and cyanide must be treatment for removal of both metals and cyanide before disposal. The study described evaluated treatment strategies involving some indigenous adsorbents and a low-cost chelating agent for treatment of a simulated wastewater containing copper and zinc, complexed with cyanide. Treatment strategies involving three adsorbents, sulfonated coal, biosorbent G. lucidum, and iron oxide coated sand (IOCS), and a chelating agent, insoluble agro-based starch xanthate (IAX), were tested. The evaluation procedure involved comparison of the performance of these treatment strategies with that of conventional treatment. Results indicate that treatment using the chelating agent IAX has the greatest potential as an alternative to the conventional treatment technique. The three adsorbents tested, although reported to be very effective in removing copper and zinc from pure systems, exhibit diminished metal removal capacity in the presence of cyanide, and hence are unsuitable.

  16. The effect of metal chelators on the production of hydroxyl radicals in thylakoids.

    Science.gov (United States)

    Snyrychová, Iva; Pospísil, Pavel; Naus, Jan

    2006-06-01

    The effect of metal chelators (EDTA, DTPA and Desferal) on the metal-catalyzed decomposition of hydrogen peroxide was studied using EPR spin-trapping spectroscopy. The formation of hydroxyl radicals (OH*) in both chemical (Fenton reaction) and biological (thylakoids) systems was stimulated by EDTA. DTPA promoted the generation of OH* in the presence of strong reducing agents, whereas in their absence it acted as an antioxidant. Desferal suppressed OH* production even in the presence of reductants. In our study, we have shown that metal chelators can both stimulate and suppress the formation of OH*, depending on the experimental conditions. In illuminated thylakoids we have observed prooxidant effect of EDTA and DTPA, possibly due to their reduction by some component of the electron transport chain. According to our results, metal chelators should not be used as antioxidants without prior testing of their effect in given samples.

  17. Bis-NHC chelate complexes of nickel(0) and platinum(0).

    Science.gov (United States)

    Brendel, Matthias; Braun, Carolin; Rominger, Frank; Hofmann, Peter

    2014-08-11

    For a long time d(10)-ML2 fragments have been known for their potential to activate unreactive bonds by oxidative addition. In the development of more active species, two approaches have proven successful: the use of strong σ-donating ligands leading to electron-rich metal centers and the employment of chelating ligands resulting in a bent coordination geometry. Combining these two strategies, we synthesized bis-NHC chelate complexes of nickel(0) and platinum(0). Bis(1,5-cyclooctadiene)nickel(0) and -platinum(0) react with bisimidazolium salts, deprotonated in situ at room temperature, to yield tetrahedral or trigonal-planar bis-NHC chelate olefin complexes. The synthesis and characterization of these complexes as well as a first example of C-C bond activation with these systems are reported. Due to the enforced cis arrangement of two NHCs, these compounds should open interesting perspectives for bond-activation chemistry and catalysis.

  18. Radiopharmaceutical stannic Sn-117m chelate compositions and methods of use

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Suresh C. (Setauket, NY); Meinken, George E. (Middle Island, NY)

    2001-01-01

    Radiopharmaceutical compositions including .sup.117m Sn labeled stannic (Sn.sup.4+) chelates are provided. The chelates are preferably polyhydroxycarboxylate, such as oxalates, tartrates, citrates, malonates, gluconates, glucoheptonates and the like. Methods of making .sup.117m Sn-labeled (Sn.sup.4+) polyhydroxycarboxylic chelates are also provided. The foregoing pharmaceutical compositions can be used in methods of preparing bone for scintigraphical analysis, for radiopharmaceutical skeletal imaging, treatment of pain resulting from metastatic bone involvement, treatment of primary bone cancer, treatment of cancer resulting from metastatic spread to bone from other primary cancers, treatment of pain resulting from rheumatoid arthritis, treatment of bone/joint disorders and to monitor radioactively the skeletal system.

  19. Conversion of agonist site to metal-ion chelator site in the beta(2)-adrenergic receptor

    DEFF Research Database (Denmark)

    Elling, C E; Thirstrup, K; Holst, Birgitte

    1999-01-01

    in the mutant receptors not by normal catecholamine ligands but instead either by free zinc ions or by zinc or copper ions in complex with small hydrophobic metal-ion chelators. Chelation of the metal ions by small hydrophobic chelators such as phenanthroline or bipyridine protected the cells from the toxic......Previously metal-ion sites have been used as structural and functional probes in seven transmembrane receptors (7TM), but as yet all the engineered sites have been inactivating. Based on presumed agonist interaction points in transmembrane III (TM-III) and -VII of the beta(2)-adrenergic receptor......, in this paper we construct an activating metal-ion site between the amine-binding Asp-113 in TM-III-or a His residue introduced at this position-and a Cys residue substituted for Asn-312 in TM-VII. No increase in constitutive activity was observed in the mutant receptors. Signal transduction was activated...

  20. Chelator-induced phytoextraction of zinc and copper by rice seedlings.

    Science.gov (United States)

    Yu, Xiao-Zhang; Wang, Dun-Qiu; Zhang, Xue-Hong

    2014-05-01

    Solution culture was carried to investigate capacity of synthetic aminopolycarboxylic acids (ethylenediamine tetraacetate, N-hydroxyethylenediaminetriacetic acid, and diethylenetriamine-pentaacetate) for enhancing botanical removal and transport of heavy metals (Cu and Zn) by plants. Biodegradable organic acids (citric acid, malic acid, and oxalic acid) were also selected as alternatives to compare them with synthesized chelating agents for effectiveness. Young rice seedlings (Oryza sativa L. cv. XZX 45) were grown in nutrient solutions treated with single or combined metal solutions in presence or absence of chelating compounds. Calculation by chemical equilibrium program VISUAL MINTEQ showed that different chelating compounds had various complex potential with Cu(2+) and Zn(2+) ions, in which synthetic chelators exhibited higher complexed capability than biodegradable organic acids. All applied synthetic aminopolycarboxylic acids significantly decreased removal of metal from nutrient solution (p 0.05), compared with the treatment without metal ligands. Synthetic aminopolycarboxylic acids significantly decreased metal concentrations in plant materials in all treatments (p < 0.01). However, biodegradable organic acids decreased metal concentrations in roots (p < 0.01), but enhanced them in shoots (p < 0.01). Results obtained indicated that synthetic aminopolycarboxylic acids decreased uptake of metals by rice seedlings, but translocation of metals complexed within plant materials was evident. Although exogenous biodegradable organic acids showed negligible effect on botanical removal of metals, metals complexed with organic acids was more mobile than those complexed with other chelating agents. These information collected here had important implication for the use of biodegradable metal chelators in transport of essential micronutrients in plant nutrition.

  1. Ethyl acetoacetate ligand distribution in the course of titanium n-butoxide chelation

    Energy Technology Data Exchange (ETDEWEB)

    Kurajica, S., E-mail: stankok@fkit.hr; Škorić, I.; Lozić, I.; Mandić, V.

    2014-10-15

    Sols obtained by chelation of titanium n-butoxide with ethyl acetoacetate, Eaa, in various ratios have been subjected to FTIR, {sup 1}H and {sup 13}C NMR, HSQC and UV–Vis spectroscopy in order to provide insight in the compounds obtained, their structure and quantitative relationships. Three compounds, the bis-chelated monomer, Ti(O{sup n}Bu){sub 2}(Eaa){sub 2}, bis-chelated dimer, (Ti(O{sup n}Bu){sub 3}Eaa){sub 2} and monochelated dimer, Ti{sub 2}(O{sup n}Bu){sub 7}Eaa have been established. As the molar ratio Eaa/Ti(O{sup n}Bu){sub 4} increases, the coordination changes from the monochelated and bis-chelated dimer to the bis-chelated monomer. Additionally, the transesterification reaction, influencing the chemical composition of the compounds was noted. The hydrolysis of the prepared sols was partial, leaving some residual butoxy and ethyl acetoacetate groups attached to titanium. Thermal treatment of the prepared amorphous gels at 350 °C yielded with the formation of nanocrystalline anatase. It was noted that high Eaa/Tnb ratio slightly retards the anatase formation. - Highlights: • Titanium n-butoxide was modified with ethyl acetoacetate in various ratios. • Among other chelate phases, previously undescribed Ti{sub 2}(O{sup n}Bu){sub 7}Eaa was obtained. • NMR-based mass balance procedure was introduced to obtain quantitative relationships. • The transesterification reaction has been noted. • Nanocrystalline anatase has been obtained by thermal treatment at 350 °C.

  2. Stereoselective coordination: a six-membered P,N-chelate tailored for asymmetric allylic alkylation.

    Science.gov (United States)

    Császár, Z; Farkas, G; Bényei, A; Lendvay, G; Tóth, I; Bakos, J

    2015-10-01

    Six-membered chelate complexes [Pd(1a-b)Cl2], (2a-b) and [Pd(1a-b)(η(3)-PhCHCHCHPh)]BF4, (3a-b) of P,N-type ligands 1a, ((2S,4S)-2-diphenyl-phosphino-4-isopropylamino-pentane) and 1b, ((2S,4S)-2-diphenyl-phosphino-4-methylamino-pentane) have been prepared. The Pd-complexes have been characterized in solution by 1D and 2D NMR spectroscopy. The observed structures were confirmed by DFT calculations and in the case of 2a also by X-ray crystallography. Unexpectedly, the coordination of the all-carbon-backbone aminophosphine 1a resulted in not only a stereospecific locking of the donor nitrogen atom into one of the two possible configurations but also the conformation of the six-membered chelate rings containing three alkyl substituents was forced into the same single chair structure showing the axially placed isopropyl group on the coordinated N-atom. The stereodiscriminative complexation of 1a led to the formation of a palladium catalyst with a conformationally rigid chelate having a configurationally fixed nitrogen and electronically different coordination sites due to the presence of P and N donors. The stereochemically fixed catalyst provided excellent ee's (up to 96%) and activities in asymmetric allylic alkylation reactions. In contrast, the chelate rings formed by 1b exist in two different chair conformations, both containing axial methyl groups, but with the opposite configurations of the coordinated N-atom. Pd-complexes of 1b provided low enantioselectivities in similar alkylations, therefore emphasizing the importance of the stereoselective coordination of N-atoms in analogous P-N chelates. The factors determining the coordination of the ligands were also studied with respect to the chelate ring conformation and the nitrogen configuration.

  3. The preparation and characterization of novel human-like collagen metal chelates

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Chenhui; Sun, Yan [Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering Northwest University, Xi' an 710069 (China); Shaanxi R and D Center of Biomaterials and Fermentation Engineering, Xi' an 710069 (China); Wang, Yaoyu [Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, Xi' an 710069 (China); Luo, Yane, E-mail: luoyane@nwu.edu.cn [Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering Northwest University, Xi' an 710069 (China); Shaanxi R and D Center of Biomaterials and Fermentation Engineering, Xi' an 710069 (China); Fan, Daidi, E-mail: fandaidi@nwu.edu.cn [Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering Northwest University, Xi' an 710069 (China); Shaanxi R and D Center of Biomaterials and Fermentation Engineering, Xi' an 710069 (China)

    2013-07-01

    In order to develop the nutritional trace elements which could be absorbed and utilized effectively, protein chelates were adopted. Calcium, copper and manganese were considered based on their physiological functions, and the new chelates of HLC-Ca, HLC-Cu and HLC-Mn were formed in MOPS or MES buffer and purified by gel chromatography, and then freeze-dried. And they were detected and analyzed by atomic absorption spectrophotometry, ultraviolet–visible absorption (UV–vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, fluorescence quenching method, circular dichroism (CD) and differential scanning calorimetry (DSC). The results showed that some chemical reactions happened between HLC and the three metal ions to form new chemical compounds. The thermodynamic parameters, ∆H, ∆G and ∆S, showed that the chelation process between HLC and metal ions was performed spontaneously. Fluorescence quenching spectra of HLC indicated that the quenching mechanism was static in nature. According to the data of DSC, the new chelates were more stable than the free HLC. And HLC-metal complex was non-toxic to the BHK21 cell through MTT assay. - Highlights: ► HLC-Ca, HLC-Cu and HLC-Mn were new chemical compounds and different to free HLC. ► Possible sites for Ca{sup 2+}, Cu{sup 2+} and Mn{sup 2+} to bind with HLC were presented. ► The chelation process between HLC and metal ions was performed spontaneously. ► The thermodynamic stability of the new chelates was higher than that of free HLC.

  4. Chelation in Metal Intoxication XLVI:Synthesis of Some α-Mercapto-β-Substituted Aryl Acrylic Acids and Their In vitro Cadmium Chelating Ability

    Institute of Scientific and Technical Information of China (English)

    MADHUMITA CHATTERJEE; VINOD K. DWIVEDI; KIRTI KHANDEKAR; SUSHIL K. TANDON

    2004-01-01

    Objective To synthesize some new α-mercapto-β-substituted aryl acrylic acids, characterize them and investigate their in vitro cadmium chelating ability. Methods Six α-mercapto-β-substituted aryl acrylic acids were prepared by the alkaline hydrolysis of 5-(aryl methylene)rhodanines, obtained from the condensation of substituted aldehydes and rhodanine following the reported procedure. The new compounds were characterized by elemental analysis, infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy. The liver and kidney from cadmium chloride pre-administered rats were homogenized and their nuclear mitochondrial fraction (NMF) and supernatant cytosol fraction (SCF) were separated. A measured volume of each fraction was dialyzed separately using "dialysis sack" against buffered-KCl medium containing a compound in the final concentration of 1×10-3 mol/L for 3 h at 37℃C. The whole content of "sack" was subjected to cadmiumestimation following digestion with conc. Nitric acid was detected using flame atomic absorption spectrometer. Results The in vitro screening showed that α-mercapto-β-(p-methoxyphenyl)acrylic acid (compound 2) and α-mercapto-β-(m-methoxy, p-hydroxyphenyl) acrylic acid (compound 4) were more effective than α-mercapto-β-thienyl acrylic acid (compound 1) and α-mercapto-β-(p-dimethylaminophenyl) acrylic acid (compound 3) in mobilizing cadmium as their dialyzable chelates. The presence of a methoxy group on the phenyl moiety (compounds 2 and 4) increases the metal chelating ability of mercapto acrylic acids. Conclusions Compounds 2 and 4 seem to have accessibility to the cellular system and capability of chelating-out the intracellularly bound cadmium.

  5. STUDY ON THE KINETICS OF POLYMERIZATION OF MMA BY COPPER(Ⅱ) CHELATING RESINS

    Institute of Scientific and Technical Information of China (English)

    WangHongzuo; JiangYuanzhang; 等

    1993-01-01

    The polymerization of MMA initiated by copper(Ⅱ) chelating resins/CCl4 system was studied.From the kinetic data,the kinetic equation of polymerization can be expressed as Rp=Ke-56400/RT[MMA]1.57[CCl4]m[RESIN-Cu]0.18 where m:3-4.5,when[CCl4] 0.1-6.93M.The free radical polymerization mechanism is proposed.The primary radicals are formed by the process of complexation-chlorine transformation among the copper(Ⅱ) chelating resin,CCl4 and methacrylate.

  6. Treatment of metal-containing wastewater by adsorption of metal-chelate complexes onto activated carbon

    Energy Technology Data Exchange (ETDEWEB)

    Shay, M.A.

    1989-01-01

    To eliminate difficulties associated with interference of chelating or complexing agents on precipitation of heavy metals from wastewaters, the feasibility of a process which utilized chelating agents in the removal of the heavy metals was investigated. Heavy metal ions were removed from simulated metal plating wastewater by sorption of a heavy metal chelate complex onto activated carbon. In this process, a chelate which might be present in a wastewater could be used in removal of a heavy metal, rather than interfere with its removal. System development of a continuous flow process consisted of bench scale column tests to answer questions about key adsorption column operating parameters. The metals investigated were Cu(II), Ni(II) and Zn(II). Hydrogen ion concentration had the largest effect on removal of heavy metalchelate complexes, but contact time and heavy metal:chelate ratio were important. The normal contact time for activated carbon columns of 30 to 60 minutes was found adequate to achieve heavy metal-chelate removals of at least 90% for citrate or EDTA complexes. For citrate complexes better removals were achieved at heavy metal:chelate ratios greater than 1:1. For EDTA, there was no advantage to ratios greater than 1:1. Increasing pH, at least to pH 9.0, increased the heavy metal chelate removal; however, for EDTA, removals greater than 90% could be achieved at a pH as low as 3.0. The maximum amount of Cu(II)-citrate complex that could be removed was 2.8 mg per gram of carbon, the maximum amount for Zn(II)citrate complex was 1.2 mg per gram of carbon, and for Ni(II)-citrate, the maximum was 1.3 mg per gram of carbon. For the EDTA complexes, the maximum removal was 2.1 mg of Cu(II)-EDTA complex per gram of carbon, 6.9 mg of Zn(II)-EDTA complex per gram of carbon, and 3.2 mg of Ni(II)-EDTA complex per gram of carbon.

  7. Copper-chelating azides for efficient click conjugation reactions in complex media.

    Science.gov (United States)

    Bevilacqua, Valentina; King, Mathias; Chaumontet, Manon; Nothisen, Marc; Gabillet, Sandra; Buisson, David; Puente, Céline; Wagner, Alain; Taran, Frédéric

    2014-06-02

    The concept of chelation-assisted copper catalysis was employed for the development of new azides that display unprecedented reactivity in the copper(I)-catalyzed azide-alkyne [3+2] cycloaddition (CuAAC) reaction. Azides that bear strong copper-chelating moieties were synthesized; these functional groups allow the formation of azide copper complexes that react almost instantaneously with alkynes under diluted conditions. Efficient ligation occurred at low concentration and in complex media with only one equivalent of copper, which improves the biocompatibility of the CuAAC reaction. Furthermore, such a click reaction allowed the localization of a bioactive compound inside living cells by fluorescence measurements.

  8. Emulsifier type, metal chelation and pH affect oxidative stability of n-3-enriched emulsions

    DEFF Research Database (Denmark)

    Haahr, Anne-Mette; Jacobsen, Charlotte

    2008-01-01

    Recent research has shown that the oxidative stability of oil-in-water emulsions is affected by the type of surfactant used as emulsifier. The aim of this study was to evaluate the effect of real food emulsifiers as well as metal chelation by EDTA and pH on the oxidative stability of a 10% n-3...... to their ability to chelate iron, scavenge free radicals, interfere with interactions between the lipid hydroperoxides and iron as well as to form a physical harrier around the oil droplets....

  9. DCCP and DICP: Construction and Analyses of Databases for Copper- and Iron-Chelating Proteins

    Institute of Scientific and Technical Information of China (English)

    Hao Wu; Yan Yang; Sheng-Juan Jiang; Ling-Ling Chen; Hai-Xia Gao; Qing-Shan Fu; Feng Li; Bin-Guang Ma; Hong-Yu Zhang

    2005-01-01

    Copper and iron play important roles in a variety of biological processes, especially when being chelated with proteins. The proteins involved in the metal binding,transporting and metabolism have aroused much interest. To facilitate the study on this topic, we constructed two databases (DCCP and DICP) containing the known copper- and iron-chelating proteins, which are freely available from the website http:∥sdbi.sdut.edu.cn/en. Users can conveniently search and browse all of the entries in the databases. Based on the two databases, bioinformatic analyses were performed, which provided some novel insights into metalloproteins.

  10. Chelation behavior of various flavonols and transfer of flavonol-chelated zinc(II) to alanylaspartic dipeptide: A PCM/DFT investigation

    Science.gov (United States)

    Yasarawan, Nuttawisit; Thipyapong, Khajadpai; Ruangpornvisuti, Vithaya

    2016-03-01

    Alanylaspartic dipeptide (AlaAsp) and zinc(II)-flavonol complex could represent a metal-binding site in proteins and a metal-ion releasing agent, respectively. Chelation of zinc(II) by either AlaAsp or flavonol ligands in aqueous solution has been examined using DFT methods with polarizable continuum model (PCM/DFT). Coordination geometry, complexation stoichiometry, coordination bond strength, preferable metal-binding site on ligands and effect of water coordination on the stability of complexes have been addressed. In several cases, the long-range corrected density functional CAM-B3LYP allows the most accurate prediction of both structural and spectroscopic data. The preferential transfer of flavonol-chelated zinc(II) to AlaAsp under solvation is attainable through the ligand-exchange reaction. The energy barrier of such reaction is significantly dependent on the degree of hydrogen bonding within the transition state. In summary, either hydroxylation or methoxylation at particular positions on the 3-hydroxyflavone backbone significantly affects the reactivity of flavonol chelates in the metal-ion transfer.

  11. Effects of nutrient trace metal speciation on algal growth in the presence of the chelator [S,S]-EDDS

    NARCIS (Netherlands)

    Schowanek, D.; McAvoy, D.; Versteeg, D.; Hanstveit, A.

    1996-01-01

    This study tests the hypothesis that the apparent toxicity of strong chelators in standard algal growth inhibition tests (e.g. method OECD 201, EC C.3., ISO 8692) is related to essential trace metal bioavailability. This hypothesis was investigated for the chelator [S,S]-ethylene diamine disuccinate

  12. Reactivity and molecular modeling of new solvatochromic mixed-ligand copper(II) chelates of 2-acetylbutyrolactone and dinitrogen bases.

    Science.gov (United States)

    Taha, A; Adly, Omima M I; Shebl, Magdy

    2015-04-01

    A new series of solvatochromic mononuclear mixed ligand chelates with the general formula: Cu(AcBL)(L)X; where AcBL=2-acetylbutyrolactonate, L=N,N,N',N'-tetramethylethylenediamine (Me4en), N,N,N',N'-tetramethylpropylene diamine (Me4pn), 1,10-phenanthroline (Phen) or 2,2'-bipyridyl (Bipy) and X=ClO4-, NO3- or Br- have been synthesized and characterized by the analytical and spectral methods, as well as magnetic and molar conductance measurements. The d-d absorption bands of Me4en-chelates as Nujol mulls or weak donor solvents solutions revealed square-planar, distorted octahedral and/or distorted trigonal bipyramid geometries for the perchlorate, nitrate and bromide chelates, respectively. However, an octahedral structure is identified for chelates in strong donor solvents. Perchlorate chelates show a remarkable color change from violet to green as the Lewis basicity of the donor solvent increases, whereas bromide chelates are mainly affected by the Lewis acidity of solvent. Specific and non-specific interactions of solvent molecules with the chelates were investigated on the basis of unified solvation model. Structural parameters of the free ligands and their Cu(II)-chelates have been calculated on the basis of semiempirical PM3 level and correlated with the experimental data.

  13. Extraction of Micronutrient Metals from Peat-based Media Using Various Chelate-ligand and Iron-source Extractants

    Science.gov (United States)

    Objectives of the study were to determine effects of chelate-ligand (experiment 1) and iron-source (experiment 2) unbuffrered extractant solutions on substrate pH and Cu, Fe, Mn, and Zn extraction from peat-based media. Chelate-ligand extractants consisted of 5 mM solutions of ethylenediaminedisucc...

  14. Characterization of radionuclide-chelating agent complexes found in low-level radioactive decontamination waste. Literature review

    Energy Technology Data Exchange (ETDEWEB)

    Serne, R.J.; Felmy, A.R.; Cantrell, K.J.; Krupka, K.M.; Campbell, J.A.; Bolton, H. Jr.; Fredrickson, J.K. [Pacific Northwest National Lab., Richland, WA (United States)

    1996-03-01

    The US Nuclear Regulatory Commission is responsible for regulating the safe land disposal of low-level radioactive wastes that may contain organic chelating agents. Such agents include ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), picolinic acid, oxalic acid, and citric acid, and can form radionuclide-chelate complexes that may enhance the migration of radionuclides from disposal sites. Data from the available literature indicate that chelates can leach from solidified decontamination wastes in moderate concentration (1--100 ppm) and can potentially complex certain radionuclides in the leachates. In general it appears that both EDTA and DTPA have the potential to mobilize radionuclides from waste disposal sites because such chelates can leach in moderate concentration, form strong radionuclide-chelate complexes, and can be recalcitrant to biodegradation. It also appears that oxalic acid and citric acid will not greatly enhance the mobility of radionuclides from waste disposal sites because these chelates do not appear to leach in high concentration, tend to form relatively weak radionuclide-chelate complexes, and can be readily biodegraded. In the case of picolinic acid, insufficient data are available on adsorption, complexation of key radionuclides (such as the actinides), and biodegradation to make definitive predictions, although the available data indicate that picolinic acid can chelate certain radionuclides in the leachates.

  15. Study on Chelating Resins XXXI Syntheses and Adsorption Properties of a New Type of Bead Resins Containing S and N

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A new type of bead crosslinked chelating resins containing coordinate atoms N and S were synthesized by the reaction of polyethyleneimine with chloromethylthiirane in suitable sovent at temperature of 2080C. These chelating resins exhibited excellent adsorption properties for precious metal ions.

  16. Iron chelators do not reduce cold-induced cell injury in the isolated perfused rat kidney model.

    NARCIS (Netherlands)

    Bartels-Stringer, M.; Wetzels, J.F.M.; Wouterse, A.C.; Steenbergen, E.; Russel, F.G.M.; Kramers, C.

    2005-01-01

    BACKGROUND: In vitro, cold-induced injury is an important contributor to renal tubular cell damage. It is mediated by iron-dependent formation of reactive oxygen species and can be prevented by iron chelation. We studied whether iron chelators can prevent cold-induced damage in the isolated perfused

  17. Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up.

    Science.gov (United States)

    Cappellini, M Domenica; Bejaoui, Mohamed; Agaoglu, Leyla; Canatan, Duran; Capra, Marcello; Cohen, Alan; Drelichman, Guillermo; Economou, Marina; Fattoum, Slaheddine; Kattamis, Antonis; Kilinc, Yurdanur; Perrotta, Silverio; Piga, Antonio; Porter, John B; Griffel, Louis; Dong, Victor; Clark, Joan; Aydinok, Yesim

    2011-07-28

    Patients with β-thalassemia require lifelong iron chelation therapy from early childhood to prevent complications associated with transfusional iron overload. To evaluate long-term efficacy and safety of once-daily oral iron chelation with deferasirox, patients aged ≥ 2 years who completed a 1-year, phase 3, randomized trial entered a 4-year extension study, either continuing on deferasirox (deferasirox cohort) or switching from deferoxamine to deferasirox (crossover cohort). Of 555 patients who received ≥ 1 deferasirox dose, 66.8% completed the study; 43 patients (7.7%) discontinued because of adverse events. In patients with ≥ 4 years' deferasirox exposure who had liver biopsy, mean liver iron concentration significantly decreased by 7.8 ± 11.2 mg Fe/g dry weight (dw; n = 103; P deferasirox and crossover cohorts, respectively. Median serum ferritin significantly decreased by 706 ng/mL (n = 196; P deferasirox use in pediatric and adult patients with β-thalassemia suggests treatment for ≤ 5 years is generally well tolerated and effectively reduces iron burden. This trial was registered at www.clinicaltrials.gov as #NCT00171210.

  18. Efficacy of a novel chelator BPCBG for removing uranium and protecting against uranium-induced renal cell damage in rats and HK-2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Yizhong; Wang, Dan [Institute of Radiation Medicine, Fudan University, Shanghai 200032 (China); Li, Zhiming [Department of Chemistry, Fudan University, Shanghai 200433 (China); Hu, Yuxing; Xu, Aihong [Institute of Radiation Medicine, Fudan University, Shanghai 200032 (China); Wang, Quanrui [Department of Chemistry, Fudan University, Shanghai 200433 (China); Shao, Chunlin [Institute of Radiation Medicine, Fudan University, Shanghai 200032 (China); Chen, Honghong, E-mail: hhchen@shmu.edu.cn [Institute of Radiation Medicine, Fudan University, Shanghai 200032 (China)

    2013-05-15

    Chelation therapy is a known effective method to increase the excretion of U(VI) from the body. Until now, no any uranium chelator has been approved for emergency medical use worldwide. The present study aimed to evaluate the efficacy of new ligand BPCBG containing two catechol groups and two aminocarboxylic acid groups in decorporation of U(VI) and protection against acute U(VI) nephrotoxicity in rats, and further explored the detoxification mechanism of BPCBG for U(VI)-induced nephrotoxicity in HK-2 cells with comparison to DTPA-CaNa{sub 3}. Chelating agents were administered at various times before or after injections of U(VI) in rats. The U(VI) levels in urine, kidneys and femurs were measured 24 h after U(VI) injections. Histopathological changes in the kidney and serum urea and creatinine and urine protein were examined. After treatment of U(VI)-exposed HK-2 cells with chelating agent, the intracellular U(VI) contents, formation of micronuclei, lactate dehydrogenase (LDH) activity and production of reactive oxygen species (ROS) were assessed. It was found that prompt, advanced or delayed injections of BPCBG effectively increased 24 h-urinary U(VI) excretion and decreased the levels of U(VI) in kidney and bone. Meanwhile, BPCBG injection obviously reduced the severity of the U(VI)-induced histological alterations in the kidney, which was in parallel with the amelioration noted in serum indicators, urea and creatinine, and urine protein of U(VI) nephrotoxicity. In U(VI)-exposed HK-2 cells, immediate and delayed treatment with BPCBG significantly decreased the formation of micronuclei and LDH release by inhibiting the cellular U(VI) intake, promoting the intracellular U(VI) release and inhibiting the production of intracellular ROS. Our data suggest that BPCBG is a novel bi-functional U(VI) decorporation agent with a better efficacy than DTPA-CaNa{sub 3}. - Highlights: ► BPCBG accelerated the urine U(VI) excretion and reduced the tissues U(VI) in rats.

  19. SYNTHESIS AND MESOMORPHIC PROPERTIES OF PALLADIUM CHELATES OF LIQUID CRYSTAL POLYSILOXANE WITH β-DIKETONE-BASED SIDE CHAINS

    Institute of Scientific and Technical Information of China (English)

    ZHOU Zhaohui; DAI Daorong; ZHANG Rongben

    1992-01-01

    A new type of palladium chelate of β-diketone-based side chain liquid crystal polysiloxane(Pd-DKLCP) has been synthesized by chelation reaction of palladium dichloride with polymeric ligand, β-diketone polysiloxane (DKLCP), using THF as solvent at R .T.. The Pd-chelation results in greatly increasing the phase transition temperature TK and the enthalpy change AHK from crystal to liquid crystal state and making the temperature range of LC state AT (A T=Tc1- TK) widened.All these chelates Pd-DKLCP's do not show TCl until decomposition at 205 ℃. It is noteworthy that the Pd-chelation can exert more positive effect on the mesomorphic behaviour of the polymer ligand than the counterpart Cu-DKLCP does. It is probable due to the bigger size of disc-like mesogen formed from β-diketone and Pd +2 ion with 4d orbital.

  20. Modelling chelate-Induced phytoextraction: functional models predicting bioavailability of metals in soil, metal uptake and shoot biomass

    Directory of Open Access Journals (Sweden)

    Pasqualina Sacco

    Full Text Available Chelate-induced phytoextraction of heavy metals from contaminated soils requires special care to determine, a priori, the best method of chelate application, in terms of both dose and timing. In fact, the chelate dose must assure the bioavailability of the metal to the plant without increasing leaching risk and giving toxic effects. Three mathematical models are here proposed for usefully interpreting the processes taking place: a increased soil bioavailability of metals by chelants; b metal uptake by plants; c variation in plant biomass. The models are implemented and validated using data from pot and lysimeter trials. Both the chelate dose and the time elapsed since its application affected metal bioavailability and plant response. Contrariwise, the distribution strategy (single vs. split application seems to produce significant differences both in plant growth and metal uptake, but not in soil metal bioavailability. The proposed models may help to understand and predict the chelate dose – effect relationship with less experimental work.

  1. Effect of chelating agent on oxidation rate of aniline in ferrous ion activated persulfate system at neutral pH

    Institute of Scientific and Technical Information of China (English)

    张永清; 谢晓芳; 黄少斌; 梁海云

    2014-01-01

    In the interest of accelerating aniline degradation, Fe2+and chelated Fe2+activated persulfate oxidations were investigated in neutral pH condition. Three kinds of chelating agents were selected including citric acid, oxalic acid and ethylenediamine tetraaceatate (EDTA) to maintain available Fe2+. The results indicate that the concentration of chelating agent and ferrous ion didn’t follow a linear relationship with the degradation rate of aniline. A 1/1 ratio of chelating agent/Fe2+results in a higher degradation rate compared to the results by other ratios. The oxidation enhancement factor using oxalic acid was found to be relatively low. In contrast, citric acid is more suitable chelating agent in the ferrous iron activated persulfate system and aniline exhibits a highest degradation with a persulfate/Fe2+/citric acid/aniline molar ratio of 50/25/25/1 compared to other molar ratios.

  2. Selection of Chelated Fe (III)/Fe (II) Catalytic Oxidation Agents for Desulfurization Based on Iron Complexation Method

    Institute of Scientific and Technical Information of China (English)

    Luo Ying; Liu Youzhi; Qi Guisheng; Guo Huidong; Zhu Zhengfeng

    2014-01-01

    Optimization of factors inlfuencing the experiments on reactions involving 8 different chelating agents and sol-uble Fe (III)/Fe (II) salts was carried out to yield chelated iron complexes. A combination of optimized inlfuencing factors has resulted in a Fe chelating capacity of the iron-based desulfurization solution to be equal to 6.83-13.56 g/L at a redox potential of 0.185-0.3. The desulfurization performance of Fe (III)/Fe (II) chelating agents was investigated on a simulated sulfur-containing industrial gas composed of H2S and N2 in a cross-lfow rotating packed bed. Test results have revealed that the proposed iron-based desulfurization solution showed a sulfur removal efifciency of over 99%along with a Fe chelating capacity exceeding 1.35 g/L. This desulfurization technology which has practical application prospect is currently in the phase of commercial scale-up study.

  3. Chelating agents improve enzymatic solubilization of pectinaceous co-processing streams

    DEFF Research Database (Denmark)

    Ravn, Helle Christine; Meyer, Anne S.

    2014-01-01

    /substrate] at 60 °C, pH 6.0 for 1 min. Characterization of the released fractions demonstrated a significantly improved effect of chelating agents for polysaccharide solubilization from FiberBind 400, PUF, and citrus peel, whereas only low amounts of polysaccharides were solubilized from the sugar beet pulp...

  4. Kinetic Studies on Forming Iso-nuclear -type Chelates of Rare Earths with p-Sulphoaminobromophosphonazo

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The kinetic behavior of forming the iso-nuclear b -type chelates of rare earth ions (RE3+) with p-sulphoaminobromophosphonazo (BPA-pSN) in ClCH2COOH-CH3COONa buffer solutions were studied by a spectrophotometric method.

  5. The impact of succimer chelation on blood cadmium in children with background exposures: a randomized trial.

    Science.gov (United States)

    Cao, Yang; Chen, Aimin; Bottai, Matteo; Caldwell, Kathleen L; Rogan, Walter J

    2013-08-01

    Succimer lowers blood lead concentrations in children, and the structure of succimer chelates of lead and cadmium are similar. Using blood samples from a randomized trial of succimer for lead poisoning, however, we found that succimer did not lower blood cadmium in children with background exposure.

  6. Metal Ions Extraction with Glucose Derivatives as Chelating Reagents in Supercritical Carbon Dioxide

    Institute of Scientific and Technical Information of China (English)

    Guo Chen YANG; Hai Jian YANG

    2006-01-01

    A series of glucose derivatives have been used as chelating reagents to extract metal ions in supercritical carbon dioxide. With perfluoro-1-octanesulfonic acid tetraethylammonium salt as additive, glucose derivatives were selective for Sr2+ and Pb2+ extraction in supercritical carbon dioxide.

  7. Use of organometallic chelates in broiler diet: effect on the performance and bone structure. Preliminary results

    Directory of Open Access Journals (Sweden)

    Biagina Chiofalo

    2010-01-01

    Full Text Available On 26,000 Ross 508 broiler chickens (two groups of 13,000 per pen the effect of dietary substitution with in organic trace minerals or organometallic chelates on performances and bones tructure c trace minerals or organometallic chelates on performances and bone structure was studied. Treatments consisted of a commercial diet integrated with 0.5% of a vitamin-mineral premix containing inorganic trace minerals (CTR or organometallic chelates (MHA using Methionine Hydroxy Analog. Production performance was measured during the 52 d trial period and bone structure was evalu- ated at the slaughter (52 d. Significant (P=0.038 higher values were observed in the finishing period (41 to 52 d for the body weight of the treated group (3560 g vs. 3358 g. The same trend was observed for the ADG (MHA 87.6 g/d vs. CTR 71 g/d; P<0.05. Concerning ash percentage significant higher values were observed in the CTR group for femur (49.01% vs. 51.45%; P<0.01 and tibia (53.87% vs. 49.79%; P<0.001; femur showed also higher values for bone radiopacity (MHA 0.21 px vs. CTR 0.26 px; P=0.035. MHA group showed significant higher value for morphometric measures of the femur and tibia. Results suggest that organometallic chelates can be included in the diet without compromising broiler performance.

  8. Modern Chemistry Techniques Applied to Metal Behavior and Chelation in Medical and Environmental Systems ? Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Sutton, M; Andresen, B; Burastero, S R; Chiarappa-Zucca, M L; Chinn, S C; Coronado, P R; Gash, A E; Perkins, J; Sawvel, A M; Szechenyi, S C

    2005-02-03

    This report details the research and findings generated over the course of a 3-year research project funded by Lawrence Livermore National Laboratory (LLNL) Laboratory Directed Research and Development (LDRD). Originally tasked with studying beryllium chemistry and chelation for the treatment of Chronic Beryllium Disease and environmental remediation of beryllium-contaminated environments, this work has yielded results in beryllium and uranium solubility and speciation associated with toxicology; specific and effective chelation agents for beryllium, capable of lowering beryllium tissue burden and increasing urinary excretion in mice, and dissolution of beryllium contamination at LLNL Site 300; {sup 9}Be NMR studies previously unstudied at LLNL; secondary ionization mass spec (SIMS) imaging of beryllium in spleen and lung tissue; beryllium interactions with aerogel/GAC material for environmental cleanup. The results show that chelator development using modern chemical techniques such as chemical thermodynamic modeling, was successful in identifying and utilizing tried and tested beryllium chelators for use in medical and environmental scenarios. Additionally, a study of uranium speciation in simulated biological fluids identified uranium species present in urine, gastric juice, pancreatic fluid, airway surface fluid, simulated lung fluid, bile, saliva, plasma, interstitial fluid and intracellular fluid.

  9. Affinity purification of copper-chelating peptides from sunflower protein hydrolysates.

    Science.gov (United States)

    Megías, Cristina; Pedroche, Justo; Yust, Maria M; Girón-Calle, Julio; Alaiz, Manuel; Millan, Francisco; Vioque, Javier

    2007-08-08

    Copper-chelating peptides were purified from sunflower protein hydrolysates by affinity chromatography using immobilized copper. A variety of protein hydrolysates were obtained by incubation with the proteases Alcalase and Flavourzyme for different periods of time. Chelating activity was indirectly determined by measuring the inhibitory effect of hydrolysates on the oxidation of beta-carotene by copper. Copper-binding peptides purified from the two hydrolysates that inhibited oxidation by copper the most contained 25.4 and 42.0% histidine and inhibited beta-carotene oxidation 8 and 3 times more than the original hydrolysates, which had 2.4 and 2.6% histidine, respectively. Thus, histidine content is not the only factor involved in antioxidant activity, and probably other factors such as peptide size and amino acid sequence are also important. This work shows that affinity chromatography can be used for the purification of copper-chelating peptides and probably other metals of nutritional interest such as calcium, iron, and zinc. In addition to their antioxidant potential, chelating peptides are of nutritional interest because they increase bioavailability of minerals.

  10. Spectroscopy, modeling and computation of metal chelate solubility in supercritical CO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    J. F. Brennecke; M. A. Stadtherr

    1999-12-10

    The overall objectives of this project were to gain a fundamental understanding of the solubility and phase behavior of metal chelates in supercritical CO{sub 2}. Extraction with CO{sub 2} is an excellent way to remove organic compounds from soils, sludges and aqueous solutions, and recent research has demonstrated that, together with chelating agents, it is a viable way to remove metals, as well. In this project the authors sought to gain fundamental knowledge that is vital to computing phase behavior, and modeling and designing processes using CO{sub 2} to separate organics and metal compounds from DOE mixed wastes. The overall program was a comprehensive one to measure, model and compute the solubility of metal chelate complexes in supercritical CO{sub 2} and CO{sub 2}/cosolvent mixtures. Through a combination of phase behavior measurements, spectroscopy and the development of a new computational technique, the authors have achieved a completely reliable way to model metal chelate solubility in supercritical CO{sub 2} and CO{sub 2}/co-contaminant mixtures. Thus, they can now design and optimize processes to extract metals from solid matrices using supercritical CO{sub 2}, as an alternative to hazardous organic solvents that create their own environmental problems, even while helping in metals decontamination.

  11. Design and Application of Latent Olefin Metathesis Catalysts Featuring S-Chelating Alkylidene Ligands

    Science.gov (United States)

    Szadkowska, Anna; Grela, Karol

    This review article is devoted to recent advances in the design and application of so-called “dormant” or “latent” ruthenium olefin metathesis catalysts bearing S-chelating alkylidene ligands. Selected ruthenium complexes containing S-donor ligands, which possess controllable initiation behaviour are presented. Applications of these complexes in olefin metathesis are described.

  12. The Mechanism of Cumene Peroxidation Catalyzed by Cobalt(Ⅱ)-Chelated Copolymer

    Institute of Scientific and Technical Information of China (English)

    Cheng-Chien Wang; Hui-Chun Chen; Chuh-Yean Chen; Chuh-Yung Chen

    2005-01-01

    @@ 1Introduction The functionalised polymers, especially for chelating polymer, have been employed to considerable effects in organic synthesis for several decades. The use of polymer groups as ligands permits the ligand surroundings to be varied and regulation of the catalytic properties of the complexes because of the flexibility of the polymer chains, their ability to adopt various conformations, and the possibility of creating various spatial distributions of metal centers immobilized on the polymer chains[1,2]. In our recently studies[3-5], the chelating copolymer with imino-diacetic acid chelating group in the polymer side chain was manufactured, and which can increase effectively amount of the chelating group within the polymer. Meanwhile, the high catalysis performance in organic synthesis had also been proved via benzaldehyde and cumene peroxidation. For cumene peroxidation,it is hardly to find such a simple catalyst with high conversion and selectivity due to hydroperoxide decomposition by a radical mechanism. The cumene peroxidation by catalyst system and its reaction mechanism as well as the kinetic study are popularly investigated object for many researchers[6-9]. However, the reaction mechanism still does not clear owing to the by-products will be produced following the different catalysts used.

  13. [Remediation of Cu-Pb-contaminated loess soil by leaching with chelating agent and biosurfactant].

    Science.gov (United States)

    Liu, Xia; Wang, Jian-Tao; Zhang, Meng; Wang, Li; Yang, Ya-Ti

    2013-04-01

    Because of its strong chelation, solubilization characteristics, the chelating agents and biosurfactant are widely used in remediation of heavy metals and organic contaminated soils. Ethylenediamine tetraacetic acid (EDTA), citric acid (CIT) and dirhamnolipid (RL2) were selected as the eluent. Batch experiments and column experiments were conducted to investigate the leaching effect of the three kinds of eluent, as well as the mixture of biosurfactant and chelating agent for Cu, Pb contaminated loess soil. The results showed that the leaching efficiencies of different eluent on Cu, Pb contaminated loess soil followed the sequence of EDTA > CIT > RL2. At an eluent concentration of 0.02 mol x L(-1), the Cu leaching efficiency was 62.74% (EDTA), 52.28% (CIT) and 15.35% (RL2), respectively; the Pb leaching efficiency was 96.10% (EDTA), 23.08% (CIT) and 14.42% (RL2), respectively. When the concentration of RL2 was 100 CMC, it had synergistic effects on the other two kinds of chelating agent in Cu leaching, and when the concentration of RL2 was 200 CMC, it had antagonism effects. The effect of RL2 on EDTA in Pb leaching was similar to that in Cu leaching. Pb leaching by CIT was inhibited in the presence of RL2. EDTA and CIT could effectively remove Cu and Pb in exchangeable states, adsorption states, carbonate salts and organic bound forms; RL2 could effectively remove Cu and Pb in exchangeable and adsorbed states.

  14. Thermodynamic Analysis of Allosteric and Chelate Cooperativity in Di- and Trivalent Ammonium/Crown-Ether Pseudorotaxanes.

    Science.gov (United States)

    Nowosinski, Karol; von Krbek, Larissa K S; Traulsen, Nora L; Schalley, Christoph A

    2015-10-16

    A detailed thermodynamic analysis of the axle-wheel binding in di- and trivalent secondary ammonium/[24]crown-8 pseudorotaxanes is presented. Isothermal titration calorimetry (ITC) data and double mutant cycle analyses reveal an interesting interplay of positive as well as negative allosteric and positive chelate cooperativity thus providing profound insight into the effects governing multivalent binding in these pseudorotaxanes.

  15. Ruthenium(II) and iridium(III) complexes featuring NHC-sulfonate chelate.

    Science.gov (United States)

    Rajaraman, A; Sahoo, A R; Hild, F; Fischmeister, C; Achard, M; Bruneau, C

    2015-10-28

    Three new complexes bearing a chelating (κ(2)C,O) NHC-SO3 ligand have been prepared. An original method for the synthesis of the imidazolium-sulfonate NHC precursor is described. The 5-membered ruthena- and irida-cycle containing complexes were fully characterized and evaluated in a series of catalytic transformations involving hydrogen auto-transfer processes.

  16. The effects of Fe-chelate type and PH on substrate grown roses

    NARCIS (Netherlands)

    Voogt, W.; Sonneveld, C.

    2009-01-01

    Substrate grown roses appear to be susceptible to chlorosis, which indicates problems with Fe or Mn uptake and hence yield reduction. In common practice this problem is often treated by the addition of extra Fe-chelate, or the use of Fe-EDDHA instead of Fe-DTPA. In previous tests, it was shown that

  17. Observation of unusual slow-relaxation of the magnetisation in a Gd-EDTA chelate.

    Science.gov (United States)

    Holmberg, Rebecca J; Ho, Le Tuan Anh; Ungur, Liviu; Korobkov, Ilia; Chibotaru, Liviu F; Murugesu, Muralee

    2015-12-21

    A Gadolinium EDTA chelate displays characteristic isotropic behaviour common of Gd(III) complexes under zero applied magnetic field, and anisotropic behaviour arising from dipolar coupling and weak spin-phonon coupling under an applied magnetic field. This surprising magnetic behaviour for Gd(III) is investigated using SQUID magnetometry and rationalized through theoretical calculations.

  18. Lanthanide Chelates as Bilayer Alignment Tools in NMR Studies of Membrane-Associated Peptides

    Science.gov (United States)

    Prosser, R. S.; Bryant, H.; Bryant, R. G.; Vold, Regitze R.

    1999-12-01

    Theequimolar complex, consisting of the lipid-like, amphiphilic chelating agent 1,11-bis[distearylamino]-diethylenetriamine pentaacetic acid (DTPA-18) and Tm3+, is shown by deuterium (2H) NMR to be useful in aligning bicelle-like model membranes, consisting of dimyristoylphosphatidylcholine (DMPC) and dihexanoylphosphatidylcholine (DHPC). As shown previously (1996, R. S. Prosser et al., J. Am. Chem. Soc. 118, 269-270), in the absence of chelate, the lanthanide ions bind loosely with the lipid phosphate groups and confer the membrane with a sufficient positive magnetic anisotropy to result in parallel alignment (i.e., average bilayer normal along the field). Apparently, DTPA-18 sequesters the lanthanide ions and inserts into the phospholipid bilayer in such a manner that bilayer morphology is preserved over a wide temperature range (35-70°C). The inherent paramagnetic shifts and line broadening effects are illustrated by 2H NMR spectra of the membrane binding peptide, Leu-enkephalin (Lenk-d2, Tyr-(Gly-d2)-Gly-Phe-Leu-OH), in the presence of varying concentrations of Tm3+, and upon addition of DTPA-18. Two conclusions could be drawn from this study: (1) The addition of Tm3+ to the bicelle system is consistent with a conformational change in the surface associated peptide, and this effect is shown to be reversed by addition of the chelate, and (2) The paramagnetic shifts are shown to be significantly reduced by addition of chelate.

  19. Comparison of the antibacterial activity of chelating agents using the agar diffusion method

    Science.gov (United States)

    The agar diffusion assay was used to examine antibacterial activity of 2 metal chelators. Concentrations of 0 to 40 mM of ethylenediaminetetraacetic acid (EDTA) and ethylenediamine-N,N’-disuccinic acid (EDDS) were prepared in 1.0 M potassium hydroxide (KOH). The pH of the solutions was adjusted to 1...

  20. Searching for new aluminium chelating agents: a family of hydroxypyrone ligands.

    Science.gov (United States)

    Toso, Leonardo; Crisponi, Guido; Nurchi, Valeria M; Crespo-Alonso, Miriam; Lachowicz, Joanna I; Mansoori, Delara; Arca, Massimiliano; Santos, M Amélia; Marques, Sérgio M; Gano, Lurdes; Niclós-Gutíerrez, Juan; González-Pérez, Josefa M; Domínguez-Martín, Alicia; Choquesillo-Lazarte, Duane; Szewczuk, Zbigniew

    2014-01-01

    Attention is devoted to the role of chelating agents in the treatment of aluminium related diseases. In fact, in spite of the efforts that have drastically reduced the occurrence of aluminium dialysis diseases, they so far constitute a cause of great medical concern. The use of chelating agents for iron and aluminium in different clinical applications has found increasing attention in the last thirty years. With the aim of designing new chelators, we synthesized a series of kojic acid derivatives containing two kojic units joined by different linkers. A huge advantage of these molecules is that they are cheap and easy to produce. Previous works on complex formation equilibria of a first group of these ligands with iron and aluminium highlighted extremely good pMe values and gave evidence of the ability to scavenge iron from inside cells. On these bases a second set of bis-kojic ligands, whose linkers between the kojic chelating moieties are differentiated both in terms of type and size, has been designed, synthesized and characterized. The aluminium(III) complex formation equilibria studied by potentiometry, electrospray ionization mass spectroscopy (ESI-MS), quantum-mechanical calculations and (1)H NMR spectroscopy are here described and discussed, and the structural characterization of one of these new ligands is presented. The in vivo studies show that these new bis-kojic derivatives induce faster clearance from main organs as compared with the monomeric analog.

  1. The iron chelator deferasirox protects mice from mucormycosis through iron starvation

    Science.gov (United States)

    Clinical and animal model data indicate that the presence of elevated available serum iron predisposes the host to mucormycosis. Here we demonstrate that deferasirox, an iron chelator recently approved for use in humans by the United States (US) Food and Drug Administration (FDA), is a highly effec...

  2. [Enhanced phytoextraction of heavy metal contaminated soil by chelating agents and auxin indole-3-acetic acid].

    Science.gov (United States)

    Zhou, Jian-min; Dang, Zhi; Chen, Neng-chang; Xu, Sheng-guang; Xie, Zhi-yi

    2007-09-01

    The environmental risk of chelating agents such as EDTA application to the heavy metals polluted soils and the stress on plant roots due to the abrupt increase metals concentration limit the wide commercial use of chelate-induced phytoextraction. Chelating agent ethylenediaminetetraacetic acid (EDTA) and nitrilotriacetic acid (NTA) and auxin indole-3-acetic acid (IAA) were used for enhancing heavy metals uptake from soils by Zea mays L. (corn) in pot experiments. The metals content in plant tissues was quantified using an inductively coupled plasma mass spectrometer (ICP-MS). The results showed that the combination of IAA and EDTA increased the biomass by about 40.0% and the contents of Cu, Zn, Cd and Pb in corn shoots by 27.0%, 26.8%, 27.5% and 32.8% respectively, as compared to those in EDTA treatment. While NTA&IAA treatment increased the biomass by about 29.9% and the contents of Cu, Zn, Cd and Pb in corn shoots by 31.8%, 27.6%, 17.0% and 26.9% respectively, as compared to those in NTA treatment. These results indicated that corn growth was promoted, and the biomass and the accumulation of heavy metals in plant shoots were increased significantly with the addition of IAA, which probably helps to change the cell membrane properties and the biomass distribution, resulting in the alleviation of the phytotoxicity of metals and the chelating agents.

  3. Comprehensive radiolabeling, stability, and tissue distribution studies of technetium-99m single amino acid chelates (SAAC).

    Science.gov (United States)

    Maresca, Kevin P; Hillier, Shawn M; Femia, Frank J; Zimmerman, Craig N; Levadala, Murali K; Banerjee, Sangeeta R; Hicks, Justin; Sundararajan, Chitra; Valliant, John; Zubieta, Jon; Eckelman, William C; Joyal, John L; Babich, John W

    2009-08-19

    Technetium tricarbonyl chemistry has been a subject of interest in radiopharmaceutical development over the past decade. Despite the extensive work done on developing chelates for Tc(I), a rigorous investigation of the impact of changing donor groups and labeling conditions on radiochemical yields and/or distribution has been lacking. This information is crucially important if these platforms are going to be used to develop molecular imaging probes. Previous studies on the coordination chemistry of the {M(CO)(3)}(+) core have established alkylamine, aromatic nitrogen heterocycles, and carboxylate donors as effective chelating ligands. These observations led to the design of tridentate ligands derived from the amino acid lysine. Such amino acid analogues provide a tridentate donor set for chelation to the metal and an amino acid functionality for conjugation to biomolecules. We recently developed a family of single amino acid chelates (SAAC) that serve this function and can be readily incorporated into peptides via solid-phase synthesis techniques. As part of these continuing studies, we report here on the radiolabeling with technetium-99m ((99m)Tc) and stability of a series of SAAC analogues of lysine. The complexes studied include cationic, neutral, and anionic complexes. The results of tissue distribution studies with these novel complexes in normal rats demonstrate a range of distribution in kidney, liver, and intestines.

  4. Organic acids rather than histidine predominate in Ni chelation in Alyssum hyperaccumulator xylem exudate

    Science.gov (United States)

    A better understanding of Ni uptake mechanisms by hyperaccumulator plants is necessary to improve Ni uptake efficiency for phytoremediation technologies i.e. phytomining. It is known that an important aspect of Ni translocation involves Ni chelation with organic ligands. However, it is still not cle...

  5. Chemotherapy triggers HIF-1-dependent glutathione synthesis and copper chelation that induces the breast cancer stem cell phenotype.

    Science.gov (United States)

    Lu, Haiquan; Samanta, Debangshu; Xiang, Lisha; Zhang, Huimin; Hu, Hongxia; Chen, Ivan; Bullen, John W; Semenza, Gregg L

    2015-08-18

    Triple negative breast cancer (TNBC) accounts for 10-15% of all breast cancer but is responsible for a disproportionate share of morbidity and mortality because of its aggressive characteristics and lack of targeted therapies. Chemotherapy induces enrichment of breast cancer stem cells (BCSCs), which are responsible for tumor recurrence and metastasis. Here, we demonstrate that chemotherapy induces the expression of the cystine transporter xCT and the regulatory subunit of glutamate-cysteine ligase (GCLM) in a hypoxia-inducible factor (HIF)-1-dependent manner, leading to increased intracellular glutathione levels, which inhibit mitogen-activated protein kinase kinase (MEK) activity through copper chelation. Loss of MEK-ERK signaling causes FoxO3 nuclear translocation and transcriptional activation of the gene encoding the pluripotency factor Nanog, which is required for enrichment of BCSCs. Inhibition of xCT, GCLM, FoxO3, or Nanog blocks chemotherapy-induced enrichment of BCSCs and impairs tumor initiation. These results suggest that, in combination with chemotherapy, targeting BCSCs by inhibiting HIF-1-regulated glutathione synthesis may improve outcome in TNBC.

  6. Ulcerated hemosiderinic dyschromia and iron deposits within lower limbs treated with a topical application of biological chelator

    Directory of Open Access Journals (Sweden)

    Eugenio Brizzio

    2012-12-01

    Full Text Available The ulcerative haemosiderinic dyschromia of chronic venous insufficiency is difficult to heal and presents a high accumulation of iron. Lactoferrin, a potent natural iron chelator, could help to scar this ulcerative haemosi - derinic dyschromia. The objective of this study was to determine whether the topical application of a liposomal gel with Lactoferrin favors scarring/degradation of the brown colored spot typical of ulcerative haemosiderinic dyschromia. Nine patients with severe chronic venous insufficiency and ulcerative haemosiderinic dyschromia (CEAP-C6, with a natural evolution of over 12 months, were included in the study. Hemo chromatosis gene mutations were investigated. The levels of serum ferritin, transferrin saturation and blood cell counts were analyzed. The presence of hemosiderin was investigated through periulcerous and ulcer fundus biopsies carried out at baseline and 30 days after treatment with Lactoferrin. The severity of the injuries (CEAP classification was evaluated at the beginning of and throughout the whole 3-month treatment period. No patient had received compression treatment during the three months previous to this therapy. Significant improvement in these injuries, with a reduction in the dimensions of the brown spot (9 of 9 at Day 90, and complete scarring with a closure time ranging from 15 to 180 days (7 of 9 were observed. The use of topical lactoferrin is a non-invasive therapeutic tool that favors clearance of hemosiderinic dyschromia and scarring of the ulcer. The success of this study was not influenced either by the hemochromatosis genetics or the iron metabolism profile observed.

  7. f-Element Ion Chelation in Highly Basic Media - Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Paine, R.T.

    2000-12-12

    A large body of data has been collected over the last fifty years on the chemical behavior of f-element ions. The ions undergo rapid hydrolysis reactions in neutral or basic aqueous solutions that produce poorly understood oxide-hydroxide species; therefore, most of the fundamental f-element solution chemistry has allowed synthetic and separations chemists to rationally design advanced organic chelating ligands useful for highly selective partitioning and separation of f-element ions from complex acidic solution matrices. These ligands and new examples under development allow for the safe use and treatment of solutions containing highly radioactive species. This DOE/EMSP project was undertaken to address the following fundamental objectives: (1) study the chemical speciation of Sr and lanthanide (Ln) ions in basic aqueous media containing classical counter anions found in waste matrices; (2) prepare pyridine N-oxide phosphonates and phosphonic acids that might act as selective chelator s for Ln ions in model basic pH waste streams; (3) study the binding of the new chelators toward Ln ions and (4) examine the utility of the chelators as decontamination and dissolution agents under basic solution conditions. The project has been successful in attacking selected aspects of the very difficult problems associated with basic pH solution f-element waste chemistry. In particular, the project has (1) shed additional light on the initial stages of Ln ion sol-gel-precipitate formulation under basic solution conditions; (2) generated new families of pyridine phosphonic acid chelators; (3) characterized the function of the chelators and (4) examined their utility as oxide-hydroxide dissolution agents. These findings have contributed significantly to an improved understanding of the behavior of Ln ions in basic media containing anions found in typical waste sludges as well as to the development of sludge dissolution agents. The new chelating reagents are easily made and could be

  8. Chelation technology: a promising green approach for resource management and waste minimization.

    Science.gov (United States)

    Chauhan, Garima; Pant, K K; Nigam, K D P

    2015-01-01

    Green chemical engineering recognises the concept of developing innovative environmentally benign technologies to protect human health and ecosystems. In order to explore this concept for minimizing industrial waste and for reducing the environmental impact of hazardous chemicals, new greener approaches need to be adopted for the extraction of heavy metals from industrial waste. In this review, a range of conventional processes and new green approaches employed for metal extraction are discussed in brief. Chelation technology, a modern research trend, has shown its potential to develop sustainable technology for metal extraction from various metal-contaminated sites. However, the interaction mechanism of ligands with metals and the ecotoxicological risk associated with the increased bioavailability of heavy metals due to the formation of metal-chelant complexes is still not sufficiently explicated in the literature. Therefore, a need was felt to provide a comprehensive state-of-the-art review of all aspects associated with chelation technology to promote this process as a green chemical engineering approach. This article elucidates the mechanism and thermodynamics associated with metal-ligand complexation in order to have a better understanding of the metal extraction process. The effects of various process parameters on the formation and stability of complexes have been elaborately discussed with respect to optimizing the chelation efficiency. The non-biodegradable attribute of ligands is another important aspect which is currently of concern. Therefore, biotechnological approaches and computational tools have been assessed in this review to illustrate the possibility of ligand degradation, which will help the readers to look for new environmentally safe mobilizing agents. In addition, emerging trends and opportunities in the field of chelation technology have been summarized and the diverse applicability of chelation technology in metal extraction from

  9. Sequence diversity and enzyme activity of ferric-chelate reductase LeFRO1 in tomato.

    Science.gov (United States)

    Kong, Danyu; Chen, Chunlin; Wu, Huilan; Li, Ye; Li, Junming; Ling, Hong-Qing

    2013-11-20

    Ferric-chelate reductase which functions in the reduction of ferric to ferrous iron on root surface is a critical protein for iron homeostasis in strategy I plants. LeFRO1 is a major ferric-chelate reductase involved in iron uptake in tomato. To identify the natural variations of LeFRO1 and to assess their effect on the ferric-chelate reductase activity, we cloned the coding sequences of LeFRO1 from 16 tomato varieties collected from different regions, and detected three types of LeFRO1 (LeFRO1(MM), LeFRO1(Ailsa) and LeFRO1(Monita)) with five amino acid variations at the positions 21, 24, 112, 195 and 582. Enzyme activity assay revealed that the three types of LeFRO1 possessed different ferric-chelate reductase activity (LeFRO1(Ailsa) > LeFRO1(MM) > LeFRO1(Monita)). The 112th amino acid residue Ala of LeFRO1 is critical for maintaining the high activity of ferric-chelate reductase, because modification of this amino acid resulted in a significant reduction of enzyme activity. Further, we showed that the combination of the amino acid residue Ile at the site 24 with Lys at the site 582 played a positive role in the enzyme activity of LeFRO1. In conclusion, the findings are helpful to understand the natural adaptation mechanisms of plants to iron-limiting stress, and may provide new knowledge to select and manipulate LeFRO1 for improving the iron deficiency tolerance in tomato.

  10. FTIR, magnetic, mass spectral, XRD and thermal studies of metal chelates of tenoxicam

    Science.gov (United States)

    Zayed, M. A.; El-Dien, F. A. Nour; Mohamed, Gehad G.; El-Gamel, Nadia E. A.

    2007-09-01

    Metal chelates of anti-inflammatory drug, tenoxicam (Ten), are synthesized and characterized using elemental analyses, IR, solid reflectance, magnetic, mass spectra, thermal analyses (TGA and DTA) and X-ray powder diffraction techniques. The chelates are found to have the general formulae [M(H 2L) 2(H 2O) x] (A) 2· yH 2O (where H 2L = neutral Ten, A = Cl in case of Ni(II) and Co(II) or AcO in case of Cu(II) and Zn(II) ions, x = 0-2 and y = 0-2.5) and [M(H 2L) 3](A) z· yH 2O (A = SO 4 in case of Fe(II) ion ( z = 1) or Cl in case of Fe(III) ( z = 3) and y = 0-4). IR spectra reveal that Ten behaves as a neutral bidentate ligand coordinated to the metal ions through the pyridyl- N and carbonyl- O of the amide moiety. The solid reflectance spectra and magnetic moment measurements reveal that these chelates have tetrahedral, square planar and octahedral geometrical structures. Mass spectra are also used to confirm the proposed formulae and the possible fragments resulted from fragmentation of Ten and its Zn(II) and Cu(II) chelates are suggested. The thermal behaviour of the chelates (TG/DTG, DTA) are discussed in detailed manner and revealed that water molecules of crystallization together with anions are removed in the first and second steps while the Ten molecules are removed in the subsequent steps. Different thermodynamic parameters are evaluated and the relative thermal stabilities of the complexes are discussed. X-ray powder diffraction patterns are used to indicate the polymorphic form of Ten and if the complexes have molecular similarity with respect to type of coordination.

  11. A calcium-collagen chelate dietary supplement attenuates bone loss in postmenopausal women with osteopenia: a randomized controlled trial.

    Science.gov (United States)

    Elam, Marcus L; Johnson, Sarah A; Hooshmand, Shirin; Feresin, Rafaela G; Payton, Mark E; Gu, Jennifer; Arjmandi, Bahram H

    2015-03-01

    Menopause leads to an increased risk for osteoporosis in women. Although drug therapies exist, increasing numbers of people prefer alternative therapies such as dietary supplements, for example, calcium, vitamin D, and collagen hydrolysates for the prevention and treatment of osteoporosis. We have previously shown that a 3-month intervention using a calcium-collagen chelate (CC) dietary supplement was efficacious in improving bone mineral density (BMD) and blood biomarkers of bone turnover in osteopenic postmenopausal women. This study reports the long-term efficacy of CC in reducing bone loss in postmenopausal women with osteopenia. Thirty-nine women were randomly assigned to one of two groups: 5 g of CC containing 500 mg of elemental calcium and 200 IU vitamin D (1,25-dihydroxyvitamin D3) or control (500 mg of calcium and 200 IU vitamin D) daily for 12 months. Total body, lumbar, and hip BMD were evaluated at baseline, 6 and 12 months using dual-energy X-ray absorptiometry. Blood was collected at baseline, 6 and 12 months to assess levels of blood biomarkers of bone turnover. Intent-to-treat (ITT) analysis was performed using repeated measures analysis of variance pairwise comparisons and multivariate analysis to assess time and group interactions. The loss of whole body BMD in women taking CC was substantially lower than that of the control group at 12 months in those who completed the study and the ITT analysis, respectively (CC: -1.33% and -0.33% vs. control: -3.75% and -2.17%; P=.026, P=.035). The CC group had significantly reduced levels of sclerostin and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) (P<.05), and higher bone-specific alkaline phosphatase/TRAP5b ratio (P<.05) than control at 6 months. These results support the use of CC in reducing bone loss in osteopenic postmenopausal women.

  12. Graphene Oxide and Gadolinium-Chelate Functionalized Poly(lactic acid) Nanocapsules Encapsulating Perfluorooctylbromide for Ultrasound/Magnetic Resonance Bimodal Imaging Guided Photothermal Ablation of Cancer.

    Science.gov (United States)

    Li, Zhenglin; Ke, Hengte; Wang, Jinrui; Miao, Zhaohua; Yue, Xiuli

    2016-03-01

    This paper successfully fabricated a novel multifunctional theranostic agent (PFOB@PLA/GO/Gd-DTPA NCs) by loading perfluorooctylbromide (PFOB) into poly(lactic acid) (PLA) nanocapsules (NCs) followed by surface functionalization with graphene oxide (GO) and gadolinium-chelate (Gd-DTPA). It was found that the resulting nanoagent could serve as a contrast agent simultaneously to enhance ultrasound (US) and magnetic resonance imaging (MRI). Benefiting from the strong absorption in the near infrared (NIR) region, the nanocapsules could efficiently kill cancer cells under NIR laser irradiation. Thus, such a single theranostic agent with the combination of realtime US imaging and high-resolution MR imaging could achieve great therapeutic effectiveness without systemic damage to the body. In addition, the cytotoxicity assay on HUVEC cells revealed a good biocompatibility of PFOB@PLA/GO/Gd-DTPA NCs, showing that the versatile nanocapsule system may hold great potential as an effective nanoplatform for contrast enhanced imaging guided photothermal therapy.

  13. Styrene-divinylbenzene copolymers loaded with organophosphorus chelating agents for rare earths separation; Copolimeros de estireno-divinilbenzeno impregnados com agentes complexantes organofosforados para separacao de terras raras

    Energy Technology Data Exchange (ETDEWEB)

    Barbosa, Celina C.R. [Instituto de Engenharia Nuclear (IEN), Rio de Janeiro, RJ (Brazil); Teixeira, Viviane G.; Coutinho, Fernanda M.B. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Inst. de Macromoleculas

    1998-12-01

    Styrene-divinylbenzene copolymers used in extraction chromatography were synthesized in presence of selective chelating agents for rare earths: DEHPA, bis (2-ethylhexyl) phosphoric acid, and EHEHPA, bis (2-ethylhexyl) phosphonic acid. The copolymers were prepared by suspension polymerization technique using the pure chelating agents and its mixture with toluene (TOL) as diluents. The influence of synthesis conditions such as chelating agent/TOL ratios, dilution degree of monomers and amount of DVB on the porous structure of the copolymers were studied. The porous structure was characterized by the apparent density, fixed pore volume, surface area and by optical and scanning electron microscopy. The performance of the copolymers in the separation process of rare earths was evaluated. The total chelating capacity of each copolymer and the chelating kinetics in relation to gadolinium ion were determined. The chelating agent content of the copolymers depend on the amount of chelating agents employed in the synthesis. The highest amount of chelating agent that can be used in the synthesis in order to produce copolymers with high chelating capacity and good mechanical properties was determined. The total chelating capacity varied with the content of the chelating agents in the copolymer and the chelating kinetics was dependent mainly on the pore diameter, because this parameter determines the diffusion rate of the ions though the copolymer structure. (author)

  14. Assessment of the Efficacy of Chelate-Assisted Phytoextraction of Lead by Coffeeweed (Sesbania exaltata Raf.

    Directory of Open Access Journals (Sweden)

    Gloria Miller

    2008-12-01

    Full Text Available Lead (Pb, depending upon the reactant surface, pH, redox potential and other factors can bind tightly to the soil with a retention time of many centuries. Soil-metal interactions by sorption, precipitation and complexation processes, and differences between plant species in metal uptake efficiency, transport, and susceptibility make a general prediction of soil metal bioavailability and risks of plant metal toxicity difficult. Moreover, the tight binding characteristic of Pb to soils and plant materials make a significant portion of Pb unavailable for uptake by plants. This experiment was conducted to determine whether the addition of ethylenediaminetetraacetic acid (EDTA, ethylene glycol tetraacetic acid (EGTA, or acetic acid (HAc can enhance the phytoextraction of Pb by making the Pb soluble and more bioavailable for uptake by coffeeweed (Sesbania exaltata Raf.. Also we wanted to assess the efficacy of chelates in facilitating translocation of the metal into the above-ground biomass of this plant. To test the effect of chelates on Pb solubility, 2 g of Pb-spiked soil (1000 mg Pb/kg dry soil were added to each 15 mL centrifuge tube. Chelates (EDTA, EGTA, HAc in a 1:1 ratio with the metal, or distilled deionized water were then added. Samples were shaken on a platform shaker then centrifuged at the end of several time periods. Supernatants were filtered with a 0.45 μm filter and quantified by inductively coupled plasma-optical emission spectrometry (ICP-OES to determine soluble Pb concentrations. Results revealed that EDTA was the most effective in bringing Pb into solution, and that maximum solubility was reached 6 days after chelate amendment. Additionally, a greenhouse experiment was conducted by planting Sesbania seeds in plastic tubes containing top soil and peat (2:1, v:v spiked with various levels (0, 1000, 2000 mg Pb/kg dry soil of lead nitrate. At six weeks after emergence, aqueous solutions of EDTA and/or HAc (in a 1:1 ratio

  15. Iron Chelators and Antioxidants Regenerate Neuritic Tree and Nigrostriatal Fibers of MPP+/MPTP-Lesioned Dopaminergic Neurons.

    Directory of Open Access Journals (Sweden)

    Pabla Aguirre

    Full Text Available Neuronal death in Parkinson's disease (PD is often preceded by axodendritic tree retraction and loss of neuronal functionality. The presence of non-functional but live neurons opens therapeutic possibilities to recover functionality before clinical symptoms develop. Considering that iron accumulation and oxidative damage are conditions commonly found in PD, we tested the possible neuritogenic effects of iron chelators and antioxidant agents. We used three commercial chelators: DFO, deferiprone and 2.2'-dypyridyl, and three 8-hydroxyquinoline-based iron chelators: M30, 7MH and 7DH, and we evaluated their effects in vitro using a mesencephalic cell culture treated with the Parkinsonian toxin MPP+ and in vivo using the MPTP mouse model. All chelators tested promoted the emergence of new tyrosine hydroxylase (TH-positive processes, increased axodendritic tree length and protected cells against lipoperoxidation. Chelator treatment resulted in the generation of processes containing the presynaptic marker synaptophysin. The antioxidants N-acetylcysteine and dymetylthiourea also enhanced axodendritic tree recovery in vitro, an indication that reducing oxidative tone fosters neuritogenesis in MPP+-damaged neurons. Oral administration to mice of the M30 chelator for 14 days after MPTP treatment resulted in increased TH- and GIRK2-positive nigra cells and nigrostriatal fibers. Our results support a role for oral iron chelators as good candidates for the early treatment of PD, at stages of the disease where there is axodendritic tree retraction without neuronal death.

  16. Electrospray ionization collision-induced dissociation mass spectrometry: a tool to characterize synthetic polyaminocarboxylate ferric chelates used as fertilizers.

    Science.gov (United States)

    Orera, Irene; Orduna, Jesús; Abadía, Javier; Alvarez-Fernández, Ana

    2010-01-01

    Fertilizers based on synthetic polyaminocarboxylate ferric chelates have been known since the 1950s to be successful in supplying Fe to plants. In commercial Fe(III)-chelate fertilizers, a significant part of the water-soluble Fe-fraction consists of still uncharacterized Fe byproducts, whose agronomical value is unknown. Although collision-induced dissociation (CID) tandem mass spectrometry (MS/MS) is a valuable tool for the identification of such compounds, no fragmentation data have been reported for most Fe(III)-chelate fertilizers. The aim of this study was to characterize the CID-MS(2) fragmentation patterns of the major synthetic Fe(III)-chelates used as Fe-fertilizers, and subsequently use this technique for the characterization of commercial fertilizers. Quadrupole-time-of-flight (QTOF) and spherical ion trap mass analyzers equipped with an electrospray ionization (ESI) source were used. ESI-CID-MS(2) spectra obtained were richer when using the QTOF device. Specific differences were found among Fe(III)-chelate fragmentation patterns, even in the case of positional isomers. The analysis of a commercial Fe(III)-chelate fertilizer by high-performance liquid chromatography (HPLC) coupled to ESI-MS(QTOF) revealed two previously unknown, Fe-containing compounds, that were successfully identified by a comprehensive comparison of the ESI-CID-MS(2)(QTOF) spectra with those of pure chelates. This shows that HPLC/ESI-CID-MS(2)(QTOF), along with the Fe(III)-chelate fragmentation patterns, could be a highly valuable tool to directly characterize the water-soluble Fe fraction in Fe(III)-chelate fertilizers. This could be of great importance in issues related to crop Fe-fertilization, both from an agricultural and an environmental point of view.

  17. Chelator free gallium-68 radiolabelling of silica coated iron oxide nanorods via surface interactions

    Science.gov (United States)

    Burke, Benjamin P.; Baghdadi, Neazar; Kownacka, Alicja E.; Nigam, Shubhanchi; Clemente, Gonçalo S.; Al-Yassiry, Mustafa M.; Domarkas, Juozas; Lorch, Mark; Pickles, Martin; Gibbs, Peter; Tripier, Raphaël; Cawthorne, Christopher; Archibald, Stephen J.

    2015-09-01

    The commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities. Herein we describe a new class of silica coated iron-oxide nanorods (NRs) coated with polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies of the coated NRs validate their composition and confirm their properties as in vivo T2 MRI contrast agents. Radiolabelling studies with the positron emitting radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the silica coating, the macrocyclic chelator was not required for preparation of highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies show the expected high liver uptake of gallium-68 radiolabelled nanorods with no significant release of gallium-68 metal ions, validating our innovation to provide a novel simple method for labelling of iron oxide NRs with a radiometal in the absence of a chelating unit that can be used for high sensitivity liver imaging.The commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities. Herein we describe a new class of silica coated iron-oxide nanorods (NRs) coated with polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies of the coated NRs validate their composition and confirm their properties as in vivo T2 MRI contrast agents. Radiolabelling studies with the positron emitting radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the silica coating, the macrocyclic chelator was not required for preparation of highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies show the expected high liver uptake of gallium-68 radiolabelled nanorods with no

  18. Lipophilic aroylhydrazone chelator HNTMB and its multiple effects on ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Singh Rakesh K

    2010-02-01

    Full Text Available Abstract Background Metal chelators have gained much attention as potential anti-cancer agents. However, the effects of chelators are often linked solely to their capacity to bind iron while the potential complexation of other trace metals has not been fully investigated. In present study, we evaluated the effects of various lipophilic aroylhydrazone chelators (AHC, including novel compound HNTMB, on various ovarian cancer cell lines (SKOV-3, OVCAR-3, NUTU-19. Methods Cell viability was analyzed via MTS cytotoxicity assays and NCI60 cancer cell growth screens. Apoptotic events were monitored via Western Blot analysis, fluorescence microscopy and TUNEL assay. FACS analysis was carried out to study Cell Cycle regulation and detection of intracellular Reactive Oxygen Species (ROS Results HNTMB displayed high cytotoxicity (IC50 200-400 nM compared to previously developed AHC (oVtBBH, HNtBBH, StBBH/206, HNTh2H/315, HNI/311; IC50 0.8-6 μM or cancer drug Deferoxamine, a hexadentate iron-chelator (IC50 12-25 μM. In a NCI60 cancer cell line screen HNTMB exhibited growth inhibitory effects with remarkable differences in specificity depending on the cell line studied (GI50 10 nM-2.4 μM. In SKOV-3 ovarian cancer cells HNTMB treatment led to chromatin fragmentation and activation of the extrinsic and intrinsic pathways of apoptosis with specific down-regulation of Bcl-2. HNTMB caused delayed cell cycle progression of SKOV-3 through G2/M phase arrest. HNTMB can chelate iron and copper of different oxidation states. Complexation with copper lead to high cytotoxicity via generation of reactive oxygen species (ROS while treatment with iron complexes of the drug caused neither cytotoxicity nor increased ROS levels. Conclusions The present report suggests that both, non-complexed HNTMB as a chelator of intracellular trace-metals as well as a cytotoxic HNTMB/copper complex may be developed as potential therapeutic drugs in the treatment of ovarian and other

  19. Regulation of copper and iron homeostasis by metal chelators: a possible chemotherapy for Alzheimer's disease.

    Science.gov (United States)

    Robert, Anne; Liu, Yan; Nguyen, Michel; Meunier, Bernard

    2015-05-19

    With the increase of life expectancy of humans in more than two-thirds of the countries in the World, aging diseases are becoming the frontline health problems. Alzheimer's disease (AD) is now one of the major challenges in drug discovery, since, with the exception of memantine in 2003, all clinical trials with drug candidates failed over the past decade. If we consider that the loss of neurons is due to a high level of oxidative stress produced by nonregulated redox active metal ions like copper linked to amyloids of different sizes, regulation of metal homeostasis is a key target. The difficulty for large copper-carrier proteins to directly extract copper ions from metalated amyloids might be considered as being at the origin of the rupture of the copper homeostasis regulation in AD brains. So, there is an urgent need for new specific metal chelators that should be able to regulate the homeostasis of metal ions, specially copper and iron, in AD brains. As a consequence of that concept, chelators promoting metal excretion from brain are not desired. One should favor ligands able to extract copper ions from sinks (amyloids being the major one) and to transfer these redox-active metal ions to copper-carrier proteins or copper-containing enzymes. Obviously, the affinity of these chelators for the metal ion should not be a sufficient criterion, but the metal specificity and the ability of the chelators to release the metal under specific biological conditions should be considered. Such an approach is still largely unexplored. The requirements for the chelators are very high (ability to cross the brain-blood barrier, lack of toxicity, etc.), few chemical series were proposed, and, among them, biochemical or biological data are scarce. As a matter of fact, the bioinorganic pharmacology of AD represents less than 1% of all articles dedicated to AD drug research. The major part of these articles deals with an old and rather toxic drug, clioquinol and related analogs, that

  20. Lanthanide chelate complementation and hydrolysis enhanced luminescent chelate in real-time reverse transcription polymerase chain reaction assays for KLK3 transcripts.

    Science.gov (United States)

    Alinezhad, Saeid; Väänänen, Riina-Minna; Lehmusvuori, Ari; Karhunen, Ulla; Soukka, Tero; Kähkönen, Esa; Taimen, Pekka; Alanen, Kalle; Pettersson, Kim

    2014-01-01

    The requirement for high-performance reporter probes in real-time detection of polymerase chain reaction (PCR) has led to the use of time-resolved fluorometry of lanthanide chelates. The aim of this study was to investigate the applicability of the principle of lanthanide chelate complementation (LCC) in comparison with a method based on hydrolysis enhancement and quenching of intact probes. A real-time reverse transcription (RT) PCR assay for kallikrein-related peptidase 3 (KLK3, model analyte) was developed by using the LCC detection method. Both detection methods were tested with a standard series of purified PCR products, 20 prostatic tissues, 20 healthy and prostate cancer patient blood samples, and female blood samples spiked with LNCaP cells. The same limit of detection was obtained with both methods, and two cycles earlier detection with the LCC method was observed. KLK3 messenger RNA (mRNA) was detected in all tissue samples and in 1 of 20 blood samples identically with both methods. The background was 30 times lower, and the signal-to-background (S/B) ratio was 3 times higher, when compared with the reference method. Use of the new reporter method provided similar sensitivity and specificity as the reference method. The lower background, the improved S/B ratio, and the possibility of melting curve analysis and single nucleotide polymorphism (SNP) detection could be advantages for this new reporter probe.

  1. L-Ascorbic acid can abrogate SVCT-2-dependent cetuximab resistance mediated by mutant KRAS in human colon cancer cells.

    Science.gov (United States)

    Jung, Soo-A; Lee, Dae-Hee; Moon, Jai-Hee; Hong, Seung-Woo; Shin, Jae-Sik; Hwang, Ih Yeon; Shin, Yu Jin; Kim, Jeong Hee; Gong, Eun-Yeung; Kim, Seung-Mi; Lee, Eun Young; Lee, Seul; Kim, Jeong Eun; Kim, Kyu-Pyo; Hong, Yong Sang; Lee, Jung Shin; Jin, Dong-Hoon; Kim, TaeWon; Lee, Wang Jae

    2016-06-01

    Colon cancer patients with mutant KRAS are resistant to cetuximab, an antibody directed against the epidermal growth factor receptor, which is an effective clinical therapy for patients with wild-type KRAS. Numerous combinatorial therapies have been tested to overcome the resistance to cetuximab. However, no combinations have been found that can be used as effective therapeutic strategies. In this study, we demonstrate that L-ascorbic acid partners with cetuximab to induce killing effects, which are influenced by sodium-dependent vitamin C transporter 2 (SVCT-2) in human colon cancer cells with a mutant KRAS. L-Ascorbic acid treatment of human colon cancer cells that express a mutant KRAS differentially and synergistically induced cell death with cetuximab in a SVCT-2-dependent manner. The ectopic expression of SVCT-2 induced sensitivity to L-ascorbic acid treatment in human colon cancer cells that do not express SVCT-2, whereas the knockdown of endogenous SVCT-2 induced resistance to L-ascorbic acid treatment in SVCT-2-positive cells. Moreover, tumor regression via the administration of L-ascorbic acid and cetuximab in mice bearing tumor cell xenografts corresponded to SVCT-2 protein levels. Interestingly, cell death induced by the combination of L-ascorbic acid and cetuximab resulted in both apoptotic and necrotic cell death. These cell death mechanisms were related to a disruption of the ERK pathway and were represented by the impaired activation of RAFs and the activation of the ASK-1-p38 pathway. Taken together, these results suggest that resistance to cetuximab in human colon cancer patients with a mutant KRAS can be bypassed by L-ascorbic acid in an SVCT-2-dependent manner. Furthermore, SVCT-2 in mutant KRAS colon cancer may act as a potent marker for potentiating L-ascorbic acid co-treatment with cetuximab.

  2. Reversible retinopathy associated with oral deferasirox therapy

    Science.gov (United States)

    Walia, Harpreet S; Yan, Jiong

    2013-01-01

    A 17-year-old girl with a history of sickle cell anaemia undergoing chronic blood transfusions and iron-chelation therapy presented for multiple ophthalmic examinations. During treatment with deferoxamine, her examination remained stable but 2 years after changing to deferasirox she presented with decreased visual acuity and only mild funduscopic changes. Marked electrophysiological abnormalities were also evident. After cessation of deferasirox, her visual acuity improved and electrophysiological responses improved. No prior reports of deferasirox-related retinopathy are available. We suggest that oral deferasirox caused a reversible retinopathy in our patient and clinicians be aware of this entity. PMID:23867877

  3. Reversible retinopathy associated with oral deferasirox therapy.

    Science.gov (United States)

    Walia, Harpreet S; Yan, Jiong

    2013-07-17

    A 17-year-old girl with a history of sickle cell anaemia undergoing chronic blood transfusions and iron-chelation therapy presented for multiple ophthalmic examinations. During treatment with deferoxamine, her examination remained stable but 2 years after changing to deferasirox she presented with decreased visual acuity and only mild funduscopic changes. Marked electrophysiological abnormalities were also evident. After cessation of deferasirox, her visual acuity improved and electrophysiological responses improved. No prior reports of deferasirox-related retinopathy are available. We suggest that oral deferasirox caused a reversible retinopathy in our patient and clinicians be aware of this entity.

  4. Solution-processed Al-chelated gelatin for highly transparent non-volatile memory applications

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yu-Chi; Wang, Yeong-Her, E-mail: yhw@ee.ncku.edu.tw [Institute of Microelectronics and Department of Electrical Engineering, Advanced Optoelectronic Technology Center, National Cheng-Kung University, Tainan 701 Taiwan (China)

    2015-03-23

    Using the biomaterial of Al-chelated gelatin (ACG) prepared by sol-gel method in the ITO/ACG/ITO structure, a highly transparent resistive random access memory (RRAM) was obtained. The transmittance of the fabricated device is approximately 83% at 550 nm while that of Al/gelatin/ITO is opaque. As to the ITO/gelatin/ITO RRAM, no resistive switching behavior can be seen. The ITO/ACG/ITO RRAM shows high ON/OFF current ratio (>10{sup 5}), low operation voltage, good uniformity, and retention characteristics at room temperature and 85 °C. The mechanism of the ACG-based memory devices is presented. The enhancement of these electrical properties can be attributed to the chelate effect of Al ions with gelatin. Results show that transparent ACG-based memory devices possess the potential for next-generation resistive memories and bio-electronic applications.

  5. Novel enterobactin analogues as potential therapeutic chelating agents: Synthesis, thermodynamic and antioxidant studies

    Science.gov (United States)

    Zhang, Qingchun; Jin, Bo; Shi, Zhaotao; Wang, Xiaofang; Liu, Qiangqiang; Lei, Shan; Peng, Rufang

    2016-09-01

    A series of novel hexadentate enterobactin analogues, which contain three catechol chelating moieties attached to different molecular scaffolds with flexible alkyl chain lengths, were prepared. The solution thermodynamic stabilities of the complexes with uranyl, ferric(III), and zinc(II) ions were then investigated. The hexadentate ligands demonstrate effective binding ability to uranyl ion, and the average uranyl affinities are two orders of magnitude higher than 2,3-dihydroxy-N1,N4-bis[(1,2-hydroxypyridinone-6-carboxamide)ethyl]terephthalamide [TMA(2Li-1,2-HOPO)2] ligand with similar denticity. The high affinity of hexadentate ligands could be due to the presence of the flexible scaffold, which favors the geometric agreement between the ligand and the uranyl coordination preference. The hexadentate ligands also exhibit higher antiradical efficiency than butylated hydroxyanisole (BHA). These results provide a basis for further studies on the potential applications of hexadentate ligands as therapeutic chelating agents.

  6. Mass-dependent and -independent fractionation of isotopes in Ni and Pb chelate complex formation reactions

    Science.gov (United States)

    Nomura, Masao; Kudo, Takashi; Adachi, Atsuhiko; Aida, Masao; Fujii, Yasuhiko

    2013-11-01

    Mass independent fractionation (MIF) has been a very interesting topic in the field of inorganic isotope chemistry, in particular, geo- and cosmo- chemistry. In the present work, we studied the isotope fractionation of Ni(II) and Pb(II) ions in complex formation with chelating reagent EDTA. To obtain clear results on the mass dependence of the isotope fractionation, we have conducted long-distance ion exchange chromatography of Ni(II) and Pb(II), using chelate complex reagent EDTA. The results apparently show that the isotope fractionation in Ni complex formation system is governed by the mass dependent rule. On the other hand the isotope fractionation in the Pb complex system is governed by the mass independent rule or the nuclear volume effect.

  7. Synthesis of Novel Chelating Adsorbents for Boron Uptake from Aqueous Solutions

    Institute of Scientific and Technical Information of China (English)

    王丽那; 齐涛; 张懿

    2006-01-01

    Two kinds of novel chelating adsorbents have been synthesized to separate boron from aqueous solutions. One is the boron-specific chelating resin, synthesized by the functionalization of macroporous poly (glycidyl methacrylate-cotrimethylolpropane trimethacrylate), with N-methylglucamine. The other is the organic-inorganic hybrid mesoporous SBA-15 with polyol functional groups, prepared by a two-step post-grafting method. The resin can adsorb boron in almost all pH range, and its maximum uptake capacity reaches 1.15 mmol/g. The present study of the polyol-functionalized SBA-15 shows that the post-grafting is successful and the resulting adsorbent has the uptake capacity of 0.63 mmol/g.

  8. Mass-dependent and -independent fractionation of isotopes in Ni and Pb chelate complex formation reactions

    Energy Technology Data Exchange (ETDEWEB)

    Nomura, Masao; Kudo, Takashi; Adachi, Atsuhiko; Aida, Masao; Fujii, Yasuhiko [Research Laboratory for Nuclear Reactors, Tokyo Institute of Technology, O-okayama Meguroku, Tokyo, 152-8550 (Japan)

    2013-11-13

    Mass independent fractionation (MIF) has been a very interesting topic in the field of inorganic isotope chemistry, in particular, geo- and cosmo- chemistry. In the present work, we studied the isotope fractionation of Ni(II) and Pb(II) ions in complex formation with chelating reagent EDTA. To obtain clear results on the mass dependence of the isotope fractionation, we have conducted long-distance ion exchange chromatography of Ni(II) and Pb(II), using chelate complex reagent EDTA. The results apparently show that the isotope fractionation in Ni complex formation system is governed by the mass dependent rule. On the other hand the isotope fractionation in the Pb complex system is governed by the mass independent rule or the nuclear volume effect.

  9. Synthesis and Characterization of α-HexadecyI-DOTA and its Gd(Ⅲ) Chelate

    Institute of Scientific and Technical Information of China (English)

    FENG,Zhi-Ming,(冯志明); LI,Feng(李峰); LEl,Chun-Hua(雷春华); CHEN,Ronga(陈蓉); LI,Xiao-Ru(李晓如)

    2004-01-01

    Synthesis and characterization of the ligand,10-(a-hexadecylcarboxymethyl)-1,4,7,10-tetraazacyclododecane1,4,7-triacetic acid (H4L),and its Gd(Ⅲ) chelate are described.Protonation constants for H4L ( lg KHi= 10.52,9.45,4.74,4.10) and the stability constant for GdL (lg KGdL- =24.50) were determined by potentiometric titrations.The results obtained show that the ligand still maintains the strong chelating properties of the parent DOTA (1,4,7,10-tetraazacyclododecane-N,N',N"N'"-tetraacetic acid) after introduction of a linear chain hexadecyl group at the acetic side chain of DOTA,and its basicity is not significantly altered.

  10. Investigating the role of metal chelation in HIV-1 integrase strand transfer inhibitors.

    Science.gov (United States)

    Bacchi, Alessia; Carcelli, Mauro; Compari, Carlotta; Fisicaro, Emilia; Pala, Nicolino; Rispoli, Gabriele; Rogolino, Dominga; Sanchez, Tino W; Sechi, Mario; Sinisi, Valentina; Neamati, Nouri

    2011-12-22

    HIV-1 integrase (IN) has been validated as an attractive target for the treatment of HIV/AIDS. Several studies have confirmed that the metal binding function is a crucial feature in many of the reported IN inhibitors. To provide new insights on the metal chelating mechanism of IN inhibitors, we prepared a series of metal complexes of two ligands (HL1 and HL2), designed as representative models of the clinically used compounds raltegravir and elvitegravir. Potentiometric measurements were conducted for HL2 in the presence of Mg(II), Mn(II), Co(II), and Zn(II) in order to delineate a metal speciation model. We also determined the X-ray structures of both of the ligands and of three representative metal complexes. Our results support the hypothesis that several selective strand transfer inhibitors preferentially chelate one cation in solution and that the metal complexes can interact with the active site of the enzyme.

  11. Theoretical study, and infrared and Raman spectra of copper(II) chelated complex with dibenzoylmethane

    DEFF Research Database (Denmark)

    Nekoei, A.-R.; Vakili, M.; Hakimi-Tabar, M.

    2014-01-01

    assignment for Cu(dbm)2 in the literatures. Density functional theory (DFT) at the B3LYP level and also MP2 calculations using different basis sets, besides Natural Bond Orbital (NBO) and Atoms-in-Molecules (AIM) analyses, have been employed to investigate the effect of methyl substitution with the phenyl......There are some discrepancies in both the vibrational assignments and in the metal-ligand (M-L) bond strengths predicted in the previous studies on the copper (II) chelated complex of dibenzoylmethane, Cu(dbm)2. Also, there is a lack of theoretical structure, Raman spectrum and full vibrational...... group on the stabilities of bis(acetylacetonate) copper (II), Cu(acac)2, and Cu(dbm)2 complexes and the electron delocalization in their chelated rings. Measured solid phase infrared and Raman bands for Cu(dbm)2 complex have been interpreted in terms of the calculated vibrational modes and detailed...

  12. The role of gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: A critical update.

    Science.gov (United States)

    Idée, Jean-Marc; Fretellier, Nathalie; Robic, Caroline; Corot, Claire

    2014-11-01

    Nephrogenic systemic fibrosis (NSF) is an iatrogenic scleroderma-like fibrosing systemic disorder occurring in patients with severe or end-stage renal disease. It was established as a new clinical entity in the year 2000. A causal role for gadolinium chelates (GC), widely used as contrast agents for magnetic resonance imaging, was suggested six years later. It rapidly appeared that the occurrence of NSF was associated with prior administration of GCs with lower thermodynamic stability, leading to warnings being published by health authorities and learned societies worldwide. Although a role for the chelated form of the less stable GCs has been proposed, the most commonly accepted hypothesis involves the gradual release of dissociated gadolinium in the body, leading to systemic fibrosis. However, the entire chain of events is still not fully understood in a causal way and many uncertainties remain.

  13. Development and evaluation of the improved iron chelating agents EHPG, HBED and their dimethyl esters.

    Science.gov (United States)

    Hershko, C; Grady, R W; Link, G

    1984-01-01

    The phenolic EDTA analogues ethylenediamine-N,N'-bis-(2- hydroxyphenylglycine ) ( EHPG ), N,N'-bis(2-hydroxybenzyl)-ethylenediamine diacetic acid ( HBED ), and their respective dimethyl esters ( dimethylEHPG and dimethylHBED ) were studied in hypertransfused rats. Radioiron bound to these compounds was cleared mainly by the liver and excreted in the bile. After a single 40 mg i.m. injection, the percentage of radioiron removed from 59Fe-ferritin-labelled hepatocytes and excreted in the bile was 4% in untreated controls, 24% for desferral , 42% for dimethylEHPG , 58% for EHPG , 63% for HBED , and 80% for dimethylHBED . DimethylHBED combines oral effectiveness with superior chelating ability, selective hepatocellular action, and low apparent toxicity. It may represent a significant advance in the development of new iron chelating drugs.

  14. Switch from antagonist to agonist after addition of a DOTA chelator to a somatostatin analog

    Energy Technology Data Exchange (ETDEWEB)

    Reubi, Jean Claude; Cescato, Renzo; Waser, Beatrice [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, PO Box 62, Berne (Switzerland); Erchegyi, Judit; Rivier, Jean E. [The Salk Institute for Biological Studies, The Clayton Foundation Laboratories for Peptide Biology, La Jolla, CA (United States)

    2010-08-15

    Peptide receptor targeting has become an increasingly attractive method to target tumors diagnostically and radiotherapeutically. Peptides linked to a variety of chelators have been developed for this purpose. They have, however, rarely been tested for their agonistic or antagonistic properties. We report here on a somatostatin antagonist that switched to an agonist upon coupling to a DOTA chelator. Two novel somatostatin analogs, 406-040-15 and its DOTA-coupled counterpart 406-051-20, with and without cold Indium labeling, were tested for their somatostatin receptor subtypes 1-5 (sst{sub 1}-sst{sub 5}) binding affinity using receptor autoradiography. Moreover, they were tested functionally for their ability to affect sst{sub 2} and sst{sub 3} internalization in vitro in HEK293 cells stably expressing the human sst{sub 2} or sst{sub 3} receptor, using an immunofluorescence microscopy-based internalization assay. All three compounds were characterized as pan-somatostatin analogs having a high affinity for all five sst. In the sst{sub 2} internalization assay, all three compounds showed an identical behavior, namely, a weak agonistic effect complemented by a weak antagonistic effect, compatible with the behavior of a partial agonist. Conversely, in the sst{sub 3} internalization assay, 406-040-15 was a full antagonist whereas its DOTA-coupled counterpart, 406-051-20, with and without Indium labeling, switched to a full agonist. Adding the DOTA chelator to the somatostatin analog 406-040-15 triggers a switch at sst{sub 3} receptor from an antagonist to an agonist. This indicates that potential radioligands for tumor targeting should always be tested functionally before further development, in particular if a chelator is added. (orig.)

  15. Chelators influenced synthesis of chitosan-carboxymethyl cellulose microparticles for controlled drug delivery

    Science.gov (United States)

    Samrot, Antony V.; Akanksha; Jahnavi, Tatipamula; Padmanaban, S.; Philip, Sheryl-Ann; Burman, Ujjala; Rabel, Arul Maximus

    2016-11-01

    In this study, polyphenolic curcumin is entrapped within microcomposites made of biopolymers chitosan (CS) and carboxymethyl cellulose (CMC) formulated by ionic gelation method. Here, different concentrations of two chelating agents, barium chloride and sodium tripolyphosphate, are used to make microcomposites. Thus, the synthesized microparticles were characterized by FTIR, and their surface morphology was studied by SEM. Drug encapsulation efficiency and the drug release kinetics of CS-CMC composites are also studied. The produced microcomposites were used to study antibacterial activity in vitro.

  16. Screening of chelating ligands to enhance mercury accumulation from historically mercury-contaminated soils for phytoextraction.

    Science.gov (United States)

    Wang, Jianxu; Xia, Jicheng; Feng, Xinbin

    2017-01-15

    Screening of optimal chelating ligands which not only have high capacities to enhance plant uptake of mercury (Hg) from soil but also can decrease bioavailable Hg concentration in soil is necessary to establish a viable chemically-assisted phytoextraction. Therefore, Brassica juncea was exposed to historically Hg-contaminated soil (total Hg, 90 mg kg(-1)) to investigate the efficiency of seven chelating agents [ammonium thiosulphate, sodium thiosulphate, ammonium sulfate, ammonium chloride, sodium nitrate, ethylenediaminetetraacetic acid (EDTA), and sodium sulfite] at enhancing Hg phytoextraction; the leaching of bioavailable Hg caused by these chelating agents was also investigated. The Hg concentration in control (treated with double-distilled water) plant tissues was below 1 mg kg(-1). The remarkably higher Hg concentration was found in plants receiving ammonium thiosulphate and sodium sulfite treatments. The bioaccumulation factors and translocation factors of ammonium thiosulphate and sodium sulfite treatments were significantly higher than those of the other treatments. The more efficient uptake of Hg by plants upon treatment with ammonium thiosulphate and sodium sulfite compared to the other treatments might be explained by the formation of special Hg-thiosulphate complexes that could be preferentially taken up by the roots and transported in plant tissues. The application of sulfite significantly increased bioavailable Hg concentration in soil compared with that in initial soil and control soil, whereas ammonium thiosulphate significantly decreased bioavailable Hg concentration. The apparent decrease of bioavailable Hg in ammonium thiosulphate-treated soil compared with that in sodium sulfite-treated soil might be attributable to the unstable Hg-thiosulphate complexes formed between thiosulphate and Hg; they could react to produce less bioavailable Hg in the soil. The results of this study indicate that ammonium thiosulphate may be an optimal chelating

  17. Curcumin induces apoptosis and protective autophagy in castration-resistant prostate cancer cells through iron chelation

    Science.gov (United States)

    Yang, Chunguang; Ma, Xueyou; Wang, Zhihua; Zeng, Xing; Hu, Zhiquan; Ye, Zhangqun; Shen, Guanxin

    2017-01-01

    Background Curcumin induces apoptosis and autophagy in different cancer cells. Moreover, chemical and biological experiments have evidenced that curcumin is a biologically active iron chelator and induces cytotoxicity through iron chelation. We thus hypothesized that curcumin may induce apoptosis and autophagy in castration-resistant prostate cancer (CRPC) cells through its iron-chelating properties. Materials and methods CRPC cells were loaded with curcumin alone or in combination with ferric ammonium citrate (FAC). Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was assessed by flow cytometry, terminal deoxynucleotidyl transferase nick end labeling (TUNEL) assay and caspase activity. Autophagy status was analyzed by the detection of autophagosomes and light chain 3-II (LC3-II) using transmission electron microscopy and Western blot. Iron-binding activity of curcumin was assessed by spectrophotometry and MTT assay. The expression levels of transferrin receptor 1 (TfR1) and iron regulatory protein 1 (IRP1) were examined by Western blot. Results Curcumin induced apoptosis and autophagy in CRPC cells. Combining curcumin with autophagy inhibitors (3-methyladenine [3-MA]) synergized the apoptotic effect of curcumin. Moreover, curcumin bound to FAC at a ratio of ~1:1, as assessed by spectrophotometry and MTT assay. Apoptosis and autophagy induced by curcumin were counteracted by equal amounts of FAC. At apoptosis- and autophagy-inducing concentrations, curcumin enhanced the expression levels of TfR1 and IRP1, indicative of iron deprivation induced by curcumin. Conclusion Together, our results indicate that curcumin induces apoptosis and protective autophagy in CRPC cells, which are at least partially dependent on its iron-chelating properties. PMID:28243065

  18. Solution mining dawsonite from hydrocarbon containing formations with a chelating agent

    Science.gov (United States)

    Vinegar, Harold J.

    2009-07-07

    A method for treating an oil shale formation comprising dawsonite includes providing heat from one or more heaters to the formation to heat the formation. Hydrocarbon fluids are produced from the formation. At least some dawsonite in the formation is decomposed with the provided heat. A chelating agent is provided to the formation to dissolve at least some dawsonite decomposition products. The dissolved dawsonite decomposition products are produced from the formation.

  19. SYNTHESIS OF A NOVEL CHELATING RESIN WITH HETEROCYCLIC RING OF S AND N

    Institute of Scientific and Technical Information of China (English)

    QU Rongjun; SUN Changmei; JI Chunnuan; WANG Chunhua; CHENG Guoxiang

    2003-01-01

    By the reaction of poly(bromoacetyl styrene) (EBPS) with thiaurea (TU), a kind of novel chelating resin with heterocyaclic ring of sulfur and nitrogen, poly[4-(2-amino)thiazoleyl-4-vinylben=ene], was synthesized. Its structure was characterized by FTIR and elemental analysis. The factors which have influence on the reaction such as reaction time, solvents, and molar ratio of reactants were investigated.

  20. Synthesis of novel boron chelate complexes and proposed mechanism of new rearrangement.

    Science.gov (United States)

    Zhang, Rui-Zhe; Feng, Xiao; Liu, Ying; Wang, Sheng-Qing; Liu, Jin-Ting; Zhao, Bao-Xiang

    2015-03-15

    We synthesized novel boron chelate complexes by the reaction of pyrazoline derivatives and boron trifluoride diethyl etherate followed by a new rearrangement. The structures of the compounds were characterized by IR, NMR and HRMS, especially, a typical compound 3c was confirmed by X-ray single crystal analysis. We proposed a mechanism of the rearrangement. Moreover, the absorption and fluorescence spectroscopy of these compounds were measured.

  1. POTENTIOMETRIC BEHAVIOR OF CHELATING ION EXCHANGE RESIN IN WATER AND IN ETHANOL—WATER MIXTURES

    Institute of Scientific and Technical Information of China (English)

    DOUHuiyuan; WANGChangshou; 等

    1993-01-01

    The potentiometric behavior of the chelating ion exchange resin D751 containing iminodiacetic acid groups has been studied at 25℃ by batch titration with alkali and acid in water and in ethanol-water mixture solvent.The titrtion curves,the amount of chemically bound counter-ions and invasive electrolytes in the resin phase,and the solvent contents the resin have been investigated.

  2. Chelators influenced synthesis of chitosan-carboxymethyl cellulose microparticles for controlled drug delivery

    Science.gov (United States)

    Samrot, Antony V.; Akanksha; Jahnavi, Tatipamula; Padmanaban, S.; Philip, Sheryl-Ann; Burman, Ujjala; Rabel, Arul Maximus

    2016-07-01

    In this study, polyphenolic curcumin is entrapped within microcomposites made of biopolymers chitosan (CS) and carboxymethyl cellulose (CMC) formulated by ionic gelation method. Here, different concentrations of two chelating agents, barium chloride and sodium tripolyphosphate, are used to make microcomposites. Thus, the synthesized microparticles were characterized by FTIR, and their surface morphology was studied by SEM. Drug encapsulation efficiency and the drug release kinetics of CS-CMC composites are also studied. The produced microcomposites were used to study antibacterial activity in vitro.

  3. Iron reverses impermeable chelator inhibition of DNA synthesis in CCl 39 cells.

    OpenAIRE

    Alcain, F J; Löw, H; Crane, F. L.

    1994-01-01

    Treatment of Chinese hamster lung fibroblasts (CCl 39 cells) with the impermeable iron(II) chelator bathophenanthroline disulfonate (BPS) inhibits DNA synthesis when cell growth is initiated with growth factors including epidermal growth factor plus insulin, thrombin, or ceruloplasmin, but not with 10% fetal calf serum. The BPS treatment inhibits transplasma membrane electron transport. The treatment leads to release of iron from the cells as determined by BPS iron(II) complex formation over ...

  4. Synthesis, Spectral Characterization and Computational Studies of Metal Chelates of 4-N-(2-Thienylideneaminoantipyrine

    Directory of Open Access Journals (Sweden)

    Sherifa Rahim

    2015-12-01

    Full Text Available Metal chelates of Schiff base derived from thiophene-2-aldehyde with 4-aminoantipyrine have been synthesized. The ligand and the complexes have been characterized by IR, molar conductance, magnetic moments, EPR, cyclic voltammetry, XRD and SEM measurements. Computational studies were also carried out. The geometry of the complexes was investigated by electronic spectral data and magnetic moment measurements. The metal complexes exhibit higher antibacterial activity than the free ligand.

  5. Synthesis, Spectral Characterization and Computational Studies of Metal Chelates of 4-N-(2-Thienylidene)aminoantipyrine

    OpenAIRE

    Sherifa Rahim; Arsha Antony; George Lukose; K. Mohanan; I. Hubert Joe; R. Selwin Joseyphus

    2015-01-01

    Metal chelates of Schiff base derived from thiophene-2-aldehyde with 4-aminoantipyrine have been synthesized. The ligand and the complexes have been characterized by IR, molar conductance, magnetic moments, EPR, cyclic voltammetry, XRD and SEM measurements. Computational studies were also carried out. The geometry of the complexes was investigated by electronic spectral data and magnetic moment measurements. The metal complexes exhibit higher antibacterial activity than the free ligand.

  6. Factors Influencing the DNA Nuclease Activity of Iron, Cobalt, Nickel, and Copper Chelates

    OpenAIRE

    Joyner, Jeff C.; Reichfield, Jared; Cowan, J.A.

    2011-01-01

    A library of complexes that included iron, cobalt, nickel, and copper chelates of cyclam, cyclen, DOTA, DTPA, EDTA, tripeptide GGH, tetrapeptide KGHK, NTA, and TACN was evaluated for DNA nuclease activity, ascorbate consumption, superoxide and hydroxyl radical generation, and reduction potential under physiologically relevant conditions. Plasmid DNA cleavage rates demonstrated by combinations of each complex and biological coreactants were quantified by gel electrophoresis, yielding second-or...

  7. Chelation-assisted palladium-catalyzed direct cyanation of 2-arylpyridine C-H bonds.

    Science.gov (United States)

    Jia, Xiaofei; Yang, Dongpeng; Zhang, Shouhui; Cheng, Jiang

    2009-10-15

    A chelation-assisted palladium-catalyzed ortho-cyanation of the sp2 C-H bond by CuCN provided aromatic nitriles in moderate to good yields. Notably, the reaction could be conducted on a 10 mmol scale. The key intermediate of the natural product of Menispermum dauricum DC was concisely synthesized by the procedure. This new approach represents an exceedingly practical method for the synthesis of aromatic nitriles and offers an attractive alternative to the traditional Sandmeyer reaction.

  8. Molecular Docking Assessment of Efficacy of Different Clinically Used Arsenic Chelator Drugs

    Directory of Open Access Journals (Sweden)

    Durjoy Majumder

    2013-01-01

    Full Text Available Arsenic contamination of ground water has become a global problem affecting specially, south-east Asian countries like Bangladesh and eastern parts of India. It also affects South America and some parts of the US. Different organs of the physiological system are affected due to contamination of inorganic arsenic in water. Animal studies with different chelators are not very conclusive as far as the multi/differential organ effect(s of arsenic is concerned. Our docking study establishes the molecular rationale of blood test for early detection of arsenic toxicity; as arsenic has a high affinity to albumin, a plasma protein and actin, a structural protein of all cells including Red Blood Cells. This study also shows that there is a little possibility of male reproductive organs toxicity by different forms of inorganic arsenic; however, female reproductive system is very much susceptible to sodium-arsenite. Through comparative analysis regarding the chelating effectiveness among the available arsenic chelator drugs, meso-2,3 dimercaptosuccinic acid (DMSA and in some cases lipoic acid is the most preferred choice of drug for removing of arsenic deposits. This computational method actually reinforces the clinical finding regarding DMSA as the most preferred drug in removal of arsenic deposits from majority of the human tissues.

  9. Theoretical study, and infrared and Raman spectra of copper(II) chelated complex with dibenzoylmethane.

    Science.gov (United States)

    Nekoei, A-R; Vakili, M; Hakimi-Tabar, M; Tayyari, S F; Afzali, R; Kjaergaard, H G

    2014-07-15

    There are some discrepancies in both the vibrational assignments and in the metal-ligand (M-L) bond strengths predicted in the previous studies on the copper (II) chelated complex of dibenzoylmethane, Cu(dbm)2. Also, there is a lack of theoretical structure, Raman spectrum and full vibrational assignment for Cu(dbm)2 in the literatures. Density functional theory (DFT) at the B3LYP level and also MP2 calculations using different basis sets, besides Natural Bond Orbital (NBO) and Atoms-in-Molecules (AIM) analyses, have been employed to investigate the effect of methyl substitution with the phenyl group on the stabilities of bis(acetylacetonate) copper (II), Cu(acac)2, and Cu(dbm)2 complexes and the electron delocalization in their chelated rings. Measured solid phase infrared and Raman bands for Cu(dbm)2 complex have been interpreted in terms of the calculated vibrational modes and detailed assignment has been presented. We concluded that, theoretically, the results of charge transfer studies, and experimentally, in-phase symmetric O-Cu-O stretching mode of these complexes are very useful measures for M-L bond strength. The electron delocalization in the chelated rings and the M-L bond strength in Cu(dbm)2 are concluded to be higher than those in Cu(acac)2. The calculated geometries and vibrational results are in good agreement with the experimental data.

  10. XAS studies of the effectiveness of iron chelating treatments of Mary Rose timbers

    Energy Technology Data Exchange (ETDEWEB)

    Berko, A; Schofield, E J; Chadwick, A V [School of Physical Sciences, University of Kent, CT2 7NR (United Kingdom); Smith, A D [STFC Daresbury Laboratory, Warrington, Cheshire, WA4 4AD (United Kingdom); Jones, A M [The Mary Rose Trust, HM Naval Base, Portsmouth, PO1 3LX (United Kingdom); Mosselmans, J F W, E-mail: a.berko@kent.ac.u [Diamond Light Source, Didcot, OX11 0DE (United Kingdom)

    2009-11-15

    The oxidation of sulfur in marine archaeological timbers under museum storage conditions is a recently identified problem, particularly for major artefacts such as historic ships excavated from the seabed. Recent work on the Vasa has stressed the role of iron in catalysing the oxidative degradation of the wood cellulose and the polyethylene glycols used to restore mechanical integrity to the timbers. In developing new treatment protocols for the long term preservation of Henry VIII of England's flagship, the Mary Rose, we are investigating the potential of chelating agents to neutralise and remove the iron products from the ships timbers. We have explored the use of aqueous solutions of chelating agents of calcium phytate, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) and ammonium citrate to extract the iron compounds. All of these solutions exhibit some level of iron removal; however the key is to find the most effective concentration at pH of around 7 of the reagent solution, to minimise the treatment time and find the most cost-effective treatment for the whole of the Mary Rose hull. Fe K-edge XAFS data from samples of Mary Rose timbers, before and after treatment by the chelating agents mentioned has been collected. The data collected provide valuable insights into the effectiveness of the treatment solutions.

  11. XAS studies of the effectiveness of iron chelating treatments of Mary Rose timbers

    Science.gov (United States)

    Berko, A.; Smith, A. D.; Jones, A. M.; Schofield, E. J.; Mosselmans, J. F. W.; Chadwick, A. V.

    2009-11-01

    The oxidation of sulfur in marine archaeological timbers under museum storage conditions is a recently identified problem, particularly for major artefacts such as historic ships excavated from the seabed. Recent work on the Vasa has stressed the role of iron in catalysing the oxidative degradation of the wood cellulose and the polyethylene glycols used to restore mechanical integrity to the timbers. In developing new treatment protocols for the long term preservation of Henry VIII of England's flagship, the Mary Rose, we are investigating the potential of chelating agents to neutralise and remove the iron products from the ships timbers. We have explored the use of aqueous solutions of chelating agents of calcium phytate, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) and ammonium citrate to extract the iron compounds. All of these solutions exhibit some level of iron removal; however the key is to find the most effective concentration at pH of around 7 of the reagent solution, to minimise the treatment time and find the most cost-effective treatment for the whole of the Mary Rose hull. Fe K-edge XAFS data from samples of Mary Rose timbers, before and after treatment by the chelating agents mentioned has been collected. The data collected provide valuable insights into the effectiveness of the treatment solutions.

  12. Effects of oral iron chelator deferasirox on human malignant lymphoma cells

    Science.gov (United States)

    Choi, Jong Gwon; Kim, Jung-Lim; Park, Joohee; Lee, Soonwook; Park, Seh Jong; Kim, Jun Suk

    2012-01-01

    Background Iron is essential for cell proliferation and viability. It has been reported that iron depletion by a chelator inhibits proliferation of some cancer cells. Deferasirox is a new oral iron chelator, and a few reports have described its effects on lymphoma cells. The goal of this study was to determine the anticancer effects of deferasirox in malignant lymphoma cell lines. Methods Three human malignant lymphoma cell lines (NCI H28:N78, Ramos, and Jiyoye) were treated with deferasirox at final concentrations of 20, 50, or 100 µM. Cell proliferation was evaluated by an MTT assay, and cell cycle and apoptosis were analyzed by flow cytometry. Western blot analysis was performed to determine the relative activity of various apoptotic pathways. The role of caspase in deferasirox-induced apoptosis was investigated using a luminescent assay. Results The MTT assay showed that deferasirox had dose-dependent cytotoxic effects on all 3 cell lines. Cell cycle analysis showed that the sub-G1 portion increased in all 3 cell lines as the concentration of deferasirox increased. Early apoptosis was also confirmed in the treated cells by Annexin V and PI staining. Western blotting showed an increase in the cleavage of PARP, caspase 3/7, and caspase 9 in deferasirox-treated groups. Conclusion We demonstrated that deferasirox, a new oral iron-chelating agent, induced early apoptosis in human malignant lymphoma cells, and this apoptotic effect is dependent on the caspase-3/caspase-9 pathway. PMID:23071474

  13. Leaching heavy metals in municipal solid waste incinerator fly ash with chelator/biosurfactant mixed solution.

    Science.gov (United States)

    Xu, Ying; Chen, Yu

    2015-07-01

    The chelator [S,S]-ethylene diamine disuccinic acid, citric acid, and biosurfactant saponin are selected as leaching agents. In this study, the leaching effect of saponin mixed with either ethylene diamine disuccinic acid or citric acid on the levels of copper, zinc, lead, and cadmium in municipal solid waste incinerator fly ash is investigated. Results indicate that saponin separately mixed with ethylene diamine disuccinic acid and citric acid exhibits a synergistic solubilisation effect on copper, zinc, lead, and cadmium leaching from fly ash. However, saponin and ethylene diamine disuccinic acid mixed solution exhibits a synergistic solubilisation effect that is superior to that of a saponin and citric acid mixed solution. The extraction rate of heavy metal in fly ash leached with a saponin and chelator mixed solution is related to the pH of the leaching solution, and the optimal range of the pH is suggested to be approximately neutral. After leaching with a saponin and chelator mixed solution, copper, zinc, lead, and cadmium contents significantly decreased (p < 0.05) in the extractable or acid-soluble and reducible fractions. By adopting the proposed approach, the leaching concentrations of copper, zinc, lead, and cadmium in treated fly ash are in accordance with Standard for Pollution Control on the Security Landfill Site for Hazardous Wastes GB18598-2001.

  14. Inhibitor ranking through QM based chelation calculations for virtual screening of HIV-1 RNase H inhibition.

    Directory of Open Access Journals (Sweden)

    Vasanthanathan Poongavanam

    Full Text Available Quantum mechanical (QM calculations have been used to predict the binding affinity of a set of ligands towards HIV-1 RT associated RNase H (RNH. The QM based chelation calculations show improved binding affinity prediction for the inhibitors compared to using an empirical scoring function. Furthermore, full protein fragment molecular orbital (FMO calculations were conducted and subsequently analysed for individual residue stabilization/destabilization energy contributions to the overall binding affinity in order to better understand the true and false predictions. After a successful assessment of the methods based on the use of a training set of molecules, QM based chelation calculations were used as filter in virtual screening of compounds in the ZINC database. By this, we find, compared to regular docking, QM based chelation calculations to significantly reduce the large number of false positives. Thus, the computational models tested in this study could be useful as high throughput filters for searching HIV-1 RNase H active-site molecules in the virtual screening process.

  15. In search of a viable reaction pathway in the chelation of a metallo-protein

    Science.gov (United States)

    Rose, Frisco; Hodak, Miroslav; Bernholc, Jerry

    2010-03-01

    Misfolded metallo-proteins are potential causal agents in the onset of neuro-degenerative diseases, such as Alzheimer's and Parkinson's Diseases (PD). Experimental results involving metal chelation have shown significant promise in symptom reduction and misfolding reversal. We explore, through atomistic simulations, potential reaction pathways for the chelation of Cu^2+ from the metal binding site in our representation of a partially misfolded α-synuclein, the protein implicated in PD. Our ab initio simulations use Density Functional Theory (DFT) and nudged elastic band to obtain the minimized energy coordinates of this reaction. Our simulations include ab initio water at the interaction site and in its first solvation shells, while the remainder is fully solvated with orbital-free DFT water representation [1]. Our ongoing studies of viable chelation agents include nicotine, caffeine and other potential reagents, we will review the best case agents in this presentation. [4pt] [1] Hodak M, Lu W, Bernholc J. Hybrid ab initio Kohn-Sham density functional theory/frozen-density orbital-free density functional theory simulation method suitable for biological systems. J. Chem. Phys. 2008 Jan;128(1):014101-9.

  16. [Enhanced Phytoextraction of Heavy Metals from Contaminated Soils Using Sedum alfredii Hance with Biodegradable Chelate GLDA].

    Science.gov (United States)

    Wei, Ze-bin; Chen, Xiao-hong; Wu, Qi-tang; Tan, Meng

    2015-05-01

    Chemically enhanced phytoextraction by hyperaccumulator has been proposed as an effective approach to remove heavy metals from contaminated soil. Pot experiment was conducted to investigate the effect of application of the biodegradable chelate GLDA (L glutamic acid N,N-diacetic acid) at different doses or the combination of GLDA with EDTA (ethylenediamine tetraacetic acid) or CIT (citric acid) on the uptake of Cd, Zn and Pb by Sedum alfredii Hance (a Zn and Cd hyperaccumulator). Experimental results showed that GLDA addition to soil significantly increased the concentrations of Cd and Zn in Sedum alfredii Hance and its Cd and Zn phytoextraction compared to the control. Additionally, GLDA at 2.5 mmol · kg(-1) resulted in the highest phytoextraction, being 2.5 and 2.6 folds of the control for Cd and Zn, respectively. However, the combined application of GLDA + EDTA (1:1) and GLDA + CIT (1 :1 and 1:3) at a total dose of 5 mmol · kg(-1) did not increase the phytoextraction of Zn and Cd, compared to the GLDA only treatment. Therefore, the biodegradable chelate GLDA could be regarded as a good chelate candidate for the phytoextraction of heavy metals of heavy metals from contaminated soils, particularly for Cd and Zn contaminated soils.

  17. Luminescent solutions and powders of new samarium complexes with N,N',O,O'-chelating ligands

    Science.gov (United States)

    Kharcheva, Anastasia V.; Nikolskiy, Kirill S.; Borisova, Nataliya E.; Ivanov, Alexey V.; Reshetova, Marina D.; Yuzhakov, Viktor I.; Patsaeva, Svetlana V.

    2016-04-01

    Imaging techniques in biology and medicine are crucial tools to obtain information on structural and functional properties of living cells and organisms. To fulfill the requirements associated with application of these techniques it appears necessary to design markers with specific characteristics. Luminescent complexes of trivalent lanthanide ions with chelating ligands are of increasing importance in biomedical applications because of their millisecond luminescence lifetime, narrow emission band, high signal-to-noise ratio and minimal photodamage to biological samples. In order to extend the available emission wavelength range the luminescent samarium chelates are highly desirable. In this study the ligands with diamides of 2,2'-bipyridin-6,6'-dicarboxylic acid were used to improve photophysical characteristics of samarium complexes. We report the luminescence characteristics of samarium complexes with novel ligands. All complexes exhibited the characteristic emission of Sm (III) ion with the lines at 565, 597, 605, 645 and 654 nm, the intensity strongly depended on the ligand. Absorption and luminescence excitation spectra of Sm (III) complexes showed main peaks in the UV range demonstrating lanthanide coordination to the ligand. The absolute lumenescence quantum yield was measured for solutions in acetonitrile with excitation at 350 nm. The largest luminescence quantum yield was found for the samarium complex Bipy 6MePy Sm (3%) being much higher that for samarium complexes reported in the literature earlier. These results prove as well that samarium chelates are potential markers for multiparametric imaging techniques.

  18. A new synthetic chelating collector for the flotation of oxidized-lead mineral

    Institute of Scientific and Technical Information of China (English)

    Yongkai Zhu; Chuanyao Sun; Weiguo Wu

    2007-01-01

    A new synthetic reagent DPTUHP [diphenyl α-(3-phenylthioureido) hexylphosphonate] containing a hydrocarbon chain nonpolar group,a thioureido,and a phosphonate easter chelating group,has proven to be an effective collector for the flotation of cerussite mineral.The synthetic method utilized the Mannich-type reaction of an N-monosubstituted thiourea,an aldehyde,and triphenyl phosphate in glacial acetic acid solution.The experimental results of flotation of the cerussite mineral show that the collector has stronger collecting ability and higher selectivity in a neutral and a slightly alkaline medium,especially in the pulp of pH=8.Using the measurements by infrared spectroscopy (IR) and X-ray photoelectron spectroscopy (XPS) of the cerussite mineral,the collector,as well as the cerussite treated with the collector,the flotation mechanism of cerussite has been discussed.It is concluded that the adsorption of collector on cerussite is a chemical adsorption through the electron donor atoms of the collector chelating the Pb ( Ⅱ ) of cerussite to form chelate.

  19. Characterization of new specific copper chelators as potential drugs for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Nguyen, Michel; Robert, Anne; Sournia-Saquet, Alix; Vendier, Laure; Meunier, Bernard

    2014-05-26

    The non-controlled redox-active metal ions, especially copper, in the brain of patients with Alzheimer disease (AD) should be considered at the origin of the intense oxidative damage in the AD brain. Several bis(8-aminoquinoline) ligands, such as 1 and PA1637, are able to chelate Cu(2+) with high affinity, and are specific chelators of copper with respect to iron and zinc. They are able to efficiently extract Cu(2+) from a metal-loaded amyloid. In addition, these tetradentate ligands are specific for the chelation of Cu(2+) compared with Cu(+). Consequently, the copper ion is easily released from the bis(8-aminoquinoline) ligand under reductive conditions, and can be trapped again by a protein having some affinity for copper such as human serum albumin (HSA) proteins. In addition, the copper is not efficiently released from [Cu(CQ)2] in reductive conditions. The catalytic production of H2O2 by [Cu(2+)-Aβ(1-28)]/ascorbate is inhibited in vitro by the bis(8-aminoquinoline) 1, suggesting that 1 should be able to play a protective role against oxidative damages induced by copper-loaded amyloids.

  20. Conjugates of Magnetic Nanoparticle -- Actinide Specific Chelator for Radioactive Waste Separation

    Energy Technology Data Exchange (ETDEWEB)

    Maninder Kaur; Huijin Zhang; Leigh Martin; Terry Todd; You Qiang

    2013-11-01

    A novel nanotechnology for the separation of radioactive waste that uses magnetic nanoparticles (MNPs) conjugated with actinide specific chelators (MNP-Che) is reviewed with a focus on design and process development. The MNP-Che separation process is an effective way of separating heat generating minor actinides (Np, Am, Cm) from spent nuclear fuel solution to reduce the radiological hazard. It utilizes coated MNPs to selectively adsorb the contaminants onto their surfaces, after which the loaded particles are collected using a magnetic field. The MNP-Che conjugates can be recycled by stripping contaminates into a separate, smaller volume of solution, and then become the final waste form for disposal after reusing number of times. Due to the highly selective chelators, this remediation method could be both simple and versatile while allowing the valuable actinides to be recovered and recycled. Key issues standing in the way of large-scale application are stability of the conjugates and their dispersion in solution to maintain their unique properties, especially large surface area, of MNPs. With substantial research progress made on MNPs and their surface functionalization, as well as development of environmentally benign chelators, this method could become very flexible and cost-effective for recycling used fuel. Finally, the development of this nanotechnology is summarized and its future direction is discussed.

  1. Comparison of chelates for enhancing Ricinus communis L. phytoremediation of Cd and Pb contaminated soil.

    Science.gov (United States)

    Zhang, Hanzhi; Guo, Qingjun; Yang, Junxing; Ma, Jie; Chen, Gang; Chen, Tongbin; Zhu, Guangxu; Wang, Jian; Zhang, Guangxin; Wang, Xin; Shao, Chunyan

    2016-11-01

    We studied chelate effects on castor bean (Ricinus communis L.) growth. These effects included Cd and Pb accumulation in plant tissues and the chemical behavior of Cd and Pb in the plant rhizosphere and non-rhizosphere. Tests were conducted in a glasshouse using the rhizobag method. Two castor bean cultivars (Zibo-3 and Zibo-9) were grown in soil contaminated with 3.53mg/kg Cd and 274mg/kg Pb. The soil was treated with citric acid (CA), ethylenediamine disuccinic acid (EDDS) or ethylenediamine tetraacetic acid (EDTA) (5mmol/kg). EDDS-treated soil produced 28.8% and 59.4% greater biomass for Zibo-3 and Zibo-9 respectively. In contrast, CA and EDTA inhibited the growth of the two cultivars. Zibo-9 had greater tolerance than Zibo-3 to chelate toxicity. Based on Cd and Pb plant uptake, EDDS could substitute for EDTA for phytoremediation of Cd in soil. EDTA was the most effective of the three chelates for Pb phytoremediation but it is less suitable for field use due to toxicology environmental persistence. Acid extractable Cd and Pb in the rhizosphere or reducible Cd and Pb in the non-rhizosphere of soil were the main influences on Cd and Pb accumulation in castor bean.

  2. Enhancing uranium solubilization in soils by citrate, EDTA, and EDDS chelating amendments.

    Science.gov (United States)

    Lozano, J C; Blanco Rodríguez, P; Tomé, F Vera; Calvo, C Prieto

    2011-12-30

    A systematic study was made of the effects of three soil amendments on the solubilization of uranium from a granitic soil. The aim was to optimize solubilization so as to enhance bioavailability for the purposes of remediation. The three amendments tested were with citrate, EDTA, and EDDS as chelating agents. The effects of pH, chelator concentration, and leaching time were studied. The most important factor in uranium solubilization was found to be the pH. In the absence of chelating agents, the greatest solubilization was obtained for alkaline conditions, with values representing about 15% of the total uranium activity in the bulk soil. There were major differences in uranium solubilization between the different amendments. The citrate treatment was the most efficient at acidic pH, particularly with the greatest concentration of citrate tested (50 mmol kg(-1)) after 6 days of treatment. Under these conditions, the uranium concentration in solution was greater by a factor of 356 than in the control suspension, and represented some 63% of the uranium concentration in the bulk soil. Under alkaline conditions, the EDTA and EDDS treatments gave the greatest uranium activity concentrations in solution, but these concentrations were much lower than those with the citrate amendment, and were not very different from the control results. The uranium extraction yield with EDDS amendment was greater than with EDTA.

  3. Diethylentriaminepenta acetic acid glucose conjugates as a cell permeable iron chelator

    Directory of Open Access Journals (Sweden)

    Mona Mosayebnia

    2014-01-01

    Full Text Available Objective: To find out whether DTPA-DG complex can enhance clearance of intracellular free iron. Materials and Methods: Diethylenetriaminepentaacetic acid-D-deoxy-glucosamine (DTPA-DG was synthesized and examined for its activity as a cell-permeable iron chelator in human hepatocellular carcinoma (HEPG2 cell line exposed to high concentration of iron sulfate and compared with deferoxamine (DFO, a prototype iron chelator. The effect of DTPA-DG on cell viability was monitored using the 3-(4,5-dimethythiazol-2-yl-2,5-diphenyl tetrazolium bromide MTT assay as well. Results: There was a significant increase of iron level after iron overload induction in HEPG2 cell culture. DTPA-DG presented a remarkable capacity to iron burden reducing with estimated 50% inhibitory concentration value of 65.77 nM. In fact, glycosyl moiety was gained access of DTPA to intracellular iron deposits through glucose transporter systems. Conclusion: DTPA-DG, more potent than DFO to sequester deposits of free iron with no profound toxic effect. The results suggest the potential of DTPA-DG in chelating iron and permitting its excretion from primary organ storage.

  4. The interactive effects of chelator, fertilizer, and rhizobacteria for enhancing phytoremediation of heavy metal contaminated soil

    Energy Technology Data Exchange (ETDEWEB)

    Chen, H.; Cutright, T.J. [Dept. of Civil Engineering, Univ. of Akron, Akron, OH (United States)

    2002-07-01

    The role of chelator, fertilizer, and enriched rhizobacteria in facilitating Cd, Cr, and Ni accumulation by Helianthus annuus was studied. It was found that by adding a synthetic chelator, EDTA, the shoot concentrations of Cd and Ni were significantly increased from 34.2 mg kg{sup -1} and 14.5 mg kg{sup -1} to 115 mg kg{sup -1} and 117 mg kg{sup -1}, respectively. However, the total biomass of plants was drastically decreased by 50 to 60%. Compared with this treatment, inoculating enriched rhizobacteria to plants grown under similar conditions maintained the surged shoot concentrations of Cd and Ni while increasing the plants biomass by more than 1.6-fold. It was also found that introducing a commercial fertilizer, Hydro-Gro trademark, to plants significantly increased the Ni accumulation by 3-fold and the plant biomass by 1.43-fold. These results suggest that combing fertilizers, chelators and/or rhizobacteria might provide a more effective approach for enhancing phytoremediation. (orig.)

  5. In Vivo Integrity and Biological Fate of Chelator-Free Zirconium-89-Labeled Mesoporous Silica Nanoparticles.

    Science.gov (United States)

    Chen, Feng; Goel, Shreya; Valdovinos, Hector F; Luo, Haiming; Hernandez, Reinier; Barnhart, Todd E; Cai, Weibo

    2015-08-25

    Traditional chelator-based radio-labeled nanoparticles and positron emission tomography (PET) imaging are playing vital roles in the field of nano-oncology. However, their long-term in vivo integrity and potential mismatch of the biodistribution patterns between nanoparticles and radio-isotopes are two major concerns for this approach. Here, we present a chelator-free zirconium-89 ((89)Zr, t1/2 = 78.4 h) labeling of mesoporous silica nanoparticle (MSN) with significantly enhanced in vivo long-term (>20 days) stability. Successful radio-labeling and in vivo stability are demonstrated to be highly dependent on both the concentration and location of deprotonated silanol groups (-Si-O(-)) from two types of silica nanoparticles investigated. This work reports (89)Zr-labeled MSN with a detailed labeling mechanism investigation and long-term stability study. With its attractive radio-stability and the simplicity of chelator-free radio-labeling, (89)Zr-MSN offers a novel, simple, and accurate way for studying the in vivo long-term fate and PET image-guided drug delivery of MSN in the near future.

  6. New series of chelated organochromium(III) complexes. [1,4,8,12-Tetraazacyclopentaedecane

    Energy Technology Data Exchange (ETDEWEB)

    Samuels, G.J.

    1979-01-01

    A kinetic and mechanistic study of the preparation of a new family of chelated organochromium(III) complexes was completed. These species were formed from organic halides and (1,4,8,12 tetraazacyclopentadecane) chromium(II) by a mechanism which involves initial halogen atom abstraction followed by subsequent radical capture by another Cr(II) complex. The rates of reaction follow the pattern expected for a S/sub H/2 process, 3/sup 0/ > 2/sup 0/ > 1/sup 0/ and I > Br > Cl. These organochromium(III) chelate complexes have the trans configuration. Electrophilic cleavage reactions by mercuric and methylmercuric ions were studied. These reactions proceed by a S/sub E/2 (open) mechanism with the reaction rates being approx. 100 times slower for the chelated species. The activation parameters were determined for five reactions. The crystal structure of (trans-chloroaquo(1,4,8,12-tetraazacyclopentadecane)chromium(III))diiodide-dihydrate is also reported. The macrocycle assumes the lowest energy conformation as predicted by strain energy calculations.

  7. Isolation of a cdc28 mutation that abrogates the dependence of S phase on completion of M phase of the budding yeast cell cycle

    Indian Academy of Sciences (India)

    Santanu Kumar Ghosh; Pratima Sinha

    2000-01-01

    We have isolated a mutation in the budding yeast Saccharomyces cerevisisae CDC28 gene that allows cdc13 cells, carrying damaged DNA, to continue with the cell division cycle. While cdc13 mutant cells are arrested as large-budded cells at the nonpermissive temperature 37°C, the cdc13 cdc28 double mutant culture showed cells with one or more buds, most of which showed apical growth. The additional buds emerged without the intervening steps of nuclear division and cell separation. We suggest that the cdc28 mutation abrogates a checkpoint function and allows cells with damaged or incompletely replicated DNA an entry to another round of cell cycle and bypasses the mitotic phase of the cell cycle.

  8. Synergistic Activities of an Efflux Pump Inhibitor and Iron Chelators against Pseudomonas aeruginosa Growth and Biofilm Formation

    DEFF Research Database (Denmark)

    Liu, Yang; Yang, Liang; Molin, Søren

    2010-01-01

    The efflux pump inhibitor phenyl-arginine-beta-naphthylamide (PA beta N) was paired with iron chelators 2,2'-dipyridyl, acetohydroxamic acid, and EDTA to assess synergistic activities against Pseudomonas aeruginosa growth and biofilm formation. All of the tested iron chelators synergistically...... inhibited P. aeruginosa growth and biofilm formation with PA beta N. PA beta N-EDTA showed the most promising activity against P. aeruginosa growth and biofilm formation....

  9. Hydroxyiminodisuccinic acid (HIDS): A novel biodegradable chelating ligand for the increase of iron bioavailability and arsenic phytoextraction

    OpenAIRE

    Rahman, M. Azizur; Hasegawa, Hiroshi; Kadohashi, K.; Maki, Teruya; Ueda, Kazumasa

    2009-01-01

    The influence of biodegradable chelating ligands on arsenic and iron uptake by hydroponically grown rice seedlings (Oryza sativa L.) was investigated. Even though the growth solution contained sufficient Fe, the growth of rice seedlings gradually decreased up to 76% with the increase of pH of the solution from 7 to 11. Iron forms insoluble ferric hydroxide complexes at neutral or alkaline pH in oxic condition. Chelating ligands produce soluble 'Fe-ligand complex' which assist Fe uptake in pla...

  10. Membrane translocation of t-SNARE protein syntaxin-4 abrogates ground-state pluripotency in mouse embryonic stem cells

    Science.gov (United States)

    Hagiwara-Chatani, Natsumi; Shirai, Kota; Kido, Takumi; Horigome, Tomoatsu; Yasue, Akihiro; Adachi, Naoki; Hirai, Yohei

    2017-01-01

    Embryonic stem (ES) and induced pluripotent stem (iPS) cells are attractive tools for regenerative medicine therapies. However, aberrant cell populations that display flattened morphology and lose ground-state pluripotency often appear spontaneously, unless glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase kinase (MEK1/2) are inactivated. Here, we show that membrane translocation of the t-SNARE protein syntaxin-4 possibly is involved in this phenomenon. We found that mouse ES cells cultured without GSK3β/MEK1/2 inhibitors (2i) spontaneously extrude syntaxin-4 at the cell surface and that artificial expression of cell surface syntaxin-4 induces appreciable morphological changes and mesodermal differentiation through dephosphorylation of Akt. Transcriptome analyses revealed several candidate elements responsible for this, specifically, an E-to P-cadherin switch and a marked downregulation of Zscan4 proteins, which are DNA-binding proteins essential for ES cell pluripotency. Embryonic carcinoma cell lines F9 and P19CL6, which maintain undifferentiated states independently of Zscan4 proteins, exhibited similar cellular behaviors upon stimulation with cell surface syntaxin-4. The functional ablation of E-cadherin and overexpression of P-cadherin reproduced syntaxin-4-induced cell morphology, demonstrating that the E- to P-cadherin switch executes morphological signals from cell surface syntaxin-4. Thus, spontaneous membrane translocation of syntaxin-4 emerged as a critical element for maintenance of the stem-cell niche. PMID:28057922

  11. New Chelators for Low Temperature Al(18)F-Labeling of Biomolecules.

    Science.gov (United States)

    Cleeren, Frederik; Lecina, Joan; Billaud, Emilie M F; Ahamed, Muneer; Verbruggen, Alfons; Bormans, Guy M

    2016-03-16

    The Al(18)F labeling method is a relatively new approach that allows radiofluorination of biomolecules such as peptides and proteins in a one-step procedure and in aqueous solution. However, the chelation of the {Al(18)F}(2+) core with the macrocyclic chelators NOTA or NODA requires heating to 100-120 °C. Therefore, we have developed new polydentate ligands for the complexation of {Al(18)F}(2+) with good radiochemical yields at a temperature of 40 °C. The stability of the new Al(18)F-complexes was tested in phosphate buffered saline (PBS) at pH 7.4 and in rat serum. The stability of the Al(18)F-L3 complex was found to be comparable to that of the previously reported Al(18)F-NODA complex up to 60 min in rat serum. Moreover, the biodistribution of Al(18)F-L3 in healthy mice showed the absence of in vivo defluorination since no significant bone uptake was observed, whereas the major fraction of activity at 60 min p.i. was observed in liver and intestines, indicating hepatobiliary clearance of the radiolabeled ligand. The acyclic chelator H3L3 proved to be a good lead candidate for labeling of heat-sensitive biomolecules with fluorine-18. In order to obtain a better understanding of the different factors influencing the formation and stability of the complex, we carried out more in-depth experiments with ligand H3L3. As a proof of concept, we successfully conjugated the new AlF-chelator with the urea-based PSMA inhibitor Glu-NH-CO-NH-Lys to form Glu-NH-CO-NH-Lys(Ahx)L3, and a biodistribution study in healthy mice was performed with the Al(18)F-labeled construct. This new class of AlF-chelators may have a great impact on PET radiochemical space as it will stimulate the rapid development of new fluorine-18 labeled peptides and other heat-sensitive biomolecules.

  12. Characterization of amorphous yttria layers deposited by aqueous solutions of Y-chelate alkoxides complex

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young-Soon, E-mail: kyscjb@i-sunam.com; Lee, Yu-Ri; Kim, Byeong-Joo; Lee, Jae-Hun; Moon, Seung-Hyun; Lee, Hunju

    2015-01-15

    Highlights: • Economical method for crack-free amorphous yttria layer deposition by dip coating. • Simpler process for planar yttria film as a diffusion barrier and nucleation layer. • Easy control over the film properties with better characteristics. • Easy control over the thickness of the deposited films. • A feasible process that can be easily adopted by HTSCC industries. - Abstract: Crack-free amorphous yttria layers were deposited by dip coating in solutions of different Y-chelate alkoxides complex. Three Y-chelate solutions of different concentrations were prepared using yttrium acetate tetrahydrate, yttrium stearic acid as Y source materials. PEG, diethanolamine were used as chelating agents, while ethanol, methanol and tetradecane were used as solvent. Three different combinations of chelating and solvents were used to prepare solutions for Y{sub 2}O{sub 3} dip coating on SUS, electropolished and non-electropolished Hastelloy C-276 substrates. The thickness of the films was varied by changing the number of dipping cycles. At an optimized condition, the substrate surface roughness (rms) value was reduced from ∼50 nm to ∼1 nm over a 10 × 10 μm{sup 2} area. After Y{sub 2}O{sub 3} deposition, MgO was deposited using ion-beam assisted deposition (IBAD), then LaMnO{sub 3} (LMO) was deposited using sputtering and GdBCO was deposited using reactive co-evaporation by deposition and reaction (RCE-DR). Detailed X-ray study indicates that LMO/MgO/Y{sub 2}O{sub 3} and GdBCO/LMO/MgO/Y{sub 2}O{sub 3} stack films have good out-of-plane and in-plane textures with strong c-axis alignment. The critical current (Ic) of GdBCO/LMO/MgO/Y{sub 2}O{sub 3} multilayer structure varied from 190 to 420 A/cm with different solutions, when measured at 77 K. These results demonstrated that amorphous yttria can be easily deposited by dip coating using Y-chelates complex as a diffusion barrier and nucleation layer.

  13. Screening of protease producing fungi for microbial digestion of seed proteins and synthesis of amino acids-metalnutrient chelates.

    Science.gov (United States)

    Deore, G B; Limaye, A S; Dushing, Y A; Dhobale, S B; Kale, S; Laware, S L

    2013-01-15

    The problem of metalnutrient deficiency is becoming more serious with the introduction of modern agricultural practices. As a result, metalnutrient deficiency is recognized as one of the critical yield limiting factors. Metalnutrients are generally offered in their sulphate or oxide forms. However, it is reported that organically bound minerals generally have a higher bioavailability than inorganic minerals. Chelation makes otherwise unavailable metalnutrients plant available. Amino acids are well known among various chelating agents. In present investigation the fungus Paecilomyces variotii PR-4 was isolated from soil and was used for production of protease and determination of its activity. Proteins from germinating seeds of chick pea, mung bean, soybean and cowpea were hydrolyzed for the production of amino acids. Amino acids were recovered, estimated and utilized for chelation of metalnutrients viz., Zn, Cu, Fe, Mn, Mg, B and Mo. The resultant chelates were employed to detect with Fourier Transform Infra-Red Spectrophotometer (FTIR) analysis. The peaks of most intensive bands in the IR spectra of ligands recorded were present in the intervals of the wave numbers 3500-3300 and 1720-1700 cm(-1). Chelation of metalnutrients led to the broadening of peak and changes of the peak position of hydroxyl groups, which indicated the binding of the carboxylic groups and primary amine groups of amino acids to the metalnutrients. The resultant amino acids-metalnutrient chelates can be utilized as organic fertilizer.

  14. A camelid anti-PrP antibody abrogates PrP replication in prion-permissive neuroblastoma cell lines.

    Directory of Open Access Journals (Sweden)

    Daryl Rhys Jones

    Full Text Available The development of antibodies effective in crossing the blood brain barrier (BBB, capable of accessing the cytosol of affected cells and with higher affinity for PrP(Sc would be of paramount importance in arresting disease progression in its late stage and treating individuals with prion diseases. Antibody-based therapy appears to be the most promising approach following the exciting report from White and colleagues, establishing the "proof-of-principle" for prion-immunotherapy. After passive transfer, anti-prion antibodies were shown to be very effective in curing peripheral but not central rodent prion disease, due to the fact that these anti-prion antibodies are relatively large molecules and cannot therefore cross the BBB. Here, we show that an anti-prion antibody derived from camel immunised with murine scrapie material adsorbed to immunomagnetic beads is able to prevent infection of susceptible N2a cells and cure chronically scrapie-infected neuroblastoma cultures. This antibody was also shown to transmigrate across the BBB and cross the plasma membrane of neurons to target cytosolic PrP(C. In contrast, treatment with a conventional anti-prion antibody derived from mouse immunised with recombinant PrP protein was unable to prevent recurrence of PrP(Sc replication. Furthermore, our camelid antibody did not display any neurotoxic effects following treatment of susceptible N2a cells as evidenced by TUNEL staining. These findings demonstrate the potential use of anti-prion camelid antibodies for the treatment of prion and other related diseases via non-invasive means.

  15. Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron-overloaded patients with β-thalassaemia: the ESCALATOR study

    Science.gov (United States)

    Taher, Ali; El-Beshlawy, Amal; Elalfy, Mohsen S; Al Zir, Kusai; Daar, Shahina; Habr, Dany; Kriemler-Krahn, Ulrike; Hmissi, Abdel; Al Jefri, Abdullah

    2009-01-01

    Objective: Many patients with transfusional iron overload are at risk for progressive organ dysfunction and early death and poor compliance with older chelation therapies is believed to be a major contributing factor. Phase II/III studies have shown that oral deferasirox 20–30 mg/kg/d reduces iron burden, depending on transfusional iron intake. Methods: The prospective, open-label, 1-yr ESCALATOR study in the Middle East was designed to evaluate once-daily deferasirox in patients ≥2 yr with β-thalassaemia major and iron overload who were previously chelated with deferoxamine and/or deferiprone. Most patients began treatment with deferasirox 20 mg/kg/d; doses were adjusted in response to markers of over- or under-chelation. The primary endpoint was treatment success, defined as a reduction in liver iron concentration (LIC) of ≥3 mg Fe/g dry weight (dw) if baseline LIC was ≥10 mg Fe/g dw, or final LIC of 1–7 mg Fe/g dw for patients with baseline LIC of 2 to <10 mg Fe/g dw. Results: Overall, 233/237 enrolled patients completed 1 yr’s treatment. Mean baseline LIC was 18.0 ± 9.1 mg Fe/g dw, while median serum ferritin was 3356 ng/mL. After 1 yr’s deferasirox treatment, the intent-to-treat population experienced a significant treatment success rate of 57.0% (P = 0.016) and a mean reduction in LIC of 3.4 mg Fe/g dw. Changes in serum ferritin appeared to parallel dose increases at around 24 wk. Most patients (78.1%) underwent dose increases above 20 mg/kg/d, primarily to 30 mg/kg/d. Drug-related adverse events were mostly mild to moderate and resolved without discontinuing treatment. Conclusions: The results of the ESCALATOR study in primarily heavily iron-overloaded patients confirm previous observations in patients with β-thalassaemia, highlighting the importance of timely deferasirox dose adjustments based on serum ferritin levels and transfusional iron intake to ensure patients achieve their therapeutic goal of maintenance or reduction in iron burden

  16. Overview of iron overload and the new iron chelator deferasirox%铁过载概述及口服祛铁新药地拉罗司

    Institute of Scientific and Technical Information of China (English)

    刘容容

    2011-01-01

    规则输血是维持重度慢性贫血患者生命的重要治疗手段,患者长期依赖输血治疗不可避免地引起体内铁沉积增加.输血相关性铁过载可导致多脏器的损害,特别是沉积在肝脏或心脏,甚至可危及生命.作为传统的铁螯合剂,去铁酮和去铁胺因其不良反应或治疗依从性差等问题无法满足临床治疗需要.地拉罗司是一种新型的口服铁螯合剂,多个Ⅱ期或Ⅲ期试验证实其在输血依赖性患者中可获得与去铁胺相似的疗效.近期前瞻性、多中心EPIC研究也证实了其祛铁疗效,且有助于改善地中海贫血患者的心脏铁沉积.本文就铁过载的临床特征、危害性以及祛铁新药地拉罗司对比传统药物的优势做一综述.%For many patients with severe chronic anemia, regular blood transfusion is the important lifesav-ing therapy available. Long-term blood transfusions will unavoidably and invariably produce accumulation of iron (iron overload) , and thereby induced iron toxicity. Transfusional hemosiderosis, particularly in the liver or heart, can cause considerable morbidity that may be fatal eventually. Traditionally, iron chelating agents include def-eriprone and deferoxamine, but they are not the satisfied treatment choice due to their side effects or non-convenience for administration. Deferasirox, a rationally-designed oral iron chelator, is validated as defined by several phase II trials. Moreover, a pivotal phase III trial revealed that its efficacy is similar to that of deferoxamine in transfusion-dependent patients. Recently reported results from the large, prospective, multicenter EPIC study confirmed its efficacy, and in this study deferasirox was also found to be capable of removing iron from the heart in patients with p-thalassemia and myocardial hemosiderosis. This review summarized the morbidity, mortality, and clinical features of iron overload, and introduced the advantages of the new chelator deferasirox over

  17. Performance of standard media in toxicological assessments with Daphnia magna: chelators and ionic composition versus metal toxicity.

    Science.gov (United States)

    Loureiro, Cláudia; Castro, Bruno B; Pereira, Joana Luísa; Gonçalves, Fernando

    2011-01-01

    Fully artificial test media can increase reproducibility and standardization in ecotoxicological assessments, but there is still a lack of convergence among ecotoxicology laboratories in aquatic test media with respect to ionic composition, chelators, and organic supplements. We compared the performance of Daphnia magna in three widely-used reconstituted media. The tested media differed in composition: (a) ADaM, an artificial medium based in a synthetic sea salt, with no a priori known chelating properties; (b) ASTM hard water supplemented with algal extract, a semi-artificial medium with unknown chelating properties; and (c) M7, a complex artificial medium containing EDTA as a chelator. All three media were suitable for rearing D. magna (although performance in M7 was suboptimal) and acute EC(50) values for reference substances (3,4-DCA, K(2)Cr(2)O(7)) were similar between media. In acute exposures to Cu and Cd, daphniids were least sensitive when reared in M7, as expected due to metal chelation by EDTA. Daphnia sensitivity to Cd was low in ADaM. Thus, these two media were suboptimal for assessing the toxicity of some metals to D. magna in acute tests. We suggest that both the ionic composition of the medium and the presence of chelators should be taken into account when metal toxicity is concerned. Chronic toxicity profiles for Cu suggested a mild chelating effect of the algal extract in ASTM medium. Still, ASTM hard water persists as one of the most suitable media for acute toxicity assessments of metals and metal-contaminated samples.

  18. Colour and stability assessment of blue ferric anthocyanin chelates in liquid pectin-stabilised model systems.

    Science.gov (United States)

    Buchweitz, M; Brauch, J; Carle, R; Kammerer, D R

    2013-06-01

    The formation of blue coloured ferric anthocyanin chelates and their colour stability during storage and thermal treatment were monitored in a pH range relevant to food (3.6-5.0). Liquid model systems were composed of different types of Citrus pectins, juices (J) and the respective phenolic extracts (E) from elderberry (EB), black currant (BC), red cabbage (RC) and purple carrot (PC) in the presence of ferric ions. For EB, BC and PC, pure blue colours devoid of a violet tint were exclusively observed for the phenolic extracts and at pH values ≥ 4.5 in model systems containing high methoxylated and amidated pectins, respectively. Colour and its stability strongly depended on the amount of ferric ions and the plant source; however, colour decay could generally be described as a pseudo-first-order kinetics. Despite optimal colour hues for RC-E and RC-J, storage and heat stabilities were poor. Highest colour intensities and best stabilities were observed for model systems containing PC-E at a molar anthocyanin:ferric ion ratio of 1:2. Ascorbic and lactic acids interfered with ferric ions, thus significantly affecting blue colour evolution and stability. Colour loss strongly depended on heat exposure with activation energies ranging between 60.5 and 78.4 kJ/mol. The comprehensive evaluation of the interrelationship of pigment source, pH conditions and pectin type on chelate formation and stability demonstrated that ferric anthocyanin chelates are promising natural blue food colourants.

  19. Chelation gradients for investigation of metal ion binding at silica surfaces.

    Science.gov (United States)

    Kannan, Balamurali; Higgins, Daniel A; Collinson, Maryanne M

    2014-08-26

    Centimeter-long surface gradients in bi- and tridentate chelating agents have been formed via controlled rate infusion, and the coordination of Cu(2+) and Zn(2+) to these surfaces has been examined as a function of distance by X-ray photoelectron spectroscopy (XPS). 3-(Trimethoxysilylpropyl)ethylenediamine and 3-(trimethoxysilylpropyl)diethylenetriamine were used as precursor silanes to form the chelation gradients. When the gradients were exposed to a metal ion solution, a series of coordination complexes formed along the length of the substrate. For both chelating agents at the three different concentrations studied, the amine content gradually increased from top to bottom as expected for a surface chemical gradient. While the Cu 2p peak area had nearly the same profile as nitrogen, the Zn 2p peak area did not and exhibited a plateau along much of the gradient. The normalized nitrogen-to-metal peak area ratio (N/M) was found to be highly dependent on the type of ligand, its surface concentration, and the type of metal ion. For Cu(2+), the N/M ratio ranged from 8 to 11 on the diamine gradient and was ∼4 on the triamine gradient, while for Zn(2+), the N/M ratio was 4-8 on diamine and 5-7 on triamine gradients. The extent of protonation of amine groups was higher for the diamine gradients, which could lead to an increased N/M ratio. Both 1:1 and 1:2 ligand/metal complexes along with dinuclear complexes are proposed to form, with their relative amounts dependent on the ligand, ligand density, and metal ion. Collectively, the methods and results described herein represent a new approach to study metal ion binding and coordination on surfaces, which is especially important to the extraction, preconcentration, and separation of metal ions.

  20. Metal ion coordination, conditional stability constants, and solution behavior of chelating surfactant metal complexes.

    Science.gov (United States)

    Svanedal, Ida; Boija, Susanne; Almesåker, Ann; Persson, Gerd; Andersson, Fredrik; Hedenström, Erik; Bylund, Dan; Norgren, Magnus; Edlund, Håkan

    2014-04-29

    Coordination complexes of some divalent metal ions with the DTPA (diethylenetriaminepentaacetic acid)-based chelating surfactant 2-dodecyldiethylenetriaminepentaacetic acid (4-C12-DTPA) have been examined in terms of chelation and solution behavior. The headgroup of 4-C12-DTPA contains eight donor atoms that can participate in the coordination of a metal ion. Conditional stability constants for five transition metal complexes with 4-C12-DTPA were determined by competition measurements between 4-C12-DTPA and DTPA, using electrospray ionization mass spectrometry (ESI-MS). Small differences in the relative strength between the coordination complexes of DTPA and 4-C12-DTPA indicated that the hydrocarbon tail only affected the chelating ability of the headgroup to a limited extent. The coordination of Cu(2+) ions was investigated in particular, using UV-visible spectroscopy. By constructing Job's plots, it was found that 4-C12-DTPA could coordinate up to two Cu(2+) ions. Surface tension measurements and NMR diffusometry showed that the coordination of metal ions affected the solution behavior of 4-C12-DTPA, but there were no specific trends between the studied divalent metal complexes. Generally, the effects of the metal ion coordination could be linked to the neutralization of the headgroup charge of 4-C12-DTPA, and the resulting reduced electrostatic repulsions between adjacent surfactants in micelles and monolayers. The pH vs concentration plots, on the other hand, showed a distinct difference between 4-C12-DTPA complexes of the alkaline earth metals and the transition metals. This was explained by the difference in coordination between the two groups of metal ions, as predicted by the hard and soft acid and base (HSAB) theory.

  1. Iron-chelating agent, deferasirox, inhibits neutrophil activation and extracellular trap formation.

    Science.gov (United States)

    Kono, Mari; Saigo, Katsuyasu; Yamamoto, Shiori; Shirai, Kohei; Iwamoto, Shuta; Uematsu, Tomoko; Takahashi, Takayuki; Imoto, Shion; Hashimoto, Makoto; Minami, Yosuke; Wada, Atsushi; Takenokuchi, Mariko; Kawano, Seiji

    2016-10-01

    Iron-chelating agents, which are frequently prescribed to transfusion-dependent patients, have various useful biological effects in addition to chelation. Reactive oxygen species (ROS) produced by neutrophils can cause pulmonary endothelial cell damage, which can lead to acute lung injury (ALI). We previously reported that deferasirox (DFS), an iron-chelating agent, inhibits phorbol myristate acetate (PMA) or formyl-methionyl-leucyl-phenylalanine (fMLP)-induced ROS production in neutrophils, in vitro. Here, we investigate whether DFS inhibits vacuolization in neutrophils and neutrophil extracellular trap (NET) formation. Human neutrophils were incubated with DFS and stimulated with PMA or fMLP. Human neutrophils were separated from heparinized peripheral blood using density gradient centrifugation, and subsequently incubated with DFS. After 10 minutes, neutrophils were stimulated by PMA or fMLP. Vacuole formation was observed by electron microscopy. For observing NET formations using microscopes, immunohistological analyses using citrullinated histone H3 and myeloperoxidase antibodies, and SYTOX Green (an impermeable DNA detection dye) staining, were conducted. NET formation was measured as the quantity of double-stranded DNA (dsDNA), using the AccuBlue Broad Range dsDNA Quantitation Kit. DFS (50 μmol/L) inhibited vacuole formation in the cytoplasm and NET formation. Additionally, 5-100 μmol/L concentration of DFS inhibited the release of dsDNA in a dose-independent manner. We demonstrate that DFS inhibits not only ROS production but also vacuolization and NET formation in neutrophils. These results suggest the possibility of protective effects of DFS against NET-related adverse effects, including ALI and thrombosis.

  2. Water-soluble chelating polymers for removal of actinides from wastewater

    Energy Technology Data Exchange (ETDEWEB)

    Jarvinen, G.D. [Los Alamos National Lab., NM (United States)

    1997-10-01

    Polymer filtration is a technology under development to selectively recover valuable or regulated metal ions from process or wastewaters. The technology uses water-soluble chelating polymers that are designed to selectively bind with metal ions in aqueous solutions. The polymers have a sufficiently large molecular weight that they can be separated and concentrated using available ultrafiltration (UF) technology. The UF range is generally considered to include molecular weights from about 3000 to several million daltons and particles sizes of about 2 to 1000 nm. Water and smaller unbound components of the solution pass freely through the UF membrane. The polymers can then be reused by changing the solution conditions to release the metal ions that are recovered in concentrated form for recycle or disposal. Some of the advantages of polymer filtration relative to technology now in use are rapid binding kinetics, high selectivity, low energy and capital costs, and a small equipment footprint. Some potential commercial applications include electroplating rinse waters, photographic processing, nuclear power plant cooling water; remediation of contaminated soils and groundwater; removal of mercury contamination; and textile, paint and dye production. The purpose of this project is to evaluate this technology to remove plutonium, americium, and other regulated metal ions from various process and waste streams found in nuclear facilities. The work involves preparation of the water-soluble chelating polymers; small-scale testing of the chelating polymer systems for the required solubility, UF properties, selectivity and binding constants; followed by an engineering assessment at a larger scale to allow comparison to competing separation technologies. This project focuses on metal-ion contaminants in waste streams at the Plutonium Facility and the Waste Treatment Facility at LANL. Potential applications at other DOE facilities are also apparent.

  3. Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis

    Science.gov (United States)

    Averette, Anna F.; Lee, Soo Chan; Kim, Taeyup; Bahn, Yong-Sun; Robbins, Nicole; Heitman, Joseph; Cowen, Leah E.

    2016-01-01

    Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which metal chelation

  4. Preparation and study of new poly-8-hydroxyquinoline chelators for an anti-Alzheimer strategy.

    Science.gov (United States)

    Deraeve, Céline; Boldron, Christophe; Maraval, Alexandrine; Mazarguil, Honoré; Gornitzka, Heinz; Vendier, Laure; Pitié, Marguerite; Meunier, Bernard

    2008-01-01

    Fourteen different ligands have been synthesized with two covalently linked 8-hydroxyquinoline motifs that favor metal complexation. These bis-chelators include different bridges at the C2 positions and different substituents to modulate their physicochemical properties. They can form metal complexes in a ratio of one ligand per metal ion with Cu II and Zn II, two metal ions involved in the formation of amyloid aggregates of the toxic Abeta-peptides in the Alzheimer disease. The apparent affinity of all bis-8-hydroxyquinoline ligands for Cu II and Zn II are similar with logK Cu II approximately 16 and logK Zn II approximately 13 and are 10,000 times more efficient than for the corresponding 8-hydroxyquinoline monomers. Their strong chelating capacities allow them to inhibit more efficiently than the corresponding monomers the precipitation of Abeta-peptides induced by Cu II and Zn II and also to inhibit the toxic formation of H2O2 due to copper complexes of Abeta. The best results were obtained with a one-atom linker between the two quinoline units. X-ray analyses of single-crystals of Cu II, Zn II or Ni II complexes of 2,2'-(2,2-propanediyl)-bis(8-hydroxyquinoline), including a one-atom linker, showed that all heteroatoms of the bis-8-hydroxyquinoline ligand chelate the same metal ion in a distorted square-planar geometry. The Cu II and Zn II complexes include a fifth axial ligand and are pentacoordinated.

  5. Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Elizabeth J Polvi

    2016-10-01

    Full Text Available Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which

  6. Effects of synthetic Zn chelates on flax response and soil Zn status

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, D.; Almendros, P.; Alvarez, J.M.

    2016-11-01

    Throughout the world, flax (Linum usitatissimum L.) is often grown in Zn-deficient soils, but appropriate fertilizer management can optimize both crop yield and micronutrient content. A greenhouse experiment was conducted on Typic Haploxeralf (pH 6.1) and Typic Calcixerept (pH 8.1) soils to study the relative efficiency of chelated Zn using two application rates of three different Zn sources [Zn-EDDHSA, ethylenediamine-di-(2-hydroxy-5-sulfophenylacetate of Zn); Zn-HEDTA, N-2-hydroxyethyl-ethylenediaminetriacetate of Zn; and Zn-EDTA, ethylenediaminetetraacetate of Zn]. Dry matter /DM) yield, Zn concentration, chlorophyll content, crude fiber and tensile properties were monitored and the soil-Zn status (available-Zn, Zn-fractions and total-Zn) was assessed. Zinc chelate applications increased the most labile forms of Zn in soils and Zn concentrations in plants. The low rate of Zn generally had a beneficial effect on DM yield and tensile properties. The exception was Zn-EDTA in the weakly acidic soil, where the highest Zn concentrations were observed in leaves and whole shoots; this coincided with the largest concentrations of labile Zn in soil. The most efficient fertilizers were Zn-EDDHSA (in both soils) and Zn-EDTA (in the calcareous soil). The relatively large amounts of labile and available Zn present in both of the soils fertilized with Zn-EDTA points to the applying this chelate at lower rate than 5 mg Zn/kg; this should, in turn, reduce the cost of Zn fertilization and minimize environmental pollution risk. (Author)

  7. Degradation of toluene, ethylbenzene, and xylene using heat and chelated-ferrous iron activated persulfate oxidation

    Science.gov (United States)

    Mondal, P.; Sleep, B.

    2014-12-01

    Toluene, ethylbenze, and xylene (TEX) are common contaminants in the subsurface. Activated persulfate has shown promise for degrading a wide variety of organic compounds. However, studies of persulfate application for in situ degradation of TEX and effects on the subsequent bioremediation are limited. In this work, degradation studies of TEX in aqueous media and soil are being conducted using heat activated and chelated-ferrous iron activated persulfate oxidation in batch and flow-through column experiments. In the batch experiments, sodium persulfate is being used at different concentrations to provide an initial persulfate to TEX molar ratios between 10:1 and 100:1. Sodium persulfate solutions are being activated at 20, 37, 60, and 80 oC temperatures for the heat activated oxidation. For the chelated-ferrous iron activated oxidation, ferrous iron and citric acid, both are being used at concentration of 5 mM. In the experiments with soil slurry, a soil to water ratio of 1 to 5 is being used. Flow through water saturated column experiments are being conducted with glass columns (45 cm in length and 4 cm in diameter) uniformly packed with soils, and equilibrated with water containing TEX at the target concentrations. Both the heat activation and chelated-ferrous iron activation of persulfate are being employed in the column experiments. Future experiments are planned to determine the suitability of persulfate oxidation of TEX on the subsequent biodegradation using batch microcosms containing TEX degrading microbial cultures. In these experiments, the microbial biomass will be monitored using total phospholipids, and the microbial community will be determined using quantitative real-time polymerase chain reaction (qPCR) on the extracted DNA. This study is expected to provide suitable operating conditions for in situ chemical oxidation of TEX with activated persulfate followed by bioremediation.

  8. Hormone Therapy

    Science.gov (United States)

    ... types of estrogen therapy relieve vaginal dryness. • Systemic estrogen protects against the bone loss that occurs early in menopause and helps prevent hip and spine fractures. • Combined estrogen and progestin therapy may reduce the risk of ...

  9. Proton Therapy

    Science.gov (United States)

    ... IMRT) Brain Tumor Treatment Brain Tumors Prostate Cancer Lung Cancer Treatment Lung Cancer Head and Neck Cancer Images related to Proton Therapy Videos related to Proton Therapy Sponsored by Please ...

  10. Radiation Therapy

    Science.gov (United States)

    ... the area is stitched shut. Another treatment, called proton-beam radiation therapy , focuses the radiation on the ... after radiation treatment ends. Sore mouth and tooth decay. If you received radiation therapy to the head ...

  11. Family Therapy

    Science.gov (United States)

    ... may be credentialed by the American Association for Marriage and Family Therapy (AAMFT). Family therapy is often short term. ... challenging situations in a more effective way. References Marriage and family therapists: The friendly mental health professionals. American Association ...

  12. Shape-controlled Synthesis of Gold Nanoparticles from Gold(III)-chelates of β-diketones

    Science.gov (United States)

    Kundu, Subrata; Pal, Anjali; Ghosh, Sujit Kumar; Nath, Sudip; Panigrahi, Sudipa; Praharaj, Snigdhamayee; Basu, Soumen; Pal, Tarasankar

    2005-12-01

    Chelating ligands with β-diketone skeleton have been employed for the first time as reductant to produce ligand stabilized gold nanoparticles of different shapes out of aqueous HAuCl4 solutions. Evolution of stable gold nanoparticles happens to be first order with respect to gold particles having rate constants ˜ ˜10-2 min-1 and subsequent chlorine insertion in the β-diketone skeleton is reported as a general feature. Spherical or triangular or hexagonal particle evolution goes selectively under the influence of different β-diketones in terms of capping and reducing capabilities of the reductants.

  13. Shape-controlled Synthesis of Gold Nanoparticles from Gold(III)-chelates of {beta}-diketones

    Energy Technology Data Exchange (ETDEWEB)

    Kundu, Subrata [Indian Institute of Technology, Department of Chemistry (India); Pal, Anjali [Indian Institute of Technology, Department of Civil Engineering (India); Ghosh, Sujit Kumar; Nath, Sudip; Panigrahi, Sudipa; Praharaj, Snigdhamayee; Basu, Soumen; Pal, Tarasankar [Indian Institute of Technology, Department of Chemistry (India)], E-mail: tpal@chem.iitkgp.ernet.in

    2005-12-15

    Chelating ligands with {beta}-diketone skeleton have been employed for the first time as reductant to produce ligand stabilized gold nanoparticles of different shapes out of aqueous HAuCl{sub 4} solutions. Evolution of stable gold nanoparticles happens to be first order with respect to gold particles having rate constants {approx}{approx}10{sup -2} min{sup -1} and subsequent chlorine insertion in the {beta}-diketone skeleton is reported as a general feature. Spherical or triangular or hexagonal particle evolution goes selectively under the influence of different {beta}-diketones in terms of capping and reducing capabilities of the reductants.

  14. THE STUDIES ON CHELATING FIBER—THE STUDIES ON THE AMIDOXIMATION OF POLYACRYLONITRILE FIBER

    Institute of Scientific and Technical Information of China (English)

    LINWeiping; LUYun; 等

    1992-01-01

    The amidoximation process of commercial polyacrylonitrile fiber was studied. The results showed that it is possible to prepare a chelating fiber, which present high adsorption capability to Au3+ and reasonable mechanical property,by the amidoximation of PAN fiber,with the increase of reaction time or agent concentration,the coversion of CN group in PAN increases rapidly at first and then increases slowly.When the reaction temperature is higher than that at which the paracrystalline region in the fiber is destroyed, the conversion of CN group increases greatly,but the mechanical property of the fiber begins to be inferior.

  15. STUDY ON THE SYNTHESIS OF POLYSTYRENE SUPPORTED MACROCYCLIC MERCAPTAL CHELATING RESIN AND ITS PROPERTIES

    Institute of Scientific and Technical Information of China (English)

    SUN Qiang; ZHANG Jinlan; XU Jiping

    1984-01-01

    Chelating resin with macrocyclic mercaptal group supported on macroporous polystyrene beads was synthesized, which showed good selectivity to Hg2+: its complexing capacity amounted to 30-60 mg Hg2+/g resin, two orders of magnitude greater than for other metal ions such as Ca2+, Zn2+,Cd2+, Pb2+ etc. This resin could restore the activity of urease which had been deactivated by poisoning with Hg2+. Its restoring power was far better than that of the mercapto-resin and common anionic exchange resins. It showed some promising use as an oral polymeric detoxifying drug for mercury poisoning.

  16. Meso-2,3-dimercaptosuccinic acid: from heavy metal chelation to CdS quantum dots

    OpenAIRE

    Sevinç, Esra; Ertaş, F. Sinem ; Ulusoy, Gülen ; Acar, Havva Yağcı; Özen, Can

    2012-01-01

    DMSA (meso-2,3-dimercaptosuccinic acid) a prescription drug and a heavy-metal chelating agent, is shown to act both as a sulfur source and a capping agent in the aqueous synthesis of CdS quantum dots under mild conditions. Release of sulfur from DMSA depends on the solution pH and the reaction temperature. Combination of 70 C and pH 7.5 was determined as the best reaction conditions for a well-controlled reaction. Changing the SH/Cd ratio from 2.5 to 7 provides QDs emitting from ...

  17. Bis-ligated Ti and Zr complexes of chelating N-heterocyclic carbenes

    KAUST Repository

    El-Batta, Amer

    2011-07-01

    In this communication we report the synthesis of novel titanium and zirconium complexes ligated by bidentate "salicylaldimine-like" N-heterocyclic carbenes (NHC). Double addition of the NHC chelate to either TiCl4(thf)2 or ZrCl4 forms bis-ligated organometallic fragments with a distorted octahedral geometry. These complexes are rare examples of group IV transition-metal NHC adducts. Preliminary catalytic tests demonstrate that in the presence of methylaluminoxane (MAO) these complexes are useful initiators for the polymerization of ethylene and the copolymerization of ethylene with norbornene and 1-octene. © 2011 Elsevier B.V. All rights reserved.

  18. Synthesis and Adsorption Properties of Chelating Resins Containing Sulfoxide and Heterocyclic Functional Groups

    Institute of Scientific and Technical Information of China (English)

    Chun Nuan JI; Xiu Juan ZHANG; Rong Jun QU; Hou CHEN; Chun Hua WANG; Chang Mei SUN

    2006-01-01

    Several of new chelating resins containing sulfoxide and heterocyclic functional groups (3-aminopyridine and 2-mercaptobenzothiazole) based on macroporous chloromethylated polystyrene were synthesized and characterized by elemental analysis and infrared spectra. Their adsorption capacities towards Zn2+, Cu2+, Pb2+, Hg2+ and Ag+ at pH 3.0 and 6.0 were investigated in detail. It was found that the adsorption capacities of the resins containing bis[(3-pyridylaminoethyl)sulfoxide or (2-benzothiazolylthioethyl)sulfoxide for the above ions were higher than that on ones containing single above-mentioned groups.

  19. Chelate-Thiolate-Coordinate Ligands Modulating the Configuration and Electrochemical Property of Dinitrosyliron Complexes (DNICs).

    Science.gov (United States)

    Yeh, Shih-Wey; Lin, Chih-Wei; Liu, Bai-Heng; Tsou, Chih-Chin; Tsai, Ming-Li; Liaw, Wen-Feng

    2015-11-01

    As opposed to the reversible redox reaction ({Fe(NO)2 }(10) reduced-form DNIC [(NO)2 Fe(S(CH2 )3 S)](2-) (1)⇌{Fe(NO)2 }(9) oxidized-form [(NO)2 Fe(S(CH2 )3 S)](-) ), the chemical oxidation of the {Fe(NO)2 }(10) DNIC [(NO)2 Fe(S(CH2 )2 S)](2-) (2) generates the dinuclear {Fe(NO)2 }(9) -{Fe(NO)2 }(9) complex [(NO)2 Fe(μ-SC2 H4 S)2 Fe(NO)2 ](2-) (3) bridged by two terminal [SC2 H4 S](2-) ligands. On the basis of the Fe K-edge pre-edge energy and S K-edge XAS, the oxidation of complex 1 yielding [(NO)2 Fe(S(CH2 )3 S)](-) is predominantly a metal-based oxidation. The smaller S1-Fe1-S2 bond angle of 94.1(1)° observed in complex 1 (S1-Fe1-S2 88.6(1)° in complex 2), compared to the bigger bond angle of 100.9(1)° in the {Fe(NO)2 }(9) DNIC [(NO)2 Fe(S(CH2 )3 S)](-) , may be ascribed to the electron-rich {Fe(NO)2 }(10) DNIC preferring a restricted bite angle to alleviate the electronic donation of the chelating thiolate to the electron-rich {Fe(NO)2 }(10) core. The extended transition state and natural orbitals for chemical valence (ETS-NOCV) analysis on the edt-/pdt-chelated {Fe(NO)2 }(9) and {Fe(NO)2 }(10) DNICs demonstrates how two key bonding interactions, that is, a FeS covalent σ bond and thiolate to the Fe d z 2 charge donation, between the chelating thiolate ligand and the {Fe(NO)2 }(9/10) core could be modulated by the backbone lengths of the chelating thiolate ligands to tune the electrochemical redox potential (E1/2 =-1.64 V for complex 1 and E1/2 =-1.33 V for complex 2) and to dictate structural rearrangement/chemical transformations (S-Fe-S bite angle and monomeric vs. dimeric DNICs).

  20. Water-soluble chelating polymers for removal of actinides from watewater

    Energy Technology Data Exchange (ETDEWEB)

    Jarvinen, G. [Los Alamos National Lab., NM (United States)

    1996-10-01

    Polymer filtration is a technology being developed to recover valuable or regulated metal ions selectively from process or wastewaters. Water-soluble chelating polymers are specially designed to bind selectively with metal ions in aqueous solutions. The polymers molecular weight is large enough so they can be separated and concentrated using available ultrafiltration technology. Water and smaller unbound components of the solution pass freely through the ultrafiltration membrane. The polymers can then be reused by changing the solution conditions to release the metal ions, which are recovered in concentrated form, for recycle or disposal.