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Sample records for chelation therapy abrogates

  1. Combinational chelation therapy abrogates lead-induced neurodegeneration in rats

    International Nuclear Information System (INIS)

    Pachauri, Vidhu; Saxena, Geetu; Mehta, Ashish; Mishra, Deepshikha; Flora, Swaran J.S.

    2009-01-01

    Lead, a ubiquitous and potent neurotoxicant causes oxidative stress which leads to numerous neurobehavioral and physiological alterations. The ability of lead to bind sulfhydryl groups or compete with calcium could be one of the reasons for its debilitating effects. In the present study, we addressed: i) if chelation therapy could circumvent the altered oxidative stress and prevent neuronal apoptosis in chronic lead-intoxicated rats, ii) whether chelation therapy could reverse biochemical and behavioral changes, and iii) if mono or combinational therapy with captopril (an antioxidant) and thiol chelating agents (DMSA/MiADMSA) is more effective than individual thiol chelator in lead-exposed rats. Results indicated that lead caused a significant increase in reactive oxygen species, nitric oxide, and intracellular free calcium levels along with altered behavioral abnormalities in locomotor activity, exploratory behavior, learning, and memory that were supported by changes in neurotransmitter levels. A fall in membrane potential, release of cytochrome c, and DNA damage indicated mitochondrial-dependent apoptosis. Most of these alterations showed significant recovery following combined therapy with captopril with MiADMSA and to a smaller extend with captopril + DMSA over monotherapy with these chelators. It could be concluded from our present results that co-administration of a potent antioxidant (like captopril) might be a better treatment protocol than monotherapy to counter lead-induced oxidative stress. The major highlight of the work is an interesting experimental evidence of the efficacy of combinational therapy using an antioxidant with a thiol chelator in reversing neurological dystrophy caused due to chronic lead exposure in rats.

  2. Comments on chelation therapy

    International Nuclear Information System (INIS)

    Wrenn, M.E.

    1981-01-01

    The primary purpose of actinide chelation is to decrease the risk from radiation-induced cancer. While occupational exposures in the past have mainly involved low specific activity 239 Pu, future exposures will increasingly involve high specific activity plutonium, americium, and curium - all of which clear more rapidly from the lung. This will tend to shift the cancer risk from lung to bone and liver. Although therapy with Ca- or Zn-DTPA rapidly removes 241 Am from the canine, the sub-human primate, and the human liver, improved methods for removal from bone and lung are needed. DTPA can remove 241 Am more easily from the growing skeleton of a child than from the mature skeleton of an adult. Investigators at Karlsruhe are developing chelation agents for oral administration and are investigating the reduction in local dose to bone resulting from chelation therapy

  3. 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.

  4. Chelation Therapy for Mercury Poisoning

    OpenAIRE

    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...

  5. Article Commentary: Chelation Therapy for Mercury Poisoning

    Directory of Open Access Journals (Sweden)

    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.

  6. Chelation therapy after the Trial to Assess Chelation Therapy: results of a unique trial

    Science.gov (United States)

    Avila, Maria D.; Escolar, Esteban; Lamas, Gervasio A.

    2014-01-01

    Purpose of review EDTA chelation therapy has been in off-label use for the treatment of atherosclerosis. We review the results of the first large-scale randomized trial of this treatment. Recent findings The trial to assess chelation therapy was a $30 million National Institutes of Health-funded study of the safety and efficacy of EDTA-based chelation infusions in 1708 post-myocardial infarction (MI) patients. The trial to assess chelation therapy demonstrated a significant (P = 0.035) 18% reduction in a combined primary endpoint of death, MI, stroke, coronary revascularization, or hospitalization for angina. In diabetic patients the benefit was more extreme, with a 41% relative reduction in risk (P = 0.0002) and a 43% reduction in total mortality (P = 0.011). Safety data were favorable. A reduction of oxidative stress by chelation of toxic metals has been proposed as a possible mechanism of action. Summary Recent research suggests that EDTA chelation may be a well-tolerated and effective treatment for post-MI patients. Future replication and mechanistic studies are important prior to implementation in all post-MI patients. PMID:25023079

  7. 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

  8. Chelation in root canal therapy reconsidered.

    Science.gov (United States)

    Zehnder, Matthias; Schmidlin, Patrick; Sener, Beatrice; Waltimo, Tuomas

    2005-11-01

    The aim of this study was to assess interactions of EDTA and citric acid (CA) with sodium hypochlorite (NaOCl), the indispensable endodontic irrigant. Other chelators were simultaneously evaluated as possible alternatives: sodium triphosphate (STP), amino tris methylenephosphonic acid (ATMA), and 1- hydroxyethylidene-1, 1-bisphosphonate (HEBP). Available chlorine was titrated in chelator-NaOCl solutions. All chelators other than HEBP and STP caused an almost complete, immediate loss of available chlorine in solution. Atomic absorbtion spectrometry and SEM evaluation of root canal walls of instrumented teeth indicated that NaOCl had no negative effect on calcium-complexing ability of chelators. STP was too weak a complexing agent to warrant further studies. Finally, CA-, EDTA-, and HEBP-NaOCl mixtures were evaluated for their antimicrobial capacity. Again, EDTA and CA negatively interfered with NaOCl, while HEBP did not.

  9. G2 checkpoint abrogator abates the antagonistic interaction between antimicrotubule drugs and radiation therapy

    International Nuclear Information System (INIS)

    Sui Meihua; Zhang Hongfang; Di Xiaoyun; Chang Jinjia; Shen Youqing; Fan Weimin

    2012-01-01

    Background and purpose: We previously demonstrated that radiation may arrest tumor cells at G2 phase, which in turn prevents the cytotoxicity of antimicrotubule drugs and results in antagonistic interaction between these two modalities. Herein we tested whether G2 abrogators would attenuate the above antagonistic interaction and improve the therapeutic efficacy of combination therapy between radiation and antimicrotubule drugs. Materials and methods: Breast cancer BCap37 and epidermoid carcinoma KB cell lines were administered with radiation, UCN-01 (a model drug of G2 abrogator), paclitaxel or vincristine, alone or in combinations. The antitumor activities of single and combined treatments were analyzed by a series of cytotoxic, apoptotic, cell cycle, morphological and biochemical assays. Results: UCN-01 significantly enhanced the cytotoxicity of radiation, antimitotic drugs, and their combined treatments in vitro. Further investigations demonstrated that UCN-01 attenuated radiation-induced G2 arrest, and subsequently repressed the inhibitory effect of radiation on drug-induced mitotic arrest and apoptosis. Conclusions: This is the first report demonstrating that G2 checkpoint abrogation represses the inhibitory effect of radiation on antimicrotubule drugs, which may be implicated in cancer combination therapy. Considering that G2 abrogators are under extensive evaluation for cancer treatment, our findings provide valuable information for this class of promising compounds.

  10. EDTA chelation therapy for cardiovascular disease: a systematic review

    Directory of Open Access Journals (Sweden)

    Wu Ping

    2005-11-01

    Full Text Available Abstract Background Numerous practitioners of both conventional and complementary and alternative medicine throughout North America and Europe claim that chelation therapy with EDTA is an effective means to both control and treat cardiovascular disease. These claims are controversial, and several randomized controlled trials have been completed dealing with this topic. To address this issue we conducted a systematic review to evaluate the best available evidence for the use of EDTA chelation therapy in the treatment of cardiovascular disease. Methods We conducted a systematic review of 7 databases from inception to May 2005. Hand searches were conducted in review articles and in any of the trials found. Experts in the field were contacted and registries of clinical trials were searched for unpublished data. To be included in the final systematic review, the studies had to be randomized controlled clinical trials. Results A total of seven articles were found assessing EDTA chelation for the treatment of cardiovascular disease. Two of these articles were subgroup analyses of one RCT that looked at different clinical outcomes. Of the remaining five studies, two smaller studies found a beneficial effect whereas the other three exhibited no benefit for cardiovascular disease from the use of EDTA chelation therapy. Adverse effects were rare but those of note included a few cases of hypocalcemia and a single case of increased creatinine in a patient on the EDTA intervention. Conclusion The best available evidence does not support the therapeutic use of EDTA chelation therapy in the treatment of cardiovascular disease. Although not considered to be a highly invasive or harmful therapy, it is possible that the use of EDTA chelation therapy in lieu of proven therapy may result in causing indirect harm to the patient.

  11. Chelation therapy to prevent diabetes-associated cardiovascular events.

    Science.gov (United States)

    Diaz, Denisse; Fonseca, Vivian; Aude, Yamil W; Lamas, Gervasio A

    2018-05-24

    For over 60 years, chelation therapy with disodium ethylene diamine tetraacetic acid (EDTA, edetate) had been used for the treatment of cardiovascular disease (CVD) despite lack of scientific evidence for efficacy and safety. The Trial to Assess Chelation Therapy (TACT) was developed and received funding from the National Institutes of Health (NIH) to ascertain the safety and efficacy of chelation therapy in patients with CVD. This pivotal trial demonstrated an improvement in outcomes in postmyocardial infarction (MI) patients. Interestingly, it also showed a particularly large reduction in CVD events and all-cause mortality in the prespecified subgroup of patients with diabetes. The TACT results may support the concept of metal chelation to reduce metal-catalyzed oxidation reactions that promote the formation of advanced glycation end products, a precursor of diabetic atherosclerosis. In this review, we summarize the epidemiological and basic evidence linking toxic metal accumulation and diabetes-related CVD, supported by the salutary effects of chelation in TACT. If the ongoing NIH-funded TACT2, in diabetic post-MI patients, proves positive, this unique therapy will enter the armamentarium of endocrinologists and cardiologists seeking to reduce the atherosclerotic risk of their diabetic patients.

  12. Protracted chelate therapy after incorporation of plutonium 239 in rats

    International Nuclear Information System (INIS)

    Gemenetzis, E.

    1976-01-01

    The author has tested in how far 239 Pu can be mobilized by Ca and Zn, Desfenioxamin B(DFDA) and by combined doses of Ca-DTPA and DFDA. The pre-experiment covered the 239 Pu-metabolism in untreated male and female rats and the distribution in dependence of the way of application. If treatment is started immediately by multiple chelate doses, the first two injections play the main part in the decorporation of 239 Pu. The combination Ca-DTPA30 + DFDA30 μMol x kg -1 is proved to be the best means of decorporation for the whole body. The efficiency of another therapy depends essentially on the treatment used, a daily treatment showing the best effects. If treatment is started later with multiple chelate doses, the total decorporation efficiency is of less value, especially in the skeleton. Aequimolar doses of Ca-DTPA and Zn-DTPA have the same degree of efficiency. This indicates that during protracted chelate treatment starting later, Ca-DTPA could be substituted by the less toxic Zn-DTPA after incorporation of 239 Pu. These results show that intermittant administration of the week's dose is more efficient than a single chelate administration of the whole week's dose at once. Permanent chelate infusion does not seem necessary in any case since it has the same effect as 3 to 5 injections per week and is difficult to carry out in medical practice. Thus, it seems advisable to divide up the weekly dose into 3-5 injections. In case of a wound contamination, the efficiency of immediate intensive treatment depends on the 239 Pu compound used, on the chelate used, and on its dosage. (orig.) [de

  13. Iron overload and chelation therapy in myelodysplastic syndromes.

    Science.gov (United States)

    Temraz, Sally; Santini, Valeria; Musallam, Khaled; Taher, Ali

    2014-07-01

    Iron overload remains a concern in MDS patients especially those requiring recurrent blood transfusions. The consequence of iron overload may be more relevant in patients with low and intermediate-1 risk MDS who may survive long enough to experience such manifestations. It is a matter of debate whether this overload has time to yield organ damage, but it is quite evident that cellular damage and DNA genotoxic effect are induced. Iron overload may play a critical role in exacerbating pre-existing morbidity or even unmask silent ones. Under these circumstances, iron chelation therapy could play an integral role in the management of these patients. This review entails an in depth analysis of iron overload in MDS patients; its pathophysiology, effect on survival, associated risks and diagnostic options. It also discusses management options in relation to chelation therapy used in MDS patients and the impact it has on survival, hematologic response and organ function. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Effectiveness of chelation therapy with time after acute uranium intoxication

    International Nuclear Information System (INIS)

    Domingo, J.L.; Ortega, A.; Llobet, J.M.; Corbella, J.

    1990-01-01

    The effect of increasing the time interval between acute uranium exposure and chelation therapy was studied in male Swiss mice. Gallic acid, 4,5-dihydroxy-1,3- benzenedisulfonic acid (Tiron), diethylenetriaminepentaacetic acid (DTPA), and 5-aminosalicylic acid (5-AS) were administered ip at 0, 0.25, 1, 4, and 24 hr after sc injection of 10 mg/kg of uranyl acetate dihydrate. Chelating agents were given at doses equal to one-fourth of their respective LD50 values. Daily elimination of uranium into urine and feces was determined for 4 days after which time the mice were killed, and the concentration of uranium was measured in kidney, spleen, and bone. The excretion of uranium was especially rapid in the first 24 hr. Treatment with Tiron or gallic acid at 0, 0.25, or 1 hr after uranium exposure significantly increased the total excretion of the metal. In kidney and bone, only administration of Tiron at 0, 0.25, or 1 hr after uranium injection, or gallic acid at 1 hr after uranium exposure significantly reduced tissue uranium concentrations. Treatment at later times (4 to 24 hr) did not increase the total excretion of the metal and did not decrease the tissue uranium concentrations 4 days after uranyl acetate administration. The results show that the length of time before initiating chelation therapy for acute uranium intoxication greatly influences the effectiveness of this therapy

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

    International Nuclear Information System (INIS)

    Levin, T.L.; Sheth, S.S.; Ruzal-Shapiro, C.; Abramson, S.; Piomelli, S.; Berdon, W.E.

    1995-01-01

    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

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

    Science.gov (United States)

    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. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Chelation therapy to treat atherosclerosis, particularly in diabetes: is it time to reconsider?

    Science.gov (United States)

    Lamas, Gervasio A; Ergui, Ian

    2016-08-01

    Case reports and case series have suggested a possible beneficial effect of chelation therapy in patients with atherosclerotic disease. Small randomized trials conducted in patients with angina or peripheral artery disease, however, were not sufficiently powered to provide conclusive evidence on clinical outcomes. The Trial to Assess Chelation Therapy (TACT) was the first randomized trial adequately powered to detect the effects of chelation therapy on clinical endpoints. We discuss results and future research. Expert commentary: Chelation reduced adverse cardiovascular events in a post myocardial infarction (MI) population. Patients with diabetes demonstrated even greater benefit, with a number needed to treat of 6.5 patients to prevent a cardiac event over 5 years, with a 41% relative reduction in risk of a cardiac event (p = 0.0002). These results led to the revision of the ACC/AHA guideline recommendations for chelation therapy, changing its classification from class III to class IIb. TACT2, a replicative trial, will assess the effects of chelation therapy on cardiovascular outcomes in diabetic patients with a prior myocardial infarction. We are seeking participating sites for TACT2.

  19. 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.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...... 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...

  1. Mixed ligand chelate therapy for plutonium and cadmium poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Schubert, J; Derr, S K [Hope Coll., Holland, MI (USA)

    1978-09-28

    Some experiments with mice are described in which complete removal of tissue deposits of /sup 239/Pu and prevention of mortality in animals given lethal doses of Cd were achieved using a mixed ligand chelate treatment (MLC). The mixed ligand consisted of diethylenetriaminepentaacetic acid and salicylic acid.

  2. Deaths associated with hypocalcemia from chelation therapy--Texas, Pennsylvania, and Oregon, 2003-2005.

    Science.gov (United States)

    2006-03-03

    Chelating agents bind lead in soft tissues and are used in the treatment of lead poisoning to enhance urinary and biliary excretion of lead, thus decreasing total lead levels in the body. During the past 30 years, environmental and dietary exposures to lead have decreased substantially, resulting in a considerable decrease in population blood lead levels (BLLs) and a corresponding decrease in the number of patients requiring chelation therapy. Chelating agents also increase excretion of other heavy metals and minerals, such as zinc and, in certain cases, calcium. This report describes three deaths associated with chelation-therapy--related hypocalcemia that resulted in cardiac arrest. Several drugs are used in the treatment of lead poisoning, including edetate disodium calcium (CaEDTA), dimercaperol (British anti-Lewisite), D-penicillamine, and meso-2,3-dimercaptosuccinic acid (succimer). Health-care providers who are unfamiliar with chelating agents and are considering this treatment for lead poisoning should consult an expert in the chemotherapy of lead poisoning. Hospital pharmacies should evaluate whether continued stocking of Na2EDTA is necessary, given the established risk for hypocalcemia, the availability of less toxic alternatives, and an ongoing safety review by the Food and Drug Administration (FDA). Health-care providers and pharmacists should ensure that Na2EDTA is not administered to children during chelation therapy.

  3. Chronic Toxic Metal Exposure and Cardiovascular Disease: Mechanisms of Risk and Emerging Role of Chelation Therapy.

    Science.gov (United States)

    Aneni, Ehimen C; Escolar, Esteban; Lamas, Gervasio A

    2016-12-01

    Over the last few decades, there has been a growing body of epidemiologic evidence linking chronic toxic metal exposure to cardiovascular disease-related morbidity and mortality. The recent and unexpectedly positive findings from a randomized, double-blind, multicenter trial of metal chelation for the secondary prevention of atherosclerotic cardiovascular disease (Trial to Assess Chelation Therapy (TACT)) have focused the discussion on the role of chronic exposure to toxic metals in the development and propagation of cardiovascular disease and the role of toxic metal chelation therapy in the secondary prevention of cardiovascular disease. This review summarizes the most recent evidence linking chronic toxic metal exposure to cardiovascular disease and examines the findings of TACT.

  4. Lead toxicosis of captive vultures: case description and responses to chelation therapy

    Science.gov (United States)

    2013-01-01

    Background Lead, a serious threat for raptors, can hamper the success of their conservation. This study reports on experience with accidental lead intoxication and responses to chelation therapy in captive Cinereous (Aegypius monachus) and Egyptian (Neophron percnopterus) Vultures. Results Soil contamination by lead-based paint sanded off the steel aviary resulted in poisoning of eight Cinereous and two Egyptian Vultures. A male Egyptian Vulture developed signs of apathy, polydipsia, polyuria, regurgitation, and stupor, and died on the next day. Liver, kidney and blood lead concentrations were 12.2, 8.16 and 2.66 μg/g, respectively. Laboratory analyses confirmed severe liver and kidney damage and anaemia. Blood Pb levels of Pb-exposed Cinereous Vultures were 1.571 ± 0.510 μg/g shortly after intoxication, decreased to 0.530 ± 0.165 μg/g without any therapy in a month and to 0.254 ± 0.097 μg/g one month after CaNa2EDTA administration. Eight months later, blood lead levels decreased to close to the background of the control group. Blood parameters of healthy Pb-non-exposed Cinereous Vultures were compared with those of the exposed group prior to and after chelation therapy. Iron levels in the lead-exposed pre-treatment birds significantly decreased after chelation. Haematocrit levels in Pb-exposed birds were significantly lower than those of the controls and improved one month after chelation. Creatine kinase was higher in pre-treatment birds than in the controls but normalised after therapy. Alkaline phosphatase increased after chelation. A marked increase in the level of lipid peroxidation measured as thiobarbituric acid reactive species was demonstrated in birds both prior to and after chelation. The ferric reducing antioxidant power was significantly lower in pre-treatment vultures and returned to normal following chelation therapy. Blood metallothionein levels in lead-exposed birds were higher than in controls. Reduced glutathione dropped after

  5. Lead toxicosis of captive vultures: case description and responses to chelation therapy.

    Science.gov (United States)

    Pikula, Jiri; Hajkova, Pavlina; Bandouchova, Hana; Bednarova, Ivana; Adam, Vojtech; Beklova, Miroslava; Kral, Jiri; Ondracek, Karel; Osickova, Jitka; Pohanka, Miroslav; Sedlackova, Jana; Skochova, Hana; Sobotka, Jakub; Treml, Frantisek; Kizek, Rene

    2013-01-16

    Lead, a serious threat for raptors, can hamper the success of their conservation. This study reports on experience with accidental lead intoxication and responses to chelation therapy in captive Cinereous (Aegypius monachus) and Egyptian (Neophron percnopterus) Vultures. Soil contamination by lead-based paint sanded off the steel aviary resulted in poisoning of eight Cinereous and two Egyptian Vultures. A male Egyptian Vulture developed signs of apathy, polydipsia, polyuria, regurgitation, and stupor, and died on the next day. Liver, kidney and blood lead concentrations were 12.2, 8.16 and 2.66 μg/g, respectively. Laboratory analyses confirmed severe liver and kidney damage and anaemia. Blood Pb levels of Pb-exposed Cinereous Vultures were 1.571 ± 0.510 μg/g shortly after intoxication, decreased to 0.530 ± 0.165 μg/g without any therapy in a month and to 0.254 ± 0.097 μg/g one month after CaNa(2)EDTA administration. Eight months later, blood lead levels decreased to close to the background of the control group. Blood parameters of healthy Pb-non-exposed Cinereous Vultures were compared with those of the exposed group prior to and after chelation therapy. Iron levels in the lead-exposed pre-treatment birds significantly decreased after chelation. Haematocrit levels in Pb-exposed birds were significantly lower than those of the controls and improved one month after chelation. Creatine kinase was higher in pre-treatment birds than in the controls but normalised after therapy. Alkaline phosphatase increased after chelation. A marked increase in the level of lipid peroxidation measured as thiobarbituric acid reactive species was demonstrated in birds both prior to and after chelation. The ferric reducing antioxidant power was significantly lower in pre-treatment vultures and returned to normal following chelation therapy. Blood metallothionein levels in lead-exposed birds were higher than in controls. Reduced glutathione dropped after CaNa(2)EDTA therapy, while

  6. Modeling the effect of succimer (DMSA; dimercaptosuccinic acid) chelation therapy in patients poisoned by lead.

    Science.gov (United States)

    van Eijkeren, Jan C H; Olie, J Daniël N; Bradberry, Sally M; Vale, J Allister; de Vries, Irma; Clewell, Harvey J; Meulenbelt, Jan; Hunault, Claudine C

    2017-02-01

    Kinetic models could assist clinicians potentially in managing cases of lead poisoning. Several models exist that can simulate lead kinetics but none of them can predict the effect of chelation in lead poisoning. Our aim was to devise a model to predict the effect of succimer (dimercaptosuccinic acid; DMSA) chelation therapy on blood lead concentrations. We integrated a two-compartment kinetic succimer model into an existing PBPK lead model and produced a Chelation Lead Therapy (CLT) model. The accuracy of the model's predictions was assessed by simulating clinical observations in patients poisoned by lead and treated with succimer. The CLT model calculates blood lead concentrations as the sum of the background exposure and the acute or chronic lead poisoning. The latter was due either to ingestion of traditional remedies or occupational exposure to lead-polluted ambient air. The exposure duration was known. The blood lead concentrations predicted by the CLT model were compared to the measured blood lead concentrations. Pre-chelation blood lead concentrations ranged between 99 and 150 μg/dL. The model was able to simulate accurately the blood lead concentrations during and after succimer treatment. The pattern of urine lead excretion was successfully predicted in some patients, while poorly predicted in others. Our model is able to predict blood lead concentrations after succimer therapy, at least, in situations where the duration of lead exposure is known.

  7. Chiral DOTA chelators as an improved platform for biomedical imaging and therapy applications.

    Science.gov (United States)

    Dai, Lixiong; Jones, Chloe M; Chan, Wesley Ting Kwok; Pham, Tiffany A; Ling, Xiaoxi; Gale, Eric M; Rotile, Nicholas J; Tai, William Chi-Shing; Anderson, Carolyn J; Caravan, Peter; Law, Ga-Lai

    2018-02-27

    Despite established clinical utilisation, there is an increasing need for safer, more inert gadolinium-based contrast agents, and for chelators that react rapidly with radiometals. Here we report the syntheses of a series of chiral DOTA chelators and their corresponding metal complexes and reveal properties that transcend the parent DOTA compound. We incorporated symmetrical chiral substituents around the tetraaza ring, imparting enhanced rigidity to the DOTA cavity, enabling control over the range of stereoisomers of the lanthanide complexes. The Gd chiral DOTA complexes are shown to be orders of magnitude more inert to Gd release than [GdDOTA] - . These compounds also exhibit very-fast water exchange rates in an optimal range for high field imaging. Radiolabeling studies with (Cu-64/Lu-177) also demonstrate faster labelling properties. These chiral DOTA chelators are alternative general platforms for the development of stable, high relaxivity contrast agents, and for radiometal complexes used for imaging and/or therapy.

  8. Combined Therapy of Iron Chelator and Antioxidant Completely Restores Brain Dysfunction Induced by Iron Toxicity

    Science.gov (United States)

    Sripetchwandee, Jirapas; Pipatpiboon, Noppamas; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2014-01-01

    Background Excessive iron accumulation leads to iron toxicity in the brain; however the underlying mechanism is unclear. We investigated the effects of iron overload induced by high iron-diet consumption on brain mitochondrial function, brain synaptic plasticity and learning and memory. Iron chelator (deferiprone) and antioxidant (n-acetyl cysteine) effects on iron-overload brains were also studied. Methodology Male Wistar rats were fed either normal diet or high iron-diet consumption for 12 weeks, after which rats in each diet group were treated with vehicle or deferiprone (50 mg/kg) or n-acetyl cysteine (100 mg/kg) or both for another 4 weeks. High iron-diet consumption caused brain iron accumulation, brain mitochondrial dysfunction, impaired brain synaptic plasticity and cognition, blood-brain-barrier breakdown, and brain apoptosis. Although both iron chelator and antioxidant attenuated these deleterious effects, combined therapy provided more robust results. Conclusion In conclusion, this is the first study demonstrating that combined iron chelator and anti-oxidant therapy completely restored brain function impaired by iron overload. PMID:24400127

  9. Design and Methodology of the Trial to Assess Chelation Therapy (TACT)

    Science.gov (United States)

    Lamas, Gervasio A.; Goertz, Christine; Boineau, Robin; Mark, Daniel B.; Rozema, Theodore; Nahin, Richard L.; Drisko, Jeanne A.; Lee, Kerry L.

    2011-01-01

    The Trial to Assess Chelation Therapy (TACT) is an NIH-sponsored, randomized, double blind, placebo-controlled, 2×2 factorial clinical trial testing the benefits and risks of 40 infusions of a multi-component Na2EDTA-chelation solution compared with placebo, and of an oral, high-dose multivitamin and mineral supplement. TACT has randomized and will follow 1708 patients for an average of approximately 4 years. The primary endpoint is a composite of all cause mortality, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. A 900 patient substudy will examine quality of life outcomes. The trial is designed to have >85% power to detect a 25% relative reduction in the primary endpoint for each treatment factor. Enrollment began in September 2003 and completed in October 2010. PMID:22172430

  10. Heavy Metals, Cardiovascular Disease, and the Unexpected Benefits of Edetate Disodium Chelation Therapy

    Science.gov (United States)

    Lamas, Gervasio A.; Navas-Acien, Ana; Mark, Daniel B.; Lee, Kerry L.

    2016-01-01

    This review summarizes evidence from 2 lines of research previously thought unrelated: the unexpectedly positive results of the Trial to Assess Chelation Therapy (TACT), and a body of epidemiological data showing that accumulation of biologically active metals, such as lead and cadmium, is an important risk factor for cardiovascular disease. Considering these 2 areas of work together may lead to the identification of new, modifiable risk factors for atherosclerotic cardiovascular disease. We examine the history of chelation up through the report of TACT. We then describe work connecting higher metal levels in the body with the future risk of cardiovascular disease. We conclude by presenting a brief overview of a newly planned National Institutes of Health trial, TACT2, in which we will attempt to replicate the findings of TACT and to establish that removal of toxic metal stores from the body is a plausible mechanistic explanation for the benefits of edetate disodium treatment. PMID:27199065

  11. Impact of educational programme regarding chelation therapy on the quality of life for B-thalassemia major children.

    Science.gov (United States)

    Abu Samra, Omayma; Auda, Wafaa; Kamhawy, Heba; Al-Tonbary, Youssef

    2015-06-01

    Objectives Thalassemia is the most common genetic disorder in Egypt, with an estimated carrier rate of 9-10%. It is a genetic blood disorder which can be fatal if proper chelation is not received. The introduction of chelating agents capable of removing excessive iron from the body has dramatically increased life expectancy and improved the overall quality of life. The aim of this study was to assess the impact of educational programmes regarding chelation therapy on the quality of life of thalassemic children. Methods The study was carried out at the Mansoura University Children's Hospital in the period between March 2010 and May 2011. It included 173 B-thalassemia children (84 boys and 89 girls) with age ranging between 8-18 years. The researcher used a predesigned interviewing questionnaire to collect data regarding children's knowledge about thalassemia and its management, especially regarding chelation therapy. The paediatric quality-of-life inventory tool (Peds QL 4.0 generic core) was also used to assess the studied children's quality of life. Results There was a significant statistical difference of the studied children's knowledge regarding chelation therapy and their quality of life. Conclusion There was a positive effect of the educational programme in improving children's knowledge score and their quality of life. Application of educational programmes for thalassemic children and their nurses regarding chelation therapy and its importance in preventing thalassemia complications is established.

  12. A Patient with Beta-Propeller Protein-Associated Neurodegeneration: Treatment with Iron Chelation Therapy

    Directory of Open Access Journals (Sweden)

    Shen-Yang Lim

    2018-05-01

    Full Text Available We present a case of beta-propeller protein-associated neurodegeneration, a form of neurodegeneration with brain iron accumulation. The patient harbored a novel mutation in the WDR45 gene. A detailed video and description of her clinical condition are provided. Her movement disorder phenomenology was characterized primarily by limb stereotypies and gait dyspraxia. The patient’s disability was advanced by the time iron-chelating therapy with deferiprone was initiated, and no clinical response in terms of cognitive function, behavior, speech, or movements were observed after one year of treatment.

  13. Enhanced removal of 241Am by DTPA chelation therapy in an adult and teenage subject

    International Nuclear Information System (INIS)

    Sasso, T.L.; Cohen, N.

    1975-01-01

    A series of Na 3 (Ca-DTPA) chelation treatments were carried out on two human subjects, an adult man and a teenage boy, who have long-term body burdens of 241 Am. The in vivo whole-body counting, bioassay of urine and feces, and various blood chemistry measurements were coordinated to coincide with this therapy schedule. Decreases in total body burdens for this treatment period were measured as 5 percent in the adult and 30 percent in the youth. High concentrations of zinc in urine and a corresponding decrease of activity of the zinc-dependent erythropoietic enzyme, ALAD, were also observed. (U.S.)

  14. Somatomedin activity before and after chelation therapy in lead-intoxicated children

    International Nuclear Information System (INIS)

    Rohn, R.D.; Hill, J.R.; Shelton, J.E.

    1982-01-01

    Somatomedin activity was measured in 21 lead-intoxicated children to determine whether plumbism interferes with the processes of statural (bone) growth. Somatomedin activity was measured both by the rabbit coastal cartilage bioassay and by radioimmunoassay of somatomedin-C. Compared to values in normal children, both the bioassay and radioimmunoassay somatomedin activity was increased. The degree of body lead burden was so extensive that the 21 study children required chelation therapy. Following EDTA or BAL + EDTA chelation therapy, the overall somatomedin activity of these children with plumbism further increased significantly. In contrast, measures of body lead burden--including blood lead levels--decreased after treatment in all lead-intoxicated youngsters. We conclude that plumbism is associated with increased somatomedin activity. Hence the increased somatomedin activity may explain why clinical experience fails to find any long-term deleterious effect of saturnism on statural (bone) growth. Possible mechanisms underlying the increased somatomedin activity in the lead-intoxicated children remain to be defined

  15. Clinical consequences of iron overload in patients with myelodysplastic syndromes: the case for iron chelation therapy.

    Science.gov (United States)

    Shammo, Jamile M; Komrokji, Rami S

    2018-06-14

    Patients with myelodysplastic syndromes (MDS) are at increased risk of iron overload due to ineffective erythropoiesis and chronic transfusion therapy. The clinical consequences of iron overload include cardiac and/or hepatic failure, endocrinopathies, and infection risk. Areas covered: Iron chelation therapy (ICT) can help remove excess iron and ultimately reduce the clinical consequences of iron overload. The authors reviewed recent (last five years) English-language articles from PubMed on the topic of iron overload-related complications and the use of ICT (primarily deferasirox) to improve outcomes in patients with MDS. Expert Commentary: While a benefit of ICT has been more firmly established in other transfusion-dependent conditions such as thalassemia, its role in reducing iron overload in MDS remains controversial due to the lack of prospective controlled data demonstrating a survival benefit. Orally administered chelation agents (e.g., deferasirox), are now available, and observational and/or retrospective data support a survival benefit of using ICT in MDS. The placebo-controlled TELESTO trial (NCT00940602) is currently examining the use of deferasirox in MDS patients with iron overload, and is evaluating specifically whether use of ICT to alleviate iron overload can also reduce iron overload-related complications in MDS and improve survival.

  16. Heavy Metals, Cardiovascular Disease, and the Unexpected Benefits of Chelation Therapy.

    Science.gov (United States)

    Lamas, Gervasio A; Navas-Acien, Ana; Mark, Daniel B; Lee, Kerry L

    2016-05-24

    This review summarizes evidence from 2 lines of research previously thought to be unrelated: the unexpectedly positive results of TACT (Trial to Assess Chelation Therapy), and a body of epidemiological data showing that accumulation of biologically active metals, such as lead and cadmium, is an important risk factor for cardiovascular disease. Considering these 2 areas of work together may lead to the identification of new, modifiable risk factors for atherosclerotic cardiovascular disease. We examine the history of chelation up through the report of TACT. We then describe work connecting higher metal levels in the body with the future risk of cardiovascular disease. We conclude by presenting a brief overview of a newly planned National Institutes of Health trial, TACT2, in which we will attempt to replicate the findings of TACT and to establish that removal of toxic metal stores from the body is a plausible mechanistic explanation for the benefits of edetate disodium treatment. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  17. 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.

  18. Iron Overload and Chelation Therapy in Non-Transfusion Dependent Thalassemia.

    Science.gov (United States)

    Bou-Fakhredin, Rayan; Bazarbachi, Abdul-Hamid; Chaya, Bachar; Sleiman, Joseph; Cappellini, Maria Domenica; Taher, Ali T

    2017-12-20

    Iron overload (IOL) due to increased intestinal iron absorption constitutes a major clinical problem in patients with non-transfusion-dependent thalassemia (NTDT), which is a cumulative process with advancing age. Current models for iron metabolism in patients with NTDT suggest that suppression of serum hepcidin leads to an increase in iron absorption and subsequent release of iron from the reticuloendothelial system, leading to depletion of macrophage iron, relatively low levels of serum ferritin, and liver iron loading. The consequences of IOL in patients with NTDT are multiple and multifactorial. Accurate and reliable methods of diagnosis and monitoring of body iron levels are essential, and the method of choice for measuring iron accumulation will depend on the patient's needs and on the available facilities. Iron chelation therapy (ICT) remains the backbone of NTDT management and is one of the most effective and practical ways of decreasing morbidity and mortality. The aim of this review is to describe the mechanism of IOL in NTDT, and the clinical complications that can develop as a result, in addition to the current and future therapeutic options available for the management of IOL in NTDT.

  19. Iron Overload and Chelation Therapy in Non-Transfusion Dependent Thalassemia

    Directory of Open Access Journals (Sweden)

    Rayan Bou-Fakhredin

    2017-12-01

    Full Text Available Iron overload (IOL due to increased intestinal iron absorption constitutes a major clinical problem in patients with non-transfusion-dependent thalassemia (NTDT, which is a cumulative process with advancing age. Current models for iron metabolism in patients with NTDT suggest that suppression of serum hepcidin leads to an increase in iron absorption and subsequent release of iron from the reticuloendothelial system, leading to depletion of macrophage iron, relatively low levels of serum ferritin, and liver iron loading. The consequences of IOL in patients with NTDT are multiple and multifactorial. Accurate and reliable methods of diagnosis and monitoring of body iron levels are essential, and the method of choice for measuring iron accumulation will depend on the patient’s needs and on the available facilities. Iron chelation therapy (ICT remains the backbone of NTDT management and is one of the most effective and practical ways of decreasing morbidity and mortality. The aim of this review is to describe the mechanism of IOL in NTDT, and the clinical complications that can develop as a result, in addition to the current and future therapeutic options available for the management of IOL in NTDT.

  20. Clinical and economic burden of infused iron chelation therapy in the United States.

    Science.gov (United States)

    Payne, Krista A; Desrosiers, Marie-Pierre; Caro, J Jaime; Baladi, Jean-François; Lordan, Noreen; Proskorovsky, Irina; Ishak, Khajak; Rofail, Diana

    2007-10-01

    Patients requiring chronic blood transfusions are at risk for iron overload, which, if not treated by iron chelation therapy (ICT), can create serious organ damage and reduce life expectancy. Current ICT requires burdensome 8- to 12-hour infusions five to seven times per week. A naturalistic study of the burden of infused ICT was conducted in four US centers. Data from the initial and most recent years of ICT were collected from medical charts of consenting thalassemia (n = 40) and sickle cell disease (n = 9) patients. Quality of life (QoL), treatment satisfaction, and ICT-related resource utilization data were also collected from a patient interview. Mean serum ferritin levels during the initial (2519 +/- 1382 ng/mL) and most recent (2741 +/- 2532 ng/mL) years remained unacceptably high and increased over time (306 +/- 2200 ng/mL; mean of 20+/- years of therapy). Within 30 days before interview, 55 percent of patients suffered at least one ICT-related adverse event; 76 percent missed at least one dose. QoL, measured by the SF-36, and treatment satisfaction appear compromised in this cohort. Although total annual costs of ICT were estimated at USD $30,000 to $35,000, drug accounted for only 50 to 60 percent of this amount. Infused ICT may not provide adequate effectiveness in the real world. High ferritin levels seem to be associated with ICT noncompliance, likely in relation to the bothersome mode of administration and side effects. The total cost of ICT appears to well exceed that of drug alone.

  1. EDTA chelation therapy alone and in combination with oral high-dose multivitamins and minerals for coronary disease: The factorial group results of the Trial to Assess Chelation Therapy.

    Science.gov (United States)

    Lamas, Gervasio A; Boineau, Robin; Goertz, Christine; Mark, Daniel B; Rosenberg, Yves; Stylianou, Mario; Rozema, Theodore; Nahin, Richard L; Terry Chappell, L; Lindblad, Lauren; Lewis, Eldrin F; Drisko, Jeanne; Lee, Kerry L

    2014-07-01

    Disodium ethylenediaminetetraacetic acid (EDTA) reduced adverse cardiac outcomes in a factorial trial also testing oral vitamins. This report describes the intent-to-treat comparison of the 4 factorial groups overall and in patients with diabetes. This was a double-blind, placebo-controlled, 2 × 2 factorial multicenter randomized trial of 1,708 post-myocardial infarction (MI) patients ≥50 years of age and with creatinine ≤2.0 mg/dL randomized to receive 40 EDTA chelation or placebo infusions plus 6 caplets daily of a 28-component multivitamin-multimineral mixture or placebo. The primary end point was a composite of total mortality, MI, stroke, coronary revascularization, or hospitalization for angina. Median age was 65 years, 18% were female, 94% were Caucasian, 37% were diabetic, 83% had prior coronary revascularization, and 73% were on statins. Five-year Kaplan-Meier estimates for the primary end point was 31.9% in the chelation + high-dose vitamin group, 33.7% in the chelation + placebo vitamin group, 36.6% in the placebo infusion + active vitamin group, and 40.2% in the placebo infusions + placebo vitamin group. The reduction in primary end point by double active treatment compared with double placebo was significant (hazard ratio 0.74, 95% CI 0.57-0.95, P = .016). In patients with diabetes, the primary end point reduction of double active compared with double placebo was more pronounced (hazard ratio 0.49, 95% CI 0.33-0.75, P < .001). In stable post-MI patients on evidence-based medical therapy, the combination of oral high-dose vitamins and chelation therapy compared with double placebo reduced clinically important cardiovascular events to an extent that was both statistically significant and of potential clinical relevance. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

  2. Removal of inhaled industrial mixed oxide aerosols from Beagle dogs by lung lavage and chelation therapy

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Mewhinney, J.A.; Eidson, A.F.; Guilmette, R.A.

    1978-01-01

    An experiment was conducted in 15 adult Beagle dogs to evaluate lung lavage and chelation therapy for the removal of inhaled particles of mixed actinide oxides. The dogs were divided into three groups of five dogs each. Each group was exposed to an aerosol from a different industrial process. Group 1 was exposed to mixed oxide material which had been calcined at 750 0 C collected from a ball milling process. Group 2 was exposed to mixed oxide material from a centerless grinding operation which had been previously heat treated to 1750 0 C. The third group was exposed to 239 PuO 2 not containing uranium from a V-blending procedure which had been heat treated at 850 0 C. After exposure, three dogs in each group were given ten lung lavages and 18 intravenous injections of calcium trisodium diethylenetriaminepentaacetate (DTPA). All dogs were sacrificed 64 days after inhalation exposure. The tissues were radioanalyzed for plutonium and americium. Fluorimetric analyses for uranium in the tissues are in progress. The urine, feces and lavage fluid are also being analyzed for plutonium, americium and uranium. The distribution of plutonium and americium expressed as percentages of the sacrifice body burden was similar in the tissues of the treated and unteated dogs. The lungs contained most of the radionuclides with a small amount in the liver, skeleton and tracheobronchial lymph nodes. The percentage of the sacrifice body burden of americium and plutonium that was present in the lung was less in the treated dogs and was higher in the TBLN's and skeleton than in the untreated dogs. The ratio of Pu/Am was higher in the lungs than in the original material obtained from the industrial sites suggesting a shorter retention time for americium than plutonium to 64 days in the dog

  3. Iron chelation therapy: clinical effectiveness, economic burden and quality of life in patients with iron overload.

    Science.gov (United States)

    Payne, Krista A; Rofail, Diana; Baladi, Jean-François; Viala, Muriel; Abetz, Linda; Desrosiers, Marie-Pierre; Lordan, Noreen; Ishak, Khajak; Proskorovsky, Irina

    2008-08-01

    This study of UK patients examines clinical, health-related quality of life (HRQOL) and economic outcomes associated with iron chelation therapy (ICT). Desferrioxamine (DFO) (Desferal; Novartis, Switzerland) and Deferiprone (Ferriprox; Apotex, Canada) are ICTs used to treat iron overload. DFO requires 8-to 12-hour infusions a minimum of five times per week. Deferiprone is administered in an oral daily regimen. Although pharmacologically efficacious, clinical effectiveness of ICT within the real-world setting is yet to be fully elucidated. A naturalistic cohort study of 60 patients (beta-thalassaemia, n=40; sickle cell disease, n=14; myelodysplastic syndromes, n=6; 63% female) receiving ICT in four UK treatment centres was conducted. Serum ferritin level data were abstracted from medical charts. Compliance, HRQOL, satisfaction and resource utilisation data were collected from interviews. Maximum ICT costs were estimated using the resource utilisation data associated with DFO. Mean serum ferritin levels, generally, remained elevated despite ICT. Compliance was suboptimal and HRQOL scores were lower than population norms. The total estimated mean weighted annual per-patient cost of DFO treatment was approximately pound19,000. DFO-related equipment, DFO drug, and home healthcare were estimated to account for 43%, 19% and 24% of costs, respectively. Other more minor components of total annual costs were for in-patient infusions, ICT home delivery services and monitoring costs. Generally, patients are not achieving target serum ferritin thresholds despite chronic treatment for iron overload. ICT appears to negatively impact HRQOL; compliance with ICT is poor; and, in the case of DFO, treatment costs well exceed the cost of DFO alone. These results suggest that current ICT in the real-world setting is suboptimal with respect to various clinical, HRQOL and economic outcomes.

  4. Experimental lead intoxication in dogs: a comparison of blood lead and urinary delta-aminolevulinic acid following intoxication and chelation therapy.

    Science.gov (United States)

    Green, R A; Selby, L A; Zumwalt, R W

    1978-01-01

    Intravenous lead administration to dogs produced an acute syndrome of lead intoxication charcterized by depression, vomiting, anorexia and weight loss. The effect of chelation therapy with calcium disodium ethylene diamine tetraacetate, penicillamine or both was determined by serially monitoring changes in blood lead and urine delta-aminolevulinic acid. Following therapy, blood lead values were significantly lower in chelated dogs than non-treated lead exposed dogs on days 7 and 10. Urine delta-aminolevulinic acid at day 7 was significantly higher in untreated lead exposed dogs than in other groups. There was no significant difference in blood lead or urine delta-aminolevulinic acid between lead intoxicated dogs which underwent the indicated chelation therapy protocols. There was, however, a trend for higher urinary delta-aminolevulinic acid excretion in those intoxicated dogs undergoing calcium disodium ethylene diamine tetraacetate therapy as opposed to those undergoing penicilamine therapy. There was no significant correlation between blood lead and urinary delta-aminolevulinic acid previous to lead exposure. However, after lead exposure significant correlation was present at days 4, 7, 10 and 14. Certain lead exposed dogs following chelation therapy were noted to have normal blood lead levels but elevated urinary delta-aminolevulinic acid suggesting that blood lead does not always correlate with metabolic effects of lead in the body. Urinary delta-aminolevulinic acid was therefore recommended as an additional laboratory parameter which improved assessment of lead exposure in dogs, particularly in determining adequacy of chelation therapy. PMID:667707

  5. Modeling the effect of succimer (DMSA; dimercaptosuccinic acid) chelation therapy in patients poisoned by lead

    NARCIS (Netherlands)

    van Eijkeren, Jan C H; Olie, J. Daniël N; Bradberry, Sally M; Vale, J Allister; de Vries, Irma; Clewell, Harvey J.; Meulenbelt, Jan; Hunault, Claudine C

    CONTEXT: Kinetic models could assist clinicians potentially in managing cases of lead poisoning. Several models exist that can simulate lead kinetics but none of them can predict the effect of chelation in lead poisoning. Our aim was to devise a model to predict the effect of succimer

  6. Consequences and costs of noncompliance with iron chelation therapy in patients with transfusion-dependent thalassemia: a literature review.

    Science.gov (United States)

    Delea, Thomas E; Edelsberg, John; Sofrygin, Oleg; Thomas, Simu K; Baladi, Jean-Francois; Phatak, Pradyumna D; Coates, Thomas D

    2007-10-01

    Patients with thalassemia major require iron chelation therapy (ICT) to prevent complications from transfusional iron overload. Deferoxamine is effective, but requires administration as a slow continuous subcutaneous or intravenous infusion five to seven times per week. Deferiprone is a three-times-daily oral iron chelator, but has limited availability in the United States. Deferasirox is a once-daily oral iron chelator that was approved in the United States in 2005 for patients older than 2 years of age with transfusional iron overload. Published evidence on rates of compliance with ICT and the association between compliance, and the incidence and costs of complications of iron overload, in patients with thalassemia major was reviewed. A total of 18 studies were identified reporting data on compliance with ICT, including 7 that examined deferoxamine only, 6 that examined deferiprone only, and 5 that compared deferoxamine and deferiprone; no studies reporting compliance with deferasirox were identified. In studies of deferoxamine only, estimated mean compliance ranged from 59 to 78 percent. Studies of deferiprone generally reported better compliance, ranging from 79 to 98 percent. Results of comparative studies of deferoxamine and deferiprone suggest that compliance may be better with oral therapy. Numerous studies demonstrate that that poor compliance with ICT results in increased risk of cardiac disease and endocrinopathies, as well as lower survival. Although data on the costs of noncompliance are limited, a recent model-based study estimated the lifetime costs of inadequate compliance with deferoxamine to be $33,142. Inadequate compliance with ICT in thalassemia major is common and results in substantial morbidity and mortality, as well as increased costs.

  7. New Insights in the Design of Bioactive Peptides and Chelating Agents for Imaging and Therapy in Oncology

    Directory of Open Access Journals (Sweden)

    Anna Lucia Tornesello

    2017-08-01

    Full Text Available Many synthetic peptides have been developed for diagnosis and therapy of human cancers based on their ability to target specific receptors on cancer cell surface or to penetrate the cell membrane. Chemical modifications of amino acid chains have significantly improved the biological activity, the stability and efficacy of peptide analogues currently employed as anticancer drugs or as molecular imaging tracers. The stability of somatostatin, integrins and bombesin analogues in the human body have been significantly increased by cyclization and/or insertion of non-natural amino acids in the peptide sequences. Moreover, the overall pharmacokinetic properties of such analogues and others (including cholecystokinin, vasoactive intestinal peptide and neurotensin analogues have been improved by PEGylation and glycosylation. Furthermore, conjugation of those peptide analogues to new linkers and bifunctional chelators (such as AAZTA, TETA, TRAP, NOPO etc., produced radiolabeled moieties with increased half life and higher binding affinity to the cognate receptors. This review describes the most important and recent chemical modifications introduced in the amino acid sequences as well as linkers and new bifunctional chelators which have significantly improved the specificity and sensitivity of peptides used in oncologic diagnosis and therapy.

  8. Satisfaction and adherence in patients with iron overload receiving iron chelation therapy as assessed by a newly developed patient instrument.

    Science.gov (United States)

    Rofail, Diana; Abetz, Linda; Viala, Muriel; Gait, Claire; Baladi, Jean-Francois; Payne, Krista

    2009-01-01

    This study assesses satisfaction with iron chelation therapy (ICT) based on a reliable and valid instrument, and explores the relationship between satisfaction and adherence to ICT. Patients in the USA and UK completed a new "Satisfaction with ICT" (SICT) instrument consisting of 28 items, three pertaining to adherence. Simple and multivariate regression analyses assessed the relationship between satisfaction with different aspects of ICT and adherence. First assessments of the SICT instrument indicate its validity and reliability. Recommended thresholds for internal consistency, convergent validity, discriminant validity, and floor and ceiling effects were met. A number of variables were identified in the simple linear regression analyses as significant predictors of "never thinking about stopping ICT," a proxy for adherence. These significant variables were entered into the multivariate model to assess the combined factor effects, explaining 42% of the total variance of "never thinking about stopping ICT." A significant and positive relationship was demonstrated between "never thinking about stopping ICT" and age (P = 0.04), Perceived Effectiveness of ICT (P = 0.003), low Burden of ICT (P = 0.002), and low Side Effects of ICT (P = 0.01). The SICT is a reliable and valid instrument which will be useful in ICT clinical trials. Furthermore, the administration of ICT by slow subcutaneous infusion negatively impacts on satisfaction with ICT which was shown to be a determinant of adherence. This points to the need for new more convenient and less burdensome oral iron chelators to increase adherence, and ultimately to improve patient outcomes.

  9. Biological behavior of 188Re-biotin chelate for multistep therapy with the avidin-biotin system

    International Nuclear Information System (INIS)

    Choi, T. H.; Ahn, S. H.; Choi, C. W.; Woo, K. S.; Jung, W. S.; Lim, S. J.; Lim, S. M.

    1999-01-01

    The purpose of this study was to test the three-step targeting of tumors in mice using biotinylated antibody, streptavidin and radiolabeled biotin for radioimmunotherapy (RAIT). Three-step pretargetting can potentially decreases harmful radiation to normal tissues in radioimmunotherapy. 188 Re from 188 W- 188 Re generator, is recently introduced in therapeutic nuclear medicine and made it possible to use whenever needed. We studied biotin-chelates MGB for use in the avidin/biotin pretargetting system. Chelates that hold radiometals with high stability under physiological conditions are essential to avoid excessive radiation damage to non-target cells. We synthesized MAG 2 GABA-Biocytin (MGB), labeled with 188 Re and evaluated biological behavior of 188 Re-MGB. biotinyl MAG 2 GABA bind the therapeutic radiometal 188 Re with excellent in vitro stability and have the required physiological properties for pretargetted therapy. In normal mice, 188 Re-MGB was excreted via hepatobiliary pathway, %ID/g of GI tract was 52.1 at 120min. In Raji cells tumor bearing nude mice, liver and colon were higher than those of normal mouse. Tumor uptake at 120min was 0.05%ID/g. 188 Re-MGB may have a role in pretargetted radioimmunotherapy

  10. Competition of dipositive metal ions for Fe (III) binding sites in chelation therapy of Iron Load

    International Nuclear Information System (INIS)

    Rehmani, Fouzia S.

    2005-01-01

    Iron overload is a condition in which excessive iron deposited in the liver, kidney and spleen of human beings in the patients of beta thalassemia and sickle cell anemia. Instead of its importance iron could be toxic when in excess, it damages the tissues. For the treatment of iron overload, a drug desferrioxamine mesylate has been used. It is linear trihydroxamic acid, a natural siderophore produced by streptomyces which removes the extra iron from body. Salicylhydroxamate type siderphore. In present research salicylhydroxamate was used for the complexation with dipositive metal ions which are available in biological environments such as Mn (II), Co (II), Ni (II) and Cu (II). The aim of our work was to study the competition reactions between Fe (III) and other dipositive ions; to calculate the thermodynamic data of chelation of these metal ions complexes with hydroxamate by computer program and comparison with hydroxamate complexes. (author)

  11. 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.

  12. 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.

  13. Cost effectiveness of once-daily oral chelation therapy with deferasirox versus infusional deferoxamine in transfusion-dependent thalassaemia patients: US healthcare system perspective.

    Science.gov (United States)

    Delea, Thomas E; Sofrygin, Oleg; Thomas, Simu K; Baladi, Jean-Francois; Phatak, Pradyumna D; Coates, Thomas D

    2007-01-01

    Deferasirox is a recently approved once-daily oral iron chelator that has been shown to reduce liver iron concentrations and serum ferritin levels to a similar extent as infusional deferoxamine. To determine the cost effectiveness of deferasirox versus deferoxamine in patients with beta-thalassaemia major from a US healthcare system perspective. A Markov model was used to estimate the total additional lifetime costs and QALYs gained with deferasirox versus deferoxamine in patients with beta-thalassaemia major and chronic iron overload from blood transfusions. Patients were assumed to be 3 years of age at initiation of chelation therapy and to receive prescribed dosages of deferasirox and deferoxamine that have been shown to be similarly effective in such patients. Compliance with chelation therapy and probabilities of iron overload-related cardiac disease and death by degree of compliance were estimated using data from published studies. Costs ($US, year 2006 values) of deferoxamine administration and iron overload-related cardiac disease were based on analyses of health insurance claims of transfusion-dependent thalassaemia patients. Utilities were based on a study of patient preferences for oral versus infusional chelation therapy, as well as published literature. Probabilistic and deterministic sensitivity analyses were employed to examine the robustness of the results to key assumptions. Deferasirox resulted in a gain of 4.5 QALYs per patient at an additional expected lifetime cost of $US126,018 per patient; the cost per QALY gained was $US28,255. The cost effectiveness of deferasirox versus deferoxamine was sensitive to the estimated costs of deferoxamine administration and the quality-of-life benefit associated with oral versus infusional therapy. Cost effectiveness was also relatively sensitive to the equivalent daily dose of deferasirox, and the unit costs of deferasirox and deferoxamine, and was more favourable in younger patients. Results of this analysis

  14. Patient Affected by Beta-Propeller Protein-Associated Neurodegeneration: A Therapeutic Attempt with Iron Chelation Therapy

    Directory of Open Access Journals (Sweden)

    Mattia Fonderico

    2017-08-01

    Full Text Available Here, we report the case of a 36-year-old patient with a diagnosis of de novo mutation of the WDR45 gene, responsible for beta-propeller protein-associated neurodegeneration, a phenotypically distinct, X-linked dominant form of Neurodegeneration with Brain Iron Accumulation. The clinical history is characterized by a relatively stable intellectual disability and a hypo-bradykinetic and hypertonic syndrome with juvenile onset. Genetic investigations and T1 and T2-weighted MR images align with what is described in literature. The patient was also subjected to PET with 18-FDG investigation and DaT-Scan study. In reporting relevant clinical data, we want to emphasize the fact that the patient received a chelation therapy with deferiprone (treatment already used in other forms of NBIA with encouraging results, which, however, had to be interrupted because the parkinsonian symptoms worsened. Conversely, the patient has benefited from non-drug therapies and, in particular, from an adapted motor activity with assisted pedaling (method in the process of validation in treatments of parkinsonian syndromes, which started before the treatment with deferiprone and still continues.

  15. Hybrid Calcium Phosphate-Polymeric Micelles Incorporating Gadolinium Chelates for Imaging-Guided Gadolinium Neutron Capture Tumor Therapy.

    Science.gov (United States)

    Mi, Peng; Dewi, Novriana; Yanagie, Hironobu; Kokuryo, Daisuke; Suzuki, Minoru; Sakurai, Yoshinori; Li, Yanmin; Aoki, Ichio; Ono, Koji; Takahashi, Hiroyuki; Cabral, Horacio; Nishiyama, Nobuhiro; Kataoka, Kazunori

    2015-06-23

    Gadolinium (Gd) chelates-loaded nanocarriers have high potential for achieving magnetic resonance imaging (MRI)-guided Gd neutron capture therapy (GdNCT) of tumors. Herein, we developed calcium phosphate micelles hybridized with PEG-polyanion block copolymers, and incorporated with the clinical MRI contrast agent Gd-diethylenetriaminepentaacetic acid (Gd-DTPA/CaP). The Gd-DTPA/CaP were nontoxic to cancer cells at the concentration of 100 μM based on Gd-DTPA, while over 50% of the cancer cells were killed by thermal neutron irradiation at this concentration. Moreover, the Gd-DTPA/CaP showed a dramatically increased accumulation of Gd-DTPA in tumors, leading to the selective contrast enhancement of tumor tissues for precise tumor location by MRI. The enhanced tumor-to-blood distribution ratio of Gd-DTPA/CaP resulted in the effective suppression of tumor growth without loss of body weight, indicating the potential of Gd-DTPA/CaP for safe cancer treatment.

  16. Is DTPA a good competing chelating agent for Th(IV) in human serum and suitable in targeted alpha therapy?

    Science.gov (United States)

    Le Du, Alicia; Sabatié-Gogova, Andrea; Morgenstern, Alfred; Montavon, Gilles

    2012-04-01

    The interaction between thorium and human serum components was studied using difference ultraviolet spectroscopy (DUS), ultrafiltration and high-pressure-anion exchange chromatography (HPAEC) with external inductively conducted plasma mass spectrometry (ICP-MS) analysis. Experimental data are compared with modelling results based on the law of mass action. Human serum transferrin (HSTF) interacts strongly with Th(IV), forming a ternary complex including two synergistic carbonate anions. This complex governs Th(IV) speciation under blood serum conditions. Considering the generally used Langmuir-type model, values of 10(33.5) and 10(32.5) were obtained for strong and weak sites, respectively. We showed that trace amounts of diethylene triamine pentaacetic acid (DTPA) cannot complex Th(IV) in the blood serum at equilibrium. Unexpectedly this effect is not related to the competition with HSTF but is due to the strong competition with major divalent metal ions for DTPA. However, Th-DTPA complex was shown to be stable for a few hours when it is formed before addition in the biological medium; this is related to the high kinetic stability of the complex. This makes DTPA a potential chelating agent for synthesis of (226)Th-labelled biomolecules for application in targeted alpha therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. The removal of inhaled 239Pu from beagle dogs by bronchopulmonary lavage and chelation therapy

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Mewhinney, J.A.; Slauson, D.O.; Miglio, J.J.; Ruoff, L.; Mersch, S.; McClellan, R.O.

    1976-01-01

    The efficacy of bronchopulmonary lavage and chelatan therapy for removing 239 Pu from beagle dogs after inhalation of 239 Pu aerosols having different solubilities has been investigated. The four aerosols used were nebulized from a solution of 239 PuCl 4 and heat treated at temperatures of 325, 600, 900 and 1150 0 C. Groups of six beagle dogs were exposed to each of the aerosols. Subsequently, three dogs in each group were treated by lavage and intravenous injections of DTPA. The remaining three dogs in each group served as untreated controls. It was found that bronchopulmonary lavage treatment was effective in removing nearly half of the 239 Pu activity from the lung regardless of the aerosol production temperature. This early removal of 239 Pu activity resulted in a significant reduction in daily dose rate and therefore cumulative α dose to lung. The effectiveness of DTPA treatment depended on aerosol production temperature, and was effective in reducing accumulation of 239 Pu in liver and skeleton of the dogs that inhaled aerosols produced at 325 0 and 600 0 C by enhancing urinary excretion of 239 Pu. (U.K.)

  18. Magnetic Resonance Imaging of Therapy-Induced Necrosis Using Gadolinium-Chelated Polyglutamic Acids

    International Nuclear Information System (INIS)

    Jackson, Edward F.; Esparza-Coss, Emilio; Wen Xiaoxia; Ng, Chaan S.; Daniel, Sherita L.; Price, Roger E.; Rivera, Belinda; Charnsangavej, Chusilp; Gelovani, Juri G.; Li Chun

    2007-01-01

    Purpose: Necrosis is the most common morphologic alteration found in tumors and surrounding normal tissues after radiation therapy or chemotherapy. Accurate measurement of necrosis may provide an early indication of treatment efficacy or associated toxicity. The purpose of this report is to evaluate the selective accumulation of polymeric paramagnetic magnetic resonance (MR) contrast agents-gadolinium p-aminobenzyl-diethylenetriaminepentaacetic acid-poly(glutamic acid) (L-PG-DTPA-Gd and D-PG-DTPA-Gd)-in necrotic tissue. Methods and Materials: Two different solid tumor models, human Colo-205 xenograft and syngeneic murine OCA-1 ovarian tumors, were used in this study. Necrotic response was induced by treatment with poly(L-glutamic acid)-paclitaxel conjugate (PG-TXL). T 1 -weighted spin-echo images were obtained immediately and up to 4 days after contrast injection and compared with corresponding histologic specimens. Two low-molecular-weight contrast agents, DTPA-Gd and oligomeric(L-glutamic acid)-DTPA-Gd, were used as nonspecific controls. Results: Initially, there was minimal tumor enhancement after injection of either L-PG-DTPA-Gd or D-PG-DTPA-Gd, but rapid enhancement after injection of low-molecular-weight agents. However, polymeric contrast agents, but not low-molecular-weight contrast agents, caused sustained enhancement in regions of tumor necrosis in both tumors treated with PG-TXL and untreated tumors. These data indicate that high molecular weight, rather than in vivo biodegradation, is necessary for the specific localization of polymeric MR contrast agents to necrotic tissue. Moreover, biotinylated L-PG-DTPA-Gd colocalized with macrophages in the tumor necrotic areas, suggesting that selective accumulation of L- and D-PG-DTPA-Gd in necrotic tissue was mediated through residing macrophages. Conclusions: Our data suggest that MR imaging with PG-DTPA-Gd may be a useful technique for noninvasive characterization of treatment-induced necrosis

  19. An instrument assessing satisfaction with iron chelation therapy: Psychometric testing from an open-label clinical trial.

    Science.gov (United States)

    Rofail, Diana; Viala, Muriel; Gater, Adam; Abetz-Webb, Linda; Baladi, Jean-Francois; Cappellini, Maria Domenica

    2010-08-01

    The Satisfaction with Iron Chelation Therapy (SICT) instrument was developed based on a literature review, in-depth patient and clinician interviews, and cognitive debriefing interviews. An, open-label, single arm, multicenter trial evaluating the efficacy and safety of deferasirox in patients diagnosed with transfusion-dependent iron overload, provided an opportunity to assess the psychometric measurement properties of the instrument. Psychometric analyses were performed using data at baseline from 273 patients with a range of transfusion-dependent iron overload conditions who were participating in a multinational study. Responsiveness was further evaluated for all patients who also had subsequent satisfaction domain scores collected at week 4. Baseline SICT domain scores had acceptable floor and ceiling effects and internal consistency reliability (Cronbach's alpha: 0.75-0.85). Item discriminant and item convergent validity were both excellent although one item in each analysis did not meet the specified criterion. Small to moderate correlations were observed between SICT and Short Form 36 Health Survey (SF-36) domain scores. Patients with the highest levels of serum ferritin at baseline (>3100 ng/mL) were the least satisfied about the Perceived Effectiveness of ICT and vice versa. Satisfaction improved in all patients, although there were no clear differences observed between groups of patients defined according to changes in serum ferritin levels from baseline to week 4 (stable, improved, or worsened). The SICT domains are reliable and valid. Further testing using a more specific criterion (such as assessing patient global ratings of change in satisfaction domains that correspond to the SICT domains) could help to establish with greater confidence the responsiveness of the instrument.

  20. Multicenter COMPACT study of COMplications in patients with sickle cell disease and utilization of iron chelation therapy.

    Science.gov (United States)

    Jordan, Lanetta; Adams-Graves, Patricia; Kanter-Washko, Julie; Oneal, Patricia A; Sasane, Medha; Vekeman, Francis; Bieri, Christine; Magestro, Matthew; Marcellari, Andrea; Duh, Mei Sheng

    2015-03-01

    Over the past few decades, lifespans of sickle cell disease (SCD) patients have increased; hence, they encounter multiple complications. Early detection, appropriate comprehensive care, and treatment may prevent or delay onset of complications. We collected longitudinal data on sickle cell disease (SCD) complication rates and associated resource utilization relative to blood transfusion patterns and iron chelation therapy (ICT) use in patients aged ≥16 years to address a gap in the literature. Medical records of 254 SCD patients ≥16 years were retrospectively reviewed at three US tertiary care centers. We classified patients into cohorts based on cumulative units of blood transfused and ICT history: ICT (Cohort 1 [C1]), ≥15 units, no ICT (Cohort 2 [C2]), and ≥15 units with ICT (Cohort 3 [C3]). We report SCD complication rates per patient per year; cohort comparisons use rate ratios (RRs). Cohorts had 69 (C1), 91 (C2), and 94 (C3) patients. Pain led to most hospitalizations (76%) and emergency department (ED) (82%) visits. Among transfused patients (C2+C3), those receiving ICT were less likely to experience SCD complications than those who did not (RR [95% CI] C2 vs. C3: 1.33 [1.25-1.42]). Similar trends (RR [95% CI]) were observed in ED visits and hospitalizations associated with SCD complications (C2 vs. C3, ED: 1.94 [1.70-2.21]; hospitalizations: 1.61 [1.45-1.78]), but not in outpatient visits. Although the most commonly reported SCD complication among all patients was pain, patients who received ICT were less likely to experience pain and other complications than those who did not. These results highlight the need for increased patient and provider education on the importance of comprehensive disease management.

  1. Chelating polymeric membranes

    KAUST Repository

    Peinemann, Klaus-Viktor; Villalobos Vazquez de la Parra, Luis Francisco; Hilke, Roland

    2015-01-01

    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.

  2. 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...

  3. 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

  4. Role of vitamin C as an adjuvant therapy to different iron chelators in young β-thalassemia major patients: efficacy and safety in relation to tissue iron overload.

    Science.gov (United States)

    Elalfy, Mohsen S; Saber, Maha M; Adly, Amira Abdel Moneam; Ismail, Eman A; Tarif, Mohamed; Ibrahim, Fatma; Elalfy, Omar M

    2016-03-01

    Vitamin C, as antioxidant, increases the efficacy of deferoxamine (DFO). To investigate the effects of vitamin C as an adjuvant therapy to the three used iron chelators in moderately iron-overloaded young vitamin C-deficient patients with β-thalassemia major (β-TM) in relation to tissue iron overload. This randomized prospective trial that included 180 β-TM vitamin C-deficient patients were equally divided into three groups (n = 60) and received DFO, deferiprone (DFP), and deferasirox (DFX). Patients in each group were further randomized either to receive vitamin C supplementation (100 mg daily) or not (n = 30). All patients received vitamin C (group A) or no vitamin C (group B) were followed up for 1 yr with assessment of transfusion index, hemoglobin, iron profile, liver iron concentration (LIC) and cardiac magnetic resonance imaging (MRI) T2*. Baseline vitamin C was negatively correlated with transfusion index, serum ferritin (SF), and LIC. After vitamin C therapy, transfusion index, serum iron, SF, transferrin saturation (Tsat), and LIC were significantly decreased in group A patients, while hemoglobin and cardiac MRI T2* were elevated compared with baseline levels or those in group B without vitamin C. The same improvement was found among DFO-treated patients post-vitamin C compared with baseline data. DFO-treated patients had the highest hemoglobin with the lowest iron, SF, and Tsat compared with DFP or DFX subgroups. Vitamin C as an adjuvant therapy possibly potentiates the efficacy of DFO more than DFP and DFX in reducing iron burden in the moderately iron-overloaded vitamin C-deficient patients with β-TM, with no adverse events. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Chelating agents in pharmacology, toxicology and therapeutics

    International Nuclear Information System (INIS)

    1988-01-01

    The proceedings contain 71 abstracts of papers. Fourteen abstracts were inputted in INIS. The topics covered include: the effects of chelating agents on the retention of 63 Ni, 109 Cd, 203 Hg, 144 Ce, 95 Nb and the excretion of 210 Po, 63 Ni, 48 V, 239 Pu, 241 Am, 54 Mn; the applications of tracer techniques for studies of the efficacy of chelation therapy in patients with heart and brain disorders; and the treatment of metal poisoning with chelating agents. (J.P.)

  6. Overview of current chelation practices

    Directory of Open Access Journals (Sweden)

    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

  7. Effect of high-dose oral multivitamins and minerals in participants not treated with statins in the randomized Trial to Assess Chelation Therapy (TACT).

    Science.gov (United States)

    Issa, Omar M; Roberts, Rhonda; Mark, Daniel B; Boineau, Robin; Goertz, Christine; Rosenberg, Yves; Lewis, Eldrin F; Guarneri, Erminia; Drisko, Jeanne; Magaziner, Allan; Lee, Kerry L; Lamas, Gervasio A

    2018-01-01

    In a prespecified subgroup analysis of participants not on statin therapy at baseline in the TACT, a high-dose complex oral multivitamins and multimineral regimen was found to have a large unexpected benefit compared with placebo. The regimen tested was substantially different from any vitamin regimen tested in prior clinical trials. To explore these results, we performed detailed additional analyses of participants not on statins at enrollment in TACT. TACT was a factorial trial testing chelation treatments and a 28-component high-dose oral multivitamins and multiminerals regimen versus placebo in post-myocardial infarction (MI) patients 50 years or older. There were 460 (27%) of 1,708 TACT participants not taking statins at baseline, 224 (49%) were in the active vitamin group and 236 (51%) were in the placebo group. Patients were enrolled at 134 sites around the United States and Canada. Daily high-dose oral multivitamins and multiminerals (6 tablets, active or placebo). The primary end point of TACT was time to the first occurrence of any component of the composite end point: all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for angina. The primary end point occurred in 137 nonstatin participants (30%), of which 51 (23%) of 224 were in the active group and 86 (36%) of 236 were taking placebo (hazard ratio, 0.62; 95% confidence interval, 0.44-0.87; P=.006). Results in the key TACT secondary end point, a combination of cardiovascular mortality, stroke, or recurrent MI, was consistent in favoring the active vitamin group (hazard ratio, 0.46; 95% confidence interval, 0.28-0.75; P=.002). Multiple end point analyses were consistent with these results. High-dose oral multivitamin and multimineral supplementation seem to decrease combined cardiac events in a stable, post-MI population not taking statin therapy at baseline. These unexpected findings are being retested in the ongoing TACT2. Copyright © 2017 The Authors. Published by Elsevier

  8. Iron overload in lower international prognostic scoring system risk patients with myelodysplastic syndrome receiving red blood cell transfusions: Relation to infections and possible benefit of iron chelation therapy.

    Science.gov (United States)

    Wong, Colleen A C; Wong, Shannon A Y; Leitch, Heather A

    2018-04-01

    An increased incidence of infections and infectious mortality has been reported in myelodysplastic syndromes (MDS) patients receiving red blood cell (RBC) transfusions. We examined incidence of infections requiring antibiotics, antifungal or antiviral medications in transfused lower International Prognostic Scoring System (IPSS) risk MDS patients and whether this differed with iron chelation therapy (ICT). 138 transfused MDS patients were lower IPSS risk. 59 received ICT; median duration was 13 months. There was no significant difference between groups in neutrophil count at first RBC transfusion or first infection. Infections included: bacterial, n = 88; viral; fungal; and mycobacterial; n = 2 each. In ICT and non-ICT patients, respectively, infections were (number [%]): patients, 23 (40.0%) and 22 (27.8%); episodes (median [range]), 2 (1-6) and 2 (1-5); hospitalizations, 16 (27.1%) and 8 (10.1%); and deaths, 0 (0%) and 1 (1.3%), p = NS for all. Median overall survival (OS) from first RBC transfusion was superior in ICT patients, p = 0.01, and remained significant in a multivariate analysis (MVA), p = 0.003. Median time to first infection (TTI) was 27 and 7.8 months, respectively, p < 0.0001, and ICT remained significant for TTI in an MVA, p = 0.02, hazard ratio 0.3. For ICT patients with blast count <5%, TTI was significantly superior (p = 0.004). In this retrospective analysis, for lower IPSS risk MDS patients receiving RBC transfusions, though number and type of infections were similar between groups and despite similar neutrophil counts, time to first infection was significantly longer in ICT patients (p < 0.0001). These results should be confirmed in larger, prospective analyses. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. 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.

  10. Mixed ligand chelate therapy for plutonium and toxic metals from energy power production. Final report, April 15, 1977-October 14, 1980

    International Nuclear Information System (INIS)

    Schubert, J.

    1980-01-01

    The results of experiments are summarized on the ability of combinations of chelating agents to modify the genotoxicity or tissue distributions. The mutagenicities of Cr and of chelating agents were determined. The metals described in the report are Pu(IV), Cd(II), Cr(III), and Cr(VI). Accurate measurements were made of the ability of CaNa 2 EDTA, CaNa 3 DTPA, and DMPS to reduce mortality in mice given doses (i.p.) of CdCl 2 well above the 100% lethal level. The efficacy in terms of the mmoles/kg needed to reduce the mortality was: DTPA > EDTA > DMPS. The combination of DTPA + DMPS proved most promising though little evidence for mixed complex formation was noted. Potentiometric titration studies the case of Pu(IV) a few combinations proved effective, but only when given shortly after Pu administration and then only in the liver but not the skeleton. It is recommended that metabolically stable chelating agents be used in combinations, especially for those combinations which may form very stable mixed ligand chelates

  11. Chelation in metal intoxication

    DEFF Research Database (Denmark)

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

    2015-01-01

    The present review provides an update of the general principles for the investigation and use of chelating agents in the treatment of intoxications by metals. The clinical use of the old chelators EDTA (ethylenediamine tetraacetate) and BAL (2,3-dimercaptopropanol) is now limited due to the incon......The present review provides an update of the general principles for the investigation and use of chelating agents in the treatment of intoxications by metals. The clinical use of the old chelators EDTA (ethylenediamine tetraacetate) and BAL (2,3-dimercaptopropanol) is now limited due...... to the inconvenience of parenteral administration, their own toxicity and tendency to increase the neurotoxicity of several metals. The hydrophilic dithiol chelators DMSA (meso-2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercapto-propanesulphonate) are less toxic and more efficient than BAL in the clinical treatment...... 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...

  12. 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

  13. Review of actinide decorporation with chelating agents

    Energy Technology Data Exchange (ETDEWEB)

    Ansoborlo, E. [CEA Valrho, Dir. de l' Energie Nucleaire (DEN/DRCP/CETAMA), 30 - Marcoule (France); Amekraz, B.; Moulin, Ch. [CEA Saclay, Dept. de Physico-Chimie (DEN/DPC/SECR), 91 - Gif sur Yvette (France); Moulin, V. [CEA Saclay, Dir. du Developpement et de l' Innovation Nucleares (DEN/DDIN/MR), 91 - Gif Sur Yvette (France); Taran, F. [CEA Saclay (DSV/DBJC/SMMCB), 91 - Gif-sur-Yvette (France); Bailly, Th.; Burgada, R. [Centre National de la Recherche Scientifique (CNRS/LCSB/UMR 7033), 93 - Bobigny (France); Henge-Napoli, M.H. [CEA Valrho, Site de Marcoule (INSTN), 30 (France); Jeanson, A.; Den Auwer, Ch.; Bonin, L.; Moisy, Ph. [CEA Valrho, Dir. de l' Energie Nucleaire (DEN/DRCP/SCPS), 30 - Marcoule (France)

    2007-10-15

    In case of accidental release of radionuclides in a nuclear facility or in the environment, internal contamination (inhalation, ingestion or wound) with actinides represents a severe health risk to human beings. It is therefore important to provide effective chelation therapy or decorporation to reduce acute radiation damage, chemical toxicity, and late radiation effects. Speciation governs bioavailability and toxicity of elements and it is a prerequisite tool for the design and success of new ligands or chelating agents. The purpose of this review is to present the state-of-the-art of actinide decorporation within biological media, to recall briefly actinide metabolism, to list the basic constraints of actinide-ligand for development, to describe main tools developed and used for decorporation studies, to review mainly the chelating agents tested for actinides, and finally to conclude on the future trends in this field. (authors)

  14. 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

  15. A new tool for the assessment of satisfaction with iron chelation therapy (ICT-Sat) for patients with β-thalassemia major.

    Science.gov (United States)

    Elalfy, Mohsen S; Massoud, Walid; Elsherif, Nayera H; Labib, Jonair H; Elalfy, Omar M; Elaasar, Safaa; von Mackensen, Sylvia

    2012-06-01

    High satisfaction with iron chelation is a major determinant for adherence to ICT in beta-thalassaemia major (β-TM) patients. In this study, a new tool to assess different domains of satisfaction for available forms of ICT was developed and validated. The impact of patients' satisfaction with ICT has been tested. Items were generated via focus groups and a preliminary version with 24 items (ICT-Sat) with an additional item for treatment preference and a knowledge questionnaire (KQ) was developed. 170 β-TM patients from three Thalassaemia centers in Egypt, aged 2-32 years received three questionnaires to fill in; the new ICT-Sat, a KQ, and a previously validated tool for satisfaction with ICT (SICT) and retested 4-6 weeks later to ensure re-test reliability. Type of chelation, drug related adverse events, compliance with ICT, and serum ferritin level (SF) during the year prior to the study as well as available cardiac T2*data were recorded. One hundred and fifty two β-TM patients completed all questionnaires; median age was 12 years. The final 15 remaining ICT-Sat items, yielding to four domain scores, explained 70.6% of the total variance. The "perceived effectiveness" and "fear and worries" domains of the ICT-Sat correlated significantly with the domains "perceived effectiveness" and "acceptance" of the SICT. Patients treated with oral ICT were more satisfied with perceived effectiveness, and their side effects. A new clinically based ICT-Sat tool was developed and revealed good psychometric characteristics. Adherence to ICT was better correlated with "perceived effectiveness" and SF level. Copyright © 2012 Wiley Periodicals, Inc.

  16. 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.

  17. Relationship among chelator adherence, change in chelators, and quality of life in thalassemia.

    Science.gov (United States)

    Trachtenberg, Felicia L; Gerstenberger, Eric; Xu, Yan; Mednick, Lauren; Sobota, Amy; Ware, Hannah; Thompson, Alexis A; Neufeld, Ellis J; Yamashita, Robert

    2014-10-01

    Thalassemia, a chronic blood disease, necessitates life-long adherence to blood transfusions and chelation therapy to reduce iron overload. We examine stability of health-related quality of life (HRQOL) in thalassemia and adherence to chelation therapy over time, especially after changes in chelator choice. Thalassemia Longitudinal Cohort participants in the USA, UK, and Canada completed the SF-36v2 (ages 14+) and the PF-28 CHQ (parents of children health status) at baseline who made a single change in chelator, but declined among participants with multiple changes and/or high iron burden (worse health status). Mental health improved among participants with lower iron burden, but iron overload was negatively associated with social functioning. Adherence did not significantly change over follow-up except for an increase after a change from deferoxamine (DFO) infusion to oral deferasirox (p = 0.03). Predictors of lower adherence for adults/adolescents at follow-up included side effects, smoking, younger age, problems preparing DFO, increased number of days per week DFO prescribed, and lower physical quality of life . Strategies to balance medical needs with family, work, and personal life may assist in adherence.

  18. THE LAWFUL CONSEQUENCES OF BIRTH CERTIFICATE ON CHILDREN ABROGATION

    Directory of Open Access Journals (Sweden)

    Natasya Immanuela Sandjojo

    2017-12-01

    Full Text Available Research due to the law on the abrogation of birth certificates against children aims to know the effect of law affecting the child, as well as review of the determination and judgment in court that play a role in the birth certificate abrogation. This research describes the importance of birth certificate because of the low public awareness to perform birth registration. The study uses normative juridical research, which faces legal issues with the process of discovering legal rules, principles, and legal doctrines, with deductive methods, starting from the general thing and then generating specific and legitimate answers. Based on the results of the study, that the abrogation of birth certificate brings great lawful consequences for the child, especially the status and position of the child, as well as the right of alimentation,  which in this study included some examples of determination and court decision about the birth certificate abrogation.

  19. Ebselen abrogates TNFα induced pro‐inflammatory response in glioblastoma

    OpenAIRE

    Tewari, Richa; Sharma, Vivek; Koul, Nitin; Ghosh, Abhishek; Joseph, Christy; Hossain Sk, Ugir; Sen, Ellora

    2008-01-01

    We investigated the pro‐inflammatory response mediated by TNFα in glioblastoma and whether treatment with organoselenium Ebselen (2‐phenyl‐1,2‐benzisoselenazol‐3[2H]one) can affect TNFα induced inflammatory response. Exposure to TNFα increased the expression of pro‐inflammatory mediator interleukin IL‐6, IL‐8, monocyte chemoattractant protein‐1 (MCP‐1) and cyclooxygenase (COX‐2). Treatment with Ebselen abrogated TNFα induced increase in pro‐inflammatory mediators. Ebselen not only abrogated T...

  20. Decorporation of metal ions by chelating agents

    International Nuclear Information System (INIS)

    Koenig, T.

    1978-01-01

    Simple model designs to simulate the effect of therapeutical chelating agents on the behaviour of metals in mammal organisms with and without excretion have been derived and analytical solutions given for the corresponding differential equations. The possibilities of these models in the short-term description of plasma kinetics of various metals, the competition of the therapeutical ligands with proteins for the metal and of the metabolism of chelating agents were tested and the properties applying extreme conceivable parameters were analyzed. The simple models were successsively expanded in logical sequence, so that it was possible to qualitatively well describe over a long period of time, the metallic kinetics in plasma, organs and urine, the retention of the ligands and their effect on the metal excretion. Two suggestions were given to describe the so-called after-effect, an increased excretion of the metal at times when the ligand is almost completely excreted and their different behaviour after injecting the metal chelate is given. Calculations on the therapy with several ligand data as well as on dose fractionation are described resting on the ratios in the plutonium-239 chosen model parameters and the determining mechanisms analyzed. (orig./MG) [de

  1. Overall survival in lower IPSS risk MDS by receipt of iron chelation therapy, adjusting for patient-related factors and measuring from time of first red blood cell transfusion dependence: an MDS-CAN analysis.

    Science.gov (United States)

    Leitch, Heather A; Parmar, Ambica; Wells, Richard A; Chodirker, Lisa; Zhu, Nancy; Nevill, Thomas J; Yee, Karen W L; Leber, Brian; Keating, Mary-Margaret; Sabloff, Mitchell; St Hilaire, Eve; Kumar, Rajat; Delage, Robert; Geddes, Michelle; Storring, John M; Kew, Andrea; Shamy, April; Elemary, Mohamed; Lenis, Martha; Mamedov, Alexandre; Ivo, Jessica; Francis, Janika; Zhang, Liying; Buckstein, Rena

    2017-10-01

    Analyses suggest iron overload in red blood cell (RBC) transfusion-dependent (TD) patients with myleodysplastic syndrome (MDS) portends inferior overall survival (OS) that is attenuated by iron chelation therapy (ICT) but may be biassed by unbalanced patient-related factors. The Canadian MDS Registry prospectively measures frailty, comorbidity and disability. We analysed OS by receipt of ICT, adjusting for these patient-related factors. TD International Prognostic Scoring System (IPSS) low and intermediate-1 risk MDS, at RBC TD, were included. Predictive factors for OS were determined. A matched pair analysis considering age, revised IPSS, TD severity, time from MDS diagnosis to TD, and receipt of disease-modifying agents was conducted. Of 239 patients, 83 received ICT; frailty, comorbidity and disability did not differ from non-ICT patients. Median OS from TD was superior in ICT patients (5·2 vs. 2·1 years; P MDS, adjusting for age, frailty, comorbidity, disability, revised IPSS, TD severity, time to TD and receiving disease-modifying agents. This provides additional evidence that ICT may confer clinical benefit. © 2017 John Wiley & Sons Ltd.

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

    International Nuclear Information System (INIS)

    Cebrian, D.; Tapia, A.; Real, A.; Morcillo, M.A.

    2007-01-01

    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)

  3. Manganese(II) chelate contrast media

    International Nuclear Information System (INIS)

    Rocklage, S.M.; Quay, S.C.

    1994-01-01

    New chelate forming compounds for use as contrast media in NMR imaging are described. Especially mentioned are manganese(II) ion chelates of N,N' dipyridoxaldiamine, N,N' diacetic acid, and salts and esters thereof. 1 fig

  4. 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.

  5. Copper chelators: chemical properties and bio-medical applications.

    Science.gov (United States)

    Tegoni, M; Valensin, D; Toso, L; Remelli, M

    2014-01-01

    Copper is present in different concentrations and chemical forms throughout the earth crust, surface and deep water and even, in trace amounts, in the atmosphere itself. Copper is one of the first metals used by humans, the first artifacts dating back 10,000 years ago. Currently, the world production of refined copper exceeds 16,000 tons/year. Copper is a micro-element essential to life, principally for its red-ox properties that make it a necessary cofactor for many enzymes, like cytochrome-c oxidase and superoxide dismutase. In some animal species (e.g. octopus, snails, spiders, oysters) copper-hemocyanins also act as carriers of oxygen instead of hemoglobin. However, these red-ox properties also make the pair Cu(+)/Cu(2+) a formidable catalyst for the formation of reactive oxygen species, when copper is present in excess in the body or in tissues. The treatment of choice in cases of copper overloading or intoxication is the chelation therapy. Different molecules are already in clinical use as chelators or under study or clinical trial. It is worth noting that chelation therapy has also been suggested to treat some neurodegenerative diseases or cardiovascular disorders. In this review, after a brief description of the homeostasis and some cases of dyshomeostasis of copper, the main (used or potential) chelators are described; their properties in solution, even in relation to the presence of metal or ligand competitors, under physiological conditions, are discussed. The legislation of the most important Western countries, regarding both the use of chelating agents and the limits of copper in foods, drugs and cosmetics, is also outlined.

  6. Chelators for investigating zinc metalloneurochemistry

    OpenAIRE

    Radford, Robert John; Lippard, Stephen J.

    2013-01-01

    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 o...

  7. To chelate or not to chelate in MDS: That is the question!

    Science.gov (United States)

    Zeidan, Amer M; Griffiths, Elizabeth A

    2018-03-08

    Myelodysplastic syndromes (MDS) are a heterogeneous group of hemopathies that exhibit physical manifestations with clinical consequences of bone marrow failure and inherent risk of progression to acute myeloid leukemia. Iron overload (IO) is common in MDS due to chronic transfusion support and disease-related alterations in iron metabolism. IO has been conclusively associated with inferior outcomes among MDS patients. Despite lack of randomized trials showing a survival impact of iron chelation therapy (ICT), ICT is recommended by experts and guidelines for select MDS patients with IO and is often used. The availability of effective oral ICT agents has reignited the controversy regarding ICT use in patients with MDS and IO. Here we summarize the studies evaluating the value of ICT in MDS and suggest a practical approach for use of these therapies. We also highlight controversies regarding use of ICT in MDS and discuss some ongoing efforts to answer these questions. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Iron overload of organism and current options of chelation treatment in onco haematology

    International Nuclear Information System (INIS)

    Guman, T.; Rothova, E.; Kafkova, A.; Fricova, M.; Dulova, I.; Stecova, N.; Hlebaskova, M.; Surova, M.; Takac, V.

    2011-01-01

    The article summarizes the biological importance of iron in the organism, primary and secondary causes of iron overload, complications in function of liver, heart and endocrine organs due to overload of iron, the pathophysiology of iron overload, transfusion risks associated with the iron overload, assessment of risk groups of patients suitable for chelation treatment fulfilling the indication criteria, treatment modalities of chelation therapy and its significance regarding the prevention and treatment effectiveness. (author)

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

    Science.gov (United States)

    Italia, Khushnooma; Colah, Roshan; Ghosh, Kanjaksha

    2013-01-01

    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.

  10. 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.

  11. 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.

  12. Chromosomal instability and the abrogated G2/M arrest in x-irradiated myelodysplastic syndrome cells

    International Nuclear Information System (INIS)

    Ban, S.; Sudo, H.; Saegusa, K.; Sagara, M.; Imai, T.; Kimura, A.

    2003-01-01

    A preliminary epidemiological study demonstrated that myelodysplastic syndrome (MDS) has an excess relative risk per sievert of 13 in atomic bomb survivors in Hiroshima. MDS is the only other radiogenic blood disease apart from leukemia. Clinically, MDS involves dysplastic hematopoiesis and an increased risk of leukemic transformation. Because it is uncertain whether MDS pathogenesis affects lymphoid progenitor cells as well as myeloid progenitor cells, we investigated the karyotypes of bone marrow cells and the micronucleus (MN) frequency in peripheral T lymphocytes of twenty- three atomic bomb survivors with MDS and five normal individuals. Aneuploidy was observed in 10 of 23 patients. Chromosome aberrations were observed in 3 of 12 patients with mild symptoms, and six of 11 patients of severe symptoms. The spontaneous- and X-ray-induced-MN frequencies were significantly higher in MDS patients than in normal individuals. Interestingly, radiation sensitivity increased along with the severity of MDS clinical subtypes. Because many of the patients in this study had not been exposed to chemo- or radiation- therapy, their unusual radiosensitivity may be related to their chromosomal or genomic instability. Immortalized lymphoid cell lines were established from B-lymphocytes infected with Epstein-Barr virus in vitro. The abrogation of radiation-induced-G2/M arrest was observed in 10 of 12 MDS-B lymphoid cell lines, but not in the normal B lymphoid cell lines. Our data suggest that the control of chromosomal stability is impaired in pluripotent stem cells of MDS patients, and that the abrogated G2/M arrest may be involved in the pathophysiology of disease progression and the high radiation sensitivity of patients

  13. Characterization of antibody-chelator conjugates: Determination of chelator content by terbium fluorescence titration

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, K.D.; Schnobrich, K.E.; Johnson, D.K. (Abbott Laboratories, Department 90M, Abbott Park, IL (United States))

    1991-01-01

    Fluorescence titrations were performed by adding varying mole ratios of terbium(III) to antibody conjugates formed by benzyl isothiocyanate derivatives of three different polyaminopolycarboxylate chelators (NTA, EDTA, and DTPA) and the results compared to values for average chelator content obtained by cobalt-57 binding assays. For two different murine monoclonal antibodies, the average chelator content obtained by terbium fluorescence titration correlated closely with that measured by the cobalt-57 binding assay. It is concluded that lanthanide fluorescence titrations provide a useful alternative to radiometal binding assays for the determination of chelator content in protein-chelator conjugates.

  14. Characterization of antibody-chelator conjugates: Determination of chelator content by terbium fluorescence titration

    International Nuclear Information System (INIS)

    Brandt, K.D.; Schnobrich, K.E.; Johnson, D.K.

    1991-01-01

    Fluorescence titrations were performed by adding varying mole ratios of terbium(III) to antibody conjugates formed by benzyl isothiocyanate derivatives of three different polyaminopolycarboxylate chelators (NTA, EDTA, and DTPA) and the results compared to values for average chelator content obtained by cobalt-57 binding assays. For two different murine monoclonal antibodies, the average chelator content obtained by terbium fluorescence titration correlated closely with that measured by the cobalt-57 binding assay. It is concluded that lanthanide fluorescence titrations provide a useful alternative to radiometal binding assays for the determination of chelator content in protein-chelator conjugates

  15. TSH Receptor Signaling Abrogation by a Novel Small Molecule.

    Science.gov (United States)

    Latif, Rauf; Realubit, Ronald B; Karan, Charles; Mezei, Mihaly; Davies, Terry F

    2016-01-01

    Pathological activation of the thyroid-stimulating hormone receptor (TSHR) is caused by thyroid-stimulating antibodies in patients with Graves' disease (GD) or by somatic and rare genomic mutations that enhance constitutive activation of the receptor influencing both G protein and non-G protein signaling. Potential selective small molecule antagonists represent novel therapeutic compounds for abrogation of such abnormal TSHR signaling. In this study, we describe the identification and in vitro characterization of a novel small molecule antagonist by high-throughput screening (HTS). The identification of the TSHR antagonist was performed using a transcription-based TSH-inhibition bioassay. TSHR-expressing CHO cells, which also expressed a luciferase-tagged CRE response element, were optimized using bovine TSH as the activator, in a 384 well plate format, which had a Z score of 0.3-0.6. Using this HTS assay, we screened a diverse library of ~80,000 compounds at a final concentration of 16.7 μM. The selection criteria for a positive hit were based on a mean signal threshold of ≥50% inhibition of control TSH stimulation. The screening resulted in 450 positive hits giving a hit ratio of 0.56%. A secondary confirmation screen against TSH and forskolin - a post receptor activator of adenylyl cyclase - confirmed one TSHR-specific candidate antagonist molecule (named VA-K-14). This lead molecule had an IC 50 of 12.3 μM and a unique chemical structure. A parallel analysis for cell viability indicated that the lead inhibitor was non-cytotoxic at its effective concentrations. In silico docking studies performed using a TSHR transmembrane model showed the hydrophobic contact locations and the possible mode of inhibition of TSHR signaling. Furthermore, this molecule was capable of inhibiting TSHR stimulation by GD patient sera and monoclonal-stimulating TSHR antibodies. In conclusion, we report the identification of a novel small molecule TSHR inhibitor, which has the

  16. 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.

  17. Chelates for Micronutrient Nutrition among Crops

    Indian Academy of Sciences (India)

    years, it has been recognised that compounds containing che- lated metals could .... when using small amounts and no build up of harmful levels. ... degradation of iron chelates. .... down by soil microorganisms into much smaller units for ab-.

  18. A bioavailable cathepsin S nitrile inhibitor abrogates tumor development.

    Science.gov (United States)

    Wilkinson, Richard D A; Young, Andrew; Burden, Roberta E; Williams, Rich; Scott, Christopher J

    2016-04-21

    Cathepsin S has been implicated in a variety of malignancies with genetic ablation studies demonstrating a key role in tumor invasion and neo-angiogenesis. Thus, the application of cathepsin S inhibitors may have clinical utility in the treatment of cancer. In this investigation, we applied a cell-permeable dipeptidyl nitrile inhibitor of cathepsin S, originally developed to target cathepsin S in inflammatory diseases, in both in vitro and in vivo tumor models. Validation of cathepsin S selectivity was carried out by assaying fluorogenic substrate turnover using recombinant cathepsin protease. Complete kinetic analysis was carried out and true K i values calculated. Abrogation of tumour invasion using murine MC38 and human MCF7 cell lines were carried out in vitro using a transwell migration assay. Effect on endothelial tube formation was evaluated using primary HUVEC cells. The effect of inhibitor in vivo on MC38 and MCF7 tumor progression was evaluated using cells propagated in C57BL/6 and BALB/c mice respectively. Subsequent immunohistochemical staining of proliferation (Ki67) and apoptosis (TUNEL) was carried out on MCF7 tumors. We confirmed that this inhibitor was able to selectively target cathepsin S over family members K, V, L and B. The inhibitor also significantly reduced MC38 and MCF7 cell invasion and furthermore, significantly reduced HUVEC endothelial tubule formation in vitro. In vivo analysis revealed that the compound could significantly reduce tumor volume in murine MC38 syngeneic and MCF7 xenograft models. Immunohistochemical analysis of MCF7 tumors revealed cathepsin S inhibitor treatment significantly reduced proliferation and increased apoptosis. In summary, these results highlight the characterisation of this nitrile cathepsin S inhibitor using in vitro and in vivo tumor models, presenting a compound which may be used to further dissect the role of cathepsin S in cancer progression and may hold therapeutic potential.

  19. Enhanced in vitro activity of tigecycline in the presence of chelating agents.

    Science.gov (United States)

    Deitchman, Amelia N; Singh, Ravi Shankar Prasad; Rand, Kenneth H; Derendorf, Hartmut

    2018-05-01

    The lack of availability of novel antibiotic agents and the rise of resistance to existing therapies has led clinicians to utilise combination therapy to adequately treat bacterial infections. Here we examined how chelators may impact the in vitro activity of tigecycline (TIG) against Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae. Minimum inhibitory concentrations (MICs) were determined by broth dilution with and without various combinations of chelators (EDTA and other tetracyclines) and metal ions (i.e. calcium, magnesium). Trimethoprim (TMP) was used as a non-chelating control. Addition of metal ions led to increases in MICs, whilst addition of EDTA led to decreases in MICs. The chelating effects of EDTA were reversed by addition of magnesium and most profoundly calcium. Similar effects of EDTA and calcium were observed for tetracycline (TET) and TMP. When other tetracyclines (TET, oxytetracycline (OXY) and chlortetracycline (CHL)) were used as chelators at concentrations below their MICs, TIG MICs decreased for P. aeruginosa but not for E. coli. Some decreases in TIG MICs were observed for K. pneumoniae when TET and CHL were added. A dose-dependent decrease in TIG MIC was observed for TET and was reversed by the addition of calcium. The presence of effects of EDTA and calcium on TMP MICs indicates that mechanisms outside of TIG chelation likely play a role in enhanced activity. Full characterisation of an unexpected interaction such as TIG-TET with different microorganisms could provide valuable insights into the underlying mechanisms and design of physiologically viable chelators as candidates for future combinations regimens. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  20. Radiopharmaceutical chelates and method of external imaging

    International Nuclear Information System (INIS)

    1976-01-01

    The preparation of the following chemicals is described: chelates of technetium-99m, cobalt-57, gallium-67, gallium-68, indium-111 or indium-113m and a substituted iminodiacetic acid or an 8-hydroxyquinoline useful as a radiopharmaceutical external imaging agent. The compounds described are suitable for intravenous injection, have an excellent in vivo stability and are good organ seekers. Tin(II) choride or other tin(II) compounds are used as chelating agents

  1. Fluid extraction using carbon dioxide and organophosphorus chelating agents

    Science.gov (United States)

    Smart, Neil G.; Wai, Chien M.; Lin, Yuehe; Kwang, Yak Hwa

    1998-01-01

    Methods for extracting metalloid and metal species from a solid or liquid material by exposing the material to a fluid solvent, particularly supercritical CO.sub.2, and a chelating agent are described. The chelating agent forms a chelate with the species, the chelate being soluble in the fluid to allow removal of the species from the material. In preferred embodiments the extraction solvent is supercritical CO.sub.2 and the chelating agent comprises an organophosphorous chelating agent, particularly sulfur-containing organophosphorous chelating agents, including mixtures of chelating agents. Examples of chelating agents include monothiophosphinic acid, di-thiophosphinic acid, phosphine sulfite, phosphorothioic acid, and mixtures thereof. The method provides an environmentally benign process for removing metal and metalloids from industrial waste solutions, particularly acidic solutions. Both the chelate and the supercritical fluid can be regenerated and the contaminant species recovered to provide an economic, efficient process.

  2. 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

  3. CaNa2EDTA chelation attenuates cell damage in workers exposed to lead--a pilot study.

    Science.gov (United States)

    Čabarkapa, A; Borozan, S; Živković, L; Stojanović, S; Milanović-Čabarkapa, M; Bajić, V; Spremo-Potparević, B

    2015-12-05

    Lead induced oxidative cellular damage and long-term persistence of associated adverse effects increases risk of late-onset diseases. CaNa2EDTA chelation is known to remove contaminating metals and to reduce free radical production. The objective was to investigate the impact of chelation therapy on modulation of lead induced cellular damage, restoration of altered enzyme activities and lipid homeostasis in peripheral blood of workers exposed to lead, by comparing the selected biomarkers obtained prior and after five-day CaNa2EDTA chelation intervention. The group of smelting factory workers diagnosed with lead intoxication and current lead exposure 5.8 ± 1.2 years were administered five-day CaNa2EDTA chelation. Elevated baseline activity of antioxidant enzymes Cu, Zn-SOD and CAT as well as depleted thiols and increased protein degradation products-carbonyl groups and nitrites, pointing to Pb induced oxidative damage, were restored toward normal values following the treatment. Lead showed inhibitor potency on both RBC AChE and BChE in exposed workers, and chelation re-established the activity of BChE, while RBC AChE remained unaffected. Also, genotoxic effect of lead detected in peripheral blood lymphocytes was significantly decreased after therapy, exhibiting 18.9% DNA damage reduction. Administration of chelation reversed the depressed activity of serum PON 1 and significantly decreased lipid peroxidation detected by the post-chelation reduction of MDA levels. Lactate dehydrogenase LDH1-5 isoenzymes levels showed evident but no significant trend of restoring toward normal control values following chelation. CaNa2EDTA chelation ameliorates the alterations linked with Pb mediated oxidative stress, indicating possible benefits in reducing health risks associated with increased oxidative damage in lead exposed populations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Peptidomimetic hydroxamate metalloproteinase inhibitors abrogate local and systemic toxicity induced by Echis ocellatus (saw-scaled) snake venom.

    Science.gov (United States)

    Arias, Ana Silvia; Rucavado, Alexandra; Gutiérrez, José María

    2017-06-15

    The ability of two peptidomimetic hydroxamate metalloproteinase inhibitors, Batimastat and Marimastat, to abrogate toxic and proteinase activities of the venom of Echis ocellatus from Cameroon and Ghana was assessed. Since this venom largely relies for its toxicity on the action of zinc-dependent metalloproteinases (SVMPs), the hypothesis was raised that toxicity could be largely eliminated by using SVMP inhibitors. Both hydroxamate molecules inhibited local and pulmonary hemorrhagic, in vitro coagulant, defibrinogenating, and proteinase activities of the venoms in conditions in which venom and inhibitors were incubated prior to the test. In addition, the inhibitors prolonged the time of death of mice receiving 4 LD 50 s of venom by the intravenous route. Lower values of IC 50 were observed for in vitro and local hemorrhagic activities than for systemic effects. When experiments were performed in conditions that simulated the actual circumstances of snakebite, i.e. by administering the inhibitor after envenoming, Batimastat completely abrogated local hemorrhage if injected immediately after venom. Moreover, it was also effective at inhibiting lethality and defibrinogenation when venom and inhibitor were injected by the intraperitoneal route. Results suggest that these, and possibly other, metalloproteinase inhibitors may become an effective adjunct therapy in envenomings by E. ocellatus when administered at the anatomic site of venom injection rapidly after the bite. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Biological behaviour of some 67Ga and 64Cu chelates

    International Nuclear Information System (INIS)

    Leonovicova, T.; Angelis, B.; Cifka, J.; Cifkova, I.

    1984-01-01

    Chelates of 67 Ga and 64 Cu with iminodiacetic acid (IDA) and its two phenyl derivatives as well as with nitrilotriacetic acid (NTA) and benzylnitrilotriacetic acid (BNTA) were prepared. All the chelates were found to be negatively charged. A study of the biological distribution of these chelates in rats during time intervals of 3 to 180 min showed that the chelate of 67 Ga with IDA substituted at a phenyl by a hydrophobic substituent is excreted by the kidneys into the urine at a much higher rate than the IDA chelate of 67 Ga. The excretion of NTA and BNTA chelates of 67 Ga is the opposite. Blood clearance of 64 Cu chelates is more rapid than that of 67 Ga chelates. Chelates of 64 Cu accumulate in the liver and with the bile are slowly excreted into the intestines, urinary excretion is negligible. (author)

  6. Decomposition rates of radiopharmaceutical indium chelates in serum

    International Nuclear Information System (INIS)

    Yeh, S.M.; Meares, C.F.; Goodwin, D.A.

    1979-01-01

    The rates at which six small aminopolycarboxylate chelates of trivalent 111 In and three protein-bound chelates of 111 In deliver indium to the serum protein transferrin have been studied in sterile human serum at pH 7.3, 37 deg C. Sterically hindered chelates containing a substituent on an ethylene carbon of EDTA decompose with rates in the range 0.03 to 0.11% per day - one to two orders of magnitude slower than other chelates. Only small differences are observed between rates of decomposition for low-molecular-weight chelates and for protein-bound chelates having analogous structures. (author)

  7. 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.

  8. Labelling of bacteria with indium chelates

    International Nuclear Information System (INIS)

    Kleinert, P.; Pfister, W.; Endert, G.; Sproessig, M.

    1985-01-01

    The indium chelates were prepared by reaction of radioactive indiumchloride with 10 μg oxine, 15 μg tropolone and 3 mg acetylacetone, resp. The formed chelates have been incubated with 10 9 germs/ml for 5 minutes, with labelling outputs from 90 to 95%. Both gram-positive (Streptococcus, Staphylococcus) and gram-negative bacteria (Escherichia coli) can be labelled. The reproductive capacity of the bacteria was not impaired. The application of indium labelled bacteria allows to show the distribution of microorganisms within the living organism and to investigate problems of bacterial adherence. (author)

  9. Bone marrow and chelatable iron in patients with protein energy ...

    African Journals Online (AJOL)

    chelatable iron is present and is excreted in the urine of children with kwashiorkor ... venous blood sample was drawn for routine biochemical and haematological .... storage.l.1:m In response to chelation, the kwashiorkor children excrete large ...

  10. WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma.

    Science.gov (United States)

    Zhukova, Nataliya; Ramaswamy, Vijay; Remke, Marc; Martin, Dianna C; Castelo-Branco, Pedro; Zhang, Cindy H; Fraser, Michael; Tse, Ken; Poon, Raymond; Shih, David J H; Baskin, Berivan; Ray, Peter N; Bouffet, Eric; Dirks, Peter; von Bueren, Andre O; Pfaff, Elke; Korshunov, Andrey; Jones, David T W; Northcott, Paul A; Kool, Marcel; Pugh, Trevor J; Pomeroy, Scott L; Cho, Yoon-Jae; Pietsch, Torsten; Gessi, Marco; Rutkowski, Stefan; Bognár, Laszlo; Cho, Byung-Kyu; Eberhart, Charles G; Conter, Cecile Faure; Fouladi, Maryam; French, Pim J; Grajkowska, Wieslawa A; Gupta, Nalin; Hauser, Peter; Jabado, Nada; Vasiljevic, Alexandre; Jung, Shin; Kim, Seung-Ki; Klekner, Almos; Kumabe, Toshihiro; Lach, Boleslaw; Leonard, Jeffrey R; Liau, Linda M; Massimi, Luca; Pollack, Ian F; Ra, Young Shin; Rubin, Joshua B; Van Meir, Erwin G; Wang, Kyu-Chang; Weiss, William A; Zitterbart, Karel; Bristow, Robert G; Alman, Benjamin; Hawkins, Cynthia E; Malkin, David; Clifford, Steven C; Pfister, Stefan M; Taylor, Michael D; Tabori, Uri

    2014-12-24

    TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, β-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of γH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.

  11. Radiopharmaceutical chelates and method of external imaging

    International Nuclear Information System (INIS)

    Loberg, M.D.; Callery, P.S.; Cooper, M.

    1977-01-01

    A chelate of technetium-99m, cobalt-57, gallium-67, gallium-68, indium-111 or indium-113m and a substituted iminodiacetic acid or an 8-hydroxyquinoline useful as a radiopharmaceutical external imaging agent. The invention also includes preparative methods therefor

  12. Use of chelating agents as immovable phase in extraction chromatography

    International Nuclear Information System (INIS)

    Sebesta, F.

    1978-01-01

    Extraction chromatography using chelating agents is reviewed. The theory of element extraction by chelating agents and factors influencing this process (pH, extracting agent concentration in organic phase, masking agent concentration in aqueous phase) are briefly considered. The effect of kinetic factors on the extraction chromatography process is discussed. Ways of preparing columns are emphasized. Examples of using chelating reagents in various extraction chromatography systems are given. β-Diketones, oximes, hydroxamic acids, dithizon, diethyl dithiocarbamic acid are chosen as chelating agents

  13. Chelating agents as stationary phase in extraction chromatography, ch. 11

    International Nuclear Information System (INIS)

    Sebesta, F.

    1975-01-01

    Chelating agents have been used largely in extraction chromatography for separations related to activation analysis, for concentration of metals from dilute solutions, and for preparation of radiochemically pure or carrier-free radionuclides. This review deals with the theory of extraction by chelating agents, the experimental technique, and the chelating agents and systems used (β-diketones, oximes, hydroxamic acid, dithizone and diethyldithiocarbamic acid)

  14. [Susceptibility of enterococci to natural and synthetic iron chelators].

    Science.gov (United States)

    Lisiecki, Paweł; Mikucki, Jerzy

    2002-01-01

    A total of 79 strains of enterococci belonging to 10 species were tested for susceptibility to natural and synthetic iron chelators. All strains produced siderophores. These enterococci were susceptible to three synthetic iron chelators only: 8-hydroxyquinoline, disodium versenate (EDTA) and o-phenanthroline. They were resistant to all other synthetic chelators: ethylenediamine-di(o-hydroxyphenylacetic acid) (EDDHA), nitrilotriacetate, 2,2'-bipiridyl, salicylic acid, 8-hydroxy-5-sulphonic acid and to all natural chelators: ovotransferrine, human apotransferrine, horse apoferritine, desferrioxamine B, ferrichrome and rhodotorulic acid. The relations between susceptibility/resistance, iron assimilation and structure and stability constants of iron chelators were discussed.

  15. 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.

  16. Vorinostat synergizes with ridaforolimus and abrogates the ridaforolimus-induced activation of AKT in synovial sarcoma cells.

    Science.gov (United States)

    Morgan, Sherif S; Cranmer, Lee D

    2014-11-18

    Curative treatments for patients with metastatic synovial sarcoma (SS) do not exist, and such patients have a poor prognosis. We explored combinations of molecularly-targeted and cytotoxic agents to identify synergistic treatment combinations in SS cells. Two SS cell lines (HS-SY-II and SYO-I) were treated with single agents or combinations of molecularly targeted therapies (HDAC inhibitor, vorinostat; mTOR inhibitor, ridaforolimus) and cytotoxic agents. After 72 hours, cell viability was measured using the MTS cell proliferation assay. Combination Indices (CI) were calculated to determine whether each combination was synergistic, additive, or antagonistic. Western Blot analysis assessed alterations in total and phospho-AKT protein levels in response to drug treatment. We determined the single-agent IC50 for ridaforolimus, vorinostat, doxorubicin, and melphalan in HS-SY-II and SYO-I. Synergism was apparent in cells co-treated with ridaforolimus and vorinostat: CI was 0.28 and 0.63 in HS-SY-II and SYO-I, respectively. Ridaforolimus/doxorubicin and ridaforolimus/melphalan exhibited synergism in both cell lines. An additive effect was observed with combination of vorinostat/doxorubicin in both cell lines. Vorinostat/melphalan was synergistic in HS-SY-II and additive in SYO-I. Western blot analysis demonstrated that ridaforolimus increased pAKT-ser473 levels; this effect was abrogated by vorinostat co-treatment. The combination of ridaforolimus and vorinostat demonstrates in vitro synergism in SS. Addition of vorinostat abrogated ridaforolimus-induced AKT activation. Since AKT activation is a possible mechanism of resistance to mTOR inhibitors, adding vorinostat (or another HDAC inhibitor) may be a route to circumvent AKT-mediated resistance to mTOR inhibitors.

  17. Obligatory reduction of ferric chelates in iron uptake by soybeans.

    Science.gov (United States)

    Chaney, R L; Brown, J C; Tiffin, L O

    1972-08-01

    The contrasting Fe(2+) and Fe(3+) chelating properties of the synthetic chelators ethylenediaminedi (o-hydroxyphenylacetate) (EDDHA) and 4,7-di(4-phenylsulfonate)-1, 10-phenanthroline (bathophenanthrolinedisulfonate) (BPDS) were used to determine the valence form of Fe absorbed by soybean roots supplied with Fe(3+)-chelates. EDDHA binds Fe(3+) strongly, but Fe(2+) weakly; BPDS binds Fe(2+) strongly but Fe(3+) weakly. Addition of an excess of BPDS to nutrient solutions containing Fe(3+)-chelates inhibited soybean Fe uptake-translocation by 99+%; [Fe(II) (BPDS)(3)](4-) accumulated in the nutrient solution. The addition of EDDHA caused little or no inhibition. These results were observed with topped and intact soybeans. Thus, separation and absorption of Fe from Fe(3+)-chelates appear to require reduction of Fe(3+)-chelate to Fe(2+)-chelate at the root, with Fe(2+) being the principal form of Fe absorbed by soybean.

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

    OpenAIRE

    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 un...

  19. Metal chelators and neurotoxicity: lead, mercury, and arsenic.

    Science.gov (United States)

    Bjørklund, Geir; Mutter, Joachim; Aaseth, Jan

    2017-12-01

    This article reviews the clinical use of the metal chelators sodium 2,3-dimercapto-1-propanesulfonate (DMPS), meso-2,3-dimercaptosuccinic acid (DMSA), and calcium disodium edetate (CaEDTA, calcium EDTA) in overexposure and poisonings with salts of lead (Pb), mercury (Hg), and arsenic (As). DMSA has considerably lower toxicity than the classic heavy metal antagonist BAL (2,3-dimercaptopropanol) and is also less toxic than DMPS. Because of its adverse effects, CaEDTA should be replaced by DMSA as the antidote of choice in treating moderate Pb poisoning. Combination therapy with BAL and CaEDTA was previously recommended in cases of severe acute Pb poisoning with encephalopathy. We suggest that BAL in such cases acted as a shuttling Pb transporter from the intra- to the extracellular space. The present paper discusses if a combination of the extracellularly distributed DMSA with the ionophore, Monensin may provide a less toxic combination for Pb mobilization by increasing both the efflux of intracellularly deposited Pb and the urinary Pb excretion. Anyhow, oral therapy with DMSA should be continued with several intermittent courses. DMPS and DMSA are also promising antidotes in Hg poisoning, whereas DMPS seems to be a more efficient agent against As poisoning. However, new insight indicates that a combination of low-dosed BAL plus DMPS could be a preferred antidotal therapy to obtain mobilization of the intracerebral deposits into the circulation for subsequent rapid urinary excretion.

  20. Isolation and characterization of iron chelators from turmeric (Curcuma longa): selective metal binding by curcuminoids.

    Science.gov (United States)

    Messner, Donald J; Surrago, Christine; Fiordalisi, Celia; Chung, Wing Yin; Kowdley, Kris V

    2017-10-01

    Iron overload disorders may be treated by chelation therapy. This study describes a novel method for isolating iron chelators from complex mixtures including plant extracts. We demonstrate the one-step isolation of curcuminoids from turmeric, the medicinal food spice derived from Curcuma longa. The method uses iron-nitrilotriacetic acid (NTA)-agarose, to which curcumin binds rapidly, specifically, and reversibly. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin each bound iron-NTA-agarose with comparable affinities and a stoichiometry near 1. Analyses of binding efficiencies and purity demonstrated that curcuminoids comprise the primary iron binding compounds recovered from a crude turmeric extract. Competition of curcuminoid binding to the iron resin was used to characterize the metal binding site on curcumin and to detect iron binding by added chelators. Curcumin-Iron-NTA-agarose binding was inhibited by other metals with relative potency: (>90% inhibition) Cu 2+  ~ Al 3+  > Zn 2+  ≥ Ca 2+  ~ Mg 2+  ~ Mn 2+ (80% by addition of iron to the media; uptake was completely restored by desferoxamine. Ranking of metals by relative potencies for blocking curcumin uptake agreed with their relative potencies in blocking curcumin binding to iron-NTA-agarose. We conclude that curcumin can selectively bind toxic metals including iron in a physiological setting, and propose inhibition of curcumin binding to iron-NTA-agarose for iron chelator screening.

  1. Mixed ligand chelates of rare earths in aqueous solution

    International Nuclear Information System (INIS)

    Lakhani, S.U.; Thakur, G.S.; Sangal, S.P.

    1981-01-01

    Mixed ligand chelates of the 1:1 trivalent lanthanoids-EDTA, HEDTA and NTA chelates-1, 2-Dihydroxybenzene (Pyrocatechol) have been investigated at 35degC and 0.2 M ionic strength maintained by NaC10 4 . The formation of mixed ligand chelates has been found in all cases. The formation of mixed ligand chelates with EDTA shows the coordination number of lanthanoids to be eight, while the mixed ligand chelates with HEDTA and NTA shows the coordination number to be seven and six respectively. The stability constants of mixed ligand chelates are smaller than the binary complexes. The order of stability constants with respect to primary ligands follows the order NTA>HEDTA>EDTA. With respect to metal ions the stability constants increases with the decrease in ionic radii such as Gd< Er< Yb. (author)

  2. Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial.

    Science.gov (United States)

    Lamas, Gervasio A; Goertz, Christine; Boineau, Robin; Mark, Daniel B; Rozema, Theodore; Nahin, Richard L; Lindblad, Lauren; Lewis, Eldrin F; Drisko, Jeanne; Lee, Kerry L

    2013-03-27

    Chelation therapy with disodium EDTA has been used for more than 50 years to treat atherosclerosis without proof of efficacy. To determine if an EDTA-based chelation regimen reduces cardiovascular events. Double-blind, placebo-controlled, 2 × 2 factorial randomized trial enrolling 1708 patients aged 50 years or older who had experienced a myocardial infarction (MI) at least 6 weeks prior and had serum creatinine levels of 2.0 mg/dL or less. Participants were recruited at 134 US and Canadian sites. Enrollment began in September 2003 and follow-up took place until October 2011 (median, 55 months). Two hundred eighty-nine patients (17% of total; n=115 in the EDTA group and n=174 in the placebo group) withdrew consent during the trial. Patients were randomized to receive 40 infusions of a 500-mL chelation solution (3 g of disodium EDTA, 7 g of ascorbate, B vitamins, electrolytes, procaine, and heparin) (n=839) vs placebo (n=869) and an oral vitamin-mineral regimen vs an oral placebo. Infusions were administered weekly for 30 weeks, followed by 10 infusions 2 to 8 weeks apart. Fifteen percent discontinued infusions (n=38 [16%] in the chelation group and n=41 [15%] in the placebo group) because of adverse events. The prespecified primary end point was a composite of total mortality, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. This report describes the intention-to-treat comparison of EDTA chelation vs placebo. To account for multiple interim analyses, the significance threshold required at the final analysis was P = .036. Qualifying previous MIs occurred a median of 4.6 years before enrollment. Median age was 65 years, 18% were female, 9% were nonwhite, and 31% were diabetic. The primary end point occurred in 222 (26%) of the chelation group and 261 (30%) of the placebo group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.99]; P = .035). There was no effect on total mortality (chelation: 87 deaths [10%]; placebo, 93 deaths [11%]; HR, 0

  3. Role of chelates in magnetic resonance imaging studies

    Directory of Open Access Journals (Sweden)

    Tripathi Laxmi

    2009-01-01

    Full Text Available Imaging studies are tests performed with a variety of techniques that produce pictures of the inside of a patient′s body. Magnetic resonance imaging (MRI is an imaging technique based on the principles of nuclear magnetic resonance. MRI uses a powerful magnetic field, radio waves, and a computer to produce detailed pictures of organs, soft tissues, bone, and virtually all other internal body structures. Chelates have a wide application in such imaging techniques. Chelates in imaging studies are used alone as radioactive agents or conjugated to monoclonal antibodies or to DNA as radioactive agents. Technetium chelates and gadolinium chelates are being widely used as magnetic resonance contrast media.

  4. 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.

  5. 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...

  6. Combined chelation based on glycosyl-mono- and bis-hydroxypyridinones for aluminium mobilization: solution and biodistribution studies.

    Science.gov (United States)

    Chaves, Sílvia; Dron, Paul I; Danalache, Florina A; Sacoto, Diana; Gano, Lurdes; Santos, M Amélia

    2009-11-01

    Taking into account the recognized interest of a poly-pharmacological strategy in chelation therapy, a study of aluminium combined chelation based on 3-hydroxy-4-pyridinone (3,4-HP) compounds with complementary properties, associated to different denticity, size and extrafunctionality, is presented herein. In particular, Al-chelation has been explored, using a tetradentate IDA bis-(3,4-HP) ligand, L, and two N-glycosyl mono-(3,4-HP) derivatives (A or B). Combined complexation studies with the tetradentate and the most promising bidentate ligand (A) evidenced the formation of ternary complexes with high thermodynamic stability (Al-L-A) being the predominant species at physiological pH. In vivo studies on the ability for radiotracer ((67)Ga) removal from loaded mice, as a model of aluminium accumulation in body, have shown that the simultaneous administration to (67)Ga-loaded mice of a mono- and a bis-(3,4-HP) chelator (e.g. A and L) leads to a rapid metal elimination from main organs and whole animal model. This may be rationalized by coadjuvation and eventual synergistic effects, due to complementary accessibility of the chelators to different cellular compartments.

  7. Chelate-assisted phytoextraction of lead from contaminated soils

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, E.M.; Sims, J.T.; Cunningham, S.D.; Huang, J.W.; Berti, W.R.

    1999-12-01

    Phytoextraction, a remediation strategy for lead (Pb)-contaminated soils that removes soil Pb through plant uptake and harvest, may be enhanced by use of synthetic chelates. The authors evaluated Pb desorption from four contaminated soils by seven chelates (CDTA, DTPA, EDDHA, EFTA, HEDTA, HEIDA, and NTA) at three rates. The three most effective chelates (CDTA, DTPA, and HEDTA) were used in greenhouse studies with an uncontaminated soil and a Pb-contaminated soil to determine the effect of chelate type and rate on growth, Pb uptake, and plant elemental composition. Lead desorption varied with chelate and soil and increased with chelate rate, averaging 948 mg Pb kg{sup {minus}1} at the 20 mmol kg{sup {minus}1} rate vs. 28 mg Pb kg{sup {minus}1} by the control. The general ranking of chelate effectiveness, based on total Pb desorbed, was HEDTA > CDTA > DTPA > EGTA > HEIDA > EDDHA {approximately} NTA. Plant uptake of Pb from the contaminated soil was enhanced by CDTA, DTPA, and HEDTA, but with even the most effective treatment (corn, high CDTA rate), the amount of Pb extracted by plants was rather low. Lead extractable by the Toxicity Characteristic Leaching Procedure (TCLP) was increased from 9 mg L{sup {minus}1} in the control to from 47 to 174 mg L{sup {minus}1} in soils treated with 20 mmol kg{sup {minus}1} CDTA or DTPA and chelates generally caused a shift in Pb from resistant to more soluble chemical fractions.

  8. 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

  9. 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…

  10. Development of iron chelators for Cooley's anemia. Final report

    International Nuclear Information System (INIS)

    Crosby, W.H.; Green, R.

    1982-01-01

    Iron chelators were screened in an iron-loaded rat model using selective radioiron probes. In all experiments, chelators D and F, in that order, induced significant loss of radioiron compared with controls. However, use of chelator D was associated with side effects, and resulted in the death of some animals. There was some evidence that chelator A also caused iron loss significantly greater than controls. Chelators B, C and E were without apparent enhancing effect on radioiron excretion. This was a blind study and the compounds used were A - 2,3-Dihydroxybenzoic acid; B - N,N1-Dimethyladipohydroxamic acid; C - DL-Phenylalanine hydroxamic acid; D - Ethylenediamine-N,N1-bis(2-hydroxphenylacetic acid); E - Propionohydroxamic acid; and F - Deferrioxamine B

  11. Sensitization of Tumor to {sup 212}Pb Radioimmunotherapy by Gemcitabine Involves Initial Abrogation of G2 Arrest and Blocked DNA Damage Repair by Interference With Rad51

    Energy Technology Data Exchange (ETDEWEB)

    Yong, Kwon Joong; Milenic, Diane E.; Baidoo, Kwamena E. [Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Brechbiel, Martin W., E-mail: martinwb@mail.nih.gov [Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

    2013-03-15

    Purpose: To elucidate the mechanism of the therapeutic efficacy of targeted α-particle radiation therapy using {sup 212}Pb-TCMC-trastuzumab together with gemcitabine for treatment of disseminated peritoneal cancers. Methods and Materials: Mice bearing human colon cancer LS-174T intraperitoneal xenografts were pretreated with gemcitabine, followed by {sup 212}Pb-TCMC-trastuzumab and compared with controls. Results: Treatment with {sup 212}Pb-TCMC-trastuzumab increased the apoptotic rate in the S-phase-arrested tumors induced by gemcitabine at earlier time points (6 to 24 hours). {sup 212}Pb-TCMC-trastuzumab after gemcitabine pretreatment abrogated G2/M arrest at the same time points, which may be associated with the inhibition of Chk1 phosphorylation and, in turn, cell cycle perturbation, resulting in apoptosis. {sup 212}Pb-TCMC-trastuzumab treatment after gemcitabine pretreatment caused depression of DNA synthesis, DNA double-strand breaks, accumulation of unrepaired DNA, and down-regulation of Rad51 protein, indicating that DNA damage repair was blocked. In addition, modification in the chromatin structure of p21 may be associated with transcriptionally repressed chromatin states, indicating that the open structure was delayed at earlier time points. Conclusion: These findings suggest that the cell-killing efficacy of {sup 212}Pb-TCMC-trastuzumab after gemcitabine pretreatment may be associated with abrogation of the G2/M checkpoint, inhibition of DNA damage repair, and chromatin remodeling.

  12. Sensitization of Tumor to 212Pb Radioimmunotherapy by Gemcitabine Involves Initial Abrogation of G2 Arrest and Blocked DNA Damage Repair by Interference With Rad51

    International Nuclear Information System (INIS)

    Yong, Kwon Joong; Milenic, Diane E.; Baidoo, Kwamena E.; Brechbiel, Martin W.

    2013-01-01

    Purpose: To elucidate the mechanism of the therapeutic efficacy of targeted α-particle radiation therapy using 212 Pb-TCMC-trastuzumab together with gemcitabine for treatment of disseminated peritoneal cancers. Methods and Materials: Mice bearing human colon cancer LS-174T intraperitoneal xenografts were pretreated with gemcitabine, followed by 212 Pb-TCMC-trastuzumab and compared with controls. Results: Treatment with 212 Pb-TCMC-trastuzumab increased the apoptotic rate in the S-phase-arrested tumors induced by gemcitabine at earlier time points (6 to 24 hours). 212 Pb-TCMC-trastuzumab after gemcitabine pretreatment abrogated G2/M arrest at the same time points, which may be associated with the inhibition of Chk1 phosphorylation and, in turn, cell cycle perturbation, resulting in apoptosis. 212 Pb-TCMC-trastuzumab treatment after gemcitabine pretreatment caused depression of DNA synthesis, DNA double-strand breaks, accumulation of unrepaired DNA, and down-regulation of Rad51 protein, indicating that DNA damage repair was blocked. In addition, modification in the chromatin structure of p21 may be associated with transcriptionally repressed chromatin states, indicating that the open structure was delayed at earlier time points. Conclusion: These findings suggest that the cell-killing efficacy of 212 Pb-TCMC-trastuzumab after gemcitabine pretreatment may be associated with abrogation of the G2/M checkpoint, inhibition of DNA damage repair, and chromatin remodeling

  13. Chelating impact assessment of biological ad chemical chelates on metal extraction from contaminated soils

    International Nuclear Information System (INIS)

    Manwar, S.; Iram, S.

    2014-01-01

    Soil contamination is the result of uncontrolled waste dumping and poor practices by humans. Of all the pollutants heavy metals are of particular concern due to their atmospheric deposition, leaching capacity and non-biodegradability. Heavy metal containing effluent is discharged into the agricultural fields and water bodies. This results in the accumulation of heavy metals in soil and the crops grown on that soil. Studies have revealed detrimental impacts on soil fertility and the poor health of animals and humans. Phytoextraction is widely researched for remediation of heavy metal contaminated soil. To enhance the effect of phytoextraction heavy metals have to be available to the plants in soluble form. In this study the potential of different chelating agents was assessed in solubilizing the heavy metals making easy for plants to uptake them. For this purpose efficient chemical and biological chelating agent had to be identified. Along with that an optimum dose and application time for chemical chelating agent was determined. Ethylenediamine tetraacetic acid (EDTA), Diethylene triamine pentaacetic acid (DTPA), Nitriloacetic acid (NTA) were applied to the soil, containing Pb, Cr, Cu and Cd, at different concentrations and application time. Aspergillus niger and Aspergillus flavus were incubated in soil for different time periods. In correspondence with findings of the study, Pb and Cr were best solubilized by 5mM EDTA. For Cd and Cu 5mM DTPA carried out efficient chelation. NTA showed relatively inadequate solubilisation, although for Cr it performed equal to EDTA. A. niger and A. flavus instead of solubilizing adsorbed the metals in their biomass. Adsorption was mainly carried out by A. niger. (author)

  14. Glyphosate, a chelating agent-relevant for ecological risk assessment?

    Science.gov (United States)

    Mertens, Martha; Höss, Sebastian; Neumann, Günter; Afzal, Joshua; Reichenbecher, Wolfram

    2018-02-01

    Glyphosate-based herbicides (GBHs), consisting of glyphosate and formulants, are the most frequently applied herbicides worldwide. The declared active ingredient glyphosate does not only inhibit the EPSPS but is also a chelating agent that binds macro- and micronutrients, essential for many plant processes and pathogen resistance. GBH treatment may thus impede uptake and availability of macro- and micronutrients in plants. The present study investigated whether this characteristic of glyphosate could contribute to adverse effects of GBH application in the environment and to human health. According to the results, it has not been fully elucidated whether the chelating activity of glyphosate contributes to the toxic effects on plants and potentially on plant-microorganism interactions, e.g., nitrogen fixation of leguminous plants. It is also still open whether the chelating property of glyphosate is involved in the toxic effects on organisms other than plants, described in many papers. By changing the availability of essential as well as toxic metals that are bound to soil particles, the herbicide might also impact soil life, although the occurrence of natural chelators with considerably higher chelating potentials makes an additional impact of glyphosate for most metals less likely. Further research should elucidate the role of glyphosate (and GBH) as a chelator, in particular, as this is a non-specific property potentially affecting many organisms and processes. In the process of reevaluation of glyphosate its chelating activity has hardly been discussed.

  15. 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.

  16. Selectivity in extraction of copper and indium with chelate extractants

    International Nuclear Information System (INIS)

    Zivkovic, D.

    2003-01-01

    Simultaneous extraction of copper and indium with chelate extractants (LIX84 and D2E11PA) was described. Stechiometry of metal-organic complexes examined using the method of equimolar ratios resulted in CuR 2 and InR 3 forms of hydrophobic extracting species. A linear correlation was obtained between logarithm of distribution coefficients and chelate agents and pH, respectively. Selectivity is generally higher with higher concentrations of chelate agents in the organic phase, and is decreased with increase of concentration of hydrogen ions in feeding phase. (Original)

  17. Mixed and chelated waste test programs with bitumen solidification

    International Nuclear Information System (INIS)

    Simpson, S.I.; Morris, M.; Vidal, H.

    1988-01-01

    This paper presents the results of bitumen solidification tests on mixed wastes and chelated wastes. The French Atomic Energy Commission (CEA) performed demonstration tests on radioactive wastes contaminated with chelating agents for Associated Technologies, Inc. (ATI). The chelated wastes were produced and concentrated by Commonwealth Edison Co. as a result of reactor decontamination at Dresden Nuclear Station, Unit 1. Law Engineering in Charlotte, N. C. produced samples and performed tests on simulated heavy metal laden radioactive waste (mixed) to demonstrate the quality of the bituminous product. The simulation is intended to represent waste produced at Oak Ridge National Labs operated by Martin-Marietta

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

    Science.gov (United States)

    Ibrahim, Ashraf S.; Gebermariam, Teclegiorgis; Fu, Yue; Lin,, Lin; Husseiny, Mohamed I.; French, Samuel W.; Schwartz, Julie; Skory, Christopher D.; Edwards, John E.; Spellberg, Brad J.

    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 isolates of Mucorales at concentrations well below clinically achievable serum levels. When administered to diabetic ketoacidotic or neutropenic mice with mucormycosis, deferasirox significantly improved survival and decreased tissue fungal burden, with an efficacy similar to that of liposomal amphotericin B. Deferasirox treatment also enhanced the host inflammatory response to mucormycosis. Most importantly, deferasirox synergistically improved survival and reduced tissue fungal burden when combined with liposomal amphotericin B. These data support clinical investigation of adjunctive deferasirox therapy to improve the poor outcomes of mucormycosis with current therapy. As iron availability is integral to the pathogenesis of other infections (e.g., tuberculosis, malaria), broader investigation of deferasirox as an antiinfective treatment is warranted. PMID:17786247

  20. The Effect of an EDTA-based Chelation Regimen on Patients with Diabetes and Prior Myocardial Infarction in TACT

    Science.gov (United States)

    Escolar, Esteban; Lamas, Gervasio A.; Mark, Daniel B.; Boineau, Robin; Goertz, Christine; Rosenberg, Yves; Nahin, Richard L.; Ouyang, Pamela; Rozema, Theodore; Magaziner, Allan; Nahas, Richard; Lewis, Eldrin F.; Lindblad, Lauren; Lee, Kerry L.

    2014-01-01

    Background The Trial to Assess Chelation Therapy (TACT) showed clinical benefit of an ethylene diamine tetraacetic acid (EDTA-based) infusion regimen in patients 50 years or older with prior myocardial infarction (MI). Diabetes prior to enrollment was a pre-specified subgroup. Methods and Results Patients received 40 infusions of EDTA chelation or placebo. 633 (37%) had diabetes (322 EDTA, 311 placebo). EDTA reduced the primary endpoint (death, reinfarction, stroke, coronary revascularization, or hospitalization for angina) [25% vs 38%, hazard ratio (HR) 0.59, 95% confidence interval (CI) (0.44, 0.79), p<0.001] over 5 years. The result remained significant after Bonferroni adjustment for multiple subgroups (99.4% CI (0.39, 0.88), adjusted p=0.002). All-cause mortality was reduced by EDTA chelation [10% vs 16%, HR 0.57, 95% CI (0.36, 0.88) p=0.011], as was the secondary endpoint (cardiovascular death, reinfarction, or stroke) [11% vs 17% HR 0.60, 95% CI (0.39, 0.91), p=0.017]. After adjusting for multiple subgroups, however, those results were no longer significant. The number needed to treat to reduce one primary endpoint was 6.5 over 5 years (95% CI (4.4, 12.7). There was no reduction in events in non-diabetics (n=1075, p=0.877), resulting in a treatment by diabetes interaction (p=0.004). Conclusions Post-MI diabetic patients age 50 or older demonstrated a marked reduction in cardiovascular events with EDTA chelation. These findings support efforts to replicate these findings and define the mechanisms of benefit. They do not, however, constitute sufficient evidence to indicate the routine use of chelation therapy for all post-MI diabetic patients. PMID:24254885

  1. 3-hydroxy-2(1H)-pyridinone chelating agents

    Science.gov (United States)

    Raymond, K.; Xu, J.

    1999-04-06

    Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. 2 figs.

  2. Chelation of di- and trivalent iron with some polyaminopolycarboxylic acids

    International Nuclear Information System (INIS)

    Hafez, M.B.; Sharabi, Nahid; Patti, Francois.

    1979-02-01

    The chelation of di- and trivalent iron with some polyaminopolycarboxylic acids was studied. The influence of pH on the formation of the complex was investigated, the molecular ratio and the stability constants were determined [fr

  3. 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.

  4. Allogeneic hematopoietic cell transplantation in first remission abrogates poor outcomes associated with high-risk pediatric acute myeloid leukemia.

    Science.gov (United States)

    Burke, Michael J; Wagner, John E; Cao, Qing; Ustun, Celalettin; Verneris, Michael R

    2013-07-01

    Despite remission rates of approximately 85% for children diagnosed with acute myeloid leukemia (AML), greater than 40% will die from relapsed disease. Patients with poor-risk molecular/cytogenetics and/or inadequate response to up-front therapy are typically considered high-risk (HR) and historically have poor outcomes with chemotherapy alone. We investigated whether allogeneic hematopoietic cell transplantation (allo-HCT) with best available donor in first remission (CR1) would abrogate the poor outcomes associated with HR AML in children and young adults treated with chemotherapy. We reviewed the outcomes of 50 consecutive children and young adults (ages 0 to 30 years) with AML who received a myeloablative allo-HCT between 2001 and 2010. Thirty-six patients (72%) were HR, defined as having FLT3-ITD mutations, 11q23 MLL rearrangements, chromosome 5 or 7 abnormalities, induction failure, and/or having persistent disease. The majority of patients received cyclophosphamide and total body irradiation conditioning, and graft-versus-host-disease (GVHD) prophylaxis was cyclosporine based. Transplantation outcomes for HR patients were compared to standard-risk patients, with no significant differences observed in overall survival (72% versus 78%, P = .72), leukemia-free survival (69% versus 79%, P = .62), relapse (11% versus 7%, P = .71), or treatment-related mortality (17% versus 14%, P = .89). Children and young adults with HR-AML have comparable outcomes to standard-risk patients following allo-HCT in CR1. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  5. In Vitro Metabolism and Stability of the Actinide Chelating Agent 3,4,3-LI(1,2-HOPO)

    OpenAIRE

    Choi, Taylor A.; Furimsky, Anna M.; Swezey, Robert; Bunin, Deborah I.; Byrge, Patricia; Iyer, Lalitha V.; Chang, Polly Y.; Abergel, Rebecca J.

    2015-01-01

    The hydroxypyridinonate ligand 3,4,3-LI(1,2-HOPO) is currently under development for radionuclide chelation therapy. The preclinical characterization of this highly promising ligand comprised the evaluation of its in vitro properties, including microsomal, plasma, and gastrointestinal fluid stability, cytochrome P450 inhibition, plasma protein binding, and intestinal absorption using the Caco-2 cell line. When mixed with active human liver microsomes, no loss of parent compound was observed a...

  6. Iron chelators ICL670 and 311 inhibit HIV-1 transcription

    International Nuclear Information System (INIS)

    Debebe, Zufan; Ammosova, Tatyana; Jerebtsova, Marina; Kurantsin-Mills, Joseph; Niu, Xiaomei; Charles, Sharroya; Richardson, Des R.; Ray, Patricio E.; Gordeuk, Victor R.; Nekhai, Sergei

    2007-01-01

    HIV-1 replication is induced by an excess of iron and iron chelation by desferrioxamine (DFO) inhibits viral replication by reducing proliferation of infected cells. Treatment of cells with DFO and 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) inhibit expression of proteins that regulate cell-cycle progression, including cycle-dependent kinase 2 (CDK2). Our recent studies showed that CDK2 participates in HIV-1 transcription and viral replication suggesting that inhibition of CDK2 by iron chelators might also affect HIV-1 transcription. Here we evaluated the effect of a clinically approved orally effective iron chelator, 4-[3,5-bis-(hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid (ICL670) and 311 on HIV-1 transcription. Both ICL670 and 311 inhibited Tat-induced HIV-1 transcription in CEM-T cells, 293T and HeLa cells. Neither ICL670 nor 311 induced cytotoxicity at concentrations that inhibited HIV-1 transcription. The chelators decreased cellular activity of CDK2 and reduced HIV-1 Tat phosphorylation by CDK2. Neither ICL670A or 311 decreased CDK9 protein level but significantly reduced association of CDK9 with cyclin T1 and reduced phosphorylation of Ser-2 residues of RNA polymerase II C-terminal domain. In conclusion, our findings add to the evidence that iron chelators can inhibit HIV-1 transcription by deregulating CDK2 and CDK9. Further consideration should be given to the development of iron chelators for future anti-retroviral therapeutics

  7. The magnesium chelation step in chlorophyll biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Weinstein, J.

    1990-11-01

    In photosynthetic organisms, the biogenesis of energy transducing membranes requires the coordinate synthesis of prosthetic groups, proteins, and various lipids. Two of the major prosthetic groups, chlorophyll and heme, share a common biosynthetic pathway that diverges at the point of metal insertion into protoporphyrin IX (Proto). Insertion of iron leads to the formation of hemes, while insertion of magnesium is the first step unique to chlorophyll formation. This project is directed toward identifying the enzyme(s) responsible for magnesium chelation and elucidating the mechanism which regulates the flux of precursors through the branch point enzymes in isolated chloroplasts. Using intact chloroplasts from greening cucumber cotyledons, we have confirmed the ATP requirement for Mg-Proto formation. Use of non-hydrolyzable ATP analogs, uncouplers and ionophores has led to the conclusions that ATP hydrolysis is necessary, but that this hydrolysis is not linked to the requirement for membrane intactness by transmembrane ion gradients or electrical potentials. The enzyme(s) are flexible with respect to the porphyrin substrate specificity, accepting porphyrins with -vinyl, -ethyl, or -H substituents at the 2 and 4 positions. The activity increases approximately four-fold during greening. Possible physiological feedback inhibitors such as heme, protochlorophyllide, and chlorophyllide had no specific effect on the activity. The activity has now been assayed in barely, corn and peas, with the system from peas almost ten-fold more active than the cucumber system. Work is continuing in pea chloroplasts with the development of a continuous assay and investigation of the feasibility of characterizing an active, organelle-free preparation. 6 figs.

  8. Abrogation of Early Apoptosis Does Not Alter Late Inhibition of Hippocampal Neurogenesis After Irradiation

    International Nuclear Information System (INIS)

    Li Yuqing; Aubert, Isabelle; Wong, C. Shun

    2010-01-01

    Purpose: Irradiation of the adult brain results in acute apoptosis of neural progenitors and vascular endothelial cells, as well as late dysfunction of neural progenitors and inhibition of neurogenesis. We sought to determine whether the early apoptotic response has a causative role in late inhibition of neurogenesis after cranial irradiation. Methods and Materials: Using a genetic approach with p53 and smpd1 transgenic mice and a pharmacologic approach with basic fibroblast growth factor (bFGF) to abrogate the early apoptotic response, we evaluated the late inhibition of neurogenesis in the hippocampal dentate gyrus after cranial irradiation. Results: In dentate gyrus, subgranular neural progenitors underwent p53-dependent apoptosis within 24 h after irradiation. Despite a near abrogation of neural progenitor apoptosis in p53-/- mice, the reduction in newborn neurons in dentate gyrus at 9 weeks after irradiation in p53-/- mice was not different from that observed in wildtype controls. Endothelial cell apoptosis after radiation is mediated by membrane damage initiated by activation of acid sphingomyelinase (ASMase). Deletion of the smpd1 gene (which encodes ASMase) attenuated the apoptotic response of endothelial cells. At 9 weeks after irradiation, the inhibition of hippocampal neurogenesis was not rescued by ASMase deficiency. Intravenous administration of bFGF protected both endothelial cells and neural progenitors against radiation-induced apoptosis. There was no protection against inhibition of neurogenesis at 9 weeks after irradiation in bFGF-treated mice. Conclusion: Early apoptotic death of neural progenitors, endothelial cells, or both does not have a causative association with late inhibition of neurogenesis after irradiation.

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

    International Nuclear Information System (INIS)

    Gao, Xiaolong; Wang, Gangmin; Shi, Ting; Shao, Zhihong; Zhao, Peng; Shi, Donglu; Ren, Jie; Lin, Chao; Wang, Peijun

    2016-01-01

    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 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 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 1 -contrast agents for magnetic resonance imaging. • GdCPUAs hold high potential for cancer theranostics.

  10. 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.

  11. In vitro and in vivo evaluation of potential aluminum chelators.

    Science.gov (United States)

    Graff, L; Muller, G; Burnel, D

    1995-10-01

    The potential for aluminium (Al) chelation by different compounds was determined using 2 in vitro techniques. The formation of stable complexes with Al in an aqueous solution was evaluated using pulse polarography. This technique allowed the influence of temperature and calcium (Ca) to be studied for each compound. Certain compounds (EDDHA, HAES, citric acid and HBED) showed great chelation in the absence of Ca2+ at a temperature of 37 +/- 1 C. An ultrafiltration technique combined with Al determination by atomic emission spectroscopy allowed the efficiency of different substances to complex Al that were previously bound to serum proteins to be estimated. The kinetics of chelation and minimum efficient concentration have been determined for all products studied. EDDHA had chelation potential similar to DFO. The real efficacies of the compounds were studied in vivo to compare the effectiveness of repeated administrations of the best chelating agents (EDDHA, DFO, HAES and tartaric acid) on the distribution and excretion of Al after repeated i.p. administrations to rats. Intraperitoneal EDDHA significantly increased urinary metal (Al, Ca, Cu, Fe and Zn) excretion. These excretions may be correlated to a renal toxic potential property.

  12. The adsorption of chelating reagents on oxide minerals

    International Nuclear Information System (INIS)

    Bryson, M.A.W.

    1984-06-01

    This work constitutes a fundamental study of the interaction between chelating reagents and oxide minerals. The adsorption mechanisms have been elucidated for most of the systems generated by the oxides of copper(II) or iron(III) and chelating reagents octyl hydroxamate, N-phenylbenzohydroxamate, salicylaldoxime, 5-nitro-salicylaldoxime or 8-hydroxyquinoline. In order to better understand the adsorption process associated with copper(II) oxide, the oxide was recrystallized to produce a coarser material with a more uniform surface. This allowed the oxide surface to be viewed under the scanning electron microscope. A detailed investigation of the effect of the system variables; pH, conditioning period, concentration, temperature, surface area and dispersing reagent on the rate of precipitation of the copper chelate species of general form, Cu(chel) 2 , was made. In addition the chemical nature of the adsorbed species and the structural form of the precipitates were determined with the aid of infra-red spectroscopy and the scanning electron microscope. On the basis of these results a model has been formulated for the adsorption processes. The precipitation process was examined in more detail by the study of the adsorption of chelate on copper metal. Contact angle measurements of air bubbles on copper metal conditioned with chelate were related to the adsorption results in an attempt to isolate the optimum conditions for flotation of oxide minerals

  13. 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.

  14. Bifunctional chelates of Rh-105 and Au-199 as potential radiotherapeutic agents

    International Nuclear Information System (INIS)

    Troutner, D.E.; Schlemper, E.O.

    1990-01-01

    Since last year we have: continued the synthesis of pentadentate bifunctional chelating agents based on diethylene triamine; studied the chelation Rh-105, Au-198 (as model for Au-199) and Tc-99m with these agents as well as chelation of Pd-109, Cu-67, In-111, and Co-57 with some of them; synthesized a new class of potential bifunctional chelating agents based on phenylene diamine; investigated the behavior of Au-198 as a model for Au-199; begun synthesis of bifunctional chelating agents based on terpyridly and similar ligands; and continued attempts to produce tetradentate bifunctional chelates based on diaminopropane. Each of these will be addressed in this report

  15. TARGETED DELETION OF INDUCIBLE HEAT SHOCK PROTEIN 70 ABROGATES THE LATE INFARCT-SPARING EFFECT OF MYOCARDIAL ISCHEMIC PRECONDITIONING

    Science.gov (United States)

    Abstract submitted for 82nd annual meeting of the American Association for Thoracic Surgery, May 4-8, 2002 in Washington D.C.Targeted Deletion of Inducible Heat Shock Protein 70 Abrogates the Late Infarct-Sparing Effect of Myocardial Ischemic PreconditioningCraig...

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

    International Nuclear Information System (INIS)

    Hnatowich, D.J.; Schlegel, P.

    1981-01-01

    Albumin microspheres have been synthesized with 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 24 hr in 50% plasma at 37 0 C, whereas with DTPA microspheres the label shows 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 h. Since labeling is by chelation, the microspheres may also be tagged with other metallic radionuclides

  17. Evaluation of macrocyclic hydroxyisophthalamide ligands as chelators for zirconium-89.

    Science.gov (United States)

    Bhatt, Nikunj B; Pandya, Darpan N; Xu, Jide; Tatum, David; Magda, Darren; Wadas, Thaddeus J

    2017-01-01

    The development of bifunctional chelators (BFCs) for zirconium-89 immuno-PET applications is an area of active research. Herein we report the synthesis and evaluation of octadentate hydroxyisophthalamide ligands (1 and 2) as zirconium-89 chelators. While both radiometal complexes could be prepared quantitatively and with excellent specific activity, preparation of 89Zr-1 required elevated temperature and an increased reaction time. 89Zr-1 was more stable than 89Zr-2 when challenged in vitro by excess DTPA or serum proteins and in vivo during acute biodistribution studies. Differences in radiometal complex stability arise from structural changes between the two ligand systems, and suggest further ligand optimization is necessary to enhance 89Zr chelation.

  18. Evaluation of macrocyclic hydroxyisophthalamide ligands as chelators for zirconium-89.

    Directory of Open Access Journals (Sweden)

    Nikunj B Bhatt

    Full Text Available The development of bifunctional chelators (BFCs for zirconium-89 immuno-PET applications is an area of active research. Herein we report the synthesis and evaluation of octadentate hydroxyisophthalamide ligands (1 and 2 as zirconium-89 chelators. While both radiometal complexes could be prepared quantitatively and with excellent specific activity, preparation of 89Zr-1 required elevated temperature and an increased reaction time. 89Zr-1 was more stable than 89Zr-2 when challenged in vitro by excess DTPA or serum proteins and in vivo during acute biodistribution studies. Differences in radiometal complex stability arise from structural changes between the two ligand systems, and suggest further ligand optimization is necessary to enhance 89Zr chelation.

  19. A bis(3-hydroxy-4-pyridinone)-EDTA derivative as a strong chelator for M3+ hard metal ions: complexation ability and selectivity.

    Science.gov (United States)

    Gama, Sofia; Dron, Paul; Chaves, Silvia; Farkas, Etelka; Santos, M Amélia

    2009-08-21

    The study of chelating compounds is very important to solve problems related to human metal overload. 3-Hydroxy-3-pyridinones (HP), namely deferiprone, have been clinically used for chelating therapy of Fe and Al over the last decade. A multi-disciplinary search for alternative molecules led us to develop poly-(3-hydroxy-4-pyridinones) to increase metal chelation efficacy. We present herein a complexation study of a new bis-(3-hydroxy-4-pyridinone)-EDTA derivative with a set of M(3+) hard metal ions (M = Fe, Al, Ga), as well as Zn(2+), a biologically relevant metal ion. Thus a systematic aqueous solution equilibrium study was performed using potentiometric and spectroscopic techniques (UV-Vis, NMR methods). These set of results enables the establishment of specific models as well as the determination of thermodynamic stability constants and coordination modes of the metal complexes. The results indicate that this ligand has a higher affinity for chelating to these hard metal ions than deferiprone, and that the coordination occurs mostly through the HP moieties. Furthermore, it was also found that this ligand has a higher selectivity for chelating to M(3+) hard metal ions (M = Fe, Al, Ga) than Zn(2+).

  20. Metallomics for Alzheimer's disease treatment: Use of new generation of chelators combining metal-cation binding and transport properties.

    Science.gov (United States)

    D'Acunto, Cosimo Walter; Kaplánek, Robert; Gbelcová, Helena; Kejík, Zdeněk; Bříza, Tomáš; Vasina, Liudmila; Havlík, Martin; Ruml, Tomáš; Král, Vladimír

    2018-04-25

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting tens of million people. Currently marketed drugs have limited therapeutic efficacy and only slowing down the neurodegenerative process. Interestingly, it has been suggested that biometal cations in the amyloid beta (Aβ) aggregate deposits contribute to neurotoxicity and degenerative changes in AD. Thus, chelation therapy could represent novel mode of therapeutic intervention. Here we describe the features of chelators with therapeutically relevant mechanism of action. We have found that the tested compounds effectively reduce the toxicity of exogenous Aβ and suppress its endogenous production as well as decrease oxidative stress. Cholyl hydrazones were found to be the most active compounds. In summary, our data show that cation complexation, together with improving transport efficacy may represent basis for eventual treatment strategy in AD. Copyright © 2018. Published by Elsevier Masson SAS.

  1. Heavy metal displacement in chelate-irrigated soil during phytoremediation

    Science.gov (United States)

    Madrid, F.; Liphadzi, M. S.; Kirkham, M. B.

    2003-03-01

    Heavy metals in wastewater sewage sludge (biosolids), applied to land, contaminate soils. Phytoremediation, the use of plants to clean up toxic heavy metals, might remove them. Chelating agents are added to soil to solubilize the metals for enhanced phytoextraction. Yet no studies follow the displacement and leaching of heavy metals in soil with and without roots following solubilization with chelates. The objective of this work was to determine the mobility of heavy metals in biosolids applied to the surface of soil columns (76 cm long; 17 cm diam.) with or without plants (barley; Hordeum vulgare L.). Three weeks after barley was planted, all columns were irrigated with the disodium salt of the chelating agent, EDTA (ethylenediamine tetraacetic acid) (0.5 g/kg soil). Drainage water, soil, and plants were analyzed for heavy metals (Cd, Cu, Fe, Mn, Ni, Pb, Zn). Total concentrations of the heavy metals in all columns at the end of the experiment generally were lower in the top 30 cm of soil with EDTA than without EDTA. The chelate increased concentrations of heavy metals in shoots. With or without plants, the EDTA mobilized Cd, Fe, Mn, Ni, Pb, and Zn, which leached to drainage water. Drainage water from columns without EDTA had concentrations of these heavy metals below detection limits. Only Cu did not leach in the presence of EDTA. Even though roots retarded the movement of Cd, Fe, Mn, Ni, Pb, and Zn through the EDTA-treated soil from 1 d (Cd) to 5 d (Fe), the drainage water from columns with EDTA had concentrations of Cd, Fe, Mn, and Pb that exceeded drinking water standards by 1.3, 500, 620, and 8.6 times, respectively. Because the chelate rendered Cd, Fe, Mn, Ni, Pb, and Zn mobile, it is suggested that the theory for leaching of soluble salts, put forward by Nielsen and associates in 1965, could be applied to control movement of the heavy metals for maximum uptake during chelate-assisted phytoremediation.

  2. Interaction of chelating agents with cadmium in mice and rats

    International Nuclear Information System (INIS)

    Eybl, V.; Sykora, J.; Koutensky, J.; Caisova, D.; Schwartz, A.; Mertl, F.

    1984-01-01

    The influence of several chelating agents (CaDTPA, ZnDTPA, CaEDTA, ZnEDTA, DMSA, D-penicillamine and DMPS, DMP and DDC) on the acute toxicity of CdCl 2 and on the whole body retention and tissue distribution of cadmium after the IV application of /sup 115mCdCl 2 was compared in mice. The chelating agents were applied immediately after the application of cadmium. CaDTPA, ZnDTPA and DMSA appeared to be the most effective antidotes. However, DMSA increased the amount of cadmium retained in kidneys. The treatement of cadmium-poisoned mice with the combination of DMSA (IP) and ZnDTPA (SC) (all the compounds were injected in equimolar dose) decreased the toxicity of cadmium more than treatment with one chelating agents (given in a 2:1 dose). However, by studying the effect of these chelating agents and their combination application of the antidotes showed little or no improvement over the results obtained with the most effective of the individual components. In the urine of rats injected with CdCl 2 and treated with the chelating agents (CaDTPA, ZnDTPA, DMSA), the presence of cadmium complexes was demonstrated. The formation of mixed ligand chelates in vivo was not proved. Experiments in mice given a single injection of /sup 115m/Cd-labeled Cd complexes of DMPS, DMSA and DTPA showed a high retention of cadmium in the organisms after the IV application of CdDMPS and CdDMSA complexes

  3. Interaction of chelating agents with cadmium in mice and rats.

    Science.gov (United States)

    Eybl, V; Sýkora, J; Koutenský, J; Caisová, D; Schwartz, A; Mertl, F

    1984-01-01

    The influence of several chelating agents (CaDTPA, ZnDTPA, CaEDTA, ZnEDTA, DMSA, D-penicillamine and DMPS, DMP and DDC) on the acute toxicity of CdCl2 and on the whole body retention and tissue distribution of cadmium after the IV application of 115mCdCl2 was compared in mice. The chelating agents were applied immediately after the application of cadmium. CaDTPA, ZnDTPA and DMSA appeared to be the most effective antidotes. However, DMSA increased the amount of cadmium retained in kidneys. The treatment of cadmium-poisoned mice with the combination of DMSA (IP) and ZnDTPA (SC) (all the compounds were injected in equimolar dose) decreased the toxicity of cadmium more than treatment with one chelating agents (given in a 2:1 dose). However, by studying the effect of these chelating agents and their combination of the retention and distribution of Cd in mice, it was demonstrated that the combined application of the antidotes showed little or no improvement over the results obtained with the most effective of the individual components. In the urine of rats injected with CdCl2 and treated with the chelating agents (CaDTPA, ZnDTPA, DMSA), the presence of cadmium complexes was demonstrated. The formation of mixed ligand chelates in vivo was not proved. Experiments in mice given a single injection of 115mCd-labeled Cd complexes of DMPS, DMSA and DTPA showed a high retention of cadmium in the organisms after the IV application of CdDMPS and CdDMSA complexes. PMID:6734561

  4. Potentiometric study of Nd3+ chelates of substituted salicylhydroxamic acids

    International Nuclear Information System (INIS)

    Deshpande, R.G.; Jahagirdar, D.V.

    1976-01-01

    The interaction of Nd 3+ ion with salicylhydroxamic acid and 5-methyl, 5-chloro, 5-bromo, 5-nitro, 4-chloro, 4-bromo and 3-chloro salicylhydroxamic acids is investigated potentiometrically by Calvin-Bjerrum titration technique at 30 0 +- 0.1 0 and ionic strength μ=0.1 M(NaClO 4 ) in 50% v/v dioxane-water mixtures. Nd 3+ forms only 1:1 chelates with these ligands. The validity of the log K= apk + b relationship is examined for these chelates. (author)

  5. 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

  6. Arsenic induces apoptosis in mouse liver is mitochondria dependent and is abrogated by N-acetylcysteine

    International Nuclear Information System (INIS)

    Santra, Amal; Chowdhury, Abhijit; Ghatak, Subhadip; Biswas, Ayan; Dhali, Gopal Krishna

    2007-01-01

    Arsenicosis, caused by arsenic contamination of drinking water supplies, is a major public health problem in India and Bangladesh. Chronic liver disease, often with portal hypertension occurs in chronic arsenicosis, contributes to the morbidity and mortality. The early cellular events that initiate liver cell injury due to arsenicosis have not been studied. Our aim was to identify the possible mechanisms related to arsenic-induced liver injury in mice. Liver injury was induced in mice by arsenic treatment. The liver was used for mitochondrial oxidative stress, mitochondrial permeability transition (MPT). Evidence of apoptosis was sought by TUNEL test, caspase assay and histology. Pretreatment with N-acetyl-L-cysteine (NAC) was done to modulate hepatic GSH level. Arsenic treatment in mice caused liver injury associated with increased oxidative stress in liver mitochondria and alteration of MPT. Altered MPT facilitated cytochrome c release in the cytosol, activation of caspase 9 and caspase 3 activities and apoptotic cell death. Pretreatment of NAC to arsenic-treated mice abrogated all these alteration suggesting a glutathione (GSH)-dependent mechanism. Oxidative stress in mitochondria and inappropriate MPT are important in the pathogenesis of arsenic induced apoptotic liver cell injury. The phenomenon is GSH dependent and supplementation of NAC might have beneficial effects

  7. 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.

  8. Loss of p53 induces M-phase retardation following G2 DNA damage checkpoint abrogation.

    Science.gov (United States)

    Minemoto, Yuzuru; Uchida, Sanae; Ohtsubo, Motoaki; Shimura, Mari; Sasagawa, Toshiyuki; Hirata, Masato; Nakagama, Hitoshi; Ishizaka, Yukihito; Yamashita, Katsumi

    2003-04-01

    Most cell lines that lack functional p53 protein are arrested in the G2 phase of the cell cycle due to DNA damage. When the G2 checkpoint is abrogated, these cells are forced into mitotic catastrophe. A549 lung adenocarcinoma cells, in which p53 was eliminated with the HPV16 E6 gene, exhibited efficient arrest in the G2 phase when treated with adriamycin. Administration of caffeine to G2-arrested cells induced a drastic change in cell phenotype, the nature of which depended on the status of p53. Flow cytometric and microscopic observations revealed that cells that either contained or lacked p53 resumed their cell cycles and entered mitosis upon caffeine treatment. However, transit to the M phase was slower in p53-negative cells than in p53-positive cells. Consistent with these observations, CDK1 activity was maintained at high levels, along with stable cyclin B1, in p53-negative cells. The addition of butyrolactone I, which is an inhibitor of CDK1 and CDK2, to the p53-negative cells reduced the floating round cell population and induced the disappearance of cyclin B1. These results suggest a relationship between the p53 pathway and the ubiquitin-mediated degradation of mitotic cyclins and possible cross-talk between the G2-DNA damage checkpoint and the mitotic checkpoint.

  9. Beclin1-induced autophagy abrogates radioresistance of lung cancer cells by suppressing osteopontin

    International Nuclear Information System (INIS)

    Chang, Seung-Hee; Minai-Tehrani, Arash; Shin, Ji-Young

    2012-01-01

    Osteopontin (OPN) serves as an indicator of resistance to radiotherapy. However, the role of OPN in the development of acquired radioresistance in human lung cancer cells has not yet been fully elucidated. Therefore, the potential importance of OPN as a marker of lung cancer with a potential significant role in the development of radioresistance against repeated radiotherapy has prompted us to define the pathways by which OPN regulates lung cancer cell growth. In addition, autophagy has been reported to play a key role in the radiosensitization of cancer cells. Here, we report that increased OPN expression through induction of nuclear p53 following irradiation was inhibited by exogenous beclin-1 (BECN1). Our results clearly show that BECN1 gene expression led to induction of autophagy and inhibition of cancer cell growth and angiogenesis. Our results suggest that the induction of autophagy abrogated the radioresistance of the cancer cells. Interestingly, we showed that knockdown of OPN by lentivirus-mediated shRNA induced the autophagy of human lung cancer cell. Taken together, these results suggest that OPN and BECN1 can be molecular targets for overcoming radioresistance by controlling autophagy. (author)

  10. Metal chelate conjugated monoclonal antibodies, wherein the metal is an α emitter

    International Nuclear Information System (INIS)

    Gansow, O.A.; Strand, M.

    1984-01-01

    Methods of manufacturing and purifying metal chelate conjugated monoclonal antibodies are described, wherein the chelated metal emits alpha radiation. The conjugates are suited for therapeutic uses being substantially free of nonchelated radiometal. (author)

  11. Chelating ligands: enhancers of quality and purity of biogas ...

    African Journals Online (AJOL)

    The quality of biogas depends largely on the percentage of methane and hydrogen sulphide gas present. High concentration of hydrogen sulphide results in low quality biogas. This work employed the use of chelating ligands in scrubbing hydrogen sulphide gas while improving the yield of methane gas. Experimental ...

  12. Studies on effect of Microbial Iron Chelators on Candida Albican

    International Nuclear Information System (INIS)

    Rehmani, Fouzia S.; Milicent, S.; Zaheer-Uddin

    2005-01-01

    Iron is an essential for the life of all microbe cells. It generally exists in the oxidized form Fe(III). Even under anaerobic reducing condition the metal appear to be taken up as Fe(III). Thus free-living microorganisms require specific and effective ferric ion transport system to cope with low availability of the metal. In iron deficient environment they produce a low molecular weight specific chelators called siderphores or microbial iron chelators. Siderphores compete for limited supplied of iron. These compounds came out of the cell but can not re-enter without iron due to high affinity of these siderphores often have more than one catechol/hydroxamate functions and are multidentate (usually hexadentate ligands). The aim of the present research is to check the effect of iron chelators, namely gallic acid and salisyl hydroxamate on the growth of Candida albican in vitro. C. albican is the opportunistic paltogen present as the normal flora inside human body. In vivo the growth of C. albican is distributed by the use of antibiotics and immuno suppressers. In cases of iron over-dosage in human being, the patients are treated with certain a-iron chelators. Hence an attempt is made to notice the effect that might be inhibition or enhancement of the organism in vitro. (author)

  13. 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.

  14. Chelation of thallium by combining deferasirox and desferrioxamine in rats.

    Science.gov (United States)

    Saljooghi, Amir Shokooh; Babaie, Maryam; Mendi, Fatemeh Delavar; Zahmati, Maliheh; Saljooghi, Zoheir Shokouh

    2016-01-01

    The hypothesis that two known chelators deferasirox (4-[3,5-bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid) and desferrioxamine (DFO) might be more efficient as combined treatment than as monotherapies in removing thallium from the body was tested in a new acute rat model. 7-week-old male Wistar rats received chelators: deferasirox (orally), DFO (intraperitoneal; i.p.), or deferasirox + DFO as 75 or 150 mg/kg dose half an hour after a single i.p. administration of 8 mg thallium/kg body weight in the form of chloride. Serum thallium concentration, urinary thallium, and iron excretions were determined by graphite furnace atomic absorption spectrometry. Both chelators were effective only at the higher dose level, while DFO was more effective than deferasirox in enhancing urinary thallium excretion, deferasirox was more effective than DFO in enhancing urinary iron excretion. In the combined treatment group, deferasirox did not increase the DFO effect on thallium and DFO 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 thallium chelators. Urinary values were more useful because of the high variability of serum results. © The Author(s) 2013.

  15. Iron chelating activity, phenol and flavonoid content of some ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-09-17

    Sep 17, 2008 ... require regular blood transfusions in order to improve both quality of ... fused red blood cells and the excess iron is deposited as ... potentiation of reactive oxygen species (ROS) and .... The percentage inhibition of ferrozine–Fe2+ complex formation was ... estimation of the chelating activity of the coexisting.

  16. Bone marrow and chelatable iron in patients with protein energy ...

    African Journals Online (AJOL)

    Objectives: To examine the iron status of malnourished children by comparing bone marrow iron deposits in children with protein energy malnutrition with those in well-nourished controls, and measuring chelatable urinary iron excretion in children with kwashiorkor. Design: Bone marrow iron was assessed histologicaHy in ...

  17. f-Element Ion Chelation in Highly Basic Media

    International Nuclear Information System (INIS)

    Paine, R.T.

    2000-01-01

    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 chelators 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

  18. Phenolic aminocarboxylic acids - new chelating agents for modifying gallium-67 biodistribution

    International Nuclear Information System (INIS)

    Hunt, F.C.; Maddalena, D.J.

    1982-01-01

    The chelating agents EDDHA and HBED were synthesised with carboxyl or sulphonyl groups in the phenolic ring to favour urinary excretion on complexing with gallium. Carboxyl EDDMA was administered to tumor-bearing rats, and its concentration in the tumours and other tissues determined by scintigraphic imaging. The chelating agents increase tumour to blood ratios by chelating gallium in vivo. (U.K.)

  19. Phenolic aminocarboxylic acids - new chelating agents for modifying gallium-67 biodistribution

    Energy Technology Data Exchange (ETDEWEB)

    Hunt, F.C.; Maddalena, D.J. (Australian Atomic Energy Commission Research Establishment, Lucas Heights)

    The chelating agents EDDHA and HBED were synthesised with carboxyl or sulphonyl groups in the phenolic ring to favour urinary excretion on complexing with gallium. Carboxyl EDDMA was administered to tumor-bearing rats, and its concentration in the tumours and other tissues determined by scintigraphic imaging. The chelating agents increase tumour to blood ratios by chelating gallium in vivo.

  20. Chelator induced phytoextraction and in situ soil washing of Cu

    International Nuclear Information System (INIS)

    Kos, Bostjan; Lestan, Domen

    2004-01-01

    In a soil column experiment, we investigated the effect of 5 mmol kg -1 soil addition of citric acid, ethylenediamine tetraacetate (EDTA), diethylenetriamine-pentaacetate (DTPA) and [S,S]-stereoisomer of ethylenediamine-disuccinate (EDDS) on phytoextraction of Cu from a vineyard soil with 162.6 mg kg -1 Cu, into the test plant Brassica rapa var. pekinensis. We also examined the use of a horizontal permeable barrier, composed of layers of nutrient enriched sawdust and apatite, for reduction of chelator induced Cu leaching. The addition of all chelators, except citric acid, enhanced Cu mobility and caused leaching of 19.5-23% of initial total Cu from the soil column. However, Cu plant uptake did not increase accordingly; the most effective was the EDDS treatment, in which plant Cu concentration reached 37.8±1.3 mg kg -1 Cu and increased by 3.3-times over the control treatment. The addition of none of the chelators in the concentration range from 5 to 15 mmol kg -1 exerted any toxic effect on respiratory soil microorganisms. When EDDS was applied into the columns with horizontal permeable barriers, only 0.53±0.32% of the initial total Cu was leached. Cu (36.7%) was washed from the 18 cm soil layer above the barrier and accumulated in the barrier. Our results indicate that rather than for a reduction of Cu leaching during rather ineffective chelate induced Cu phytoextraction, horizontal permeable barriers could be more effective in a new remediation technique of controlled in situ soil washing of Cu with biodegradable chelates

  1. 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.

  2. Targeting ILK and β4 integrin abrogates the invasive potential of ovarian cancer

    International Nuclear Information System (INIS)

    Choi, Yoon Pyo; Kim, Baek Gil; Gao, Ming-Qing; Kang, Suki; Cho, Nam Hoon

    2012-01-01

    Highlights: ► The potential of targeting ILK and integrins for highly aggressive ovarian cancer. ► Unanticipated synergistic effect for the combination of ILK/β4 integrin. ► Combination of ILK/β4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. ► Targeting of β4 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 β1 and β4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of β1 and β4 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 β4 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 β4 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 β4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.

  3. 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.

  4. Inhibition of GRP78 abrogates radioresistance in oropharyngeal carcinoma cells after EGFR inhibition by cetuximab.

    Directory of Open Access Journals (Sweden)

    Chaonan Sun

    Full Text Available The EGFR-specific mAb cetuximab is one of the most effective treatments for oropharyngeal carcinoma, while patient responses to EGFR inhibitors given alone are modest. Combination treatment with radiation can improve the efficacy of treatment through increasing radiosensitivity, while resistance to radiation after administration of cetuximab limits its efficiency. Radiation and drugs can damage the endoplasmic reticulum (ER homeostatic state and result in ER stress (ERS, subsequently causing resistance to radiation and drugs. Whether the ERS pathway is involved in radioresistance after administration of cetuximab has not been reported. Herein, we show that cetuximab could increase the radiosensitivity of FaDu cells but not Detroit562 cells. In addition, cetuximab inhibited the radiation-induced activation of the ERS signalling pathway IRE1α/ATF6-GRP78 in FaDu cells, while this effect was absent in Detroit562 cells. Silencing GRP78 increased the radiosensitivity of oropharyngeal carcinoma cells and inhibited radiation-induced DNA double-strand-break (DSB repair and autophagy. More interestingly, silencing GRP78 abrogated resistance to cetuximab and radiation in Detroit562 cells and had a synergistic effect with cetuximab in increasing the radiosensitivity of FaDu cells. Immunohistochemistry showed that overexpression of both GRP78 and EGFR was associated with a poor prognosis in oropharyngeal carcinoma patients (P<0.05. Overall, the results of this study show that radioresistance after EGFR inhibition by cetuximab is mediated by the ERS signalling pathway IRE1α/ATF6-GRP78. This suppression was consequently unable to inhibit radiation-induced DSB repair and autophagy in oropharyngeal carcinoma cells, which conferred resistance to radiotherapy and cetuximab. These results suggest that the cooperative effects of radiotherapy and cetuximab could be further improved by inhibiting GRP78 in non-responsive oropharyngeal carcinoma patients.

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

    International Nuclear Information System (INIS)

    Ahad, Amjid; Ganai, Ajaz Ahmad; Mujeeb, Mohd; Siddiqui, Waseem Ahmad

    2014-01-01

    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

  6. Selective induction of cyclin B protein abrogates the G2 delay after irradiation

    International Nuclear Information System (INIS)

    Kao, G.; Muschel, R.J.; Maity, A.; Kunig, A.; McKenna, W.G.

    1996-01-01

    Purpose/Objective: Irradiation of tumor cells commonly results in G2 delay, which has been postulated to allow DNA repair and cell survival. The G2 delay after irradiation is also often marked in some cell lines by delayed expression of cyclin B protein, suggesting a role for cyclin B regulation. Investigations of these hypotheses however has been hampered by the inability to selectively perturb the G2 delay in a physiologic manner. Materials and Methods: We have devised a system, with which we are able to selectively induce cyclin B protein expression in vivo at specific points in the cell cycle, by transfecting Hela cells with an expression vector under control of a dexamethasone-inducible promoter. Experiments were subsequently performed by synchronizing, releasing, irradiating, inducing, and harvesting these cells through the cell cycle. Results: Irradiation with 5 Gy led to a pronounced G2 delay, reflected by markedly slowed progression into mitosis, concomitant with reduced expression of cyclin B protein. Induction of cyclin B after radiation in these cells abrogated the G2 delay by approximately doubling the rate at which the cells re-enter mitosis. Treatment of irradiated untransfected control cells with dexamethasone, in which cyclin B is not induced, led to minimal changes. Studies of effects of cyclin B induction on cyclin B localization (using immunofluorescence), cdc2 phosphorylation and activation will also be presented. Conclusion: This system should allow further investigations into fundamental mechanisms of cell cycle regulation after irradiation and DNA damage. This also provides direct evidence for the first time that cyclin B protein regulation may play a role in the G2 delay following irradiation in Hela cells, perhaps complementing phosphorylation events

  7. KNK437, abrogates hypoxia-induced radioresistance by dual targeting of the AKT and HIF-1α survival pathways

    International Nuclear Information System (INIS)

    Oommen, Deepu; Prise, Kevin M.

    2012-01-01

    Highlights: ► KNK437, a benzylidene lactam compound, is a novel radiosensitizer. ► KNK437 inhibits AKT signaling and abrogates the accumulation of HIF-1α under hypoxia. ► KNK437 abrogates hypoxia induced resistance to radiation. -- Abstract: KNK437 is a benzylidene lactam compound known to inhibit stress-induced synthesis of heat shock proteins (HSPs). HSPs promote radioresistance and play a major role in stabilizing hypoxia inducible factor-1α (HIF-1α). HIF-1α is widely responsible for tumor resistance to radiation under hypoxic conditions. We hypothesized that KNK437 sensitizes cancer cells to radiation and overrides hypoxia-induced radioresistance via destabilizing HIF-1α. Treatment of human cancer cells MDA-MB-231 and T98G with KNK437 sensitized them to ionizing radiation (IR). Surprisingly, IR did not induce HSPs in these cell lines. As hypothesized, KNK437 abrogated the accumulation of HIF-1α in hypoxic cells. However, there was no induction of HSPs under hypoxic conditions. Moreover, the proteosome inhibitor MG132 did not restore HIF-1α levels in KNK437-treated cells. This suggested that the absence of HIF-1α in hypoxic cells was not due to the enhanced protein degradation. HIF-1α is mainly regulated at the level of post-transcription and AKT is known to modulate the translation of HIF-1α mRNA. Interestingly, pre-treatment of cells with KNK437 inhibited AKT signaling. Furthermore, down regulation of AKT by siRNA abrogated HIF-1α levels under hypoxia. Interestingly, KNK437 reduced cell survival in hypoxic conditions and inhibited hypoxia-induced resistance to radiation. Taken together, these data suggest that KNK437 is an effective radiosensitizer that targets multiple pro-survival stress response pathways.

  8. A randomized, controlled study evaluating effects of amlodipine addition to chelators to reduce iron loading in patients with thalassemia major.

    Science.gov (United States)

    Eghbali, Aziz; Kazemi, Hamideh; Taherahmadi, Hassan; Ghandi, Yazdan; Rafiei, Mohammad; Bagheri, Bahador

    2017-12-01

    Cardiomyopathy due to iron overload can be fatal in patients with thalassemia major. Calcium channel blockers seem to be effective to reduce iron loading. Our goal was to study effects of amlodipine addition to chelators on iron loading in patients with thalassemia major. This randomized, controlled, and single-center trial was performed on 56 patients with thalassemia major. Patients were randomized 1:1 to combined group (iron chelator plus amlodipine) or control group (iron chelator) for 1 year. Iron content was measured by magnetic resonance imaging; heart T2*, and liver T2*. Serum ferritin was also measured. After 12 months of treatment, myocardial T2* values had significant improvement in combined group (21.9 ± 8.0 ms to 24.5 ± 7.6 ms; P < .05); Difference between two groups was significant (P = .02). Combined treatment had no effect on hepatic T2* value (9.6 ± 2.8 ms to 9.5 ± 3.6 ms); difference between two groups was not significant (P = .2). In addition, a significant reduction was seen in serum ferritin levels in two groups. Mild gastrointestinal upset was the most common untoward effect. Addition of amlodipine to iron chelators has beneficial effects for reduction of iron loading in patients with thalassemia major. This combination therapy seems safe. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. 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

  10. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Improved paramagnetic chelate for molecular imaging with MRI

    International Nuclear Information System (INIS)

    Winter, Patrick; Athey, Phillip; Kiefer, Garry; Gulyas, Gyongyi; Frank, Keith; Fuhrhop, Ralph; Robertson, David; Wickline, Samuel; Lanza, Gregory

    2005-01-01

    The relaxivity and transmetallation of two lipophilic paramagnetic chelates incorporated onto perfluorocarbon nanoparticles, i.e., gadolinium-methoxy-tetraazacyclododecane-tetraacetic acid phosphatidylethanolamine (Gd-MeO-DOTA-PE) and gadolinium-methoxy-tetraazacyclododecane-tetraacetic acid triglycine phosphatidylethanolamine (Gd-MeO-DOTA-triglycine-PE (Gd-MeO-DOTA-triglycine-PE)), were compared to a prototypic gadolinium-diethylene-triamine-pentaacetic acid bis-oleate (Gd-DTPA-BOA) paramagnetic formulation. Nanoparticles with MeO-DOTA-based chelates demonstrated higher relaxivity (40% higher for Gd-MeO-DOTA-PE and 55% higher for Gd-MeO-DOTA-triglycine-PE) and less transmetallation than the original Gd-DTPA-BOA-based agent

  12. Treatment of some radioactive wastes by using new chelating membranes

    International Nuclear Information System (INIS)

    Hegazy, S.A.; El-Adham, K.; Abdel Geleel, M.; Soliman, S.A.

    2000-01-01

    The preparation of chelating membranes containing nitrile and carboxylic acid as functional groups was investigated. The modification of such membranes by chemical treatments to produce significant changes in their properties was studied. This modification results in a higher rate of exchange and higher capacity. The applicability of such modified membranes in the removal of Co-60 and Cs-137 from their wastes were tested. The dependence of these radioactive nuclides uptake on the time and degree of grafting for H CI-, NH 2 OH-and KOH-treated membranes was investigated. It was found that the adsorption rate and capacity were higher for KOH-treated membrane than those for the NH 2 OH and H CI treated ones. The prepared grafted membranes have a good affinity towards the adsorption or chelation with Co-60 and Cs-137. This result may make such prepared materials acceptable for practicable use in some radioactive waste treatments and recovery

  13. Chelation studies involving decontamination of light lanthanides by polyaminopolycarboxylic

    International Nuclear Information System (INIS)

    Hassan, N.E.H.

    1985-01-01

    The present thesis constitutes chelation studies involving decontamination of light lanthanides, cobalt , and uranium with 2,2-bis-acryloyliminomethylene- acid (BAETA) using the spectrophotometric method. the work carried out aimed to clear up the effectiveness of BAETA as a decontaminating agent for radioactive nuclides from human body . the thesis includes a general introduction , outlines the aim of work and contains three main chapters . the results of the work are discussed at the end of the thesis. the first chapter deals with a comprehensive survey of the relevant literature. this includes the metabolism and toxicity of cerium, uranium, cobalt and Ln +3 elements, general methodologies of internal decontamination, choice and effectiveness of chelating agents

  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...... OEP-Cu in the liquid or solid cores of the nanoparticles in the presence of a lipid sink. RESULTS: (1) The size of the nanoparticles was found to be strongly dependent on the Reynolds number and the initial concentration of components for the fast injection technique. At high Reynolds number (2181......), a minimum value for the particle diameter of ∼30nm was measured. (2) Copper was chelated by OEP in a 1:1mol ratio with an association constant of 2.57×10(5)M(-1). (3) The diameter of the nanoparticles was not significantly affected by the presence of OEP or OEP-Cu. The percentage of encapsulation of copper...

  15. Iron chelates: a challenge to chemists and Moessbauer spectroscopists

    Energy Technology Data Exchange (ETDEWEB)

    Homonnay, Z., E-mail: homonnay@chem.elte.hu; Szilagyi, P. A.; Vertes, A. [Eoetvoes Lorand University, Laboratory of Nuclear Chemistry, Institute of Chemistry (Hungary); Kuzmann, E. [Hungarian Academy of Sciences, Department of Nuclear Chemistry, Chemical Research Center (Hungary); Sharma, V. K. [Florida Institute of Technology (United States); Molnar, G.; Bousseksou, A. [CNRS UPR-8241, Laboratoire de Chimie de Coordination (France); Greneche, J.-M. [Universite du Maine, Laboratoire de Physique de l' Etat Condense, CNRS UMR 6087 (France); Brausam, A.; Meier, R.; Eldik, R. van [University of Erlangen-Nuernberg, Institute for Inorganic Chemistry (Germany)

    2008-02-15

    The speciation of iron in aqueous solutions containing Fe{sup 3+} and selected chelates such as EDTA, EDDA, CDTA and HEDTA has been studied using transmission {sup 57}Fe Moessbauer spectrometry in frozen solutions. The protonation of various complexes as well as binuclear complex formation could be detected as a function of pH. Autoreduction of Fe{sup 3+} to Fe{sup 2+} was observed in several cases. Reaction with hydrogen peroxide proved to be rather different for the four ligands, while the dihapto complex [XFe({eta}{sup 2}-O{sub 2})]{sup 3-} had surprisingly identical Moessbauer parameters for X = EDTA, CDTA or HEDTA. Paramagnetic spin relaxation observed in the Moessbauer spectra was found to be strongly influenced by the identity of the chelating ligand, despite the basically spin-spin origin of the phenomenon.

  16. Improved paramagnetic chelate for molecular imaging with MRI

    Science.gov (United States)

    Winter, Patrick; Athey, Phillip; Kiefer, Garry; Gulyas, Gyongyi; Frank, Keith; Fuhrhop, Ralph; Robertson, David; Wickline, Samuel; Lanza, Gregory

    2005-05-01

    The relaxivity and transmetallation of two lipophilic paramagnetic chelates incorporated onto perfluorocarbon nanoparticles, i.e., gadolinium-methoxy-tetraazacyclododecane-tetraacetic acid phosphatidylethanolamine (Gd-MeO-DOTA-PE) and gadolinium-methoxy-tetraazacyclododecane-tetraacetic acid triglycine phosphatidylethanolamine (Gd-MeO-DOTA-triglycine-PE (Gd-MeO-DOTA-triglycine-PE)), were compared to a prototypic gadolinium-diethylene-triamine-pentaacetic acid bis-oleate (Gd-DTPA-BOA) paramagnetic formulation. Nanoparticles with MeO-DOTA-based chelates demonstrated higher relaxivity (40% higher for Gd-MeO-DOTA-PE and 55% higher for Gd-MeO-DOTA-triglycine-PE) and less transmetallation than the original Gd-DTPA-BOA-based agent.

  17. Self-assembled polymeric chelate nanoparticles as potential theranostic agents

    Czech Academy of Sciences Publication Activity Database

    Škodová, Michaela; Černoch, Peter; Štěpánek, Petr; Chánová, Eliška; Kučka, Jan; Kálalová, Zuzana; Kaňková, Dana; Hrubý, Martin

    2012-01-01

    Roč. 13, č. 18 (2012), s. 4244-4250 ISSN 1439-4235 R&D Projects: GA ČR GPP207/10/P054; GA ČR GA202/09/2078; GA ČR GAP304/12/0950 Institutional research plan: CEZ:AV0Z40500505 Institutional support: RVO:61389013 Keywords : chelate s * nanoparticles * polymers Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.349, year: 2012

  18. 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.

  19. Polymeric metal chelates with piperazine(bis)dithiocarbamate

    International Nuclear Information System (INIS)

    Larionov, S.V.; Kosareva, L.A.; Ikorskij, V.N.; Uskov, E.M.

    1982-01-01

    Roentgenoamorphous polymer chelates of Fe 3 , Co 2 , Ni 2 , Cu 2 , Zn 2 , Cd 2 , Pb 2 with tetradentate bridge ligand piperazine-(bis) dithiocarbamate have been synthesized. IR spectra in the region 200-400 cm - 1 point to coordination of sulphur atoms of groups CS 2- with metals. It is found that among the polymers synthesized CuLxH 2 O possesses the lowest electric resistance

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

    Science.gov (United States)

    Harkness, J.B.L.; Doctor, R.D.; Wingender, R.J.

    1985-08-05

    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. 3 figs.

  1. Reaction of gadolinium chelates with ozone and hydroxyl radicals.

    Science.gov (United States)

    Cyris, Maike; Knolle, Wolfgang; Richard, Jessica; Dopp, Elke; von Sonntag, Clemens; Schmidt, Torsten C

    2013-09-03

    Gadolinium chelates are used in increasing amounts as contrast agents in magnetic resonance imaging, and their fate in wastewater treatment has recently become the focus of research. Oxidative processes, in particular the application of ozone, are currently discussed or even implemented for advanced wastewater treatment. However, reactions of the gadolinium chelates with ozone are not yet characterized. In this study, therefore, rate constants with ozone were determined for the three commonly used chelates Gd-DTPA, Gd-DTPA-BMA, and Gd-BT-DO3A, which were found to be 4.8 ± 0.88, 46 ± 2.5, and 24 ± 1.5 M(-1) s(-1), respectively. These low rate constants indicate that a direct reaction with ozone in wastewater is negligible. However, application of ozone in wastewater leads to substantial yields of (•)OH. Different methods have been applied and compared for determination of k((•)OH+Gd chelate). From rate constants determined by pulse radiolysis experiments (k((•)OH+Gd-DTPA) = 2.6 ± 0.2 × 10(9) M(-1) s(-1), k((•)OH+Gd-DTPA-BMA) = 1.9 ± 0.7 × 10(9) M(-1) s(-1), k((•)OH+Gd-BT-DO3A) = 4.3 ± 0.2 × 10(9) M(-1) s(-1)), it is concluded that a reaction in wastewater via (•)OH radicals is feasible. Toxicity has been tested for educt and product mixtures of both reactions. Cytotoxicity (MTT test) and genotoxicity (micronuclei assay) were not detectable.

  2. 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

  3. Mercury removal in utility wet scrubber using a chelating agent

    Science.gov (United States)

    Amrhein, Gerald T.

    2001-01-01

    A method for capturing and reducing the mercury content of an industrial flue gas such as that produced in the combustion of a fossil fuel or solid waste adds a chelating agent, such as ethylenediaminetetraacetic acid (EDTA) or other similar compounds like HEDTA, DTPA and/or NTA, to the flue gas being scrubbed in a wet scrubber used in the industrial process. The chelating agent prevents the reduction of oxidized mercury to elemental mercury, thereby increasing the mercury removal efficiency of the wet scrubber. Exemplary tests on inlet and outlet mercury concentration in an industrial flue gas were performed without and with EDTA addition. Without EDTA, mercury removal totaled 42%. With EDTA, mercury removal increased to 71%. The invention may be readily adapted to known wet scrubber systems and it specifically provides for the removal of unwanted mercury both by supplying S.sup.2- ions to convert Hg.sup.2+ ions into mercuric sulfide (HgS) and by supplying a chelating agent to sequester other ions, including but not limited to Fe.sup.2+ ions, which could otherwise induce the unwanted reduction of Hg.sup.2+ to the form, Hg.sup.0.

  4. Chelate forms of biometalls. Theoretical aspects of obtaining and characteristics

    Directory of Open Access Journals (Sweden)

    A. Kapustyan

    2017-04-01

    Full Text Available The problem of microelements bioavailability is highlighted and the correct ways of its solution are substantiated as a result of generalization of theoretical aspects of obtaining of the biometals chelate forms. The characteristics of the main biogenic elements, their physiological significance, electrochemical properties are presented. The main examples of the participation of biometals in various biological processes are given. The properties and the structure peculiarities of biometals coordination complexes are considered in detail. It is shown that in obtaining of biometals chelate forms, there is the mutual selectivity and the affinity of biometals and ligands. The main factors of obtaining a hard metal complex are given. Potential bioligands for obtaining bioavailable forms of microelements are detailed. Among them there are amino acids, peptides, proteins, nucleic acids, carbohydrates. The possible character of complexation depending on the nature of the bioligand is indicated. Practical examples of preparation of biometals mixed ligand complexes are given. The expediency of using metabolic products and processing of lactic acid bacteria as promising components of mixed ligand chelate complexes is substantiated. These substances contain in their composition a mass of potential donor atoms that are capable to form covalent and coordination bonds with biomethalles, and also possess high biological and immunotropic activities. The use of this system in the biocoordination compounds of the "metals of life" can provide a synergistic effect of the components, significantly to expand the range of their physiological activity and to increase the degree of assimilation by the body.

  5. High precision isotopic ratio analysis of volatile metal chelates

    International Nuclear Information System (INIS)

    Hachey, D.L.; Blais, J.C.; Klein, P.D.

    1980-01-01

    High precision isotope ratio measurements have been made for a series of volatile alkaline earth and transition metal chelates using conventional GC/MS instrumentation. Electron ionization was used for alkaline earth chelates, whereas isobutane chemical ionization was used for transition metal studies. Natural isotopic abundances were determined for a series of Mg, Ca, Cr, Fe, Ni, Cu, Cd, and Zn chelates. Absolute accuracy ranged between 0.01 and 1.19 at. %. Absolute precision ranged between +-0.01-0.27 at. % (RSD +- 0.07-10.26%) for elements that contained as many as eight natural isotopes. Calibration curves were prepared using natural abundance metals and their enriched 50 Cr, 60 Ni, and 65 Cu isotopes covering the range 0.1-1010.7 at. % excess. A separate multiple isotope calibration curve was similarly prepared using enriched 60 Ni (0.02-2.15 at. % excess) and 62 Ni (0.23-18.5 at. % excess). The samples were analyzed by GC/CI/MS. Human plasma, containing enriched 26 Mg and 44 Ca, was analyzed by EI/MS. 1 figure, 5 tables

  6. Antibacterial and antibiofilm effects of iron chelators against Prevotella intermedia.

    Science.gov (United States)

    Moon, Ji-Hoi; Kim, Cheul; Lee, Hee-Su; Kim, Sung-Woon; Lee, Jin-Yong

    2013-09-01

    Prevotella intermedia, a major periodontopathogen, has been shown to be resistant to many antibiotics. In the present study, we examined the effect of the FDA-approved iron chelators deferoxamine (DFO) and deferasirox (DFRA) against planktonic and biofilm cells of P. intermedia in order to evaluate the possibility of using these iron chelators as alternative control agents against P. intermedia. DFRA showed strong antimicrobial activity (MIC and MBC values of 0.16 mg ml(-1)) against planktonic P. intermedia. At subMICs, DFRA partially inhibited the bacterial growth and considerably prolonged the bacterial doubling time. DFO was unable to completely inhibit the bacterial growth in the concentration range tested and was not bactericidal. Crystal violet binding assay for the assessment of biofilm formation by P. intermedia showed that DFRA significantly decreased the biofilm-forming activity as well as the biofilm formation, while DFO was less effective. DFRA was chosen for further study. In the ATP-bioluminescent assay, which reflects viable cell counts, subMICs of DFRA significantly decreased the bioactivity of biofilms in a concentration-dependent manner. Under the scanning electron microscope, P. intermedia cells in DFRA-treated biofilm were significantly elongated compared to those in untreated biofilm. Further experiments are necessary to show that iron chelators may be used as a therapeutic agent for periodontal disease.

  7. 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.

  8. f-Element Ion Chelation in Highly Basic Media

    International Nuclear Information System (INIS)

    Paine, Robert T.

    1999-01-01

    High-level radioactive waste (HLW) generated in the DOE complex is stored in tanks at several sites, but predominantly it is found at the Hanford reservation. Much of the material has been exposed to high pHs, consequently the waste exists in a complex, poorly understood mixture of solids, gels and solutions. The final waste remediation plan may involve chemical separation of fractions and a suitable, well developed molecular chemistry basis for performing these separations is not available. Indeed, the fundamental chemical behavior of most radioactive nuclides in basic media is not known. The goal of this project is to undertake fundamental studies of the coordination chemistry of f-element species in basic aqueous solutions containing common waste treatment ions (e.g., NO3 -, CO3 2-, organic carboxylates, and EDTA), as well as new waste scrubbing chelators produced in this study. The experimental agenda includes: 1. Studies of the speciation of Sr and Ln ions in basic solutions wit h and without common counterions; 2. Preparations of new multifunctional ligands that may act as strong, ion-specific chelators for Sr and/or Ln ions in basic media; and 3. Studies of the coordination and dissolution behavior of oxide-hydroxide species, as well as in insoluble sols, gels, and precipitates in combination with new chelating ligands. It is anticipated that this coordination chemistry will facilitate the design of advanced separation schemes required for handling the complex waste matrices found at the Hanford HLW facility

  9. Chelated mineral supplements for Nelore: quality and early embryonic development

    Directory of Open Access Journals (Sweden)

    Camila Pasa

    2014-01-01

    Full Text Available ABSTRACT. Pasa C., Hatamoto-Zervoudakis L.K., Zervoudakis J.T. & Soares L. [Chelated mineral supplements for Nelore: quality and early embryonic development.] Suplementos minerais quelatados para vacas Nelore: qualidade e desenvolvimento embrionário inicial. Revista Brasileira de Medicina Veterinária, 36(1:29-34, 2014. Programa de Pós-Graduação em Ciência Animal, Faculdade de Agronomia e Medicina Veterinária, Universidade Federal do Mato Grosso, Av. Fernando Corrêa da Costa, 2367, Bairro Boa Esperança, Cuiabá, MT 78060-900, Brasil. E-mail: pasa_camila@hotmail.com The objective of this study was to evaluate the quality and early development of embryos produced with oocytes of cows supplemented with copper, zinc and selenium in a non-chelated and chelated. The experiment was conducted in Cuiabá-MT during the months April to July 2009. We used 24 adult Nellore multiparous, aged, average weights of the initial 36 months, 395 kg and mean body condition score 4.8, respectively randomly divided into 2 groups: control group (CG, supplemented with conventional mineral and Supplemented Group (GS, animals supplemented with zinc, copper and selenium chelated. Each group was kept in a paddock of Brachiaria brizantha cv Marandu received 1 kg of animal per day. chelated mineral supplementation (GS and conventional mineral (GC delivered via the protein supplement was given during a period of 99 days with daily average 1kg/cabeça. During the experimental period were two follicular aspirations, one to 59 days and another at 99 days of supplementation. Every two weeks the animals were weighed and ECC evaluated. oocytes viable (grades I, II and III were used for in vitro production of embryos. The experiment was completely randomized and data were analyzed by ANOVA and a significance level of 10%. There was no effect (p> 0.10 of supplementation with chelated minerals on the percentage of cleaved oocytes, total embryos produced, percentage of produced

  10. 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.

  11. Species-Dependent Chelation of 241Am by DTPA Di-ethyl Ester

    Science.gov (United States)

    Huckle, James E.; Sadgrove, Matthew P.; Mumper, Russell J.; Jay, Michael

    2014-01-01

    Diethylenetriaminepentaacetic acid (DTPA) is an FDA approved chelating agent for enhancing the elimination of transuranic elements such as americium from the body. Early access to therapy minimizes deposition of these radionuclides in tissues such as the bone. Due to its poor oral bioavailability, DTPA is administered as an IV injection, delaying access. Therefore a diethyl-ester analog of DTPA, named C2E2, was synthesized as a means to increase oral absorption. As a hexadentate ligand, it was hypothesized that C2E2 was capable of binding americium directly. Therefore, the protonation constants and americium stability constant for C2E2 were determined by potentiometric titration and a solvent extraction method, respectively. C2E2 was shown to bind americium with a log K of 19.6. The concentrations of C2E2, its metabolite C2E1, and DTPA required to achieve effective binding in rat, beagle, and human plasma were studied in vitro. Dose response curves for each ligand were established and the 50% maximal effective concentrations were determined for each species. As expected, higher concentrations of C2E2 were required to achieve the same degree of binding as DTPA. The results indicated that chelation in beagle plasma is more representative of the human response than rats. Finally, the pharmacokinetics of C2E2 were investigated in beagles and the data was fit to a two-compartment model with elimination from the central compartment, along with first-order absorption. Based on the in vitro data, a 100 mg kg−1 dose of C2E2 can be expected to have an effective duration of action of 3.8 hours in beagles. PMID:25706138

  12. Species-dependent chelation of (241)Am by DTPA Di-ethyl ester.

    Science.gov (United States)

    Huckle, James E; Sadgrove, Matthew P; Mumper, Russell J; Jay, Michael

    2015-04-01

    Diethylenetriaminepentaacetic acid (DTPA) is an FDA-approved chelating agent for enhancing the elimination of transuranic elements such as americium from the body. Early access to therapy minimizes deposition of these radionuclides in tissues such as the bone. Due to its poor oral bioavailability, DTPA is administered as an IV injection, delaying access. Therefore, a diethyl-ester analog of DTPA, named C2E2, was synthesized as a means to increase oral absorption. As a hexadentate ligand, it was hypothesized that C2E2 was capable of binding americium directly. Therefore, the protonation constants and americium stability constant for C2E2 were determined by potentiometric titration and a solvent extraction method, respectively. C2E2 was shown to bind americium with a log K of 19.6. The concentrations of C2E2, its metabolite C2E1, and DTPA required to achieve effective binding in rat, beagle, and human plasma were studied in vitro. Dose response curves for each ligand were established, and the 50% maximal effective concentrations were determined for each species. As expected, higher concentrations of C2E2 were required to achieve the same degree of binding as DTPA. The results indicated that chelation in beagle plasma is more representative of the human response than rats. Finally, the pharmacokinetics of C2E2 were investigated in beagles, and the data was fit to a two-compartment model with elimination from the central compartment, along with first-order absorption. Based on the in vitro data, a 100 mg kg dose of C2E2 can be expected to have an effective duration of action of 3.8 h in beagles.

  13. Rates of cuticular penetration of chelated Fe(III): role of humidity, concentration, adjuvants, temperature, and type of chelate.

    Science.gov (United States)

    Schönherr, Jörg; Fernández, Victoria; Schreiber, Lukas

    2005-06-01

    Time courses of cuticular penetration of FeCl3 and Fe(III) complexes of citric acid, EDTA, EDDHA (Sequestrene 138Fe), imidodisuccinic acid (IDHA), and ligninsulfonic acid (Natrel) were studied using astomatous cuticular membranes (CMs) isolated from Populus x canescens leaves. At 100% relative humidity, the Fe(III) chelates disappeared exponentially with time from the surface of the CMs; that is, penetration was a first-order process that can be described using rate constants or half-times of penetration (t(1/2)). Half-times ranged from 20 to 30 h. At 90% humidity, penetration rates were insignificant with the exception of Natrel, for which t(1/2) amounted to 58 h. Rate constants were independent of temperature (15, 25, and 35 degrees C). Permeability decreased with increasing Fe chelate concentration (IDHA and EDTA). At 100% humidity, half-times measured with FeIDHA were 11 h (2 mmol L(-1)), 17 h (10 mmol L(-1)) and 36 h (20 mmol L(-1)), respectively. In the presence of FeEDTA, penetration of CaCl2 was slowed greatly. Half-times for penetration of CaCl2, which were 1.9 h in the absence of FeEDTA, rose to 3.12 h in the presence of an equimolar concentration of EDTA and 13.3 h when the FeEDTA concentration was doubled. Hence, Fe chelates reduced permeability of CMs to CaCl2 and to the Fe chelates themselves. It is suggested that Fe chelates reduced the size of aqueous pores. This view is supported by the fact that rate constants for calcium salts were about 5 times higher than for Fe chelates with the same molecular weights. Adding Tween 20 (5 g L(-1)) as a humectant did not increase permeability to FeIDHA at 90% humidity and below, while addition of glycine betaine did. Penetration of FeCl3 applied at 5 g L(-1) (pH 1.5) was not a first order process as rate constants decreased rapidly with time. Only 2% of the dose penetrated during the first 2 h and less than that in the subsequent 8 h. Recovery was only 70%. This was attributed to the formation of insoluble Fe

  14. Study of cyclization of chelating compounds using electrospray ionization mass spectrometry

    International Nuclear Information System (INIS)

    Shi Ying; Campbell, J.A.

    2000-01-01

    Electrospray ionization mass spectrometry (ESI-MS) was used for the study of cyclization of organic chelating compounds (chelators). Four chelating compounds were studied: Symmetrical ethylenediaminediacetic acid (s-EDDA), Unsymmetrical ethylenediaminediacetic acid (u-EDDA), N-(2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA), and N-(2-hydroxyethyl)iminodiacetic acid (HEIDA). The chelators were cyclized with treatments of acids and heating. The open and cyclized form of the chelators were semi-quantified by both positive and negative ion modes ESI-MS. The kinetics of chelator cyclization was studied as a function of reaction temperature and the pH of the matrix. The cyclization of s-EDDA was found to be a pseudo-first order reaction in s-EDDA and overall second order. The cyclizations of HEIDA and HEDTA are reversible reactions. Higher temperature and lower pH favors cyclization. (author)

  15. Effect of other metals on iron bioavailability in presence of a selective chelator

    International Nuclear Information System (INIS)

    Rehman, F.S.

    1995-01-01

    Iron (III) is generally very easily chelated by a number of chelators in the biological environment, either supplied by food or already present there. One of the these chelator is gallic acid. The stability constants of the complexes formed between gallic acid and other trace metals have been determined by a potentiometric method. The data obtained was computed with the help of computer program B est . The resulted Beta values were compared with already known values of iron gallic acid complexes. (author)

  16. Photocatalyzed removal of lead ion from lead-chelator solution

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Young Hyun; Na, Jung Won; Sung, Ki Woung [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1994-07-01

    The present study was undertaken to examine the influence of such chelating agents on the ease and speed of photocatalyzed metal removal and deposition. With excess EDTA, the free EDTA competes with Pb for oxidation, and at a ten fold excess, no lead oxidation (hence removal) occurs. With insufficient EDTA, the corresponding initial concentration of Pb-EDTA is decreased; after its destruction, the remaining Pb{sup 2+} is removed more slowly, at rates found with lead nitrate solution. The net result is that the maximum rate of lead deposition occurs at the stoichiometric ratio of 1:1 EDTA : Pb{sup 2+}.

  17. Optimized conditions for chelation of yttrium-90-DOTA immunoconjugates.

    Science.gov (United States)

    Kukis, D L; DeNardo, S J; DeNardo, G L; O'Donnell, R T; Meares, C F

    1998-12-01

    Radioimmunotherapy (RIT) with 90Y-labeled immunoconjugates has shown promise in clinical trials. The macrocyclic chelating agent 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA) binds 90Y with extraordinary stability, minimizing the toxicity of 90Y-DOTA immunoconjugates arising from loss of 90Y to bone. However, reported 90Y-DOTA immunoconjugate product yields have been typically only BAD) was conjugated to the monoclonal antibody Lym-1 via 2-iminothiolane (2IT). The immunoconjugate product, 2IT-BAD-Lym-1, was labeled in excess yttrium in various buffers over a range of concentrations and pH. Kinetic studies were performed in selected buffers to estimate radiolabeling reaction times under prospective radiopharmacy labeling conditions. The effect of temperature on reaction kinetics was examined. Optimal radiolabeling conditions were identified and used in eight radiolabeling experiments with 2IT-BAD-Lym-1 and a second immunoconjugate, DOTA-peptide-chimeric L6, with 248-492 MBq (6.7-13.3 mCi) of 90Y. Ammonium acetate buffer (0.5 M) was associated with the highest uptake of yttrium. On the basis of kinetic data, the time required to chelate 94% of 90Y (four half-times) under prospective radiopharmacy labeling conditions in 0.5 M ammonium acetate was 17-148 min at pH 6.5, but it was only 1-10 min at pH 7.5. Raising the reaction temperature from 25 degrees C to 37 degrees C markedly increased the chelation rate. Optimal radiolabeling conditions were identified as: 30-min reaction time, 0.5 M ammonium acetate buffer, pH 7-7.5 and 37 degrees C. In eight labeling experiments under optimal conditions, a mean product yield (+/- s.d.) of 91%+/-8% was achieved, comparable to iodination yields. The specific activity of final products was 74-130 MBq (2.0-3.5 mCi) of 90Y per mg of monoclonal antibody. The immunoreactivity of 90Y-labeled immunoconjugates was 100%+/-11%. The optimization of 90Y-DOTA chelation conditions represents an important advance in 90Y RIT

  18. Acidizing reservoirs while chelating iron with sulfosalicylic acid

    Energy Technology Data Exchange (ETDEWEB)

    McLaughlin, W A; Berkshire, D C

    1980-09-30

    A well treating process is described in which an aqueous solution of a strong acid capable of dissolving solids in a manner increasing the permeability of a subterranean earth formation is injected into a subterranean reservoir that contains an asphaltenic oil. At least the first injected portion of the aqueous acid and a solution or homogeneous dispersion of at least enough 5-sulfosalicylic acid to chelate with and prevent the formation of iron-asphaltene solids are included with substantially all of the ferric ions that become dissolved within the strong acid solution that enters the earth formation. 10 claims.

  19. Characterization and thermogravimetric analysis of lanthanide hexafluoroacetylacetone chelates.

    Science.gov (United States)

    Shahbazi, Shayan; Stratz, S Adam; Auxier, John D; Hanson, Daniel E; Marsh, Matthew L; Hall, Howard L

    2017-01-01

    This work reports the thermodynamic characterizations of organometallic species as a vehicle for the rapid separation of volatile nuclear fission products via gas chromatography due to differences in adsorption enthalpy. Because adsorption and sublimation thermodynamics are linearly correlated, there is considerable motivation to determine sublimation enthalpies. A method of isothermal thermogravimetric analysis, TGA-MS and melting point analysis are employed on thirteen lanthanide 1,1,1,5,5,5-hexafluoroacetylacetone complexes to determine sublimation enthalpies. An empirical correlation is used to estimate adsorption enthalpies of lanthanide complexes on a quartz column from the sublimation data. Additionally, four chelates are characterized by SC-XRD, elemental analysis, FTIR and NMR.

  20. Uranium and neodymium biosorption using novel chelating polysaccharide.

    Science.gov (United States)

    Elsalamouny, Ahmed R; Desouky, Osman A; Mohamed, Saad A; Galhoum, Ahmed A; Guibal, Eric

    2017-11-01

    A direct reaction is described to prepare hydrophobic α-aminomethylphosphonic acid as a novel chitosan-based material. It exhibits chelating properties for polyvalent metal ions such as U(VI) and Nd(III) ions. The new sorbent was fully characterized using Elemental analysis, scanning electron microscope (SEM) and FTIR spectra. Different parameters were examined in order to evaluate the optimum conditions for U(VI) and Nd(III) ions biosorption. Sorption mechanisms of metal ions were investigated using kinetic and isotherm models. In addition, the sorbent selectivity was tested for both metal ions together in a binary solution. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. The influence of functional groups on the permeation and distribution of antimycobacterial rhodamine chelators.

    Science.gov (United States)

    Moniz, T; Leite, A; Silva, T; Gameiro, P; Gomes, M S; de Castro, B; Rangel, M

    2017-10-01

    We formerly hypothesized a mechanism whereby the antimycobacterial efficiency of a set of rhodamine labelled iron chelators is improved via the rhodamine fluorophore which enhances the chelators' permeation properties through membranes. To validate our hypothesis in a cellular context and to understand the influence of the structure of the fluorophore on the chelator's uptake and distribution within macrophages we now report comparative confocal microscopy studies performed with a set of rhodamine labelled chelators. We identify the functional groups of the chelator's framework that favor uptake by macrophages and conclude that the antimycobacterial effect is strongly related with the capacity of the chelator to distribute within the host cell and its compartments, a property that is closely related with the chelators' ability to interact with membranes. The quantification of the chelators' interaction with membranes was assessed through measurement of the corresponding partition constants in liposomes. The overall results support that the compounds which are preferentially taken up are the most efficient antimycobacterial chelators and for that reason we infer that the biological activity is modulated by the structural features of the fluorophore. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    OpenAIRE

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

    2016-01-01

    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-shel...

  3. Spectroscopy, modeling and computation of metal chelate solubility in supercritical CO2. 1998 annual progress report

    International Nuclear Information System (INIS)

    Brennecke, J.F.; Chateauneuf, J.E.; Stadtherr, M.A.

    1998-01-01

    'This report summarizes work after 1 year and 8 months (9/15/96-5/14/98) of a 3 year project. Thus far, progress has been made in: (1) the measurement of the solubility of metal chelates in SC CO 2 with and without added cosolvents, (2) the spectroscopic determination of preferential solvation of metal chelates by cosolvents in SC CO 2 solutions, and (3) the development of a totally reliable computational technique for phase equilibrium computations. An important factor in the removal of metals from solid matrices with CO 2 /chelate mixtures is the equilibrium solubility of the metal chelate complex in the CO 2 .'

  4. The human papillomavirus type 58 E7 oncoprotein modulates cell cycle regulatory proteins and abrogates cell cycle checkpoints

    International Nuclear Information System (INIS)

    Zhang Weifang; Li Jing; Kanginakudru, Sriramana; Zhao Weiming; Yu Xiuping; Chen, Jason J.

    2010-01-01

    HPV type 58 (HPV-58) is the third most common HPV type in cervical cancer from Eastern Asia, yet little is known about how it promotes carcinogenesis. In this study, we demonstrate that HPV-58 E7 significantly promoted the proliferation and extended the lifespan of primary human keratinocytes (PHKs). HPV-58 E7 abrogated the G1 and the postmitotic checkpoints, although less efficiently than HPV-16 E7. Consistent with these observations, HPV-58 E7 down-regulated the cellular tumor suppressor pRb to a lesser extent than HPV-16 E7. Similar to HPV-16 E7 expressing PHKs, Cdk2 remained active in HPV-58 E7 expressing PHKs despite the presence of elevated levels of p53 and p21. Interestingly, HPV-58 E7 down-regulated p130 more efficiently than HPV-16 E7. Our study demonstrates a correlation between the ability of down-regulating pRb/p130 and abrogating cell cycle checkpoints by HPV-58 E7, which also correlates with the biological risks of cervical cancer progression associated with HPV-58 infection.

  5. 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.

  6. Abrogation of the presenilin 1/beta-catenin interaction and preservation of the heterodimeric presenilin 1 complex following caspase activation.

    Science.gov (United States)

    Tesco, G; Kim, T W; Diehlmann, A; Beyreuther, K; Tanzi, R E

    1998-12-18

    beta-Catenin has previously been shown to interact with presenilin 1 (PS1) in transfected cells. Here we report that beta-catenin co-immunoprecipitates with the endogenous C-terminal fragment of presenilin 1 (PS1-CTF) but not with the endogenous CTF of presenilin 2 (PS2-CTF) in H4 human neuroglioma cells. During staurosporine (STS)-induced cell death, beta-catenin and PS1-CTF undergo a caspase-mediated cleavage. After 12 h of STS treatment, the beta-catenin.PS1-CTF interaction is abrogated. While PS1-CTF immunoprecipitated with all caspase-cleaved species of beta-catenin, beta-catenin holoprotein did not co-immunoprecipitate with the "alternative" caspase-derived PS1-CTF (PS1-aCTF). Thus, the abrogation of the beta-catenin.PS1-CTF complex was due to caspase cleavage of PS1-CTF. beta-Catenin co-immunoprecipitated with PS1-NTF, but only when PS1-NTF was associated with PS1-CTF. Even though PS1-NTF.CTF complex stability was not altered by caspase cleavage, its ability to bind beta-catenin was abolished. Thus, while the PS1-NTF.CTF complex is preserved after caspase cleavage, it may no longer be fully functional.

  7. Abrogating endocrine resistance by targeting ERα and PI3K in breast cancer

    International Nuclear Information System (INIS)

    Fox, Emily M.; Arteaga, Carlos L.; Miller, Todd W.

    2012-01-01

    Antiestrogen therapies targeting estrogen receptor α (ER) signaling are a mainstay for patients with ER+ breast cancer. While many cancers exhibit resistance to antiestrogen therapies, a large body of clinical and experimental evidence indicates that hyperactivation of the phosphatidylinositol 3-kinase (PI3K) pathway promotes antiestrogen resistance. In addition, continued ligand-independent ER signaling in the setting of estrogen deprivation may contribute to resistance to endocrine therapy. PI3K activates several proteins which promote cell cycle progression and survival. In ER+ breast cancer cells, PI3K promotes ligand-dependent and -independent ER transcriptional activity. Models of antiestrogen-resistant breast cancer often remain sensitive to estrogen stimulation and PI3K inhibition, suggesting that clinical trials with combinations of drugs targeting both the PI3K and ER pathways are warranted. Herein, we review recent findings on the roles of PI3K and ER in antiestrogen resistance, and clinical trials testing drug combinations which target both pathways. We also discuss the need for clinical investigation of ER downregulators in combination with PI3K inhibitors.

  8. 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.

  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. Abrogation of cisplatin-induced hepatotoxicity in mice by xanthorrhizol is related to its effect on the regulation of gene transcription

    International Nuclear Information System (INIS)

    Hwan Kim, Seong; Ok Hong, Kyoung; Chung, Won-Yoon; Kwan Hwang, Jae; Park, Kwang-Kyun

    2004-01-01

    Cisplatin is a widely used anticancer drug, but at high dose, it can produce undesirable side effects such as hepatotoxicity. Because Curcuma xanthorrhiza Roxb. (Zingiberaceae) has been traditionally used to treat liver disorders, the protective effect of xanthorrhizol, which is isolated from C. xanthorrhiza, on cisplatin-induced hepatotoxicity was evaluated in mice. The pretreatment of xanthorrhizol (200 mg/kg/day, po) for 4 days prevented the hepatotoxicity induced by cisplatin (45 mg/kg, ip) with statistical significance. Interestingly, it abrogated cisplatin-induced DNA-binding activity of nuclear factor-kappaB (NF-κB), which consequently affected mRNA expression levels of NF-κB-dependent genes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), even in part. It also attenuated the cisplatin-suppressed DNA-binding activity of activator protein 1 (AP-1). Using differential display reverse transcription-polymerase chain reaction (DDRT-PCR), seven upregulated genes including S100 calcium binding protein A9 (S100A9) mRNA and antigenic determinant for rec-A protein mRNA and five downregulated genes including caseinolytic protease X (ClpX) mRNA and ceruloplasmin (CP) mRNA by cisplatin were identified. Although these mRNA expression patterns were not totally consistent with gel shift patterns, altered expression levels by cisplatin were reversed by the pretreatment of xanthorrhizol. In conclusion, the ability of xanthorrhizol to regulate the DNA-binding activities of transcription factors, NF-κB and AP-1, could be one possible mechanism to elucidate the preventive effect of xanthorrhizol on cisplatin-induced hepatotoxicity. Furthermore, genes identified in this study could be helpful to understand the mechanism of cisplatin-induced hepatotoxicity. Finally, the combination treatment of xanthorrhizol and cisplatin may provide more advantage than single treatment of cisplatin in cancer therapy

  11. Synthesis of LaNiO3 perovskite type by chelating precursor method using EDTA: optimization of chelating content

    International Nuclear Information System (INIS)

    Santos, Jose Carlos dos; Pedrosa, Anne Michelle Garrido; Mesquita, Maria Eliane; Souza, Marcelo Jose Barros de

    2011-01-01

    The perovskites are strategic materials due their catalytic, electronic and magnetic properties. These properties are influenced by the calcination and synthesis conditions. In this work was carried out the synthesis of LaNiO 3 perovskite type by chelating precursor method using EDTA and also was studied the optimization of the EDTA content in the synthesis. The synthesized materials were characterized by X-ray diffraction (XRD), thermal gravimetric analysis (TG) and Infrared Spectroscopy (FTIR). In the optimization of the EDTA content the lowest ratio of metal / EDTA used was 1.0 / 0.1, where it was possible to obtain monophasic perovskite. (author)

  12. Detoxication and removal of uranium by phenolic chelating agents

    International Nuclear Information System (INIS)

    Luo Meichu; Chen Guibao; Li Landi

    1992-01-01

    The use of phenolic chelating agents for detoxication and removal of uranyl nitrate in mice and rats is reported. Antidotal test: 8102, 7601 and 811 were given 2 mM/kg subcutaneously to mice and 1 mM/kg intramuscularly to rats when the animals were injected i.p. with different doses (100-500 mg/kg) of uranyl nitrate. The results showed that the antidotal effects of 8102 and 7601 were better than 811 in augmenting survival, survival time (day) and renal factor (kidney weight/body weight x100). 8102 was superior to 7601 against higher dose of uranyl nitrate intoxication. Removal test: five phenolic chelating agents (8102, 7601, 811, 7603 and 8307) were studied in rats. The results obtained demonstrated that 8102 and 7601 were better than 811, 7603 and 8307 in increasing U excretion in the urine after acute uranyl nitrate intoxication. The effects of different doses (300-1000 μM/kg) of 8102 was superior to 7601 in increasing U excretion in the urine and decreasing U deposition in the tissues. The toxicity and dose of 8102 in treating uranium intoxication are discussed

  13. Selective separation of indium by iminodiacetic acid chelating resin

    International Nuclear Information System (INIS)

    Fortes, M.C.B.; Benedetto, J.S.; Martins, A.H.

    2007-01-01

    - 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 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 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 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 R IRC748. (author)

  14. O-Hydroxyl- or o-amino benzylamine-tacrine hybrids: multifunctional biometals chelators, antioxidants, and inhibitors of cholinesterase activity and amyloid-β aggregation.

    Science.gov (United States)

    Mao, Fei; Huang, Ling; Luo, Zonghua; Liu, Anqiu; Lu, Chuanjun; Xie, Zhiyong; Li, Xingshu

    2012-10-01

    In an effort to identify novel multifunctional drug candidates for the treatment of Alzheimer's disease (AD), a series of hybrid molecules were synthesised by reacting N-(aminoalkyl)tacrine with salicylic aldehyde or derivatives of 2-aminobenzaldehyde. These compounds were then evaluated as multifunctional anti-Alzheimer's disease agents. All of the hybrids are potential biometal chelators, and in addition, most of them were better antioxidants and inhibitors of cholinesterases and amyloid-β (Aβ) aggregation than the lead compound tacrine. Compound 7c has the potential to be a candidate for AD therapy: it is a much better inhibitor of acetylcholinesterase (AChE) than tacrine (IC(50): 0.55 nM vs 109 nM), has good biometal chelation ability, is able to inhibit Aβ aggregation and has moderate antioxidant activity (1.22 Trolox equivalents). Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. 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

  16. KINETICS OF THE OXIDATION OF FERROUS CHELATES OF EDTA AND HEDTA IN AQUEOUS-SOLUTION

    NARCIS (Netherlands)

    WUBS, HJ; BEENACKERS, AACM

    1993-01-01

    The kinetics of the reaction of oxygen with ferrous chelates of EDTA and HEDTA was studied in a stirred cell reactor under industrial conditions. The temperature was varied from 20 to 60-degrees-C and the concentration of the ferrous chelate ranged from 0 to 100 mol/m3. The initial pH was 7.5. Under

  17. Antioxidant, Iron-chelating and Anti-glucosidase Activities of Typha ...

    African Journals Online (AJOL)

    Iron chelating activity was assessed using a ferrozine-based assay. Anti- glucosidase activity was determined using 4-nitrophenyl ... flavonoid (TF) content was determined based an aluminum chloride colorimetric assay [6]. TF content was ..... Dietary iron restriction or iron chelation protects from diabetes and loss of β-cell.

  18. Fluoride ion recognition by chelating and cationic boranes.

    Science.gov (United States)

    Hudnall, Todd W; Chiu, Ching-Wen; Gabbaï, François P

    2009-02-17

    Because of the ubiquity of fluoride ions and their potential toxicity at high doses, researchers would like to design receptors that selectively detect this anion. Fluoride is found in drinking water, toothpaste, and osteoporosis drugs. In addition, fluoride ions also can be detected as an indicator of uranium enrichment (via hydrolysis of UF(6)) or of the chemical warfare agent sarin, which releases the ion upon hydrolysis. However, because of its high hydration enthalpy, the fluoride anion is one of the most challenging targets for anion recognition. Among the various recognition strategies that are available, researchers have focused a great deal of attention on Lewis acidic boron compounds. These molecules typically interact with fluoride anions to form the corresponding fluoroborate species. In the case of simple triarylboranes, the fluoroborates are formed in organic solvents but not in water. To overcome this limitation, this Account examines various methods we have pursued to increase the fluoride-binding properties of boron-based receptors. We first considered the use of bifunctional boranes, which chelate the fluoride anion, such as 1,8-diborylnaphthalenes or heteronuclear 1-boryl-8-mercurio-naphthalenes. In these molecules, the neighboring Lewis acidic atoms can cooperatively interact with the anionic guest. Although the fluoride binding constants of the bifunctional compounds exceed those of neutral monofunctional boranes by several orders of magnitude, the incompatibility of these systems with aqueous media limits their utility. More recently, we have examined simple triarylboranes whose ligands are decorated by cationic ammonium or phosphonium groups. These cationic groups increase the electrophilic character of these boranes, and unlike their neutral analogs, they are able to complex fluoride in aqueous media. We have also considered cationic boranes, which form chelate complexes with fluoride anions. Our work demonstrates that Coulombic and chelate

  19. 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.

  20. 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.

  1. Preparation, characterization, magnetic and thermal studies of some chelate polymers of first series transition metal ions

    International Nuclear Information System (INIS)

    Ukey, Vaishali V.; Juneja, H.D.; Borkar, S.D.; Ghubde, R.S.; Naz, S.

    2006-01-01

    Azelaoyl-bis-hydroxamic acid used as bis ligand for the preparation of chelate polymers of Mn(II), Co(II), Ni(II) and Zn(II). These chelate polymers have been synthesized by refluxing the metal acetate and bis ligand as 1:1 stoichiometry. In the present work, structural determination of these newly synthesized chelate polymers has been studied on the basis of elemental analyses, infrared and reflectance spectral, magnetic and thermal studies. The decomposition temperature and the order of reaction have been determined by TGA analysis. On the basis of these studies, the Zn(II) chelate polymer has tetrahedral geometry, whereas Mn(II), Co(II) and Ni(II) chelate polymers have octahedral geometry and have the thermal stability in the order Ni(II) > Mn(II) > Zn(II) > Co(II)

  2. Studies of the competition for thorium ion between chelating agents and bovine serum albumin

    International Nuclear Information System (INIS)

    Luo Meichu; Zhang Meizhen; Sun Meizhen; Chen Shijie

    1995-01-01

    Fourteen chelation agents (polyaminopolcarboxylate type--TTHA, DTPA, EDTA; phenolicpolycarboxylate type--811, 8102, 7601, 7602, 7603, 7616, 7711, 7724, 7803, 7804, 8307) were studied their competitive ability to mobilize the thorium with bovine serum albumin (BSA). The experimental results showed that the competitive ability of TTHA, 8102, 811 to chelate Thorium with BSA were the strongest, and EDTA was the worst in all chelating agents. The measured order of the competitive ability of chelators is basically consistent with animal experimental results in vivo. The parameter F is defined as the competitive ability of chelators. F is taken as a screening criterion for de-corporate thorium which is simple, quick and effective method in vitro

  3. Increase of CTGF mRNA expression by respiratory syncytial virus infection is abrogated by caffeine in lung epithelial cells.

    Science.gov (United States)

    Kunzmann, Steffen; Krempl, Christine; Seidenspinner, Silvia; Glaser, Kirsten; Speer, Christian P; Fehrholz, Markus

    2018-04-16

    Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infection in early childhood. Underlying pathomechanisms of elevated pulmonary morbidity in later infancy are largely unknown. We found that RSV-infected H441 cells showed increased mRNA expression of connective tissue growth factor (CTGF), a key factor in airway remodeling. Additional dexamethasone treatment led to further elevated mRNA levels, indicating additive effects. Caffeine treatment prevented RSV-mediated increase of CTGF mRNA. RSV may be involved in airway remodeling processes by increasing CTGF mRNA expression. Caffeine might abrogate these negative effects and thereby help to restore lung homeostasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. 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

  5. Preparation, Spectroscopic Investigation and Biological Activity of New Mixed Ligand Chelates

    International Nuclear Information System (INIS)

    Alassbaly, F.S.; Ajaily, M.M.E.

    2014-01-01

    Preparation and investigation of new Co(II), Ni(II), Zn(II) and Cr(III) chelates with mixed ligands including Schiff base (L1) formed from the condensation of 4-dimethylaminobenzaldehyde with 2-aminophenol and anthranilic acid (L2) were studied. The obtained Schiff base and mixed ligand chelates were subjected to several physiochemical techniques, in terms of CHN elemental analyses, molar conductivity, magnetic moment measurements, infrared, proton nuclear magnetic resonance, electronic and mass spectra. The analytical data showed the formation of the Schiff base compound and the ratio of metal to ligands of the chelates are 1:1:1(M:L1:L2). The infrared spectral data exhibited that the used ligands behaving as bidentate ligands towards the metal ions. The proton nuclear magnetic resonance spectral data showed the signals of the active groups in the ligands which entered in chelation with Zn(II) metal ion. The electronic spectral results showed the existence of pie (phenyl ring) and n = pie (C=N) of the ligands and suggested the geometrical structures of the chelates. Meanwhile, the mass spectral data revealed the fragmentations of the Schiff base, anthranilic acid and their Ni(II) mixed ligand chelate has been preformed the only chelate conducted for justification. All the prepared mixed chelates were non-electrolyte in nature. The antibacterial activity of the Schiff base, anthranilic acid, metal salts and mixed ligand chelates were studied and found to be that mixed ligand chelates have the most biological activity in comparison to the free ligands and salts. (author)

  6. 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...... a principal in vivo role of the uPA-uPAR interaction in cell-associated fibrinolysis critical for suppression of fibrin accumulation and fibrin-associated inflammation and provides a valuable model for further exploration of this multifunctional receptor....

  7. Modeling systemic and renal gadolinium chelate transport with MRI

    Energy Technology Data Exchange (ETDEWEB)

    Votaw, John R.; Martin, Diego [Emory University Hospital, Department of Radiology, Atlanta, GA (United States)

    2008-01-15

    The advent of modern MRI scanners and computer equipment permits the rapid sequential collection of images of gadolinium chelate (Gd) transit through the kidney. The excellent spatial and temporal (0.9 s) resolution permits analyzing the shape of the recovered curves with a sophisticated model that includes both space and time. The purpose of this manuscript is to present such a mathematical model. By building into the model significant physical processes that contribute to the shape of the measured curve, quantitative values can be assigned to important parameters. In this work, quantitative values are determined for blood dispersion through the cardio-pulmonary system, systemic clearance rate of Gd, blood flow into each kidney, blood transit time in each kidney, the extraction rate of Gd across the capillary membrane, interstitial distribution volume, and the GFR for each kidney. (orig.)

  8. Kinetic study of ion exchange in phosphoric acid chelating resin

    International Nuclear Information System (INIS)

    Brikci-Nigassa, Mounir; Hamouche, Hafida

    1995-11-01

    Uranium may be recovered as a by product of wet phosphoric acid using a method based on specific ion exchange resins. These resins called chelates contain amino-phosphonic functional groups. The resin studied in this work is a purolite S-940; uranium may be loaded on this resin from 30% P2O5 phosphoric acid in its reduced state. The influence of different parameters on the successive steps of the process have been studied in batch experiments: uranium reduction, loading and oxydation. Uranium may be eluted with ammonium carbonate and the resin regeneration may be done with hydrochloric acid.Ferric ions reduce the effective resin capacity considerably and inert fixation conditions are proposed to enhance uranium loading

  9. 3,4,5-trihydroxybenzoic acid as chelating agent

    International Nuclear Information System (INIS)

    Agrawal, M.D.; Bhandari, C.S.; Dixit, M.K.; Sogani, N.C.

    1976-01-01

    Stability constants of praseodymium chelates of 3,4,5-trihydroxy sodium benzoate are determined by using Bjerrum-Calvin pH titration techniques at constant ionic strength 0.1M-sodium perchlorate and at 28+-0.1 0 C. Values calculated by different methods are in good agreement. The study reveals that during complexation only one proton of the ligand molecule is replaced by the metal and oxygen of adjacent phenolic group acts as a coordinating atom. IR and NMR spectral studies of the ligand reveal that one of the OH groups (in meta position to carboxylic group) remains free while two other phenolic groups are involved in intramolecular hydrogen bonding. One water molecule is found attached in crystalline gallic acid. (author)

  10. Mesoporous organosilica nanotubes containing a chelating ligand in their walls

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiao; Goto, Yasutomo; Maegawa, Yoshifumi; Inagaki, Shinji, E-mail: inagaki@mosk.tytlabs.co.jp [Toyota Central R and D Laboratories, Inc., Nagakute, Aichi 480-1192 (Japan); Japan Science and Technology Agency (JST)/ACT-C, Nagakute, Aichi, 480-1192 (Japan); Ohsuna, Tetsu [Toyota Central R and D Laboratories, Inc., Nagakute, Aichi 480-1192 (Japan)

    2014-11-01

    We report the synthesis of organosilica nanotubes containing 2,2′-bipyridine chelating ligands within their walls, employing a single-micelle-templating method. These nanotubes have an average pore diameter of 7.8 nm and lengths of several hundred nanometers. UV-vis absorption spectra and scanning transmission electron microscopy observations of immobilized nanotubes with an iridium complex on the bipyridine ligands showed that the 2,2′-bipyridine groups were homogeneously distributed in the benzene-silica walls. The iridium complex, thus, immobilized on the nanotubes exhibited efficient catalytic activity for water oxidation using Ce{sup 4+}, due to the ready access of reactants to the active sites in the nanotubes.

  11. Thermometric studies on the Fe(III)-EDTA chelate.

    Science.gov (United States)

    Dot, K

    1978-02-01

    A DeltaH of -11.5 +/- 0.5 kJ/mole has been determined for the formation of the Fe(III)-EDTA chelate at 25.0 degrees and mu = 0.1(= [HClO(4)] + [NaClO(4)]) by a direct thermometric titration procedure. The entropy change, DeltaS, has been calculated to be 440 J.mole(-1) .deg(-1) by combining the result of the heat measurements with the free energy change obtained from the stability constant previously determined. A relationship between the DeltaS values and the standard partial molal entropies of the tervalent metal ions is discussed. In addition, conditions for the thermometric titration of Fe(III) with NA(4)EDTA at room temperature have been investigated. Iron(III) can be determined in the presence of fairly large amounts of phosphate, Cr(III), Mn(II) and Al(III).

  12. Mesoporous organosilica nanotubes containing a chelating ligand in their walls

    Directory of Open Access Journals (Sweden)

    Xiao Liu

    2014-11-01

    Full Text Available We report the synthesis of organosilica nanotubes containing 2,2′-bipyridine chelating ligands within their walls, employing a single-micelle-templating method. These nanotubes have an average pore diameter of 7.8 nm and lengths of several hundred nanometers. UV-vis absorption spectra and scanning transmission electron microscopy observations of immobilized nanotubes with an iridium complex on the bipyridine ligands showed that the 2,2′-bipyridine groups were homogeneously distributed in the benzene-silica walls. The iridium complex, thus, immobilized on the nanotubes exhibited efficient catalytic activity for water oxidation using Ce4+, due to the ready access of reactants to the active sites in the nanotubes.

  13. Chelation and stabilization of berkelium in oxidation state +IV

    Science.gov (United States)

    Deblonde, Gauthier J.-P.; Sturzbecher-Hoehne, Manuel; Rupert, Peter B.; An, Dahlia D.; Illy, Marie-Claire; Ralston, Corie Y.; Brabec, Jiri; de Jong, Wibe A.; Strong, Roland K.; Abergel, Rebecca J.

    2017-09-01

    Berkelium (Bk) has been predicted to be the only transplutonium element able to exhibit both +III and +IV oxidation states in solution, but evidence of a stable oxidized Bk chelate has so far remained elusive. Here we describe the stabilization of the heaviest 4+ ion of the periodic table, under mild aqueous conditions, using a siderophore derivative. The resulting Bk(IV) complex exhibits luminescence via sensitization through an intramolecular antenna effect. This neutral Bk(IV) coordination compound is not sequestered by the protein siderocalin—a mammalian metal transporter—in contrast to the negatively charged species obtained with neighbouring trivalent actinides americium, curium and californium (Cf). The corresponding Cf(III)-ligand-protein ternary adduct was characterized by X-ray diffraction analysis. Combined with theoretical predictions, these data add significant insight to the field of transplutonium chemistry, and may lead to innovative Bk separation and purification processes.

  14. 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.

  15. Impact of iron overload and potential benefit from iron chelation in low-risk myelodysplastic syndrome.

    Science.gov (United States)

    Shenoy, Niraj; Vallumsetla, Nishanth; Rachmilewitz, Eliezer; Verma, Amit; Ginzburg, Yelena

    2014-08-07

    Myelodysplastic syndromes (MDSs) are a group of heterogeneous clonal bone marrow disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, and potential for malignant transformation. Lower/intermediate-risk MDSs are associated with longer survival and high red blood cell (RBC) transfusion requirements resulting in secondary iron overload. Recent data suggest that markers of iron overload portend a relatively poor prognosis, and retrospective analysis demonstrates that iron chelation therapy is associated with prolonged survival in transfusion-dependent MDS patients. New data provide concrete evidence of iron's adverse effects on erythroid precursors in vitro and in vivo. Renewed interest in the iron field was heralded by the discovery of hepcidin, the main serum peptide hormone negative regulator of body iron. Evidence from β-thalassemia suggests that regulation of hepcidin by erythropoiesis dominates regulation by iron. Because iron overload develops in some MDS patients who do not require RBC transfusions, the suppressive effect of ineffective erythropoiesis on hepcidin may also play a role in iron overload. We anticipate that additional novel tools for measuring iron overload and a molecular-mechanism-driven description of MDS subtypes will provide a deeper understanding of how iron metabolism and erythropoiesis intersect in MDSs and improve clinical management of this patient population. © 2014 by The American Society of Hematology.

  16. 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.

  17. Acidic tumor microenvironment abrogates the efficacy of mTORC1 inhibitors.

    Science.gov (United States)

    Faes, Seraina; Duval, Adrian P; Planche, Anne; Uldry, Emilie; Santoro, Tania; Pythoud, Catherine; Stehle, Jean-Christophe; Horlbeck, Janine; Letovanec, Igor; Riggi, Nicolo; Demartines, Nicolas; Dormond, Olivier

    2016-12-05

    Blocking the mechanistic target of rapamycin complex-1 (mTORC1) with chemical inhibitors such as rapamycin has shown limited clinical efficacy in cancer. The tumor microenvironment is characterized by an acidic pH which interferes with cancer therapies. The consequences of acidity on the anti-cancer efficacy of mTORC1 inhibitors have not been characterized and are thus the focus of our study. Cancer cell lines were treated with rapamycin in acidic or physiological conditions and cell proliferation was investigated. The effect of acidity on mTORC1 activity was determined by Western blot. The anticancer efficacy of rapamycin in combination with sodium bicarbonate to increase the intratumoral pH was tested in two different mouse models and compared to rapamycin treatment alone. Histological analysis was performed on tumor samples to evaluate proliferation, apoptosis and necrosis. Exposing cancer cells to acidic pH in vitro significantly reduced the anti-proliferative effect of rapamycin. At the molecular level, acidity significantly decreased mTORC1 activity, suggesting that cancer cell proliferation is independent of mTORC1 in acidic conditions. In contrast, the activation of mitogen-activated protein kinase (MAPK) or AKT were not affected by acidity, and blocking MAPK or AKT with a chemical inhibitor maintained an anti-proliferative effect at low pH. In tumor mouse models, the use of sodium bicarbonate increased mTORC1 activity in cancer cells and potentiated the anti-cancer efficacy of rapamycin. Combining sodium bicarbonate with rapamycin resulted in increased tumor necrosis, increased cancer cell apoptosis and decreased cancer cell proliferation as compared to single treatment. Taken together, these results emphasize the inefficacy of mTORC1 inhibitors in acidic conditions. They further highlight the potential of combining sodium bicarbonate with mTORC1 inhibitors to improve their anti-tumoral efficacy.

  18. Characterization of commercial iron chelates and their behavior in an alkaline and calcareous soil.

    Science.gov (United States)

    Cantera, Rodrigo G; Zamarreño, Angel M; García-Mina, José M

    2002-12-18

    Iron deficiency is a common problem for many plants grown in alkaline and calcareous soils. To correct this problem, iron is supplied to plants as chelates. Several iron chelates are sold under diverse trademarks with different characteristics. This work evaluated 18 commercial products containing the most representative chelated iron sources used in agricultural practice in Spain when the study was done, namely the ferric chelates of EDDHA, EDDHMA, EDDCHA, EDDHSA, EDTA, and DTPA. The chelates were comprehensively characterized and quantitated by several techniques, including several chromatographic methods. Iron and chelate dynamics in soil were also studied in a model alkaline and calcareous soil. Results indicate that, in this model soil, among the different iron compounds studied only FeEDDHA and analogues have the capacity to maintain soluble iron in soil solution over time. These results are in agreement with general experience under field conditions. Furthermore, among the different ortho-ortho isomers of FeEDDHA's, FeEDDHSA and FeEDDCHA showed greater capacity than FeEDDHA and FeEDDHMA to maintain the chelated iron in soil solution over time.

  19. Synthesis of novel bifunctional chelators and their use in preparing monoclonal antibody conjugates for tumor targeting

    International Nuclear Information System (INIS)

    Westerberg, D.A.; Carney, P.L.; Rogers, P.E.; Kline, S.J.; Johnson, D.K.

    1989-01-01

    Bifunctional derivatives of the chelating agents ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid, in which a p-isothiocyanatobenzyl moiety is attached at the methylene carbon atom of one carboxymethyl arm, was synthesized by reductive alkylation of the relevant polyamine with (p-nitrophenyl)pyruvic acid followed by carboxymethylation, reduction of the nitro group, and reaction with thiophosgene. The resulting isothiocyanate derivatives reacted with monoclonal antibody B72.3 to give antibody-chelator conjugates containing 3 mol of chelator per mole of immunoglobulin, without significant loss of immunological activity. Such conjugates, labeled with the radioisotopic metal indium-111, selectively bound a human colorectal carcinoma implanted in nude mice when given intravenously. Uptake into normal tissues was comparable to or lower than that reported for analogous conjugates with known bifunctional chelators. It is concluded that substitution with a protein reactive group at this position in polyaminopolycarboxylate chelators does not alter the chelating properties of these molecules to a sufficient extent to adversely affect biodistribution and thus provides a general method for the synthesis of such chelators

  20. 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.

  1. Quercetin abrogates chemoresistance in melanoma cells by modulating ΔNp73

    International Nuclear Information System (INIS)

    Thangasamy, Thilakavathy; Sittadjody, Sivanandane; Mitchell, Geoffrey C; Mendoza, Erin E; Radhakrishnan, Vijayababu M; Limesand, Kirsten H; Burd, Randy

    2010-01-01

    The alkylating agent Dacarbazine (DTIC) has been used in the treatment of melanoma for decades, but when used as a monotherapy for cancer only moderate response rates are achieved. Recently, the clinical use of Temozolomide (TMZ) has become the more commonly used analog of DTIC-related oral agents because of its greater bioavailability and ability to cross the blood brain barrier. The response rates achieved by TMZ are also unsatisfactory, so there is great interest in identifying compounds that could be used in combination therapy. We have previously demonstrated that the bioflavonoid quercetin (Qct) promoted a p53-mediated response and sensitized melanoma to DTIC. Here we demonstrate that Qct also sensitizes cells to TMZ and propose a mechanism that involves the modulation of a truncated p53 family member, ΔNp73. DB-1 melanoma (p53 wildtype), and SK Mel 28 (p53 mutant) cell lines were treated with TMZ (400 μM) for 48 hrs followed by Qct (75 μM) for 24 hrs. Cell death was determined by Annexin V-FITC staining and immunocytochemical analysis was carried out to determine protein translocation. After treatment with TMZ, DB-1 cells demonstrated increased phosphorylation of Ataxia telangiectasia mutated (ATM) and p53. However, the cells were resistant to TMZ-induced apoptosis and the resistance was associated with an increase in nuclear localization of ΔNp73. Qct treatment in combination with TMZ abolished drug insensitivity and caused a more than additive induction of apoptosis compared to either treatment alone. Treatment with Qct, caused redistribution of ΔNp73 into the cytoplasm and nucleus, which has been associated with increased p53 transcriptional activity. Knockdown of ΔNp73 restored PARP cleavage in the TMZ treated cells, confirming its anti-apoptotic role. The response to treatment was predominantly p53 mediated as the p53 mutant SK Mel 28 cells showed no significant enhancement of apoptosis. This study demonstrates that Qct can sensitize cells to TMZ

  2. Quercetin abrogates chemoresistance in melanoma cells by modulating ΔNp73

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Vijayababu M

    2010-06-01

    Full Text Available Abstract Background The alkylating agent Dacarbazine (DTIC has been used in the treatment of melanoma for decades, but when used as a monotherapy for cancer only moderate response rates are achieved. Recently, the clinical use of Temozolomide (TMZ has become the more commonly used analog of DTIC-related oral agents because of its greater bioavailability and ability to cross the blood brain barrier. The response rates achieved by TMZ are also unsatisfactory, so there is great interest in identifying compounds that could be used in combination therapy. We have previously demonstrated that the bioflavonoid quercetin (Qct promoted a p53-mediated response and sensitized melanoma to DTIC. Here we demonstrate that Qct also sensitizes cells to TMZ and propose a mechanism that involves the modulation of a truncated p53 family member, ΔNp73. Methods DB-1 melanoma (p53 wildtype, and SK Mel 28 (p53 mutant cell lines were treated with TMZ (400 μM for 48 hrs followed by Qct (75 μM for 24 hrs. Cell death was determined by Annexin V-FITC staining and immunocytochemical analysis was carried out to determine protein translocation. Results After treatment with TMZ, DB-1 cells demonstrated increased phosphorylation of Ataxia telangiectasia mutated (ATM and p53. However, the cells were resistant to TMZ-induced apoptosis and the resistance was associated with an increase in nuclear localization of ΔNp73. Qct treatment in combination with TMZ abolished drug insensitivity and caused a more than additive induction of apoptosis compared to either treatment alone. Treatment with Qct, caused redistribution of ΔNp73 into the cytoplasm and nucleus, which has been associated with increased p53 transcriptional activity. Knockdown of ΔNp73 restored PARP cleavage in the TMZ treated cells, confirming its anti-apoptotic role. The response to treatment was predominantly p53 mediated as the p53 mutant SK Mel 28 cells showed no significant enhancement of apoptosis. Conclusion

  3. Different photoluminescent properties of binary and ternary europium chelates doped in PMMA

    International Nuclear Information System (INIS)

    Liu Hongguo; Park, Seongtae; Jang, Kiwan; Zhang Wansong; Seo, Hyo-Jin; Lee, Yong-Ill

    2003-01-01

    Two kinds of europium-β-diketone chelates, binary Eu(DBM) 3 and ternary Eu(DBM) 3 phen were doped in poly(methyl methacrylate) (PMMA). These chelates show very different photoluminescent (PL) behaviors: the hypersensitive 5 D 0 → 7 F 2 emission bands of Eu(DBM) 3 phen change slightly with the molar ratios, while those of Eu(DBM) 3 change obviously and regularly with the molar ratios. The results of the luminescent lifetimes of 5 D 0 levels show that the binary chelate exists as two kinds of species in the doped systems, and the lifetimes and contents of each species change with the molar ratios, while the ternary chelate exists as one kind of species in the doped systems. X-ray diffraction (XRD) patterns of the binary chelate doped systems give some diffraction peaks that are different from those of pure chelate and change with the molar ratios, indicating new kinds of crystal structures formed, and consequently, the first coordination sphere of Eu 3+ ion changes; while those of the ternary chelate doped systems just show amorphous diffraction halos of the host, indicating that the ternary chelate exist in an amorphous state and disperse well in the host. The FTIR spectra of PMMA also change gradually with increasing the molar ratios of the doped two kinds of chelates, and the XRD patterns show that the amorphous halos of PMMA in the doped systems are different from those of pure PMMA and change with the molar ratios, too, suggesting the interaction between the guest and the host

  4. 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.

  5. Synthesis of a new technetium radiotracer containing para-toluidine by tridentate chelation (N,N,O)

    International Nuclear Information System (INIS)

    Makhloufi, Amel

    2011-01-01

    Neuro degenerative diseases (Alzheimer, Parkinson, Creutzfeld-Jacob. and others) have an increasingly important impact as well on the economic plan as social. The diagnosis procedure and current therapies remain expensive and the assumption of responsibility of the patient is seldom assured. These last years, the development of new radiopharmaceuticals with aiming diagnosis procedure started again the interest for the search for new molecules. The asset of the synthesis of our technetium radiotracer, a tridentate chelate complex (N, N, O) resides in the facility of its obtaining; marking with the kit Alberto is done at a temperature about 90 degree approximately and this could consequently facilitate its implementation in the units of radiodiagnosis. Of lipophilic nature, neutral and of suitable molecular weight, the main challenge for this molecule would be to check its capacity to cross the blood-brain barrier by studying its cerebral extraction.

  6. Chelating extractants of improved selectivity. Progress report, September 1, 1976--October 31, 1977

    International Nuclear Information System (INIS)

    Freiser, H.

    1977-07-01

    New means of characterizing metal chelating reagent selectivity have been developed and incorporated into a theoretical factor analysis of the chelate stability constants of 24 metal ions with 14 ligands of the EDTA family. The factor analysis will be extended to extracting ligand families. A computer-controlled automated metal chelate stability constant apparatus has been assembled and successfully tested. A high performance liquid chromatograph has been set up and preliminary examination of comparison of reversed phase chromatographic separation of metal ions with their solvent extraction behavior begun

  7. [Bifunctional chelates of Rh-105, Au-199, and other metallic radionuclides as potential radiotherapeutic agents

    International Nuclear Information System (INIS)

    1991-01-01

    Progress during this period is reported under the following headings: Diethylenetriamine based and related bifunctional chelating agents and their complexation with Rh-105, Au-198, Pd-109, cu-67, In-111, and Co-57; studies of Pd-109, Rh-105 and Tc-99m with bifunctional chelates based on phenylenediamine; establishment of an appropriate protein assay method for conjugated proteins; studies of new bifunctional Bi, Tri and tetradentate amine oxime ligands with Rh-105; IgG and antibody B72.3 conjugation studies by HPLC Techniques with bifunctional metal chelates; and progress on ligand systems for Au(III)

  8. [Bifunctional chelates of Rh-105, Au-199, and other metallic radionuclides as potential radiotherapeutic agents

    Energy Technology Data Exchange (ETDEWEB)

    1991-12-31

    Progress during this period is reported under the following headings: Diethylenetriamine based and related bifunctional chelating agents and their complexation with Rh-105, Au-198, Pd-109, cu-67, In-111, and Co-57; studies of Pd-109, Rh-105 and Tc-99m with bifunctional chelates based on phenylenediamine; establishment of an appropriate protein assay method for conjugated proteins; studies of new bifunctional Bi, Tri and tetradentate amine oxime ligands with Rh-105; IgG and antibody B72.3 conjugation studies by HPLC Techniques with bifunctional metal chelates; and progress on ligand systems for Au(III).

  9. (Bifunctional chelates of Rh-105, Au-199, and other metallic radionuclides as potential radiotherapeutic agents)

    Energy Technology Data Exchange (ETDEWEB)

    1991-01-01

    Progress during this period is reported under the following headings: Diethylenetriamine based and related bifunctional chelating agents and their complexation with Rh-105, Au-198, Pd-109, cu-67, In-111, and Co-57; studies of Pd-109, Rh-105 and Tc-99m with bifunctional chelates based on phenylenediamine; establishment of an appropriate protein assay method for conjugated proteins; studies of new bifunctional Bi, Tri and tetradentate amine oxime ligands with Rh-105; IgG and antibody B72.3 conjugation studies by HPLC Techniques with bifunctional metal chelates; and progress on ligand systems for Au(III).

  10. AAZTA: an ideal chelating agent for the development of {sup 44}Sc PET imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Gabor; Szikra, Dezso; Trencsenyi, Gyoergy [Scanomed Ltd., Debrecen (Hungary); University of Debrecen, Medical Imaging Clinic (Hungary); Fekete, Aniko [University of Debrecen, Medical Imaging Clinic (Hungary); Garai, Ildiko [Scanomed Ltd., Debrecen (Hungary); Giani, Arianna M.; Negri, Roberto [Dipartimento di Scienze del Farmaco, Universita del Piemonte Orientale, Novara (Italy); Masciocchi, Norberto [Dipartimento di Scienza e Alta Tecnologia e To.Sca.Lab, Universita degli Studi dell' Insubria, Como (Italy); Maiocchi, Alessandro; Uggeri, Fulvio [Bracco Imaging spa, Bracco Research Centre, Colleretto Giacosa (Italy); Toth, Imre [Department of Inorganic and Analytical Chemistry, University of Debrecen (Hungary); Aime, Silvio [Dipartimento di Biotecnologie Molecolari e Scienze della Salute, Centro di Imaging Molecolare e Preclinico, Universita degli Studi di Torino (Italy); Giovenzana, Giovanni B. [Dipartimento di Scienze del Farmaco, Universita del Piemonte Orientale, Novara (Italy); CAGE Chemicals srl, Novara (Italy); Baranyai, Zsolt [Bracco Imaging spa, Bracco Research Centre, Colleretto Giacosa (Italy); Department of Inorganic and Analytical Chemistry, University of Debrecen (Hungary)

    2017-02-13

    Unprecedented fast and efficient complexation of Sc{sup III} was demonstrated with the chelating agent AAZTA (AAZTA=1,4-bis(carboxymethyl)-6-[bis(carboxymethyl)] amino-6-methylperhydro-1,4-d iazepine) under mild experimental conditions. The robustness of the {sup 44}Sc(AAZTA){sup -} chelate and conjugated biomolecules thereof is further shown by in vivo PET imaging in healthy and tumor mice models. The new results pave the way towards development of efficient Sc-based radiopharmaceuticals using the AAZTA chelator. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  11. Design, synthesis, and evaluation of polyhydroxamate chelators for selective complexation of actinides

    International Nuclear Information System (INIS)

    Gopalan, A.; Jacobs, H.; Koshti, N.; Stark, P.; Huber, V.; Dasaradhi, L.; Caswell, W.; Smith, P.; Jarvinen, G.

    1995-01-01

    Specific chelating polymers targeted for actinides have much relevance to problems involving remediation of nuclear waste. Goal is to develop polymer supported, ion specific extraction systems for removing actinides and other hazardous metal ions from wastewaters. This is part of an effort to develop chelators for removing actinide ions such as Pu from soils and waste streams. Selected ligands are being attached to polymeric backbones to create novel chelating polymers. These polymers and other water soluble and insoluble polymers have been synthesized and are being evaluated for ability to selectively remove target metal ions from process waste streams

  12. Assessment of the body burden of chelatable lead: a model and its application to lead workers

    Energy Technology Data Exchange (ETDEWEB)

    Araki, S.; Ushio, K.

    1982-05-01

    A hypothetical model was introduced to estimate the body burden of chelatable lead from the mobilisation yield of lead by calcium disodium ethylenediamine tetra-acetate. It was estimated that, on average, 14 and 19% of the body burden was mobilized into the urine during the 24 hours after an injection of 53.4 mumol and 107 mumol CaEDTA per kg bodyweight, respectively. The body burden of chelatable lead ranged from 4 mumol to 120 mumol in lead workers with blood lead concentrations of 0.3-2.9 mumol/kg. There were linear relationships between blood lead concentrations and body burden of chelatable lead on a log scale.

  13. HIV-1 Nef mutations abrogating downregulation of CD4 affect other Nef functions and show reduced pathogenicity in transgenic mice

    International Nuclear Information System (INIS)

    Hanna, Zaher; Priceputu, Elena; Hu, Chunyan; Vincent, Patrick; Jolicoeur, Paul

    2006-01-01

    HIV-1 Nef has the ability to downmodulate CD4 cell surface expression. Several studies have shown that CD4 downregulation is required for efficient virus replication and high infectivity. However, the pathophysiological relevance of this phenomenon in vivo, independently of its role in sustaining high virus loads, remains unclear. We studied the impact of the CD4 downregulation function of Nef on its pathogenesis in vivo, in the absence of viral replication, in the CD4C/HIV transgenic (Tg) mouse model. Two independent Nef mutants (RD35/36AA and D174K), known to abrogate CD4 downregulation, were tested in Tg mice. Flow cytometry analysis showed that downregulation of murine CD4 was severely decreased or abrogated on Tg T cells expressing respectively Nef RD35/36AA and Nef D174K . Similarly, the severe depletion of double-positive CD4 + CD8 + and of single-positive CD4 + CD8 - thymocytes, usually observed with Nef Wt , was not detected in Nef RD35/36AA and Nef D174K Tg mice. However, both mutant Tg mice showed a partial depletion of peripheral CD4 + T cells. This was accompanied, as previously reported for Net Wt Tg mice, by the presence of an activated/memory-like phenotype (CD69 + , CD25 + , CD44 + , CD45RB Low , CD62 Low ) of CD4 + T cells expressing Nef RD35/36AA and to a lesser extent Nef D174K . In addition, both mutants retained the ability to block CD4 + T cell proliferation in vitro after anti-CD3 stimulation, but not to enhance apoptosis/death of CD4 + T cells. Therefore, it appears that Nef-mediated CD4 downregulation is associated with thymic defects, but segregates independently of the activated/memory-like phenotype, of the partial depletion and of the impaired in vitro proliferation of peripheral CD4 + T cells. Histopathological assessment revealed the total absence of or decrease severity and frequency of organ AIDS-like diseases (lung, heart and kidney pathologies) in respectively Nef RD35/36AA and Nef D174K Tg mice, relative to those developing in

  14. Complementary and Alternative Therapies in ALS

    Science.gov (United States)

    Bedlack, Richard S.; Joyce, Nanette; Carter, Gregory T.; Pagononi, Sabrina; Karam, Chafic

    2015-01-01

    Synopsis Given the severity of their illness and lack of effective disease modifying agents, it is not surprising that most patients with ALS consider trying complementary and alternative therapies. Some of the most commonly considered alternative therapies include special diets, nutritional supplements, cannabis, acupuncture, chelation and energy healing. This chapter reviews these in detail. We also describe 3 models by which physicians may frame discussions about alternative therapies: paternalism, autonomy and shared decision making. Finally, we review a program called ALSUntangled which using shared shared decision making to review alternative therapies for ALS. PMID:26515629

  15. Chelating ion exchange with macroreticular hydroxamic acid resins

    International Nuclear Information System (INIS)

    Phillips, R.J.

    1980-01-01

    The synthesis, reactions, and analytical applications of hydroxamic acids, including chelating resins with this functional group, are reviewed. A procedure for attaching N-phenyl hydroxamic acid groups to Amberlite XAD-4 is described. The extraction of 20 metal ions from 2 M hydrochloric acid by this resin is discussed. Conditions for the quantitative extraction and back-extraction of 9 ions are reported. Results are compared with work on solvent extraction with N-phenylbenzohydroxamic acid. Procedures for attaching N-methyl and N-unsubstituted hydroxamic acid groups to Amberlite XAD-4 are described. The N-phenyl, N-methyl, and N-unsubstituted hydroxamic acid resins are compared with respect to metal-ion complexation. The scope of applications for hydroxamic acid resins is investigated by studying the extraction of 19 metal ions as a function of pH. The resins are especially suitable for the extraction of zirconium(IV), titanium(IV), and uranium(IV) from strongly acidic solution. Aluminum(III) is separated from calcium and phosphate by extraction at pH 4. The use of the resins for the purification of reagents, concentration of trace constituents, and chromatographic separation is demonstrated

  16. Synthesis of a novel bicyclic bifunctional chelating agent

    International Nuclear Information System (INIS)

    Sweet, M.P.; Mease, R.C.; Joshi, V.; Srivastava, S.C.

    1994-01-01

    Semi-rigid ligands such as cyclohexyl EDTA (CDTA) and 4-isothiocyanato-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (4-ICE) form chelates that are more stable in vivo compared to those of EDTA or DTPA. The authors have synthesized a new class of ligands in which the metal-binding polyaminocarboxylate groups are incorporated onto the rigid bicyclo[2.2.2]octane ring system. These ligands are expected to contribute to even higher in vivo stability of radiometal complexes. The synthesis of the first in this series of ligands (2.3-diaminobicyclo[2.2.2]octane-N,N,N',N'-tetraacetic acid, BODTA) began with a Diels-Alder reaction of 1,3-diacetylimidazolin-2-one and 1,3-cyclohexadiene. Base hydrolysis afforded the diamine. Following alkylation of the diamine with ethyl iodoacetate and hydrogenation of the double bond, hydrolysis of the esters gave BODTA. For initial conjugation with proteins, an average of one carboxylic acid of BODTA was converted into an NHS ester. In vivo testing of radioimmunoconjugates, prepared using this method, is in progress

  17. Assessment of toxicity on chelating agent DTPA (diethylenetriaminepentaacetic acid)

    International Nuclear Information System (INIS)

    Fukuda, Satoshi

    1989-01-01

    DTPA (diethylenetriaminepentaacetic acid) is a very important chelating agent to decorporate the radionuclides such as plutonium and americium from human body. However, before DTPA will be administered to humans, the toxicity should be clarified. This report described the summary on data of DTPA toxicities obtained from animal experiments and assessment on the safety for humans, based on the results that compared their data among animal species. In short, Ca-DTPA is less toxic than Zn-DTPA when it is injected intravenously, while Zn-DTPA is less toxic than Ca-DTPA when it is administered orally. Both DTPAs acted on the serum calcium metabolism and induced the functional damages of cardiovascular system. Particularly, it is stressed that Zn-DTPA by intravenous injection occurred the heart failure, increases of blood pressure and pulse with hypocalcemia in even normal rats and beagle dogs. Other side effects by both DTPAs were also observed in the intestine, liver, kidney and bone. It is estimated that there are almost no species differences on DTPA toxicity between animals and humans. As a result, it is concluded that DTPA should be used very carefully for humans, with reference to the results obtained from animal experiments. (author) 61 refs

  18. Assessment of toxicity on chelating agent DTPA (diethylenetriaminepentaacetic acid)

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Satoshi (National Inst. of Radiological Sciences, Chiba (Japan))

    1989-09-01

    DTPA (diethylenetriaminepentaacetic acid) is a very important chelating agent to decorporate the radionuclides such as plutonium and americium from human body. However, before DTPA will be administered to humans, the toxicity should be clarified. This report described the summary on data of DTPA toxicities obtained from animal experiments and assessment on the safety for humans, based on the results that compared their data among animal species. In short, Ca-DTPA is less toxic than Zn-DTPA when it is injected intravenously, while Zn-DTPA is less toxic than Ca-DTPA when it is administered orally. Both DTPAs acted on the serum calcium metabolism and induced the functional damages of cardiovascular system. Particularly, it is stressed that Zn-DTPA by intravenous injection occurred the heart failure, increases of blood pressure and pulse with hypocalcemia in even normal rats and beagle dogs. Other side effects by both DTPAs were also observed in the intestine, liver, kidney and bone. It is estimated that there are almost no species differences on DTPA toxicity between animals and humans. As a result, it is concluded that DTPA should be used very carefully for humans, with reference to the results obtained from animal experiments. (author) 61 refs.

  19. Chelating water-soluble polymers for waste minimization

    International Nuclear Information System (INIS)

    Smith, B.; Cournoyer, M.; Duran, B.; Ford, D.; Gibson, R.; Lin, M.; Meck, A.; Robinson, P.; Robison, T.

    1996-01-01

    Within the DOE complex and in industry there is a tremendous need for advanced metal ion recovery and waste minimization techniques. This project sought to employ capabilities for ligand-design and separations chemistry in which one can develop and evaluate water- soluble chelating polymers for recovering actinides and toxic metals from various process streams. Focus of this work was (1) to develop and select a set of water-soluble polymers suitable for a selected waste stream and (2) demonstrate this technology in 2 areas: removal of (a) actinides and toxic RCRA metals from waste water and (b) recovery of Cu and other precious metals from industrial process streams including from solid catalysts and aqueous waste streams. The R ampersand D was done in 4 phases for each of the 2 target areas: polymer synthesis for scaleup, equipment assembly, process demonstration at a DOE or industrial site, and advanced ligand/polymer synthesis. The TA- 50 site at Los Alamos was thought to be appropriate due to logistics and to its being representative of similar problems throughout the DOE complex

  20. Mechanisms of oxide dissolution by acid chelating agents

    International Nuclear Information System (INIS)

    Blesa, M.A.; Maroto, A.J.G.

    1982-01-01

    In this paper, the different possible rate controlling processes in the dissolution of metallic oxides are examined. In particular, the following situations are assessed: mass-transfer control; coupling of mass-transfer and reactions at the interface; interface equilibration with the solution; various interface disruption and reconstruction phenomena. For each of the above mentioned cases, the influence of variables such as reagent concentration, temperature, pH, fluid hydrodynamics and general and specific catalysts is discussed. Depending upon the particular situation it is found that a more rational basis for the development of reagent is given by these considerations. The influence of chelating agents on both the thermodynamics and kinetics of the process is discussed, and the results of experimental studies in batch on magnetite and various ferrites are presented and discussed. For this purpose, several reagents were studied, including some very effective ones like thioglycolic acid, and others commonly used in actual decontamination, like ethylenediaminetetraacetic acid and oxalic acid. The relation to other (reductive) chemical decontamination procedures is discussed. The relevance of these studies to decontamination of metallic surfaces is discussed

  1. Chelatable trace zinc causes low, irreproducible KDAC8 activity.

    Science.gov (United States)

    Toro, Tasha B; Edenfield, Samantha A; Hylton, Brandon J; Watt, Terry J

    2018-01-01

    Acetylation is an important regulatory mechanism in cells, and emphasis is being placed on identifying substrates and small molecule modulators of this post-translational modification. However, the reported in vitro activity of the lysine deacetylase KDAC8 is inconsistent across experimental setups, even with the same substrate, complicating progress in the field. We detected trace levels of zinc, a known inhibitor of KDAC8 when present in excess, even in high-quality buffer reagents, at concentrations that are sufficient to significantly inhibit the enzyme under common reaction conditions. We hypothesized that trace zinc in solution could account for the observed variability in KDAC8 activity. We demonstrate that addition of chelators, including BSA, EDTA, and citrate, and/or the use of a phosphate-based buffer instead of the more common tris-based buffer, eliminates the inhibition from low levels of zinc as well as the dependence of specific activity on enzyme concentration. This results in high KDAC8 activity that is consistent across buffer systems, even using low concentrations of enzyme. We report conditions that are suitable for several assays to increase both enzyme activity and reproducibility. Our results have significant implications for approaches used to identify substrates and small molecule modulators of KDAC8 and interpretation of existing data. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. ATMP-stabilized iron nanoparticles: chelator-controlled nanoparticle synthesis

    Science.gov (United States)

    Greenlee, Lauren F.; Rentz, Nikki S.

    2014-11-01

    In this study, we characterize iron nanoparticles synthesized in water in the presence of a phosphonate chelator, amino tris(methylene phosphonic acid) (ATMP) for a range of molar ratios of ATMP to iron. An increase in the molar ratio from 0.05 to 0.8 decreases nanoparticle size from approximately 150 nm to less than 10 nm. Zeta potential measurements were used to evaluate colloidal stability. Zeta potential values varied as a function of pH, and zeta potential values decreased with increasing pH. At lower molar ratios of ATMP to iron, the zeta potential varied between 15 and -40 mV, passing through an isoelectric point at pH 7.5. At higher ratios, the zeta potential was negative across the measured pH range of 2-12 and varied from -2 to -55 mV. Diffraction analysis indicates that ATMP-stabilized iron nanoparticles may have a nano-crystalline structure, potentially with regions of amorphous iron. Characterization results of ATMP-stabilized iron nanoparticles are compared to results obtained for carboxymethyl cellulose (CMC)-stabilized iron nanoparticles. CMC stabilization caused similar peak broadening in diffraction spectra as for ATMP, suggesting similar nano-crystalline/amorphous structure; however, an increase in the molar ratio of CMC to iron did not cause the same reduction in nanoparticle size as was observed for ATMP-stabilized iron nanoparticles.

  3. The performance of 2-nitroso-1-naphthol chelating pigment in paint ...

    African Journals Online (AJOL)

    The performance of 2-nitroso-1-naphthol chelating pigment in paint formulation with gum Arabic and polyvinyl acetate as binders, Paper I: UV- visible spectroscopy, viscosity and breaking stress of the paints.

  4. Study of chelating agent as a surface modifier for retarding corrosion attack on ferrous metal

    International Nuclear Information System (INIS)

    Nur Ubaidah Saidin; Muhamad Daud; Siti Radiah Mohd Kamarudin; Zaifol Samsu; Azali Muhamad; Rusni Rejab; Mohd Saari Ripin; Mohd Shariff Sattar

    2010-01-01

    A different concentration of chelating agents in electrolyte of 3.5 % NaCl was applied to bare ferrous metal and tested for their effectiveness as a corrosion retardant. The performance of the samples was measured using corrosion measurement system. The results indicated that the contribution of chelating agent was expediting the reduction of the passive film. The anodic behavior was clearly found to be influenced by the concentration of the chelating agent. It was also found that some of the corrosion was apparently converted to protective layer over a period of time. Excessive moisture caused breakdown of film by removing the unreacted chelating agent and causing regrowth of the existing rust. (author)

  5. 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.

  6. Effect of calcium chelators on physical changes in casein micelles in concentrated micellar casein solutions

    NARCIS (Netherlands)

    Kort, de E.J.P.; Minor, M.; Snoeren, T.H.M.; Hooijdonk, van A.C.M.; Linden, van der E.

    2011-01-01

    The effect of calcium chelators on physical changes of casein micelles in concentrated micellar casein solutions was investigated by measuring calcium-ion activity, viscosity and turbidity, and performing ultracentrifugation. The highest viscosities were measured on addition of sodium

  7. 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.

  8. A Zinc Chelator TPEN Attenuates Airway Hyperresponsiveness Airway Inflammation in Mice In Vivo

    Directory of Open Access Journals (Sweden)

    Satoru Fukuyama

    2011-01-01

    Conclusions: In pulmonary allergic inflammation induced in mice immunized with antigen without alum, zinc chelator inhibits airway inflammation and hyperresponsiveness. These findings suggest that zinc may be a therapeutic target of allergic asthma.

  9. Hydrolysis of Some C,N-Chelated Organotin(IV) Species Used in Catalysis

    OpenAIRE

    Švec, P.

    2012-01-01

    This work deals with the reactivity of the selected C, N-chelated organotin (IV) species towards cyclohexene oxide, ethylene carbonate, and CO2. Structure of organotin(IV) hydrolytic products isolated from respective reaction mixtures was described.

  10. Diagnostic compositions containing a chelate of radioactive indium and 8-hydroxyquinoline

    International Nuclear Information System (INIS)

    Goedemans, W.T.

    1981-01-01

    There are disclosed aqueous, radioassaying solutions of a chelate of radioactive indium and an 8-hydroxyquinoline, having an essential absence of an organic solvent, e.g., alcohol or chloroform. The solutions are useful in radioassaying warmblooded animals. (author)

  11. Point mutations in EBV gH that abrogate or differentially affect B cell and epithelial cell fusion

    International Nuclear Information System (INIS)

    Wu Liguo; Hutt-Fletcher, Lindsey M.

    2007-01-01

    Cell fusion mediated by Epstein-Barr virus requires three conserved glycoproteins, gB and gHgL, but activation is cell type specific. B cell fusion requires interaction between MHC class II and a fourth virus glycoprotein, gp42, which complexes non-covalently with gHgL. Epithelial cell fusion requires interaction between gHgL and a novel epithelial cell coreceptor and is blocked by excess gp42. We show here that gp42 interacts directly with gH and that point mutations in the region of gH recognized by an antibody that differentially inhibits epithelial and B cell fusion significantly impact both the core fusion machinery and cell-specific events. Substitution of alanine for glycine at residue 594 completely abrogates fusion with either B cells or epithelial cells. Substitution of alanine for glutamic acid at residue 595 reduces fusion with epithelial cells, greatly enhances fusion with B cells and allows low levels of B cell fusion even in the absence of gL

  12. Dexamethasone abrogates the antimicrobial and antibiofilm activities of different drugs against clinical isolates of Staphylococcus aureus and Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Aquila Rodrigues

    2017-01-01

    Full Text Available Staphylococcus aureus and Pseudomonas aeruginosa are part of the human microbiota and are also important bacterial pathogens, for which therapeutic options are lacking nowadays. The combined administration of corticosteroids and antimicrobials is commonly used in the treatment of infectious diseases to control inflammatory processes and to minimize potential toxicity of antimicrobials, avoiding sequelae. Although different pharmaceutical dosage forms of antimicrobials combined to corticosteroids are available, studies on the interference of corticosteroids on the pharmacological activity of antimicrobials are scarce and controversial. Here, we provide evidence of the interference of dexamethasone on the pharmacological activity of clinically important antimicrobial drugs against biofilms and planktonic cells of S. aureus and P. aeruginosa. Broth microdilution assays of minimal inhibitory concentration (MIC, minimum bactericidal concentration (MBC, and minimum biofilm eradication concentration (MBEC of gentamicin, chloramphenicol, oxacillin, ceftriaxone and meropenem were conducted with and without the addition of dexamethasone. The effect of all drugs was abrogated by dexamethasone in their MIC, MBC, and MBEC, except gentamicin and meropenem, for which the MBC was not affected in some strains. The present study opens doors for more investigations on in vitro and in vivo effects and safety of the combination of antimicrobials and glucocorticoids.

  13. 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.

  14. Disruption of IL-21 signaling affects T cell-B cell interactions and abrogates protective humoral immunity to malaria.

    Directory of Open Access Journals (Sweden)

    Damián Pérez-Mazliah

    2015-03-01

    Full Text Available Interleukin-21 signaling is important for germinal center B-cell responses, isotype switching and generation of memory B cells. However, a role for IL-21 in antibody-mediated protection against pathogens has not been demonstrated. Here we show that IL-21 is produced by T follicular helper cells and co-expressed with IFN-γ during an erythrocytic-stage malaria infection of Plasmodium chabaudi in mice. Mice deficient either in IL-21 or the IL-21 receptor fail to resolve the chronic phase of P. chabaudi infection and P. yoelii infection resulting in sustained high parasitemias, and are not immune to re-infection. This is associated with abrogated P. chabaudi-specific IgG responses, including memory B cells. Mixed bone marrow chimeric mice, with T cells carrying a targeted disruption of the Il21 gene, or B cells with a targeted disruption of the Il21r gene, demonstrate that IL-21 from T cells signaling through the IL-21 receptor on B cells is necessary to control chronic P. chabaudi infection. Our data uncover a mechanism by which CD4+ T cells and B cells control parasitemia during chronic erythrocytic-stage malaria through a single gene, Il21, and demonstrate the importance of this cytokine in the control of pathogens by humoral immune responses. These data are highly pertinent for designing malaria vaccines requiring long-lasting protective B-cell responses.

  15. Hesperidin protects against cyclophosphamide-induced hepatotoxicity by upregulation of PPARγ and abrogation of oxidative stress and inflammation.

    Science.gov (United States)

    Mahmoud, Ayman M

    2014-09-01

    The most important reason for the non-approval and withdrawal of drugs by the Food and Drug Administration is hepatotoxicity. Therefore, this study was undertaken to evaluate the protective effects of hesperidin against cyclophosphamide (CYP)-induced hepatotoxicity in Wistar rats. The rats received a single intraperitoneal dose of CYP of 200 mg/kg body mass, followed by treatment with hesperidin, orally, at doses of 25 and 50 mg/kg for 11 consecutive days. CYP induced hepatic damage, as evidenced by the significantly elevated levels of serum pro-inflammatory cytokines, serum transaminases, liver lipid peroxidation, and nitric oxide. As a consequence, there was reduced glutathione content, and the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, were markedly reduced. In addition, CYP administration induced a considerable downregulation of peroxisome proliferator activated receptor gamma (PPARγ) and upregulation of nuclear factor-kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) mRNA expression. Hesperidin, in a dose-dependent manner, rejuvenated the altered markers to an almost normal state. In conclusion, hesperidin showed a potent protective effect against CYP-induced oxidative stress and inflammation leading to hepatotoxicity. The study suggests that hesperidin exerts its protective effect against CYP-induced hepatotoxicity through upregulation of hepatic PPARγ expression and abrogation of inflammation and oxidative stress.

  16. Silencing of poly(ADP-ribose) glycohydrolase sensitizes lung cancer cells to radiation through the abrogation of DNA damage checkpoint

    Energy Technology Data Exchange (ETDEWEB)

    Nakadate, Yusuke [Shien-Lab, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Kodera, Yasuo; Kitamura, Yuka [Shien-Lab, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Tachibana, Taro [Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Tamura, Tomohide [Division of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Koizumi, Fumiaki, E-mail: fkoizumi@ncc.go.jp [Division of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan)

    2013-11-29

    Highlights: •Radiosensitization by PARG silencing was observed in multiple lung cancer cells. •PAR accumulation was enhanced by PARG silencing after DNA damage. •Radiation-induced G2/M arrest and checkpoint activation were impaired by PARG siRNA. -- Abstract: Poly(ADP-ribose) glycohydrolase (PARG) is a major enzyme that plays a role in the degradation of poly(ADP-ribose) (PAR). PARG deficiency reportedly sensitizes cells to the effects of radiation. In lung cancer, however, it has not been fully elucidated. Here, we investigated whether PARG siRNA contributes to an increased radiosensitivity using 8 lung cancer cell lines. Among them, the silencing of PARG induced a radiosensitizing effect in 5 cell lines. Radiation-induced G2/M arrest was largely suppressed by PARG siRNA in PC-14 and A427 cells, which exhibited significantly enhanced radiosensitivity in response to PARG knockdown. On the other hand, a similar effect was not observed in H520 cells, which did not exhibit a radiosensitizing effect. Consistent with a cell cycle analysis, radiation-induced checkpoint signals were not well activated in the PC-14 and A427 cells when treated with PARG siRNA. These results suggest that the increased sensitivity to radiation induced by PARG knockdown occurs through the abrogation of radiation-induced G2/M arrest and checkpoint activation in lung cancer cells. Our findings indicate that PARG could be a potential target for lung cancer treatments when used in combination with radiotherapy.

  17. Surgical Stress Abrogates Pre-Existing Protective T Cell Mediated Anti-Tumor Immunity Leading to Postoperative Cancer Recurrence.

    Directory of Open Access Journals (Sweden)

    Abhirami A Ananth

    Full Text Available Anti-tumor CD8+ T cells are a key determinant for overall survival in patients following surgical resection for solid malignancies. Using a mouse model of cancer vaccination (adenovirus expressing melanoma tumor-associated antigen (TAA-dopachrome tautomerase (AdDCT and resection resulting in major surgical stress (abdominal nephrectomy, we demonstrate that surgical stress results in a reduction in the number of CD8+ T cell that produce cytokines (IFNγ, TNFα, Granzyme B in response to TAA. This effect is secondary to both reduced proliferation and impaired T cell function following antigen binding. In a prophylactic model, surgical stress completely abrogates tumor protection conferred by vaccination in the immediate postoperative period. In a clinically relevant surgical resection model, vaccinated mice undergoing a positive margin resection with surgical stress had decreased survival compared to mice with positive margin resection alone. Preoperative immunotherapy with IFNα significantly extends survival in surgically stressed mice. Importantly, myeloid derived suppressor cell (MDSC population numbers and functional impairment of TAA-specific CD8+ T cell were altered in surgically stressed mice. Our observations suggest that cancer progression may result from surgery-induced suppression of tumor-specific CD8+ T cells. Preoperative immunotherapies aimed at targeting the prometastatic effects of cancer surgery will reduce recurrence and improve survival in cancer surgery patients.

  18. 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Theoretical analysis of the influence of chelate-ring size and vicinal effects on electronic circular dichroism spectra of cobalt(III) EDDA-type complexes.

    Science.gov (United States)

    Wang, Ai; Wang, Yuekui; Jia, Jie; Feng, Lixia; Zhang, Chunxia; Liu, Linlin

    2013-06-20

    To assess the contributions of configurational and vicinal effects as well as chelate-ring size to rotational strengths, the geometries of a series of cobalt(III) complexes [Co(EDDA-type)(L)](±) with the tetradentate EDDA-type ligands, EDDA (ethylenediamine-N,N'-diacetate), DMEDDA (N,N'-dimethylethylenediamine-N,N'-diacetate), DEEDDA (N,N'-diethylethylenediamine-N,N'-diacetate), and a bidentate ancillary ligand L (L = ethylenediamine, oxalate, carbonate, (S)-alanine, and malonate) in aqueous solution have been optimized at the DFT/B3LYP/6-311++G(2d,p) level of theory. Based on the optimized geometries, the excitation energies and oscillator and rotational strengths have been calculated using the time-dependent density functional theory (TDDFT) method with the same functional and basis set. The calculated circular dichroism (CD) curves are in excellent agreement with the observed ones except for some small red or blue shifts in peak wavelengths. For the influence of chelate-ring size of the bidentate ligands on the CD intensities, a qualitative analysis together with the quantitative TDDFT calculation reveal that it depends on the symmetry of the cobalt-EDDA backbone. For the s-cis-isomers, the influence is negligible due to the perturbation is symmetric. For the uns-cis-isomers, the perturbation is unsymmetric. Since a small ring size means a large perturbation, this leads to the integral CD intensities decreasing with increasing the chelate ring size. The vicinal effects of asymmetric nitrogens incorporate both the substitutent effects and conformational relaxation effects, with the former being dominant. By analyzing the contributions of chiral arrays to rotational strengths, we found that the part of contributions dominated by the S-type chiral nitrogens could be considered as a good measure for the vicinal effects of chiral nitrogens. In addition, we found that the twist form (δ/λ) of the backbone ethylenediamine ring (E-ring) of the coordinated EDDA

  20. 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.

  1. A review of pitfalls and progress in chelation treatment of metal poisonings.

    Science.gov (United States)

    Andersen, Ole; Aaseth, Jan

    2016-12-01

    Most acute and chronic human metal poisonings are due to oral or inhalation exposure. Almost 80% of published animal experiments on chelation in metal poisoning used single or repeated intraperitoneal, intramuscular or intravenous administration of metal and chelator, impeding extrapolation to clinical settings. Intramuscular administration of dimercaptopropanol (BAL) has until now been used in acute arsenic, lead, and mercury poisonings, but repeated BAL administration increased the brain uptake of As, Pb and Hg in experimental animals. Also, diethyl dithiocarbamate (DDC) has been used as antidote in acute experimental animal parenteral Cd poisoning, and both DDC and tetraethylthiuram disulfide (TTD, disulfiram, Antabuse) have been used in nickel allergic patients. However, even one dose of DDC given immediately after oral Cd or Ni increased their brain uptake considerably. The calcium salt of ethylenediamminetetraacetic acid (CaEDTA) but not dimercaptosuccinic acid (DMSA) increased the brain uptake of Pb. In oral Cd or Hg poisoning, early oral administration of DMSA or dimercaptopropane sulfonate (DMPS) increased survival and reduced intestinal metal uptake. Oral administration of Prussian Blue or resins with fixed chelating groups that are not absorbed offer chelation approaches for decorporation after oral exposure to various metals. Diethylenetriaminepentaacetic acid (DTPA) nebulizers for pulmonary chelation after inhalation exposure need further development. Also, combined chelation with more than one compound may offer extensive advances. Solid knowledge on the chemistry of metal chelates together with relevant animal experiments should guide development of chelation procedures to alleviate and not aggravate the clinical status of poisoned patients. Copyright © 2016 Elsevier GmbH. All rights reserved.

  2. Mathematical modeling of the effects of aerobic and anaerobic chelate biodegradation on actinide speciation

    International Nuclear Information System (INIS)

    Banaszak, J.E.; VanBriesen, J.; Rittmann, B.E.; Reed, D.T.

    1998-01-01

    Biodegradation of natural and anthropogenic chelating agents directly and indirectly affects the speciation, and, hence, the mobility of actinides in subsurface environments. We combined mathematical modeling with laboratory experimentation to investigate the effects of aerobic and anaerobic chelate biodegradation on actinide [Np(IV/V), Pu(IV)] speciation. Under aerobic conditions, nitrilotriacetic acid (NTA) biodegradation rates were strongly influenced by the actinide concentration. Actinide-chelate complexation reduced the relative abundance of available growth substrate in solution and actinide species present or released during chelate degradation were toxic to the organisms. Aerobic bio-utilization of the chelates as electron-donor substrates directly affected actinide speciation by releasing the radionuclides from complexed form into solution, where their fate was controlled by inorganic ligands in the system. Actinide speciation was also indirectly affected by pH changes caused by organic biodegradation. The two concurrent processes of organic biodegradation and actinide aqueous chemistry were accurately linked and described using CCBATCH, a computer model developed at Northwestern University to investigate the dynamics of coupled biological and chemical reactions in mixed waste subsurface environments. CCBATCH was then used to simulate the fate of Np during anaerobic citrate biodegradation. The modeling studies suggested that, under some conditions, chelate degradation can increase Np(IV) solubility due to carbonate complexation in closed aqueous systems

  3. Chelate chase of radiopharmaceuticals reversibly bound to monoclonal antibodies improves dosimetry

    International Nuclear Information System (INIS)

    Goodwin, D.A.; Smith, S.I.; Meares, C.F.; David, G.S.; McTigue, M.; Finston, R.A.

    1986-01-01

    One hundred micrograms of monoclonal antibody (MoAb) CHA 255 with a binding constant Kb of 4 x 10 9 was complexed with indium-111 labeled BLEDTA II, GLEDTA IV, benzyl EDTA, and an EDTA conjugate of Fab. The 24-hour tumor and organ distribution in BALB/c mice bearing KHJJ tumors was studied for each compound alone, the antibody complex, and 3 hours following a chelate chase of the antibody complex. Whole-body biological half-life was measured for 7 days with and without a chelate chase for each antibody complex. The 24-hour whole-body counts dropped 20-60% within 3 hours of administering the chelate chase. Blood concentration fell over 89% within 3 hours of administering the chase and there was a decrease in concentration in all organs, except the kidneys, of 10 to 85%. Theoretical equivalent human doses were calculated from the 24-hour organ concentrations, effective half-life, and MIRD 11 S values (absorbed dose per cumulated activity). Liver and spleen were the target organs, with the dose ranging from 0.50 to 3.91 rads per millicurie. The reduction in organ radiation dose varied up to 95% following the chelate chase. Rapid selective renal clearance of chelate labeled radiopharmaceuticals by competitive inhibition (chelate chase) of their reversible binding to monoclonal antibodies, greatly improves the radiation dosimetry of tumor imaging agents. 28 references, 5 figures, 5 tables

  4. Chelating effect of silver nitrate by chitosan on its toxicity and growth performance in broiler chickens

    Directory of Open Access Journals (Sweden)

    Yemdjie Mane Divine Doriane

    2017-06-01

    Full Text Available Objective: This study was conducted to investigate the chelating effect of silver nitrate (AgNO3 by chitosan on growth performances, hematological and biochemical parameters, and the histopathological structure of the liver and the kidney in broiler chicken. Materials and methods: A total of 192 day-old Cobb 500 strain chicks were randomly assigned to 3 treatments of 64 chicks each. Control group was fed on basal diet without supplement (R0 and the two others groups were fed on rations supplemented with 10 mg of unchelated (RAg or chelated (RCs-Ag AgNO3 per Kg of feed, respectively. Parameters that have been studied consisted of feed intake, weight gain, blood and serum biochemical, and histopathological analyses of liver and kidney. Results: Results revealed that chelation of AgNO3 by chitosan did not have any effect on growth performances and hematological parameters in chicken. However, chelated and unchelated AgNO3 increased the serum content in triglyceride, and cholesterol and decreased the serum content in creatinin, albumin and alanine aminotransferase (ALAT. Chelating AgNO3 with chitosan prevented and corrected the toxicity induced on the histological structure of liver and kidney. Conclusion: Chitosan can be used as a chelating agent to alleviate the harmful effects of AgNO3 as silver ion for poultry. [J Adv Vet Anim Res 2017; 4(2.000: 187-193

  5. Mathematical modelling of the effects of aerobic and anaerobic chelate biodegradation on actinide speciation

    International Nuclear Information System (INIS)

    Banaszak, J.E.; VanBriesen, J.M.; Rittmann, B.E.; Reed, D.T.

    1998-01-01

    Biodegradation of natural and anthropogenic chelating agents directly and indirectly affects the speciation, and hence, the mobility of actinides in subsurface environments. We combined mathematical modelling with laboratory experimentation to investigate the effects of aerobic and anaerobic chelate biodegradation on actinide [Np(IV/V), Pu(IV)] speciation. Under aerobic conditions, nitrilotriacetic acid (NTA) biodegradation rates were strongly influenced by the actinide concentration. Actinide-chelate complexation reduced the relative abundance of available growth substrate in solution and actinide species present or released during chelate degradation were toxic to the organisms. Aerobic bioutilization of the chelates as electron-donor substrates directly affected actinide speciation by releasing the radionuclides from complexed form into solution, where their fate was controlled by inorganic ligands in the system. Actinide speciation was also indirectly affected by pH changes caused by organic biodegradation. The two concurrent processes of organic biodegradation and actinide aqueous chemistry were accurately linked and described using CCBATCH, a computer model developed at Northwestern University to investigate the dynamics of coupled biological and chemical reactions in mixed waste subsurface environments. CCBATCH was then used to simulate the fate of Np during anaerobic citrate biodegradation. The modelling studies suggested that, under some conditions, chelate degradation can increase Np(IV) solubility due to carbonate complexation in closed aqueous systems. (orig.)

  6. Development of chelate tagging method of protein at low temperature

    International Nuclear Information System (INIS)

    Oida, Shigeru; Sekiya, Keizo

    1999-01-01

    This study aimed at development of a protein labelling method at a low temperature, available for functional proteins, such as antibodies and enzymes mostly unstable at high temperatures. A solution of anti-mouse IgG antibody added with EDTA was incubated with 51 CrCl 3 at 4degC for 24 hours. After stopping the reaction with 100-fold amount of EDTA-2Na, the solution was fractionated into antibody fraction and metal fraction by HPLC. After incubation, non-specific Cr adsorption on the antibody in no relation to the chelate reagent was chased with 10-fold amount of CrCl 3 . To remove free Cr, the sample solution was incubated with 10 to 50-fold ICB-EDTA solution containing N,N-dimethyl-formamide. Then, the amount of Cr-labelling on the antibody was determined. In Western-blotting, chick actin was applied onto SDS-polyacrylamide gel electrophoresis. One part of the lane was stained with brilliant-blue and the other was transferred on nitrocellulose membrane by semi-dry method and stained with panceau-S. Anti-actin monoclonal antibody and anti-mouse IgG antibody were used as the first antibody and the second one, respectively. When incubated with ICB-EDTA for 3 days, labelling reached the maximum level. Although labelling of the second antibody was performed with maleimido-C 3 -benzyl EDTA and 45 Ca as a substitute for 51 Cr, the rate of labelling was lower than the rate for a combination of ICB-EDTA and 51 Cr. Autoradiography of the anti-mouse IgG preparation after SDS-acrylamide gel electrophoresis revealed that radioactivity was detected on the site of H-chain but not L-chain. This indicates that 51 Cr labelling of protein is stable even under the conditions of SDS denaturation. (M.N.)

  7. Resinas quelantes amidoxímicas Amidoxime chelating resins

    Directory of Open Access Journals (Sweden)

    Fernanda M. B. Coutinho

    1999-12-01

    Full Text Available Resinas quelantes com grupos amidoxima foram sintetizadas por copolimerização em suspensão de acrilonitrila (AN e divinilbenzeno (DVB e subsequente modificação química dos grupos ciano por reação com hidroxilamina. Na copolimerização, a proporção de divinilbenzeno e o grau de diluição foram variados. Gelatina e carbonato de cálcio foram usados como estabilizadores de suspensão e sulfato de sódio foi adicionado para reduzir a solubilidade da acrilonitrila em água, por meio do efeito salting out. Os copolímeros de AN/DVB e as resinas amidoxímicas obtidos foram caracterizados por meio de densidade aparente, área específica, volume de poros e teor de nitrogênio. As resinas amidoxímicas foram também avaliadas em relação a capacidade de complexação de íons cobre.Chelating resins with amidoxime groups were synthesized by suspension copolymerization of acrylonitrile (AN and divinylbenzene (DVB and subsequent chemical modification of cyano groups by reaction with hydroxylamine. In the copolymerization, the proportion of divinylbenzene and the dilution degree were varied. Gelatin and calcium carbonate were used as suspension stabilizers and sodium sulphate was added in order to reduce acrylonitrile solubility in water, by salting out effect. The AN/DVB copolymers and amidoxime resins obtained were characterized by apparent density, surface area, pore volume and by the content of nitrogen. The amidoxime resins were also evaluated in relation to the complexation capacity of copper ion.

  8. Chelation of intracellular calcium blocks insulin action in the adipocyte

    International Nuclear Information System (INIS)

    Pershadsingh, H.A.; Shade, D.L.; Delfert, D.M.; McDonald, J.M.

    1987-01-01

    The hypothesis that intracellular Ca 2+ is an essential component of the intracellular mechanism of insulin action in the adipocyte was evaluated. Cells were loaded with the Ca 2+ chelator quin-2, by preincubating them with quin-2 AM, the tetrakis(acetoxymethyl) ester of quin-2. Quin-2 loading inhibited insulin-stimulated glucose transport without affecting basal activity. The ability of insulin to stimulate glucose uptake in quin-2-loaded cells could be partially restored by preincubating cells with buffer supplemented with 1.2 mM CaCl 2 and the Ca 2+ ionophore A23187. These conditions had no effect on basal activity and omission of CaCl 2 from the buffer prevented the restoration of insulin-stimulated glucose uptake by A23187. Quin-2 loading also inhibited insulin-stimulated glucose oxidation and the ability of insulin to inhibit cAMP-stimulated lipolysis without affecting their basal activities. Incubation of cells with 100 μM quin-2 or quin-2 AM had no effect on intracellular ATP concentration or the specific binding of 125 I=labeled insulin to adipocytes. These findings suggest that intracellular Ca 2+ is an essential component in the coupling of the insulin-activated receptor complex to cellular physiological/metabolic machinery. Furthermore, differing quin-2 AM dose-response profiles suggest the presence of dual Ca 2+ -dependent pathways in the adipocyte. One involves insulin stimulation of glucose transport and oxidation, whereas the other involves the antilipolytic action of insulin

  9. Decontamination of process equipment using recyclable chelating solvent

    International Nuclear Information System (INIS)

    Jevec, J.; Lenore, C.; Ulbricht, S.

    1995-01-01

    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. With sufficient decontamination, some of the material from DOE facilities could be released as scrap into the commercial sector for recycle, thereby reducing the volume of radioactive waste requiring disposal. Although recycling may initially prove to be more costly than current disposal practices, rapidly increasing disposal costs are expected to make recycling more and more cost effective. Additionally, recycling is now perceived as the ethical choice in a world where the consequences of replacing resources and throwing away reusable materials are impacting the well-being of the environment. Current approaches to the decontamination of metals most often involve one of four basic process types: (1) chemical, (2) manual and mechanical, (3) electrochemical, and (4) ultrasonic. open-quotes Hardclose quotes chemical decontamination solutions, capable of achieving decontamination factors (Df's) of 50 to 100, generally involve reagent concentrations in excess of 5%, tend to physically degrade the surface treated, and generate relatively large volumes of secondary waste. open-quotes Softclose quotes chemical decontamination solutions, capable of achieving Df's of 5 to 10, normally consist of reagents at concentrations of 0.1 to 1%, generally leave treated surfaces in a usable condition, and generate relatively low secondary waste volumes. Under contract to the Department of Energy, the Babcock ampersand Wilcox Company is developing a chemical decontamination process using chelating agents to remove uranium compounds and other actinide species from process equipment

  10. 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.

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

    International Nuclear Information System (INIS)

    Durbin, P.W.; Schmidt, C.T.

    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

  12. Mutations that abrogate transactivational activity of the feline leukemia virus long terminal repeat do not affect virus replication

    International Nuclear Information System (INIS)

    Abujamra, Ana L.; Faller, Douglas V.; Ghosh, Sajal K.

    2003-01-01

    The U3 region of the LTR of oncogenic Moloney murine leukemia virus (Mo-MuLV) and feline leukemia viruses (FeLV) have been previously reported to activate expression of specific cellular genes in trans, such as MHC class I, collagenase IV, and MCP-1, in an integration-independent manner. It has been suggested that transactivation of these specific cellular genes by leukemia virus U3-LTR may contribute to the multistage process of leukemogenesis. The U3-LTR region, necessary for gene transactivational activity, also contains multiple transcription factor-binding sites that are essential for normal virus replication. To dissect the promoter activity and the gene transactivational activity of the U3-LTR, we conducted mutational analysis of the U3-LTR region of FeLV-A molecular clone 61E. We identified minimal nucleotide substitution mutants on the U3 LTR that did not disturb transcription factor-binding sites but abrogated its ability to transactivate the collagenase gene promoter. To determine if these mutations actually have altered any uncharacterized important transcription factor-binding site, we introduced these U3-LTR mutations into the full-length infectious molecular clone 61E. We demonstrate that the mutant virus was replication competent but could not transactivate cellular gene expression. These results thus suggest that the gene transactivational activity is a distinct property of the LTR and possibly not related to its promoter activity. The cellular gene transactivational activity-deficient mutant FeLV generated in this study may also serve as a valuable reagent for testing the biological significance of LTR-mediated cellular gene activation in the tumorigenesis caused by leukemia viruses

  13. 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.

  14. Prevalence of growth hormone deficiency in adult polytransfused β-thalassemia patients and correlation with transfusional and chelation parameters.

    Science.gov (United States)

    Poggi, M; Pascucci, C; Monti, S; Pugliese, P; Lauri, C; Amodeo, G; Girelli, G; Toscano, V

    2010-09-01

    Dysfunction of GH-IGF-I axis has been described in many patients affected by β-thalassemia major (TM), especially in children and in adolescents. Recent studies have demonstrated the necessity to evaluate adult patients affected by TM to establish the presence of this alteration which could be relevant in the pathogenesis of cardiac and bone disease, frequently present in this hematological condition. The pathogenesis of this alteration, correlated in the past with iron overload, is not yet completely understood. The aim of this paper is to evaluate GH-IGF-I axis in a group of adult polytransfused β-thalassemic patients (TM) and to correlate the results with transfusional and chelation parameters. We performed an arginine plus GHRH stimulation test in 28 adult TM patients. Ferritin, IGF-I, liver enzymes, and liver iron concentration, assessed by a superconducting quantum interference device (SQUID) susceptometer were also determined. Moreover, in each patient we evaluated the bone status by a dual-energy X-ray absorptiometry study. We found the presence of GH deficit in 9 patients (32.1%). There were no significant differences between the two groups regarding the value of ferritin, liver enzymes, and liver iron concentration, assessed by SQUID. The group affected by GH deficit showed a worse bone profile. This study confirms the necessity to screen the status of GH/IGF-I axis in this group of patients, even in adult age. The presence of GH deficiency does not seem to be correlated with the efficacy parameters of transfusional and chelation therapy. Other mechanisms, additional to iron overload, could therefore play a role in the pathogenesis of this clinical condition. The presence of GH deficit seems to be very important on clinical aspects, like bone disease, that are crucial for quality of life in these patients.

  15. Further characterization of loss of heterozygosity enhanced by p53 abrogation in human lymphoblastoid TK6 cells: disappearance of endpoint hotspots.

    Science.gov (United States)

    Yatagai, Fumio; Morimoto, Shigeko; Kato, Takesi; Honma, Masamitsu

    2004-06-13

    Loss of heterozygosity (LOH) is the predominant mechanism of spontaneous mutagenesis at the heterozygous thymindine kinase locus (tk) in TK6 cells. LOH events detected in spontaneous TK(-) mutants (110 clones from p53 wild-type cells TK6-20C and 117 clones from p53-abrogated cells TK6-E6) were analyzed using 13 microsatellite markers spanning the whole of chromosome 17. Our analysis indicated an approximately 60-fold higher frequency of terminal deletions in p53-abrogated cells TK6-E6 compared to p53 wild-type cells TK6-20C whereas frequencies of point mutations (non-LOH events), interstitial deletions, and crossing over events were found to increase only less than twofold by such p53 abrogation. We then made use of an additional 17 microsatellite markers which provided an average map-interval of 1.6Mb to map various LOH endpoints on the 45Mb portion of chromosome 17q corresponding to the maximum length of LOH tracts (i.e. from the distal marker D17S932 to the terminal end). There appeared to be four prominent peaks (I-IV) in the distribution of LOH endpoints/Mb of Tk6-20C cells that were not evident in p53-abrogated cells TK6-E6, where they appeared to be rather broadly distributed along the 15-20Mb length (D17S1807 to D17S1607) surrounding two of the peaks that we detected in TK6-20C cells (peaks II and III). We suggest that the chromosomal instability that is so evident in TK6-E6 cells may be due to DNA double-strand break repair occurring through non homologous end-joining rather than allelic recombination.

  16. Metal-chelating active packaging film enhances lysozyme inhibition of Listeria monocytogenes.

    Science.gov (United States)

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

    2014-07-01

    Several studies have demonstrated that metal chelators enhance the antimicrobial activity of lysozyme. This study examined the effect of metal-chelating active packaging film on the antimicrobial activity of lysozyme against Listeria monocytogenes. Polypropylene films were surface modified by photoinitiated graft polymerization of acrylic acid (PP-g-PAA) from the food contact surface of the films to impart chelating activity based on electrostatic interactions. PP-g-PAA exhibited a carboxylic acid density of 113 ± 5.4 nmol cm(-2) and an iron chelating activity of 53.7 ± 9.8 nmol cm(-2). The antimicrobial interaction of lysozyme and PP-g-PAA depended on growth media composition. PP-g-PAA hindered lysozyme activity at low ionic strength (2.48-log increase at 64.4 mM total ionic strength) and enhanced lysozyme activity at moderate ionic strength (5.22-log reduction at 120 mM total ionic strength). These data support the hypothesis that at neutral pH, synergy between carboxylate metal-chelating films (pKa(bulk) 6.45) and lysozyme (pI 11.35) is optimal in solutions of moderate to high ionic strength to minimize undesirable charge interactions, such as lysozyme absorption onto film. These findings suggest that active packaging, which chelates metal ions based on ligand-specific interactions, in contrast to electrostatic interactions, may improve antimicrobial synergy. This work demonstrates the potential application of metal-chelating active packaging films to enhance the antimicrobial activity of membrane-disrupting antimicrobials, such as lysozyme.

  17. Synergy and antagonism between iron chelators and antifungal drugs in Cryptococcus.

    Science.gov (United States)

    Lai, Yu-Wen; Campbell, Leona T; Wilkins, Marc R; Pang, Chi Nam Ignatius; Chen, Sharon; Carter, Dee A

    2016-10-01

    Fungal infections remain very difficult to treat, and developing new antifungal drugs is difficult and expensive. Recent approaches therefore seek to augment existing antifungals with synergistic agents that can lower the therapeutic dose, increase efficacy and prevent resistance from developing. Iron limitation can inhibit microbial growth, and iron chelators have been employed to treat fungal infections. In this study, chequerboard testing was used to explore combinations of iron chelators with antifungal agents against pathogenic Cryptococcus spp. with the aim of determining how disruption to iron homeostasis affects antifungal susceptibility. The iron chelators ethylenediaminetetraacetic acid (EDTA), deferoxamine (DFO), deferiprone (DFP), deferasirox (DSX), ciclopirox olamine and lactoferrin (LF) were paired with the antifungal agents amphotericin B (AmB), fluconazole, itraconazole, voriconazole and caspofungin. All chelators except for DFO increased the efficacy of AmB, and significant synergy was seen between AmB and LF for all Cryptococcus strains. Addition of exogenous iron rescued cells from the antifungal effect of LF alone but could not prevent inhibition by AmB + LF, indicating that synergy was not due primarily to iron chelation but to other properties of LF that were potentiated in the presence of AmB. Significant synergy was not seen consistently for other antifungal-chelator combinations, and EDTA, DSX and DFP antagonised the activity of azole drugs in strains of Cryptococcus neoformans var. grubii. This study highlights the range of interactions that can be induced by chelators and indicates that most antifungal drugs are not enhanced by iron limitation in Cryptococcus. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  18. Olivine-type cathode for rechargeable batteries: Role of chelating agents

    International Nuclear Information System (INIS)

    Kandhasamy, Sathiyaraj; Singh, Pritam; Thurgate, Stephen; Ionescu, Mihail; Appadoo, Dominique; Minakshi, Manickam

    2012-01-01

    Highlights: ► Olivine powder was synthesized by sol–gel method using a range of chelating agents. ► Role of chelating agents in olivine cathode was investigated for battery application. ► Battery was fabricated with olivine cathode, Zn anode and aqueous electrolyte. ► Synergetic effect of additives (CA + TEA + PVP) led to improved storage capacity. - Abstract: Olivine (LiCo 1/3 Mn 1/3 Ni 1/3 PO 4 ) powders were synthesized at 550–600 °C for 6 h in air by a sol–gel method using multiple chelating agents and used as a cathode material for rechargeable batteries. Range of chelating agents like a weak organic acid (citric acid – CA), emulsifier (triethanolamine – TEA) and non-ionic surfactant (polyvinylpyrrolidone – PVP) in sol–gel wet chemical synthesis were used. The dependence of the physicochemical properties of the olivine powders such as particle size, morphology, structural bonding and crystallinity on the chelating agent was extensively investigated. Among the chelating agents used, unique cycling behavior (75 mAh/g after 25 cycles) is observed for the PVP assisted olivine. This is due to volumetric change in trapped organic layer for first few cycles. The trapped organic species in the electrode–electrolyte interface enhances the rate of lithium ion diffusion with better capacity retention. In contrast, CA and TEA showed a gradual capacity fade of 30 and 38 mAh/g respectively after multiple cycles. The combination of all the three mixed chelating agents showed an excellent electrochemical behavior of 100 mAh/g after multiple cycles and the synergistic effect of these agents are discussed.

  19. Organically complexed copper, zinc, and chelating agents in the rivers of Western Puerto Rico

    International Nuclear Information System (INIS)

    Montgomery, J.R.; Echevarria, J.E.

    1975-01-01

    The method for determining soluble chelators gives their concentration in copper-equivalent chelating capacity units in fresh or slightly brackish (less than 3 percent salinity) water. The mean concentration of chelators in the Rio Guanajibo for December 1973 and January 1974 was 0.4 mg of copper per liter of water (N = 21, SD = 0.2) and for February 1974, 0.9 mg/liter (N = 8, SD = 0.4). The combined mean for the Rio Anasco and Culebrinas was 0.5 mg/liter (N = 7, SD = 0.4) in January and February 1974. The mean concentration of ionic copper was 0.5 μg/liter (N = 7, SD = 0.6) and of ionic zinc, 0.2 μg/liter (N = 8, SD = 0.1) in the Rio Guanajibo from November 1972 to February 1973. The concentration of organically bound copper was 0.3 μ/liter (N = 7, SD = 0.2) and that of organically bound zinc was 0.6 μg/liter (N = 8, SD = 0.6); this indicates that there was more than a sufficient quantity of chelator available in the river to complex all the soluble copper. The presence of a high ratio of Ca 2+ to Cu 2+ probably prevents the formation of larger concentrations of organically complexed copper. The mean concentration of chelating agents in the Guanajibo River seems to be directly related to the increased organic input from municipalities and a sugar mill. The concentration of chelators in tropical rivers appears to be higher than that found in Canadian lakes. The mean concentration for particulate organic carbon (POC) was 3653 μg atoms/liter (SD = 3653, N = 29). The dissolved reactive phosphate (DRP) ranged from a mean of 1.1 μg atom/liter. No significant correlation could be found between POC, DRP, and the concentration of chelators

  20. [15]aneN4S: synthesis, thermodynamic studies and potential applications in chelation therapy.

    Science.gov (United States)

    Torres, Nuno; Gonçalves, Sandrina; Fernandes, Ana S; Machado, J Franco; de Brito, Maria J Villa; Oliveira, Nuno G; Castro, Matilde; Costa, Judite; Cabral, Maria F

    2014-01-03

    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.

  1. Chelating polymeric particles intended for the therapy of Wilson’s disease

    Czech Academy of Sciences Publication Activity Database

    Škodová, Michaela; Kučka, Jan; Vetrík, Miroslav; Skopal, Jan; Walterová, Zuzana; Sedláček, Ondřej; Štěpánek, Petr; Mattová, J.; Poučková, P.; Urbánek, P.; Hrubý, Martin

    2013-01-01

    Roč. 73, č. 11 (2013), s. 1426-1431 ISSN 1381-5148 R&D Projects: GA ČR GAP304/12/0950; GA ČR GA13-08336S Institutional support: RVO:61389013 Keywords : Wilson’s disease * polymer beads * copper metabolism Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.822, year: 2013

  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. Is Chelation Therapy Efficient for the Treatment of Intravenous Metallic Mercury Intoxication?

    Czech Academy of Sciences Publication Activity Database

    Pelclová, D.; Vlčková, Š.; Bezdíček, O.; Vaněčková, M.; Urban, P.; Ridzoň, P.; Diblik, P.; Navrátil, Tomáš; Klusáčková, P.; Vlček, K.; Benešová, O.; Třeštík, P.; Homolka, J.; Zakharov, S.

    2017-01-01

    Roč. 120, č. 6 (2017), s. 628-633 ISSN 1742-7835 Institutional support: RVO:61388955 Keywords : elemental mercury * injection * children Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 3.176, year: 2016

  4. A study on the adsorption and subsurface transport of radioactive solutes in the presence of chelating agents

    International Nuclear Information System (INIS)

    Baik, Min Hoon

    1994-02-01

    In this study, adsorption and transport models were developed to analyze the effect of chelating agents on the adsorption and subsurface transport of radioactive solutes. The effect of chelating agents on the adsorption of radioactive solutes was analyzed by developing an adsorption model based upon the extended concept of distribution coefficient reflecting the presence of chelating agents. Also, a batch adsorption experiment was conducted in order to validate the developed adsorption model and to investigate the effect of chelating agent on the adsorption of radioactive metal solutes. In this experiment, a Cobalt(II)/EDTA/Bentonite system was considered as a representative chelation/adsorption system. It was found from the results that the presence of chelating agents significantly reduced the adsorbing capacity of geologic media such as clay minerals and soils. Thus it was concluded that the presence of chelating agents even in a small amount could contribute to the mobilization of radioactive solutes from radioactive waste burial sites by reducing the adsorbing capacity of geologic media. The effect of chelating agents on the transport of radioactive solutes in subsurface porous media was analyzed by formulating an advective-dispersive transport model which incorporated chelate formation, adsorption, decay, and degradations and by introducing the concept of a tenad. Particularly the governing equation for the tenad of radioactive solutes, M, was presented as a linear partial differential form by introducing the extended distribution coefficient, K D . The calculated results from the model showed that the transport rate of the chelated radionuclides was much greater than that of the free ionic radionuclides. This much faster transport of the chelated radionuclides was found to be due to the lower retardation factor of the chelated radionuclides than the free ionic radionuclides. The effect of parameters on the transport of radioactive solutes was also analyzed

  5. 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

  6. 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.

  7. Targeted Catalytic Inactivation of Angiotensin Converting Enzyme by Lisinopril-Coupled Transition Metal Chelates

    Science.gov (United States)

    Joyner, Jeff C.; Hocharoen, Lalintip; Cowan, J. A.

    2012-01-01

    A series of compounds that target reactive transition metal chelates to somatic Angiotensin Converting Enzyme (sACE-1) have been synthesized. Half maximal inhibitory concentrations (IC50) and rate constants for both inactivation and cleavage of full length sACE-1 have been determined and evaluated in terms of metal-chelate size, charge, reduction potential, coordination unsaturation, and coreactant selectivity. Ethylenediamine-tetraacetic acid (EDTA), nitrilotriacetic acid (NTA), 1,4,7,10-tetraazacyclo-dodecane-1,4,7,10-tetraacetic acid (DOTA), and tripeptide GGH were linked to the lysine sidechain of lisinopril by EDC/NHS coupling. The resulting amide-linked chelate-lisinopril (EDTA-lisinopril, NTA-lisinopril, DOTA-lisinopril, and GGH-lisinopril) conjugates were used to form coordination complexes with iron, cobalt, nickel and copper, such that lisinopril could mediate localization of the reactive metal chelates to sACE-1. ACE activity was assayed by monitoring cleavage of the fluorogenic substrate Mca-RPPGFSAFK(Dnp)-OH, a derivative of bradykinin, following pre-incubation with metal-chelate-lisinopril compounds. Concentration-dependent inhibition of sACE-1 by metal-chelate-lisinopril complexes revealed IC50 values ranging from 44 nM to 4,500 nM for Ni-NTA-lisinopril and Ni-DOTA-lisinopril, respectively, versus 1.9 nM for lisinopril. Stronger inhibition was correlated with smaller size and lower negative charge of the attached metal chelates. Time-dependent inactivation of sACE-1 by metal-chelate-lisinopril complexes revealed a remarkable range of catalytic activities, with second order rate constants as high as 150,000 M−1min−1 (Cu-GGH-lisinopril), while catalyst-mediated cleavage of sACE-1 typically occurred at much lower rates, indicating that inactivation arose primary from sidechain modification. Optimal inactivation of sACE-1 was observed when the reduction potential for the metal center was poised near 1000 mV, reflecting the difficulty of protein

  8. Targeted catalytic inactivation of angiotensin converting enzyme by lisinopril-coupled transition-metal chelates.

    Science.gov (United States)

    Joyner, Jeff C; Hocharoen, Lalintip; Cowan, J A

    2012-02-22

    A series of compounds that target reactive transition-metal chelates to somatic angiotensin converting enzyme (sACE-1) have been synthesized. Half-maximal inhibitory concentrations (IC(50)) and rate constants for both inactivation and cleavage of full-length sACE-1 have been determined and evaluated in terms of metal chelate size, charge, reduction potential, coordination unsaturation, and coreactant selectivity. Ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and tripeptide GGH were linked to the lysine side chain of lisinopril by 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride/N-hydroxysuccinimide coupling. The resulting amide-linked chelate-lisinopril (EDTA-lisinopril, NTA-lisinopril, DOTA-lisinopril, and GGH-lisinopril) conjugates were used to form coordination complexes with iron, cobalt, nickel, and copper, such that lisinopril could mediate localization of the reactive metal chelates to sACE-1. ACE activity was assayed by monitoring cleavage of the fluorogenic substrate Mca-RPPGFSAFK(Dnp)-OH, a derivative of bradykinin, following preincubation with metal chelate-lisinopril compounds. Concentration-dependent inhibition of sACE-1 by metal chelate-lisinopril complexes revealed IC(50) values ranging from 44 to 4500 nM for Ni-NTA-lisinopril and Ni-DOTA-lisinopril, respectively, versus 1.9 nM for lisinopril. Stronger inhibition was correlated with smaller size and lower negative charge of the attached metal chelates. Time-dependent inactivation of sACE-1 by metal chelate-lisinopril complexes revealed a remarkable range of catalytic activities, with second-order rate constants as high as 150,000 M(-1) min(-1) (Cu-GGH-lisinopril), while catalyst-mediated cleavage of sACE-1 typically occurred at much lower rates, indicating that inactivation arose primarily from side chain modification. Optimal inactivation of sACE-1 was observed when the reduction potential for the

  9. 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. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

  10. Self-diffusion coefficient of iron as affected by chelating agents using tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Massoud, M.A.; Abd-El-Sabour, M.F. (Agriculture Dept. for Soil and Water Research, Nuclear Research Centre, A.E.A., Cairo (Egypt)); Omar, M.A. (Ain Shams Univ., Cairo (Egypt). Faculty of Agriculture)

    1983-01-01

    The effect of Fe/sub 2/(So/sub 4/)/sub 3/, Fe-DTPA, and Fe-EDDHA on the self-diffusion coefficient of Fe in some soils of Egypt was studied. The effect of chelating compounds on the ratio between solid phase fraction of the labile Fe and its concentration in the soil solution (capacity factor) was also studied. The data reveals the following items of more interesting: 1) The use of chelating agents, i.e., DTPA and EDDHA increased the amount of Fe in soil solution, hence the capacity factor was decreased using these compounds. It seems that as the addition of Fe was in the chelated form in soil solution, the slight loss of 59Fe from solution when 59Fe - chelate was used could be attributed to the isotopic exchange with soil Fe. 2) It was found that the addition of either Fe-DTPA or Fe-EDDHA significantly increased the self-diffusion of Fe in soil as compared with Fe/sub 2/(So/sub 4/)/sub 3/. It was also noticed that the self-diffusion for Fe in the alluvial soil was greater than in the calcareous one due to the instance competition between Ca and Fe for the chelating ligands in the calcareous soil. It was also seen that soil texture affects Fe self-diffusion.

  11. Immobilization of Fe chelators on sepharose gel and its effect on their chemical properties.

    Science.gov (United States)

    Yehuda, Zehava; Hadar, Yitzhak; Chen, Yona

    2003-09-24

    Iron chelates are usually costly and easily leached beyond the root zone. This creates a need to frequently replenish the rhizosphere with chelated Fe and might contaminate groundwater with organic compounds and metals. The development of a slow-release Fe fertilizer that will efficiently supply Fe to plants while exhibiting high resistance toward leaching and/or degradation in the rhizosphere has been the focus of this study. Desferrioxamine B (DFOB) and ethylenediaminebis(o-hydroxyphenylacetic acid) (EDDHA) were immobilized on Sepharose. (13)C NMR and FTIR measurements confirmed that coupling of DFOB to the gel did not appear to influence its ability to chelate Fe(3+) or its binding nature. Isotherms for the immobilized ligands were determined in the presence of 1 mM HEDTA, at 25 degrees C and at an ionic strength of 0.1 M. The isotherms showed a high affinity of Fe(3+) to the ligands and binding up to saturation level throughout the pH range examined (4.0-9.0). The K(app) values for the immobilized Fe chelates were determined using a modified Scatchard model and found to be lower than the soluble ones. This decrease in K(app) might facilitate Fe uptake from these chelates by plants.

  12. Metal-chelating compounds produced by ectomycorrhizal fungi collected from pine plantations.

    Science.gov (United States)

    Machuca, A; Pereira, G; Aguiar, A; Milagres, A M F

    2007-01-01

    To investigate the in vitro production of metal-chelating compounds by ectomycorrhizal fungi collected from pine plantations in southern Chile. Scleroderma verrucosum, Suillus luteus and two isolates of Rhizopogon luteolus were grown in solid and liquid modified Melin-Norkans (MMN) media with and without iron addition and the production of iron-chelating compounds was determined by Chrome Azurol S (CAS) assay. The presence of hydroxamate and catecholate-type compounds and organic acids was also investigated in liquid medium. All isolates produced iron-chelating compounds as detected by CAS assay, and catecholates, hydroxamates as well as oxalic, citric and succinic acids were also detected in all fungal cultures. Scleroderma verrucosum produced the greatest amounts of catecholates and hydroxamates whereas the highest amounts of organic acids were detected in S. luteus. Nevertheless, the highest catecholate, hydroxamate and organic acid concentrations did not correlate with the highest CAS reaction which was observed in R. luteolus (Yum isolate). Ectomycorrhizal fungi produced a variety of metal-chelating compounds when grown in liquid MMN medium. However, the addition of iron to all fungi cultures reduced the CAS reaction, hydroxamate and organic acid concentrations. Catecholate production was affected differently by iron, depending on the fungal isolate. The ectomycorrhizal fungi described in this study have never been reported to produce metal-chelating compound production. Moreover, apart from some wood-rotting fungi, this is the first evidence of the presence of catecholates in R. luteolus, S. luteus and S. verrucosum cultures.

  13. Effect of different chelated zinc sources on the growth and yield of maize (Zea mays L.

    Directory of Open Access Journals (Sweden)

    M. Tahir

    2009-05-01

    Full Text Available A field study was conducted at Agronomic Research Area, University of Agriculture, Faisalabad during spring, 2007 to evaluate the effect of different chelated zinc sources on growth and yield of maize (Zea mays L.. Crop was sown on well prepared soil in 1st week of March, 2007. The experiment was laid out according to randomized complete block design. The treatments comprised of different chelated zinc sources: ZnSO4-DTPA, ZnSO4-Fulvate, ZnSO4-Lignosulphonate, ZnSO4-EDTA and ZnSO4-H2O along with control (no zinc, repeated three times. Results showed that number of cobs plant-1, grain rows cob-1 and oil contents did not differ significantly. However, differences among treatments for plant height at harvest (cm, leaf area plant-1 (cm2, stem diameter (cm, cob length (cm, cob diameter (cm, 100-grains weight (g, number of grains cob-1, grains weight cob-1(g, biological yield (tons ha-1, grain yield (tons ha-1 and protein contents (% were significantly higher. Moreover, results also revealed that ZnSO4-DPTA was found the most effective Zn chelated source among all the treatments. Rest of the chelating agents were not too impressive as they showed varied response for different variables. The result of this experiment suggest further experimentation to explore behaviour of Zn-DTPA with other macro and micro nutrients and to calculate cost benefit ratio for use ofZn chelated compounds.

  14. 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.

  15. Self-diffusion coefficient of iron as affected by chelating agents using tracer technique

    International Nuclear Information System (INIS)

    Massoud, M.A.; Abd-El-Sabour, M.F.; Omar, M.A.

    1983-01-01

    The effect of Fe 2 (So 4 ) 3 , Fe-DTPA, and Fe-EDDHA on the self-diffusion coefficient of Fe in some soils of Egypt was studied. The effect of chelating compounds on the ratio between solid phase fraction of the labile Fe and its concentration in the soil solution (capacity factor) was also studied. The data reveals the following items of more interesting: 1) The use of chelating agents, i.e., DTPA and EDDHA increased the amount of Fe in soil solution, hence the capacity factor was decreased using these compounds. It seems that as the addition of Fe was in the chelated form in soil solution, the slight loss of 59Fe from solution when 59Fe - chelate was used could be attributed to the isotopic exchange with soil Fe. 2) It was found that the addition of either Fe-DTPA or Fe-EDDHA significantly increased the self-diffusion of Fe in soil as compared with Fe 2 (So 4 ) 3 . It was also noticed that the self-diffusion for Fe in the alluvial soil was greater than in the calcareous one due to the instance competition between Ca and Fe for the chelating ligands in the calcareous soil. It was also seen that soil texture affects Fe self-diffusion

  16. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Preparation of novel polyamine-type chelating resin with hyperbranched structures and its adsorption performance

    Science.gov (United States)

    Zhao, Wei; Wang, Huan; Li, Yuhong; Li, Chenxi

    2018-01-01

    This paper explored the method of combining atom transfer radical polymerization (ATRP) technology and hyperbranched polymer principle to prepare the high capacity chelating resin. First, surface-initiated atom transfer radical polymerization (SI-ATRP) method was used to graft glycidyl methacrylate (GMA) on chloromethylated cross-linked styrene-divinylbenzene resin, and then the novel polyamine chelating resin with a kind of hyperbranched structure was prepared through the amination reaction between amino group of (2-aminoethyl) triamine and epoxy group in GMA. This resin had a selective effect on As(V) and Cr(VI) at a relatively low pH and can be used for the disposal of waste water containing As(V) and Cr(VI). It had a relatively strong adsorption effect on Cu(II), Pb(II), Cd(II) and Cr(III) and can be used for the disposal of heavy metal ion waste water. The finding was that, the adsorption capacity of resin on the studied heavy metal ions was higher than that of the chelating resin synthesized by traditional technology and also higher than that of the resin modified by ATRP technology and bifunctional chelator, indicating that the combination of ATRP and hyperbranched polymer concept is an effective method to prepare chelating resin with high capacity. PMID:29515875

  18. Preparation of novel polyamine-type chelating resin with hyperbranched structures and its adsorption performance

    Science.gov (United States)

    Chen, Youning; Zhao, Wei; Wang, Huan; Li, Yuhong; Li, Chenxi

    2018-02-01

    This paper explored the method of combining atom transfer radical polymerization (ATRP) technology and hyperbranched polymer principle to prepare the high capacity chelating resin. First, surface-initiated atom transfer radical polymerization (SI-ATRP) method was used to graft glycidyl methacrylate (GMA) on chloromethylated cross-linked styrene-divinylbenzene resin, and then the novel polyamine chelating resin with a kind of hyperbranched structure was prepared through the amination reaction between amino group of (2-aminoethyl) triamine and epoxy group in GMA. This resin had a selective effect on As(V) and Cr(VI) at a relatively low pH and can be used for the disposal of waste water containing As(V) and Cr(VI). It had a relatively strong adsorption effect on Cu(II), Pb(II), Cd(II) and Cr(III) and can be used for the disposal of heavy metal ion waste water. The finding was that, the adsorption capacity of resin on the studied heavy metal ions was higher than that of the chelating resin synthesized by traditional technology and also higher than that of the resin modified by ATRP technology and bifunctional chelator, indicating that the combination of ATRP and hyperbranched polymer concept is an effective method to prepare chelating resin with high capacity.

  19. Effect of the chelation of metal cation on the antioxidant activity of chondroitin sulfates.

    Science.gov (United States)

    Ajisaka, Katsumi; Oyanagi, Yutaka; Miyazaki, Tatsuo; Suzuki, Yasuhiro

    2016-06-01

    The antioxidant potencies of chondroitin sulfates (CSs) from shark cartilage, salmon cartilage, bovine trachea, and porcine intestinal mucosa were compared by three representative methods for the measurement of the antioxidant activity; DPPH radical scavenging activity, superoxide radical scavenging activity, and hydroxyl radical scavenging activity. CSs from salmon cartilage and bovine trachea showed higher potency in comparison with CSs from shark cartilage and porcine intestinal mucosa. Next, CS from salmon cartilage chelating with Ca(2+), Mg(2+), Mn(2+), or Zn(2+) were prepared, and their antioxidant potencies were compared. CS chelating with Ca(2+) or Mg(2+) ions showed rather decreased DPPH radical scavenging activity in comparison with CS of H(+) form. In contrast, CS chelating with Ca(2+) or Mg(2+) ion showed remarkably enhanced superoxide radical scavenging activity than CS of H(+) or Na(+) form. Moreover, CS chelating with divalent metal ions, Ca(2+), Mg(2+), Mn(2+), or Zn(2+), showed noticeably higher hydroxyl radical scavenging activity than CS of H(+) or Na(+) form. The present results revealed that the scavenging activities of, at least, superoxide radical and hydroxyl radical were enhanced by the chelation with divalent metal ions.

  20. The stability of DOTA-chelated radiopharmaceuticals within 225Ac decay pathway studied with density functional theory.

    Science.gov (United States)

    Karolak, Aleksandra; Khabibullin, Artem; Budzevich, Mikalai; Martinez, M.; Doliganski, Michael; McLaughlin, Mark; Woods, Lilia; Morse, David

    Ligand structures encapsulating metal ions play a central role as contrast agents in Magnetic Resonance Imaging (MRI) or as agents delivering toxic cargo directly to tumor cells in targeted cancer therapy. The structural stability and interaction with solutions of such complexes are the key elements in understanding the foundation of delivery process. We present a comparative study for the 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelated to radioactive isotopes of 225Ac, 221Fr, 217At, 213Bi and a control 68Gd. Using density functional theory methods we investigate the structural stability of complexes for cancer therapy including binding energies, charge transfer, electron densities. The van der Waals interactions are included in the simulations to take into account weak dispersion forces present in such structures. Our results reveal that Ac-DOTA, Bi-DOTA and Gd-DOTA are the most stable complexes in the group. We also show that the water environment is a key ingredient for the structural coordination of the DOTA structures. Support from the US Department of Energy under Grant No. DE-FG02-06ER46297 is acknowledged.

  1. Facile deferration of commercial fertilizers containing iron chelates for their NMR analysis.

    Science.gov (United States)

    Laghi, Luca; Alcañiz, Sara; Cerdán, Mar; Gomez-Gallego, Mar; Sierra, Miguel Angel; Placucci, Giuseppe; Cremonini, Mauro Andrea

    2009-06-24

    Ethylenediamine-N,N'-bis(o-hydroxyphenylacetic) acid (o,o-EDDHA) is widely used in commercial formulations as a Fe(3+) chelating agent to remedy iron shortage in calcareous and alkaline soils. Commercially available o,o-EDDHA-Fe(3+) formulations contain a mixture of EDDHA regioisomers (o,p-EDDHA and p,p-EDDHA), together with other, still uncharacterized, products. NMR spectroscopy can be applied to their study as long as iron is accurately removed prior to the observation. This paper shows that it is possible to obtain a deferrated solution of the organic ligands present in commercial fertilizers containing the EDDHA-Fe(3+) chelate by treating the chelate with ferrocyanide, thus forming Prussian Blue that can be easily removed by centrifugation. This iron removal process does not cause significant losses of the o,o-EDDHA ligand or its minor structural isomers.

  2. Antioxidant and mercury chelating activity of Psidium guajava var. pomifera L. leaves hydroalcoholic extract.

    Science.gov (United States)

    Pinho, Antonio Ivanildo; Oliveira, Cláudia Sirlene; Lovato, Fabricio Luís; Waczuk, Emily Pansera; Piccoli, Bruna Candia; Boligon, Aline Augusti; Leite, Nadghia Figueredo; Coutinho, Henrique Douglas Melo; Posser, Thais; Da Rocha, João Batista Teixeira; Franco, Jeferson Luis

    2017-01-01

    Mercury (Hg) is widely distributed in the environment and is known to produce several adverse effects in organisms. The aim of the present study was to examine the in vitro antioxidant activity and Hg chelating ability of the hydroalcoholic extract of Psidium guajava leaves (HEPG). In addition, the potential protective effects of HEPG against Hg(II) were evaluated using a yeast model (Saccharomyces cerevisiae). HEPG was found to exert significant antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl scavenger and inhibition of lipid peroxidation induced by Fe(II) assays in a concentration-dependent manner. The extract also exhibited significant Hg(II) chelating activity. In yeast, Hg(II) induced a significant decrease in cell viability. In contrast, HEPG partially prevented the fall in cell viability induced by Hg(II). In conclusion, HEPG exhibited protective effects against Hg(II)-mediated toxicity, which may be related to both antioxidant and Hg(II)-chelating activities.

  3. Removal of heavy elements from Contaminated Matrices using amidoxime chelating starch

    International Nuclear Information System (INIS)

    Shama, S.A.; Wally, S.A.; Aly, H.F.

    2012-01-01

    The synthesis of a amidoxime chelating starch was carried out by grafting of acrylonitrile onto starch using the mutual irradiation techniques at dose rate 2.5 kGy. Conversion of nitrile groups of the grafted copolymer into the amidoxime was carried out by treatment with hydroxylamine under alkaline solution. The amidoxime chelating starch was characterized by FT-IR spectra, TG, Particle size, Surface area, SEM, and Elemental analyses. The chelating behavior of the prepared resin was carried out by using uranium. The binding capacity of uranium ion by the amidoxime resin was carried out by the batch technique. The sorption capacity was high for uranium, 86.9 mg/g at ph 6.5. The kinetic exchange rate was fast. It was observed that the uranium uptake ratio reaches 50% at 10 min (t 1/2 ). The treatment process using amidoxime sorbent is efficient to remove uranium from the waste solution of the FMPP plant.

  4. Isotopic measurement of uranium using NP-type chelate resin beads

    International Nuclear Information System (INIS)

    Wu Lanbi; Chen Wenpo; Wang Shijun

    1994-08-01

    NP-type chelate resin beads is used as a carrier of samples in the isotopic measurements of uranium by mass spectrometry. The results show that its absorption efficiency for uranium can be greater than 50%. It is one order magnitude higher than that strong basic anion resin, however, the ionization efficiencies of both are almost the same. Therefore, the amount of uranium required for isotopic analysis can be reduced one order of magnitude. This method has been used for isotopic analysis of uranium in NP-type chelate resin beads contained 10 -9 ∼ 10 -7 g uranium. For standard sample UTB-500, the external precision of measurements are within +-0.2%, for natural uranium samples are within +- 0.5%. The application of NP-type chelate resin beads in the isotopic measurement of uranium is a new creative achievement. It has been used in the depletion test of uranium-atomic vapor laser isotope separation

  5. Preparation and Properties of the Chitosan/PVA Blend for Heavy Metals Chelation

    Directory of Open Access Journals (Sweden)

    Zuhair Jabbar Abdul Ameer

    2016-09-01

    Full Text Available Current research based on the use of extracted chitosan mixed with Polyvinyl alcohol to manufacture blend that can been used in water purification from heavy metals such as copper, this due to chitosan properties and its ability to chelation these metals because of the presence of the functional groups in their structure. The blend has been treated with borax to increase the viscosity, and then high density polyethylene granulated coated with polymer solution to increase the surface area for chelation. The ultraviolet test showed the efficiency of blend to chelation of copper ions through lower the copper ions absorbance peak after each stage where the solution of copper ions pass on the polymer blend containing chitosan.

  6. Microbial screening of thorium(IV) and dioxouranium(VI) chelates with oxine and phenols

    International Nuclear Information System (INIS)

    Kapadia, M.A.; Patel, M.M.; Patel, G.P.; Joshi, J.D.

    2007-01-01

    In the present investigation synthesis, characterization of mixed ligand chelates of the type MA 2 L 2 , where, M = Th 4+ and UO 2 2+ , A 8-hydroxyquinoline (oxine) and L = phenols, H2L I = catechol, H 2 L 2 pyrogallol, H 2 L 3 = 2,3-dihydroxy naphthalene, H 2 L 4 = 1,5-dihydroxy naphthalene and H 2 L 5 = 1,7-dihydroxy naphthalene have been reported. Their geometry have been elucidated on the basis of elemental analyses, thermogravimetric, magnetic moments, NMR, IR and electronic spectra. A study of thermal properties has also been carried out. The antimicrobial activity of 8-hydroxyquinoline and MA 2 L 2 chelates have been determined and described. All the chelates showed an effective antimicrobial activity than the free ligand. (author)

  7. Modeling for Colloid and Chelator Facilitated Nuclide Transport in Radioactive Waste Disposal System

    International Nuclear Information System (INIS)

    Lee, Youn Myoung; Jeong, Jong Tae

    2010-08-01

    A modeling study and development of a total system performance assessment (TSPA) program template, by which assessment of safety and performance for a radioactive waste repository with normal and/or abnormal nuclide release cases can be made has been developed. Colloid and chelator facilitated transport that is believed to result for faster nuclide transport in various mediabothinthegeosphereandbiospherehas been evaluated deterministically and probabilistically to demonstrate the capability of the template developed through this study. To this end colloid and chelator facilitated nuclide transport has been modeled rather strainghtforwardly with assumed data through this study by utilizing some powerful function offered by GoldSim. An evaluation in view of apparent influence of colloid and chelator on the nuclide transport in the various media in and around a repository system with data assumed are illustrated

  8. Assessment of the body burden of chelatable lead: a model and its application to lead workers.

    Science.gov (United States)

    Araki, S; Ushio, K

    1982-01-01

    A hypothetical model was introduced to estimate the body burden of chelatable lead from the mobilisation yield of lead by calcium disodium ethylenediamine tetra-acetate (CaEDTA). It was estimated that, on average, 14 and 19% of the body burden was mobilised into the urine during the 24 hours after an injection of 53.4 mumol (20 mg) and 107 mumol (40 mg) CaEDTA per kg bodyweight, respectively. The body burden of chelatable lead ranged from 4 mumol (0.8 mg) to 120 mumol (24.9 mg) (mean 37 mumol (7.7 mg) in lead workers with blood lead concentrations of 0.3-2.9 mumol/kg (6-60 microgram/100 g) (mean 1.4 mumol/kg (29 microgram/100 g)). There were linear relationships between blood lead concentrations and body burden of chelatable lead on a log scale. PMID:6802167

  9. Enhancement of 67Ga tumor-to-blood ratios by chelating agent

    International Nuclear Information System (INIS)

    Saji, Hideo; Yokoyama, Akira; Hata, Naotaka; Misaki, Atsushi; Tanaka, Hisashi.

    1980-01-01

    Chelating agent, such as, CaEDTA, CaDTPA, D-penicillamine, DMSA, desferoxamine, NTA, cysteine ethyl ester, BAL, α-MPG, phthalein complexone, were tested as a possible contrast enhancing agent for tumor imaging with 67 Ga-citrate. The intravenous administration of a chelating agent to Ehrlich's tumor bearing mice, one hour after the injection of 67 Ga-citrate, accelerated the blood clearance with only a very slight change of activity in the target, increasing the tumor-to-blood ratio, and consequently achieving a better visualization. Among the tested chelating agents, D-penicillamine showed the highest target-to-nontarget ratio at a shorter time: a good tumor-to-blood ratio, performed after 24 hr with non-treated animals, was achieved in only 1-3 hr with post-treated animals. Thus, D-penicillamine hold a considerable promise as a contrast enhancing agent for future clinical use. (author)

  10. Molecular engineering of lanthanide ion chelating phospholipids generating assemblies with a switched magnetic susceptibility.

    Science.gov (United States)

    Isabettini, Stéphane; Massabni, Sarah; Hodzic, Arnel; Durovic, Dzana; Kohlbrecher, Joachim; Ishikawa, Takashi; Fischer, Peter; Windhab, Erich J; Walde, Peter; Kuster, Simon

    2017-08-09

    Lanthanide ion (Ln 3+ ) chelating amphiphiles are powerful molecules for tailoring the magnetic response of polymolecular assemblies. Mixtures of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dimyristoyl-sn-glycero-3-phospho-ethanolamine-diethylene triaminepentaacetate (DMPE-DTPA) complexed to Ln 3+ deliver highly magnetically responsive bicelles. Their magnetic properties are readily tuned by changing the bicellar size or the magnetic susceptibility Δχ of the bilayer lipids. The former technique is intrinsically bound to the region of the phase diagram guarantying the formation of bicelles. Methods aiming towards manipulating the Δχ of the bilayer are comparatively more robust, flexible and lacking. Herein, we synthesized a new Ln 3+ chelating phospholipid using glutamic acid as a backbone: DMPE-Glu-DTPA. The chelate polyhedron was specifically engineered to alter the Δχ, whilst remaining geometrically similar to DMPE-DTPA. Planar asymmetric assemblies hundreds of nanometers in size were achieved presenting unprecedented magnetic alignments. The DMPE-Glu-DTPA/Ln 3+ complex switched the Δχ, achieving perpendicular alignment of assemblies containing Dy 3+ and parallel alignment of those containing Tm 3+ . Moreover, samples with chelated Yb 3+ were more alignable than the Tm 3+ chelating counterparts. Such a possibility has never been demonstrated for planar Ln 3+ chelating polymolecular assemblies. The physico-chemical properties of these novel assemblies were further studied by monitoring the alignment behavior at different temperatures and by including 16 mol% of cholesterol (Chol-OH) in the phospholipid bilayer. The DMPE-Glu-DTPA/Ln 3+ complex and the resulting assemblies are promising candidates for applications in numerous fields including pharmaceutical technologies, structural characterization of membrane biomolecules by NMR spectroscopy, as contrasting agents for magnetic resonance imaging, and for the development of smart optical gels.

  11. On-load chelating agent treatments for conventional and nuclear power stations

    International Nuclear Information System (INIS)

    Turner, D.J.

    1978-01-01

    The paper is concerned with the application of on-load chelating agent treatments to those types of water circuit for which they are not currently available: high pressure drum boilers, sub-critical once-through boilers and water reactors. An attempt was made to see whether the most thermally stable types of chelating agent are likely to be sufficiently strong chelating agents either to dissolve established Fe 3 O 4 deposits or to prevent their precipitation from solution. It seems likely that they are strong enough to prevent Fe 3 O 4 depositing in a once-through boiler, through some may require that mildly reducing conditions are maintained. They would not be effective in a high pressure drum boiler (at 350 0 C) unless much more strongly reducing conditions could be maintained. For such boilers it would probably be better to seek multidentate ligands of less than maximum thermal stability. There are some indications that chelating agents based on carbon chains are more stable than NTA or EDTA so that citric acid or some of the unidentified chelating agents recently found to be produced radiolytically may have potential in the treatment of high pressure drum boilers. The prospects for periodic full-load cleaning seem less good for both types of boiler. There may also be a role for radiolytically produced chelating agents in alleviating some of the problems caused by the deposition of radioactive corrosion products in water reactor circuits. The chances for successful development fall from quite good to very low down the series SGHWR moderator circuit, PWR primary circuit, ammonia dosed BWR, neutral chemistry BWR (including SGHWR). (author)

  12. 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.

  13. Controlling lipid oxidation via a biomimetic iron chelating active packaging material.

    Science.gov (United States)

    Tian, Fang; Decker, Eric A; Goddard, Julie M

    2013-12-18

    Previously, a siderophore-mimetic metal chelating active packaging film was developed by grafting poly(hydroxamic acid) (PHA) from the surface of polypropylene (PP) films. The objective of the current work was to demonstrate the potential applicability of this PP-g-PHA film to control iron-promoted lipid oxidation in food emulsions. The iron chelating activity of this film was investigated, and the surface chemistry and color intensity of films were also analyzed after iron chelation. In comparison to the iron chelating activity in the free Fe(3+) solution, the PP-g-PHA film retained approximately 50 and 30% of its activity in nitrilotriacetic acid (NTA)/Fe(3+) and citric acid/Fe(3+) solutions, respectively (pH 5.0), indicating a strong chelating strength for iron. The ability of PP-g-PHA films to control lipid oxidation was demonstrated in a model emulsion system (pH 3.0). PP-g-PHA films performed even better than ethylenediaminetetraacetic acid (EDTA) in preventing the formation of volatile oxidation products. The particle size and ζ potential results of emulsions indicated that PP-g-PHA films had no adverse effects on the stability of the emulsion system. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) analysis suggested a non-migratory nature of the PP-g-PHA film surface. These results suggest that such biomimetic, non-migratory metal chelating active packaging films have commercial potential in protecting foods against iron-promoted lipid oxidation.

  14. Selective chelation-supercritical fluid extraction of metal ions from waste materials

    International Nuclear Information System (INIS)

    Wai, C.N.; Laintz, K.E.; Yonker, C.R.

    1993-01-01

    The removal of toxic organics, metals, and radioisotopes from solids or liquids is a major concern in the treatment of industrial and nuclear wastes. For this reason, developing methods for selective separation of toxic metals and radioactive materials from solutions of complex matrix is an important problem in environmental research. Recent developments indicate supercritical fluids are good solvents for organic compounds. Many gases become supercritical fluids under moderate temperatures and pressures. For example, the critical temperature and pressure of carbon dioxide are 31 degrees C and 73 atm, respectively. The high diffusivity, low viscosity, and T-P dependence of solvent strength are some attractive properties of supercritical fluid extraction (SFE). Since CO 2 offers the additional benefits of stability and non-toxicity, the SFE technique avoids generation of organic liquid waste and exposure of personnel to toxic solvents. While direct extraction of metal ions by supercritical fluids is highly inefficient, these ions when complexed with organic ligands become quite soluble in supercritical fluids. Specific ligands can be used to achieve selective extraction of metal ions in this process. After SFE, the fluid phase can be depressurized for precipitation of the metal chelates and recycled. The ligand can also be regenerated for repeated use. The success of this selective chelation-supercritical fluid extraction (SC-SFE) process depends on a number of factors including the efficiencies of the selective chelating agents, solubilities of metal chelates in supercritical fluids, rate of extraction, ease of regeneration of the ligands, etc. In this report, the authors present recent results on the studies of the solubilities of metal chelates in supercritical CO 2 , experimental ions from aqueous solution, and the development of selective chelating agents (ionizable crown ethers) for the extraction of lanthanides and actinides

  15. Benzimidazolyl methyliminodiacetic acids: new bifunctional chelators of technetium for hepatobiliary scintigraphy

    International Nuclear Information System (INIS)

    Hunt, F.C.; Wilson, J.G.; Maddalena, D.J.

    1979-01-01

    Dimethyl- and chloro- substituted benzimidazolyl methyliminodiacetic acids have been synthesized and evaluated as new bifunctional chelators of /sup 99m/Tc. Stannous chelates of these compounds were prepared as freeze-dried kits and labeled with /sup 99m/Tc. The radiopharmaceuticals thus prepared were rapidly excreted by the hepatobiliary system of rats and rabbits with little urinary excretion. The chloro- compound had a higher biliary and lesser urinary excretion than the dimethyl- however both technetium complexes provided good scintigraphic images of the hepatobiliary system in animals. The compounds behaved similarly to the /sup 99m/Tc-lidocaine iminodiacetic acid [HIDA] complexes with respect to their biliary elimination

  16. Synthesis and physicochemical analysis of Sm (II, III) acetylacetone chelate complexes

    International Nuclear Information System (INIS)

    Kostyuk, N.N.; Dik, T.A.; Trebnikov, A.G.

    2004-01-01

    Sm (II, III) acetylacetone chelate complexes were synthesized by electrochemical method. It was shown that anode dissolution of the metal samarium over acetylacetone leads to formation of the Sm (II, III) chelate complexes: xSm(acac)2 · ySm(acac)3 · zH(acac). Factors x, y and z depend on quantity of the electricity, which flew through the electrolysis cell. The compositions of the obtained substances were confirmed by the physicochemical analysis (ultimate analysis, IR-, mass spectroscopy and thermal analysis (thermogravimetric, isothermal warming-up and differential scanning colorimetry). (Authors)

  17. 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.

  18. An optimized antibody-chelator conjugate for imaging of carcinoembryonic antigen with indium-111

    International Nuclear Information System (INIS)

    Sumerdon, G.A.; Rogers, P.E.; Lombardo, C.M.; Schnobrich, K.E.; Melvin, S.L.; Tribby, I.I.E.; Stroupe, S.D.; Johnson, D.K.; Hobart, E.D.

    1990-01-01

    A monoclonal antibody to carcinoembryonic antigen showing minimal cross-reactivity with blood cells and normal tissues was derivatized with benzylisothiocyanate derivatives of EDTA and DTPA. Seven chelators per immunoglobulin could be incorporated without loss of immunoreactivity. The resulting conjugates, labeled with indium-111, showed low liver uptake in animals. A cold kit, comprising the DTPA conjugate at a molarity of antibody bound chelator exceeding 1 x 10 -4 M, gave radiochemical yields of indium labeled antibody of ≥ 95% and was stable for 1 yr. (author)

  19. Assessment of the body burden of chelatable lead: a model and its application to lead workers.

    OpenAIRE

    Araki, S; Ushio, K

    1982-01-01

    A hypothetical model was introduced to estimate the body burden of chelatable lead from the mobilisation yield of lead by calcium disodium ethylenediamine tetra-acetate (CaEDTA). It was estimated that, on average, 14 and 19% of the body burden was mobilised into the urine during the 24 hours after an injection of 53.4 mumol (20 mg) and 107 mumol (40 mg) CaEDTA per kg bodyweight, respectively. The body burden of chelatable lead ranged from 4 mumol (0.8 mg) to 120 mumol (24.9 mg) (mean 37 mumol...

  20. Removal of inhaled 241Am oxide particles from beagle dogs by combined treatment with lung lavage and a chelating agent

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Mewhinney, J.A.; Mo, T.; Slauson, D.O.

    1978-01-01

    This experiment was performed to evaluate combined therapy of lung lavage and chelation treatments to remove inhaled particles of 241 Am oxide. Twenty-four Beagle dogs were divided into four groups of 6 dogs each. Each group was exposed to an aerosol of different-sized particles of 241 Am oxide: monodisperse particles with AD of 0.75, 1.5 or 3.0 μm; polydisperse particles with AMAD = 1.5 μm. Three dogs in each group were treated with 5 lung lavages of the right lung (day 2, 7, 14, 28 and 42), and 5 lavages of the left lung (days 2, 10, 21, 35, and 49). In addition, each of the treated dogs was given 22 μmoles of trisodium calcium diethylenetriaminepentaacetate (Na 3 Ca DTPA) by intravenous injection 18 times from day 1 to 52 after exposure. The remaining 3 dogs in each group were untreated control dogs. All of the dogs were sacrificed 64 days after exposure and tissues, excreta, and lavage fluids were analyzed for 241 Am activity. Tissue distribution of 241 Am activity at sacrifice varied with aerosol particle size. Less 241 Am activity was found in the lungs of the dogs exposed to 0.75 and 1.5 μm AD aerosols groups than in those exposed to 3.0 μm particles. Lung lavage removed from 24 to 58% of the initial lung burden (ILB). Particle size did not affect the usefulness of lung lavage but it did influence the effectiveness of Na 3 Ca DTPA treatment. Na 3 Ca DTPA enhanced urinary excretion of 241 Am; dogs exposed to 0.75 μm particles excreted 31% of the ILB, and those exposed to 3.0 μm particles excreted only 10%. This experiment showed the effectiveness of combined treatment with lung lavage and chelation therapy for the removal of 241 Am oxide in the first 64 days after exposure. (author)

  1. Hepatobiliary delivery of polyaminopolycarboxylate chelates: Synthesis and characterization of a cholic acid conjugate of EDTA and biodistribution and imaging studies with its indium-111 chelate

    Energy Technology Data Exchange (ETDEWEB)

    Betebenner, D.A.; Carney, P.L.; Zimmer, A.M.; Kazikiewicz, J.M.; Bruecher, E.S.; Sherry, A.D.; Johnson, D.K. (Abbott Laboratories, Abbott Park, Illinois (USA))

    1991-03-01

    A conjugate in which the steroid nucleus of cholic acid was linked to EDTA via an 11-atom spacer was obtained by reacting the succinimidyl ester of cholic acid with the amine formed by reaction of a benzyl isothiocyanate derivative of EDTA with N-(tert-butoxycarbonyl)ethylenediamine and subsequent deprotection. Potentiometric titration studies with model complexes showed that the EDTA moiety retained the ability to form 1:1 chelates of high thermodynamic stability, although formation constants were some 3-4 log K units lower for complexes of the conjugate than for the analogous chelates with underivatized EDTA. A complex formed between the cholic acid-EDTA conjugate and 111InIII was clearly rapidly into the liver when injected iv into mice, with subsequent excretion from the liver into the gastrointestinal tract being complete within 1 h of injection. Radioscintigraphic imaging studies conducted in a rabbit given the 111In-labeled conjugate also showed early liver uptake followed by rapid clearance from the liver into the intestine, with good visualization of the gallbladder in images obtained at 20-25 min postinjection. It is concluded that conjugation to cholic acid provides a useful means for the hepatobiliary delivery of EDTA chelates that otherwise exhibit predominantly extracellular distribution and renal clearance.

  2. Hepatobiliary delivery of polyaminopolycarboxylate chelates: Synthesis and characterization of a cholic acid conjugate of EDTA and biodistribution and imaging studies with its indium-111 chelate

    International Nuclear Information System (INIS)

    Betebenner, D.A.; Carney, P.L.; Zimmer, A.M.; Kazikiewicz, J.M.; Bruecher, E.S.; Sherry, A.D.; Johnson, D.K.

    1991-01-01

    A conjugate in which the steroid nucleus of cholic acid was linked to EDTA via an 11-atom spacer was obtained by reacting the succinimidyl ester of cholic acid with the amine formed by reaction of a benzyl isothiocyanate derivative of EDTA with N-(tert-butoxycarbonyl)ethylenediamine and subsequent deprotection. Potentiometric titration studies with model complexes showed that the EDTA moiety retained the ability to form 1:1 chelates of high thermodynamic stability, although formation constants were some 3-4 log K units lower for complexes of the conjugate than for the analogous chelates with underivatized EDTA. A complex formed between the cholic acid-EDTA conjugate and 111InIII was clearly rapidly into the liver when injected iv into mice, with subsequent excretion from the liver into the gastrointestinal tract being complete within 1 h of injection. Radioscintigraphic imaging studies conducted in a rabbit given the 111In-labeled conjugate also showed early liver uptake followed by rapid clearance from the liver into the intestine, with good visualization of the gallbladder in images obtained at 20-25 min postinjection. It is concluded that conjugation to cholic acid provides a useful means for the hepatobiliary delivery of EDTA chelates that otherwise exhibit predominantly extracellular distribution and renal clearance

  3. Characterization of radionuclide-chelating agent complexes found in low-level radioactive decontamination waste. Literature review

    International Nuclear Information System (INIS)

    Serne, R.J.; Felmy, A.R.; Cantrell, K.J.; Krupka, K.M.; Campbell, J.A.; Bolton, H. Jr.; Fredrickson, J.K.

    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

  4. 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

  5. Oxidative degradation stability and hydrogen sulfide removal performance of dual-ligand iron chelate of Fe-EDTA/CA.

    Science.gov (United States)

    Miao, Xinmei; Ma, Yiwen; Chen, Zezhi; Gong, Huijuan

    2017-09-05

    Catalytic oxidation desulfurization using chelated iron catalyst is an effective method to remove H 2 S from various gas streams including biogas. However, the ligand of ethylenediaminetetraacetic acid (EDTA), which is usually adopted to prepare chelated iron catalyst, is liable to be oxidative degraded, and leads to the loss of desulfurization performance. In order to improve the degradation stability of the iron chelate, a series of iron chelates composed of two ligands including citric acid (CA) and EDTA were prepared and the oxidative degradation stability as well as desulfurization performance of these chelated iron catalysts were studied. Results show that the iron chelate of Fe-CA is more stable than Fe-EDTA, while for the desulfurization performance, the situation is converse. For the dual-ligand iron chelates of Fe-EDTA/CA, with the increase of mol ratio of CA to EDTA in the iron chelate solution, the oxidative degradation stability increased while the desulfurization performance decreased. The results of this work showed that Fe-EDTA/CA with a mol ratio of CA:EDTA = 1:1 presents a relative high oxidative degradation stability and an acceptable desulfurization performance with over 90% of H 2 S removal efficiency.

  6. 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.

  7. Coupling fast water exchange to slow molecular tumbling in Gd3+ chelates: why faster is not always better.

    Science.gov (United States)

    Avedano, Stefano; Botta, Mauro; Haigh, Julian S; Longo, Dario L; Woods, Mark

    2013-08-05

    The influence of dynamics on solution state structure is a widely overlooked consideration in chemistry. Variations in Gd(3+) chelate hydration with changing coordination geometry and dissociative water exchange kinetics substantially impact the effectiveness (or relaxivity) of monohydrated Gd(3+) chelates as T1-shortening contrast agents for MRI. Theory shows that relaxivity is highly dependent upon the Gd(3+)-water proton distance (rGdH), and yet this distance is almost never considered as a variable in assessing the relaxivity of a Gd(3+) chelate as a potential contrast agent. The consequence of this omission can be seen when considering the relaxivity of isomeric Gd(3+) chelates that exhibit different dissociative water exchange kinetics. The results described herein show that the relaxivity of a chelate with "optimal" dissociative water exchange kinetics is actually lower than that of an isomeric chelate with "suboptimal" dissociative water exchange. When the rate of molecular tumbling of these chelates is slowed, an approach that has long been understood to increase relaxivity, the observed difference in relaxivity is increased with the more rapidly exchanging ("optimal") chelate exhibiting lower relaxivity than the "suboptimally" exchanging isomer. The difference between the chelates arises from a non-field-dependent parameter: either the hydration number (q) or rGdH. For solution state Gd(3+) chelates, changes in the values of q and rGdH are indistinguishable. These parametric expressions simply describe the hydration state of the chelate--i.e., the number and position of closely associating water molecules. The hydration state (q/rGdH(6)) of a chelate is intrinsically linked to its dissociative water exchange rate kex, and the interrelation of these parameters must be considered when examining the relaxivity of Gd(3+) chelates. The data presented herein indicate that the changes in the hydration parameter (q/rGdH(6)) associated with changing dissociative

  8. 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.

  9. 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

    2006-06-01

    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.

  10. Bill project aiming at abrogating exclusive search permits for unconventional hydrocarbon searches, and at prohibiting their exploration and exploitation of the national territory

    International Nuclear Information System (INIS)

    2011-01-01

    After having briefly recalled the origin of shale gases, their extraction process and the evolution of their production in the USA, the authors outline the extremely negative environmental impacts of the fracking technique (hydraulic fracturing): water pollution, air pollution, soil pollution, existence of numerous drilling sites which would degrade landscapes, water and soil contamination risks. As some search permits have already been awarded, and while taking these negative consequences into account, the authors propose a bill project to prohibit these explorations, to abrogate the existing permits, and to ensure public information before bestowing such search permits and exploitation concessions

  11. Investigation on the influence of metal ion impurities on the complexation behavior of generator produced {sup 90}Y with different bifunctional chelators

    Energy Technology Data Exchange (ETDEWEB)

    Pandey, Usha; Gamre, Naresh; Chakravarty, Rubel; Pillai, Maroor Raghavan Ambikalmajan; Dash, Ashutosh [Bhabha Atomic Research Centre, Trombay, Mumbai (India). Radiopharmaceuticals Div.

    2014-07-01

    While the {sup 90}Sr/{sup 90}Y generator is the exclusive source of obtaining 'no carrier added' {sup 90}Y for targeted therapy, the presence of trace metals in the radiolabeling solutions poses a serious challenge owing to their ability to diminish the {sup 90}Y complexation yields with bifunctional chelators (BFCs). p-SCN-Bn-PCTA is a novel ligand having faster complexation kinetics with a number of radiometals. In this work, a systematic investigation was performed to evaluate the chelating ability of p-SCN-Bn-PCTA for {sup 90}Y and the influence of trace metal ions on it's complexation with {sup 90}Y in comparison to p-SCN-Bn-DTPA and p-SCN-Bn-DOTA using {sup 90}YCl{sub 3} obtained from an electrochemical generator. Results from our study indicate that while p-SCN-Bn-PCTA gave very good radiolabeling yields with {sup 90}Y when the reaction was carried out by heating for few minutes, it was most sensitive to the presence of trace metals, especially Fe(III). An independent and useful observation is that p-SCN-Bn-PCTA could be considered as the ligand of choice for assessing the chemical purity of generator derived {sup 90}Y.

  12. 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.

  13. Isolation and Utilization of Corn Cobs Hemisellulose as Chelating Agent for Lead Ions

    International Nuclear Information System (INIS)

    Muchlisyam; Harahap, U; Silalahi, J.; Zul Alfian

    2013-01-01

    Corn cobs is an agricultural byproduct containing polysaccharide composed of cellulose, hemicelluloses and lignin. Hemicelluloses has a hydroxyl and carbonyl functional groups which can be used as chelating agent for metal ions. The purpose of this study was to isolate and evaluate corncobs hemicelluloses as a chelating agent toward lead ion. Graphite furnace spectrophotometry at 283.3 nm was used to determine the residual lead ion in solution. The research's result showed that the highest yield of hemicelluloses (12.04 %) was obtained from delignication with 0,03 M NaOH in 60 % ethanol and 3 % H 2 O 2 , hemicelluloses isolation with 500 ml of 0.2 M NaOH, and precipitation with 1:4 ratio of 10 % acetic acid in 95 % ethanol. The 300 mg corn cobs hemicelluloses has chelating effect for 40 mg lead solution at (39.52±0.1350) mg or 98.80 %, that the corn cobs hemicelluloses can be used as a chelating agent for lead. (author)

  14. Effect of inorganic chelate of zinc and restaurant residual oil added ...

    African Journals Online (AJOL)

    Effect of inorganic chelate of zinc and restaurant residual oil added to feed mixture ... The interaction effects of RRO and ZnO did not result to a significant change in ... Therefore, the effects of RRO deteriorated the quality of meat by raising the ...

  15. 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

  16. Effectiveness of DTPA Chelate on Cd Availability in Soils Treated with Sewage Sludge

    Directory of Open Access Journals (Sweden)

    Pegah Houshyar

    2017-09-01

    Full Text Available Application of sewage sludge as a fertilizer on farmlands is a common practice in most countries. Although the practice may play a positive role in plant performance, the organic amendments introduced may increase the soil heavy metals content. This study was conducted in Arak, Iran, to investigate the effectiveness of DTPA chelate on corn Cd availability in a sewage sludge treated soil. The treatments consisted of sewage sludge (0, 15, and 30 t ha-1 polluted with cadmium applied at 0, 5, 10, and 15 mg kg-1 as well as DTPA applied at 0 and 1.5 mmol kg-1 soil. Corn plants were then grown in the soil in each treatmnent and, on day 60, the physic-chemical characteristics and Cd quantities were measured ion both the corn plants and soil samples. Application of 1.5 m mol of DTPA chelate in soil contaminated with 5 mg Cd led to a significant increase in the soil available Cd content. It was also observed that application of DTPA chelate to soils containing 30 t ha-1 of sewage sludge polluted with 10 mg Cd increased root and shoot Cd concentrations by 17 and 25%, respectively. Results indicated the effectiveness of DTPA chelate in reducing Cd phytoremediation with increasing sewage sludge loading rate. This was evidenced by the lowest phytoremediation effectiveness observed for the treatment with the greatest sewage sludge loading (30 t ha-1 and the lowest cadmium pollution (5 mg Cd.

  17. Production of chelating agents by Pseudomonas aeruginosa grown in the presence of thorium and uranium

    International Nuclear Information System (INIS)

    Premuzic, E.T.; Lin, M.; Francis, A.J.; Schubert, J.

    1986-01-01

    Chelating agents produced by microorganisms enhance the dissolution of iron increasing the mobility and bioavailability of the metal. Since some similarities exist in the biological behavior of ferric, thorium and uranyl ions, microorganisms resistant to these metals and which grow in their presence may produce sequestering agents of Th and U, and other metals in a manner similar to the complexation of iron by siderophores. The ability of P. aeruginosa to elaborate sequestering agents in medium containing thorium or uranium salts was tested. Uranium has a stronger inhibitory effect on growth of the organism than thorium at similar concentrations. Analyses of the culture media have shown, that relative to the control, and under the experimental conditions used, the microorganisms have produced several new chelating agents for thorium and uranium. Extracts containing these chelating agents have been tested for their decorporation potential. In vitro mouse liver bioassay and in vivo mouse toxicity tests indicate that their efficiency is comparable to DTPA and DFOA and that they are virtually non-toxic to mice. The bacterially produced compounds resemble, but are not identical to the known iron chelating siderophores isolated from microorganisms. Some of their chemical properties are also discussed. (author)

  18. [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.

  19. Spectroscopy, modeling and computation of metal chelate solubility in supercritical CO2

    International Nuclear Information System (INIS)

    Brennecke, J.F.; Stadtherr, M.A.

    1999-01-01

    The overall objectives of this project were to gain a fundamental understanding of the solubility and phase behavior of metal chelates in supercritical CO 2 . Extraction with CO 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 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 2 and CO 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 2 and CO 2 /co-contaminant mixtures. Thus, they can now design and optimize processes to extract metals from solid matrices using supercritical CO 2 , as an alternative to hazardous organic solvents that create their own environmental problems, even while helping in metals decontamination

  20. Molecular characterization of whey protein hydrolysate fractions with ferrous chelating and enhanced iron solubility capabilities.

    Science.gov (United States)

    O'Loughlin, Ian B; Kelly, Phil M; Murray, Brian A; FitzGerald, Richard J; Brodkorb, Andre

    2015-03-18

    The ferrous (Fe2+) chelating capabilities of WPI hydrolysate fractions produced via cascade membrane filtration were investigated, specifically 1 kDa permeate (P) and 30 kDa retentate (R) fractions. The 1 kDa-P possessed a Fe2+ chelating capability at 1 g L(-1) equivalent to 84.4 μM EDTA (for 30 kDa-R the value was 8.7 μM EDTA). Fourier transformed infrared (FTIR) spectroscopy was utilized to investigate the structural characteristics of hydrolysates and molecular interactions with Fe2+. Solid-phase extraction was employed to enrich for chelating activity; the most potent chelating fraction was enriched in histidine and lysine. The solubility of ferrous sulfate solutions (10 mM) over a range of pH values was significantly (Piron solubility was improved by 72% in the presence of the 1 kDa-P fraction following simulated gastrointestinal digestion (SGID) compared to control FeSO4·7H2O solutions.

  1. Toxicity of copper chelates of azomethines and amino acids for Chlorella pyrenoidosa

    Energy Technology Data Exchange (ETDEWEB)

    Barashkov, G.K.; Rukhadze, E.G.; Talyzenkova, G.P.

    1979-01-01

    The authors have attempted to assess the toxicity of copper-containing compounds from the point of view of their interrelationship with the structural characteristics of the chelate compound and the structure of the ligand. The copper chelates of the azomethines tested may be provisionally divided into three types: A - complexes with N-alkly-azomethines; B - complexes with N-aryl-azomethines; C - binuclear complexes. Consideration was also given to chelates with aromatic and heterocyclic amino acids and to heteroligand chelates in which the copper atom coordinates azomethine and an amino acid simultaneously. Toxicity was determined by the method previously described and expressed as a critical concentration (C/sub cr/, mg Cu/liter) and in relative toxicity units (T/sub c/). The compounds investigated were obtained from the interaction between a bidentant ligand of an azomethine or anamino acid and copper acetate in a water-alcohol medium at pH 6-8. Since they are not very soluble in water, true solutions were obtained by using dimethyl sulfoxide.

  2. Subcritical wet air oxidation of organic solvents and chelating agents of the nuclear fuel

    International Nuclear Information System (INIS)

    Bachir, Souley

    1999-01-01

    This document deals with the environment control, more specially organic solvents and chelating agents destruction, employed in the nuclear industry. This work details the subcritical wet air oxidation process. Another part of the document deals with the possible coupling between this process and the biodegradation technic in the framework of the sewage sludges treatment. (A.L.B.)

  3. Fluorescence detection of flavonols in HPLC by postcolumn chelation with aluminum

    NARCIS (Netherlands)

    Hollman, Peter C H; Van Trijp, J. M P; Buysman, Michel N C P

    1996-01-01

    Flavonols are dietary antioxidants which may prevent coronary heart disease. To be able to study absorption of flavonols in humans, we developed a postcolumn derivatization with aluminum for HPLC with fluorescence detection. Variables governing postcolumn chelation, such as water content, buffer,

  4. 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. © 2013.

  5. Chelating extractants of improved selectivity. Progress report for period November 1, 1977--July 31 1978

    International Nuclear Information System (INIS)

    Freiser, H.

    1978-08-01

    During the current contract period, the high susceptibility of lanthanide chelate stability to steric hindrance was confirmed. The increase in coordination number of lanthanides from lanthanum to ytterbium as evidenced from extraction equilibria serves to increase their separability. 8-Quinolinol immobilized on silica can separate lanthanide ions

  6. Photostability of solutions of rare earth chelates in organic solvents and polymers

    International Nuclear Information System (INIS)

    Karasev, V.E.; Mirochnik, A.G.; Lysun, T.V.; Vovna, V.I.

    1990-01-01

    Consideration is given to results of comparative study of photochemical properties of rare erath chelate complexes (adducts of rare earth β-diketonates with triphenylphosphine oxide, hexamethylphosphotriamide, phenanthroline) in organic solvents and polymers. Effect of excitation conditions, composition, solvent, nature of ligand and rare earth ion on photolysis rate was investigated. 9 refs.; 2 figs.; 4 tabs

  7. Functionalized dithiocarbamate chelating resin for the removal of Co2+ from simulated wastewater

    Science.gov (United States)

    Shi, Xuewei; Fu, Linwei; Wu, Yanyang; Zhao, Huiling; Zhao, Shuangliang; Xu, Shouhong

    2017-12-01

    Industrial wastewater that contains trace amounts of heavy metal ions is often seen in petrochemical industry. While this wastewater can not be directly discharged, it is difficult to treat due to the low concentration of metal ions. Introducing chelating reagents into this wastewater for selective ion adsorption, followed by a mechanical separation process, provides an appealing solution. Toward the success of this technology, the development of effective chelating resins is of key importance. In the present work, a chelating resin containing amino and dithiocarbamate groups was reported for the removal of Co(II) metal ions in trace concentrations from simulated wastewater. By investigating the adsorption performance of the chelating resin at different solution pH values, adsorbent dosages, contact time, initial ion concentrations, and adsorption temperatures, the maximum adsorption capacity of the resin for Co(II) was identified to be 24.89 mg g-1 for a 2 g L-1 adsorbent dosage and a pH value of 5. After four adsorption-desorption cycles, 97% of the adsorption capacity of the resin was maintained. The adsorption kinetics and thermodynamics were analyzed and discussed as well.

  8. Various types of metal complexes based on chelating {beta}-diketones and their structural analogues

    Energy Technology Data Exchange (ETDEWEB)

    Skopenko, Viktor V; Amirkhanov, Vladimir M; Sliva, T Yu [Department of Chemistry, Kyiv National Taras Shevchenko University (Ukraine); Vasilchenko, Igor S; Anpilova, E L; Garnovskii, Alexander D [Institute of Physical and Organic Chemistry, Rostov State University, Rostov-on-Don (Russian Federation)

    2004-08-31

    Data on the synthesis and structures of {beta}-diketonates and their N,P-containing structural analogues are generalised and described systematically. The possibility of creating diverse metal complexes with various modes of coordination of typical chelating ligands is discussed.

  9. Various types of metal complexes based on chelating β-diketones and their structural analogues

    International Nuclear Information System (INIS)

    Skopenko, Viktor V; Amirkhanov, Vladimir M; Sliva, T Yu; Vasilchenko, Igor S; Anpilova, E L; Garnovskii, Alexander D

    2004-01-01

    Data on the synthesis and structures of β-diketonates and their N,P-containing structural analogues are generalised and described systematically. The possibility of creating diverse metal complexes with various modes of coordination of typical chelating ligands is discussed.

  10. Value of 1.0-M gadolinium chelates: review of preclinical and clinical data on gadobutrol

    International Nuclear Information System (INIS)

    Tombach, Bernd; Heindel, Walter

    2002-01-01

    Several preclinical and clinical studies with the first commercially available highly concentrated Gd-chelate gadobutrol (1 mol/l) are reviewed. Physicochemical, pharmacological, and pharmacokinetic properties, safety analysis, as well as experimental and clinical efficacy studies are highlighted in comparison with 0.5-M Gd-chelates. The 1-mol gadobutrol has been proven to be safe in an examined dose range from 0.04 up to 0.5 mmol/kg body weight (b.w.). Even in patients with chronic renal impairment, including hemodialysis, gadobutrol can safely be applied at doses up to 0.3 mmol/kg b.w. For contrast-enhanced MRI in the equilibrium phase, efficacy data analysis shows comparable results to other commercially available extracellular Gd-chelates with lower Gd-concentrations (0.5 M). Studies focused on the potential benefit of a tighter bolus, such as brain perfusion imaging using T2*-effects, document the superiority of a highly concentrated Gd contrast agent. For contrast-enhanced MRA, clinical studies are still ongoing; therefore, the ultimate potential of a more compact bolus, using 1-M Gd-chelates, for contrast-enhanced MRI, has still to be analyzed, especially for time-resolved magnetic resonance angiography. (orig.)

  11. Bis-ligated Ti and Zr complexes of chelating N-heterocyclic carbenes

    KAUST Repository

    El-Batta, Amer; Waltman, Andrew W.; Grubbs, Robert H.

    2011-01-01

    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

  12. C,N-Chelated Organotin(IV) Azides: Synthesis, Structure and Use within the Click Chemistry.

    Czech Academy of Sciences Publication Activity Database

    Švec, P.; Bartoš, K.; Růžičková, Z.; Cuřínová, Petra; Dušek, L.; Turek, J.; de Proft, F.; Růžička, A.

    2016-01-01

    Roč. 40, č. 7 (2016), s. 5808-5817 ISSN 1144-0546 Grant - others:FWO(BE) 12T6615N Institutional support: RVO:67985858 Keywords : organotin(IV)azides * click chemistry * chelation Subject RIV: CC - Organic Chemistry Impact factor: 3.269, year: 2016

  13. Iron-chelating agents never suppress Fenton reaction but participate in quenching spin-trapped radicals

    International Nuclear Information System (INIS)

    Li Linxiang; Abe, Yoshihiro; Kanagawa, Kiyotada; Shoji, Tomoko; Mashino, Tadahiko; Mochizuki, Masataka; Tanaka, Miho; Miyata, Naoki

    2007-01-01

    Hydroxyl radical formation by Fenton reaction in the presence of an iron-chelating agent such as EDTA was traced by two different assay methods; an electron spin resonance (ESR) spin-trapping method with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), and high Performance liquid chromatography (HPLC)-fluorescence detection with terephthalic acid (TPA), a fluorescent probe for hydroxyl radicals. From the ESR spin-trapping measurement, it was observed that EDTA seemed to suppress hydroxyl radical formation with the increase of its concentration. On the other hand, hydroxyl radical formation by Fenton reaction was not affected by EDTA monitored by HPLC assay. Similar inconsistent effects of other iron-chelating agents such as nitrylotriacetic acid (NTA), diethylenetriamine penta acetic acid (DTPA), oxalate and citrate were also observed. On the addition of EDTA solution to the reaction mixture 10 min after the Fenton reaction started, when hydroxyl radical formation should have almost ceased but the ESR signal of DMPO-OH radicals could be detected, it was observed that the DMPO-OH· signal disappeared rapidly. With the simultaneous addition of Fe(II) solution and EDTA after the Fenton reaction ceased, the DMPO-OH· signal disappeared more rapidly. The results indicated that these chelating agents should enhance the quenching of [DMPO-OH]· radicals by Fe(II), but they did not suppress Fenton reaction by forming chelates with iron ions

  14. f-Element Ion Chelation in Highly Basic Media - Final Report

    International Nuclear Information System (INIS)

    Paine, R.T.

    2000-01-01

    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

  15. Zn availability in nutrient solutions for cucumber (Cucumis sativus L) in hydroponics as affected by Fe-chelates and pH

    NARCIS (Netherlands)

    Voogt, W.; Sonneveld, C.

    2017-01-01

    In soil-less culture systems Fe is usually supplied as chelate to ensure an adequate availability of this element. As chelates have affinity for many metal ions these chelates will interact with other cation nutrients in nutrient solutions. This affects the availability of Fe and other nutrients.

  16. 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

  17. Zn2+ chelation by serum albumin improves hexameric Zn2+-insulin dissociation into monomers after exocytosis.

    Directory of Open Access Journals (Sweden)

    José A G Pertusa

    Full Text Available β-cells release hexameric Zn2+-insulin into the extracellular space, but monomeric Zn2+-free insulin appears to be the only biologically active form. The mechanisms implicated in dissociation of the hexamer remain unclear, but they seem to be Zn2+ concentration-dependent. In this study, we investigate the influence of albumin binding to Zn2+ on Zn2+-insulin dissociation into Zn2+-free insulin and its physiological, methodological and therapeutic relevance. Glucose and K+-induced insulin release were analyzed in isolated mouse islets by static incubation and perifusion experiments in the presence and absence of albumin and Zn2+ chelators. Insulin tolerance tests were performed in rats using different insulin solutions with and without Zn2+ and/or albumin. Albumin-free buffer does not alter quantification by RIA of Zn2+-free insulin but strongly affects RIA measurements of Zn2+-insulin. In contrast, accurate determination of Zn2+-insulin was obtained only when bovine serum albumin or Zn2+ chelators were present in the assay buffer solution. Albumin and Zn2+ chelators do not modify insulin release but do affect insulin determination. Preincubation with albumin or Zn2+ chelators promotes the conversion of "slow" Zn2+-insulin into "fast" insulin. Consequently, insulin diffusion from large islets is ameliorated in the presence of Zn2+ chelators. These observations support the notion that the Zn2+-binding properties of albumin improve the dissociation of Zn2+-insulin into subunits after exocytosis, which may be useful in insulin determination, insulin pharmacokinetic assays and islet transplantation.

  18. Photophysical investigation of energy transfer luminescence of lanthanide chelates with aromatic polyaminocarboxylate ligands in aqueous solutions

    International Nuclear Information System (INIS)

    Hoshino, Hitoshi; Saitoh, Takashi; Yotsuyanagi, Takao

    1995-01-01

    Some photophysical data including emission lifetimes (τ), total emission quantum yields (Φ), and ligand phosphorescence data are reported for the energy-transfer luminescence of the Eu(III) chelate of Quin 2 and the Tb(III) chelate of BAPTA: Quin 2 means 2-[(2-amino-5-methylphenoxy)methyl]-6-methoxy-8-aminoquinoline-N,N,N',N'-tetraacetic acid; BAPTA means 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. The energy diagrams for the ligand T 1 and the metal-center f-f levels are proposed. The τ values of Tb(III)-BAPTA chelates are 1.73 ms in H 2 O and 3.44 ms in D 2 O. The Eu(III)-Quin 2 chelate system shows a bi-exponential decay of emission; τ=0.048 and 0.20 ms in H 2 O and 0.066 and 1.44 ms in D 2 O. The Quin 2 chelate is kinetically inert, so that the interchange of these two conformer structures are very slow at room temperature. The number of water molecules in the primary coordination sphere is calculated from the lifetime data to be 1.9-2.4 for Eu-Quin 2 and 0.5 for Tb-BAPTA. The Φ values in aqueous solutions are rather small in these systems; 0.009 for Tb-BAPTA and 0.0023 for Eu-Quin 2, but these are enough counterbalanced by the large molar absorptivities giving the great sensitization factors for the ions; the sensitization factors against each aqua ion are 1380 for Eu-Quin 2 and 1600 for Tb-BAPTA. (author)

  19. Thermodynamic stability and relaxation studies of small, triaza-macrocyclic Mn(II) chelates.

    Science.gov (United States)

    de Sá, Arsénio; Bonnet, Célia S; Geraldes, Carlos F G C; Tóth, Éva; Ferreira, Paula M T; André, João P

    2013-04-07

    Due to its favorable relaxometric properties, Mn(2+) is an appealing metal ion for magnetic resonance imaging (MRI) contrast agents. This paper reports the synthesis and characterization of three new triazadicarboxylate-type ligands and their Mn(2+) chelates (NODAHep, 1,4,7-triazacyclononane-1,4-diacetate-7-heptanil; NODABA, 1,4,7-triazacyclononane-1,4-diacetate-7-benzoic acid; and NODAHA, 1,4,7-triazacyclononane-1,4-diacetate-7-hexanoic acid). The protonation constants of the ligands and the stability constants of the chelates formed with Mn(2+) and the endogenous Zn(2+) ion have been determined by potentiometry. In overall, the thermodynamic stability of the chelates is lower than that of the corresponding NOTA analogues (NOTA = 1,4,7-triazacyclononane-1,4,7-triacetate), consistent with the decreased number of coordinating carboxylate groups. Variable temperature (1)H NMRD and (17)O NMR measurements have been performed on the paramagnetic chelates to provide information on the water exchange rates and the rotational dynamics. The values of the (17)O chemical shifts are consistent with the presence of one water molecule in the first coordination sphere of Mn(2+). The three complexes are in the slow to intermediate regime for the water exchange rate, and they all display relatively high rotational correlation times, which explain the relaxivity values between 4.7 and 5.8 mM(-1) s(-1) (20 MHz and 298 K). These relaxivities are higher than expected for Mn(2+) chelates of such size and comparable to those of small monohydrated Gd(3+) complexes. The amphiphilic [Mn(NODAHep)] forms micelles above 22 mM (its critical micellar concentration was determined by relaxometry and fluorescence), and interacts with HSA via its alkylic carbon chain providing a 60% relaxivity increase at 20 MHz due to a longer tumbling time.

  20. Characterization of amorphous yttria layers deposited by aqueous solutions of Y-chelate alkoxides complex

    Science.gov (United States)

    Kim, Young-Soon; Lee, Yu-Ri; Kim, Byeong-Joo; Lee, Jae-Hun; Moon, Seung-Hyun; Lee, Hunju

    2015-01-01

    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 Y2O3 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 μm2 area. After Y2O3 deposition, MgO was deposited using ion-beam assisted deposition (IBAD), then LaMnO3 (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/Y2O3 and GdBCO/LMO/MgO/Y2O3 stack films have good out-of-plane and in-plane textures with strong c-axis alignment. The critical current (Ic) of GdBCO/LMO/MgO/Y2O3 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.

  1. In vitro metabolism and stability of the actinide chelating agent 3,4,3-LI(1,2-HOPO).

    Science.gov (United States)

    Choi, Taylor A; Furimsky, Anna M; Swezey, Robert; Bunin, Deborah I; Byrge, Patricia; Iyer, Lalitha V; Chang, Polly Y; Abergel, Rebecca J

    2015-05-01

    The hydroxypyridinonate ligand 3,4,3-LI(1,2-HOPO) is currently under development for radionuclide chelation therapy. The preclinical characterization of this highly promising ligand comprised the evaluation of its in vitro properties, including microsomal, plasma, and gastrointestinal fluid stability, cytochrome P450 inhibition, plasma protein binding, and intestinal absorption using the Caco-2 cell line. When mixed with active human liver microsomes, no loss of parent compound was observed after 60 min, indicating compound stability in the presence of liver microsomal P450. At the tested concentrations, 3,4,3-LI(1,2-HOPO) did not significantly influence the activities of any of the cytochromal isoforms screened. Thus, 3,4,3-LI(1,2-HOPO) is unlikely to cause drug-drug interactions by inhibiting the metabolic clearance of coadministered drugs metabolized by these enzymes. Plasma protein-binding assays revealed that the compound is protein-bound in dogs and less extensively in rats and humans. In the plasma stability study, the compound was stable after 1 h at 37°C in mouse, rat, dog, and human plasma samples. Finally, a bidirectional permeability assay demonstrated that 3,4,3-LI(1,2-HOPO) is not permeable across the Caco-2 monolayer, highlighting the need to further evaluate the effects of various compounds with known permeability enhancement properties on the permeability of the ligand in future studies. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  2. 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.

  3. Antimicrobial Properties of Copper Nanoparticles and Amino Acid Chelated Copper Nanoparticles Produced by Using a Soya Extract

    Science.gov (United States)

    DeAlba-Montero, I.; Morales-Sánchez, Elpidio; Araujo-Martínez, Rene

    2017-01-01

    This paper reports a comparison of the antibacterial properties of copper-amino acids chelates and copper nanoparticles against Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis. These copper-amino acids chelates were synthesized by using a soybean aqueous extract and copper nanoparticles were produced using as a starting material the copper-amino acids chelates species. The antibacterial activity of the samples was evaluated by using the standard microdilution method (CLSI M100-S25 January 2015). In the antibacterial activity assays copper ions and copper-EDTA chelates were included as references, so that copper-amino acids chelates can be particularly suitable for acting as an antibacterial agent, so they are excellent candidates for specific applications. Additionally, to confirm the antimicrobial mechanism on bacterial cells, MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) was carried out. A significant enhanced antimicrobial activity and a specific strain were found for copper chelates over E. faecalis. Its results would eventually lead to better utilization of copper-amino acids chelate for specific application where copper nanoparticles can be not used. PMID:28286459

  4. Effects of lead and chelators on growth, photosynthetic activity and Pb uptake in Sesbania drummondii grown in soil

    International Nuclear Information System (INIS)

    Ruley, Adam T.; Sharma, Nilesh C.; Sahi, Shivendra V.; Singh, Shree R.; Sajwan, Kenneth S.

    2006-01-01

    Effects of lead (Pb) and chelators, such as EDTA, HEDTA, DTPA, NTA and citric acid, were studied to evaluate the growth potential of Sesbania drummondii in soils contaminated with high concentrations of Pb. S. drummondii seedlings were grown in soil containing 7.5 g Pb(NO 3 ) 2 and 0-10 mmol chelators/kg soil for a period of 2 and 4 weeks and assessed for growth profile (length of root and shoot), chlorophyll a fluorescence kinetics (F v /F m and F v /F o ) and Pb accumulations in root and shoot. Growth of plants in the presence of Pb + chelators was significantly higher (P v /F m and F v /F o values of treated seedlings remained unaffected, indicating normal photosynthetic efficiency and strength of plants in the presence of chelators. On application of chelators, while root uptake of Pb increased four-five folds, shoot accumulations increased up to 40-folds as compared to controls (Pb only) depending on the type of chelator used. Shoot accumulations of Pb varied from 0.1 to 0.42% (dry weight) depending on the concentration of chelators used. - Sesbania drummondii tolerates and accumulates high concentrations of Pb

  5. 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.

  6. 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

  7. 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.

  8. Investigation on the influence of metal ion impurities on the complexation behavior of generator produced {sup 90}Y with bifunctional chelators

    Energy Technology Data Exchange (ETDEWEB)

    Pandey, Usha; Gamre, Naresh; Dash, Ashutosh [Isotope Applications and Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai (India)

    2014-05-01

    The {sup 90}Sr/ {sup 90}Y generator is the exclusive source of 'no carrier added' {sup 90}Y for targeted therapy. However, the concomitant presence of trace metals diminishes the complexation of {sup 90}Y with bifunctional chelators (BFCs). A systematic investigation was performed to evaluate the influence of trace metals on the complexation of {sup 90}Y (from an electrochemical generator) with BFCs such as p-SCN-Bn-PCTA, p-SCN-Bn-DTPA and p-SCN-Bn-DOTA. Our study indicates that while p-SCN-Bn-DTPA was least affected by most of the trace metals studied, p-SCN-Bn-PCTA was most sensitive to their presence and hence could be the ligand of choice for assessing the chemical purity of generator derived {sup 90}Y. (author)

  9. Phytoremediation of metals contaminated dredged sediments: Use of synthetic chelates in metals phytoextraction

    Science.gov (United States)

    Sahut, C.; Geniaut, G.; Lillo, M. P.

    2003-05-01

    (in Times 10 points) The waterways maintenance leads to a large volume of dredged polluted sediments, to be disposed of, every year. As the economic disposal of dredged sediment is a single line along the stream they can behave as a sink of pollutant and a migration in the environment is observed. Chelate-enhanced phytoremediation has been proposed as an effective tool for the extraction of heavy metals from dredged sediment by plants. Lysimeters studies were conducted to study the phytoremediation of sediments with EDTA and lactic acid used as synthetic chelators. EDTA appeared to enhance metal solubility by plant uptake did not increase accordingly. Futhermore EDTA enhance metal leaching which could lead 10 groungwater pollution. To prevent these unwanted side-effects, careful management of phytoremediation and of the use of EDTA seems necessary.

  10. Determination of cadmium in seawater by chelate vapor generation atomic fluorescence spectrometry

    Science.gov (United States)

    Sun, Rui; Ma, Guopeng; Duan, Xuchuan; Sun, Jinsheng

    2018-03-01

    A method for the determination of cadmium in seawater by chelate vapor generation (Che-VG) atomic fluorescence spectrometry is described. Several commercially available chelating agents, including ammonium pyrrolidine dithiocarbamate (APDC), sodium dimethyl dithiocarbamate (DMDTC), ammonium dibutyl dithiophosphate (DBDTP) and sodium O,O-diethyl dithiophosphate (DEDTP), are compared with sodium diethyldithiocarbamate (DDTC) for the Che-VG of cadmium, and results showed that DDTC and DEDTP had very good cadmium signal intensity. The effect of the conditions of Che-VG with DDTC on the intensity of cadmium signal was investigated. Under the optimal conditions, 85 ± 3% Che-VG efficiency is obtained for cadmium. The detection limit (3σ) obtained in the optimal conditions was 0.19 ng ml- 1. The relative standard deviation (RSD, %) for ten replicate determinations at 2 ng ml- 1 Cd was 3.42%. The proposed method was successfully applied to the ultratrace determination of cadmium in seawater samples by the standard addition method.

  11. Fusaric acid induces a notochord malformation in zebrafish via copper chelation.

    Science.gov (United States)

    Yin, Emily S; Rakhmankulova, Malika; Kucera, Kaury; de Sena Filho, Jose Guedes; Portero, Carolina E; Narváez-Trujillo, Alexandra; Holley, Scott A; Strobel, Scott A

    2015-08-01

    Over a thousand extracts were tested for phenotypic effects in developing zebrafish embryos to identify bioactive molecules produced by endophytic fungi. One extract isolated from Fusarium sp., a widely distributed fungal genus found in soil and often associated with plants, induced an undulated notochord in developing zebrafish embryos. The active compound was isolated and identified as fusaric acid. Previous literature has shown this phenotype to be associated with copper chelation from the active site of lysyl oxidase, but the ability of fusaric acid to bind copper ions has not been well described. Isothermal titration calorimetry revealed that fusaric acid is a modest copper chelator with a binding constant of 4.4 × 10(5) M(-1). These results shed light on the toxicity of fusaric acid and the potential teratogenic effects of consuming plants infected with Fusarium sp.

  12. The use of dihexyldithiocarbamate in reverse-phase HPLC of metal chelates

    Science.gov (United States)

    Fatimah, S. S.; Bahti, H. H.; Hastiawan, I.; Permanasari, A.

    2018-05-01

    Dialkyldithiocarbamates have long been used as chelating agents in reverse-phase HPLC of transition metals. In the previous study, an alkyl homolog of this type of ligand, namely dihexyldithiocarbamate (DHDTC), was synthesized and characterized. The use of this particular ligand in the revese-phase HPLC of some selected transition metal ions is now reported for the first time. The mobile phase comprising of the flow rate and of the detection, in the separation of the metal chelates of Cd (II), Fe (III), Cu (II), and Co (III), were investigated on a C-18 column. The results showed that dihexylditiocarbamate could be used for separating Cd (II), Fe(III), Cu(II), and Co(III). Therefore, it could be used in simultaneous analysis.

  13. Lanthanide-binding peptides with two pendant aminodiacetate arms: impact of the sequence on chelation.

    Science.gov (United States)

    Niedźwiecka, Agnieszka; Cisnetti, Federico; Lebrun, Colette; Gateau, Christelle; Delangle, Pascale

    2012-03-21

    Lanthanide complexes with a series of hexapeptides-incorporating two unnatural chelating amino acids with aminodiacetate groups, Ada(1) and Ada(2)-have been examined in terms of their speciation, structure, stability and luminescence properties. Whereas Ada(2) acts as a tridentate donor in all cases, Ada(1) may act as a tetradentate donor thanks to the coordination of the amide carbonyl function assisted by the formation of a six-membered chelate ring. The position of the Ada(1) residue in the sequence is demonstrated to be critical for the lanthanide complex speciation and structure. Ada(1) promotes the coordination of the backbone amide function to afford a highly dehydrated Ln complex and an S-shape structure of the peptide backbone, only when found in position 2.

  14. Molecular Docking Assessment of Efficacy of Different Clinically Used Arsenic Chelator Drugs

    OpenAIRE

    Durjoy Majumder; Sayan Mukherjee

    2013-01-01

    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 m...

  15. Chelation in metal intoxication. VIII. Removal of chromium from organs of potassium chromate administered rats.

    Science.gov (United States)

    Behari, J R; Tandon, S K

    1980-03-01

    Some polyaminocarboxylic acids were examined for their ability to mobilize chromium from certain vital organs, their subcellular fractions, and blood cells of potassium chromate administered rats. Hexamethylene 1,6-diamino tetraacetic acid (TDTA), triethylene tetramine hexaacetic acid (TTHA), and ethylene diamine di (O-hydroxylphenyl acetic acid) (EDDHA) may be useful in preventing or reducing chromate toxicity. No definite relationship could be observed between the structure of the chelating agents and their chromium-removing capacity.

  16. Lutetium-177 and iodine-131 loaded chelating polymer microparticles intended for radioembolization of liver malignancies

    Czech Academy of Sciences Publication Activity Database

    Hrubý, Martin; Škodová, Michaela; Macková, Hana; Skopal, Jan; Tomeš, Marek; Kropáček, Martin; Zimová, Jana; Kučka, Jan

    2011-01-01

    Roč. 71, č. 12 (2011), s. 1155-1159 ISSN 1381-5148 R&D Projects: GA ČR GPP207/10/P054; GA MŠk 1M0505 Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z10480505 Keywords : macroporous chelating beads * radioembolization * quinoline-8-ol Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.479, year: 2011

  17. Salivary proline-rich protein may reduce tannin-iron chelation: a systematic narrative review

    OpenAIRE

    Delimont, Nicole M.; Rosenkranz, Sara K.; Haub, Mark D.; Lindshield, Brian L.

    2017-01-01

    Background Tannins are often cited for antinutritional effects, including chelation of non-heme iron. Despite this, studies exploring non-heme iron bioavailability inhibition with long-term consumption have reported mixed results. Salivary proline-rich proteins (PRPs) may mediate tannin-antinutritional effects on non-heme iron bioavailability. Aim To review evidence regarding biochemical binding mechanisms and affinity states between PRPs and tannins, as well as effects of PRPs on non-heme ir...

  18. Chelating polymeric beads as potential therapeutics for Wilson’s disease

    Czech Academy of Sciences Publication Activity Database

    Mattová, J.; Poučková, P.; Kučka, Jan; Škodová, Michaela; Vetrík, Miroslav; Štěpánek, Petr; Urbánek, P.; Petřík, M.; Nový, Z.; Hrubý, Martin

    2014-01-01

    Roč. 62, 1 October (2014), s. 1-7 ISSN 0928-0987 R&D Projects: GA ČR GAP304/12/0950; GA ČR GA13-08336S; GA MPO FR-TI4/625 Institutional support: RVO:61389013 Keywords : Wilson’s disease * polymer beads * chelators Subject RIV: CA - Inorganic Chemistry Impact factor: 3.350, year: 2014

  19. Micronutrient metal speciation is controlled by competitive organic chelation in grassland soils

    Energy Technology Data Exchange (ETDEWEB)

    Boiteau, Rene M.; Shaw, Jared B.; Pasa Tolic, Ljiljana; Koppenaal, David W.; Jansson, Janet K.

    2018-05-01

    Many elements are scarcely soluble in aqueous conditions found in high pH environments, such as calcareous grassland soils, unless complexed to strong binding organic ligands. To overcome this limitation, some plants and microbes produce chelators that solubilize micronutrient metals such as Fe, Ni, Cu, and Zn from mineral phases. These complexes are taken up by organisms via specific membrane receptors, thereby differentially impacting the bioavailability of these metals to the plant and microbial community. Although the importance of these chelation strategies for individual organisms has been well established, little is known about which pathways coexist within rhizosphere microbiomes or how they interact and compete for metal binding. Identifying these metallo-organic species within natural ecosystems has remained a formidable analytical challenge due to the vast diversity of compounds and poorly defined metabolic processes in complex soil matrix. Herein, we employed recently developed liquid chromatography (LC) mass spectrometry (MS) methods to characterize the speciation of water-soluble dissolved trace elements (Fe, Ni, Cu, and Zn) from Kansas Prairie soil. Both plant and fungal chelators were identified, revealing compound-specific patterns of chelation to biologically essential metals. Numerous metabolites typically implicated in plant iron acquisition and homeostasis, including mugineic acids, deoxymugineic acid, nicotianamine, and hydroxynicotianamine, dominated the speciation of divalent metals such as Ni, Cu, and Zn (2-57 pmol / g soil). In contrast, the fungal siderophore ferricrocine bound comparatively more trivalent Fe (9pmol / g soil). These results define biochemical pathways that underpin the regulation of metals in the grassland rhizosphere. They also raise new questions about the competition of these compounds for metal binding and their bioavailability to different members of the rhizosphere population. Even small structural differences

  20. Switch from antagonist to agonist after addition of a DOTA chelator to a somatostatin analog

    International Nuclear Information System (INIS)

    Reubi, Jean Claude; Cescato, Renzo; Waser, Beatrice; Erchegyi, Judit; Rivier, Jean E.

    2010-01-01

    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 1 -sst 5 ) binding affinity using receptor autoradiography. Moreover, they were tested functionally for their ability to affect sst 2 and sst 3 internalization in vitro in HEK293 cells stably expressing the human sst 2 or sst 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 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 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 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.)

  1. 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

  2. Protection against SR 4233 (tirapazamine) aerobic cytotoxicity by the metal chelators desferrioxamine and tiron

    International Nuclear Information System (INIS)

    Herscher, L.L.; Krishna, M.C.; Cook, J.A.

    1994-01-01

    Metal chelating agents and antioxidants were evaluated as potential protectors against aerobic SR 4233 cytotoxicity in Chinese hamster V79 cells. The differential protection of aerobic and hypoxic cells by two metal chelators, desferrrioxamine and Tiron, is discussed in the context of their potential use in the on-going clinical trials with SR 4233. Cytotoxicity was evaluated using clonogenic assay. SR 4233 exposure was done in glass flasks as a function of time either alone or in the presence of the following agents: superoxide dismutase, catalase, 5,5-dimethyl-1-pyrroline, Trolox, ICRF-187, desferrioxamine, Tiron (1,2-dihydroxybenzene-3,5-disulfonate), and ascorbic acid. Experiments done under hypoxic conditions were carried out in specially designed glass flasks that were gassed with humidified nitrogen/carbon dioxide mixture and with a side-arm reservoir from which SR 4233 was added to cell media after hypoxia was obtained. Electron paramagnetic resonance studies were also performed. Electron paramagnetic resonance and spectrophotometry experiments suggest that under aerobic conditions SR 4233 undergoes futile redox cycling to produce superoxide. Treatment of cells during aerobic exposure to SR 4233 with the enzymes superoxide dismutase and catalase, the spin trapping agent DMPO, the water-soluble vitamin E analog Trolox, and the metal chelator ICRF-187 provided little or no protection against aerobic SR 4233 cytotoxicity. However, two other metal chelators, desferrioxamine and Tiron afforded significant protection against minimal protection to hypoxic cells treated with SR 4233. One potential mechanism of aerobic cytotoxicity is redox cycling of SR 4233 with molecular oxygen resulting in several potentially toxic oxidative species that overburden the intrinsic intracellular detoxification systems such as superoxide dismutase, catalase, and glutathione peroxidase. 23 refs., 4 figs., 1 tab

  3. Metal-Chelate Immobilization of Lipase onto Polyethylenimine Coated MCM-41 for Apple Flavor Synthesis.

    Science.gov (United States)

    Sadighi, Armin; Motevalizadeh, Seyed Farshad; Hosseini, Morteza; Ramazani, Ali; Gorgannezhad, Lena; Nadri, Hamid; Deiham, Behnaz; Ganjali, Mohammad Reza; Shafiee, Abbas; Faramarzi, Mohammad Ali; Khoobi, Mehdi

    2017-08-01

    An enzyme immobilized on a mesoporous silica nanoparticle can serve as a multiple catalyst for the synthesis of industrially useful chemicals. In this work, MCM-41 nanoparticles were coated with polyethylenimine (MCM-41@PEI) and further modified by chelation of divalent metal ions (M = Co 2+ , Cu 2+ , or Pd 2+ ) to produce metal-chelated silica nanoparticles (MCM-41@PEI-M). Thermomyces lanuginosa lipase (TLL) was immobilized onto MCM-41, MCM-41@PEI, and MCM-41@PEI-M by physical adsorption. Maximum immobilization yield and efficiency of 75 ± 3.5 and 65 ± 2.7% were obtained for MCM@PEI-Co, respectively. The highest biocatalytic activity at extremely acidic and basic pH (pH = 3 and 10) values were achieved for MCM-PEI-Co and MCM-PEI-Cu, respectively. Optimum enzymatic activity was observed for MCM-41@PEI-Co at 75 °C, while immobilized lipase on the Co-chelated support retained 70% of its initial activity after 14 days of storage at room temperature. Due to its efficient catalytic performance, MCM-41@PEI-Co was selected for the synthesis of ethyl valerate in the presence of valeric acid and ethanol. The enzymatic esterification yield for immobilized lipase onto MCM-41@PEI-Co was 60 and 53%, respectively, after 24 h of incubation in n-hexane and dimethyl sulfoxide media. Graphical Abstract Divalent metal chelated polyethylenimine coated MCM-41 (MCM-41@PEI-M) was used for immobilization of Thermomyces lanuginosa lipase catalyzing green apple flavor preparation.

  4. Micronutrient metal speciation is driven by competitive organic chelation in grassland soils.

    Science.gov (United States)

    Boiteau, R.; Shaw, J. B.; Paša-Tolić, L.; Koppenaal, D.; Jansson, J.

    2017-12-01

    Many elements are scarcely soluble in aqueous conditions found in high pH environments, such as calcareous grassland soils, unless complexed to strong binding organic ligands. To overcome this limitation, some plants and microbes produce chelators that solubilize micronutrient metals such as Fe, Ni, Cu, and Zn from mineral phases. These complexes are taken up by organisms via specific membrane receptors, thereby differentially impacting the bioavailability of these metals to the plant and microbial community. Although the importance of these chelation strategies for individual organisms has been well established, little is known about which pathways coexist within rhizosphere microbiomes or how they interact and compete for metal binding. Identifying these metallo-organic species within natural ecosystems has remained a formidable analytical challenge due to the vast diversity of compounds and poorly defined metabolic processes in complex soil matrix. Herein, we employed recently developed liquid chromatography (LC) mass spectrometry (MS) methods to characterize the speciation of water-soluble dissolved trace elements (Fe, Ni, Cu, and Zn) from Kansas Prairie soil. Both plant and fungal chelators were identified, revealing compound-specific patterns of chelation to biologically essential metals. Numerous metabolites typically implicated in plant iron acquisition and homeostasis, including mugineic acids, deoxymugineic acid, nicotianamine, and hydroxynicotianamine, dominated the speciation of divalent metals such as Ni, Cu, and Zn (2-57 pmol / g soil). In contrast, the fungal siderophore ferricrocine bound comparatively more trivalent Fe (9pmol / g soil). These results define biochemical pathways that underpin the regulation of metals in the grassland rhizosphere. They also raise new questions about the competition of these compounds for metal binding and their bioavailability to different members of the rhizosphere population.

  5. Bioinspired Interfacial Chelating-like Reinforcement Strategy toward Mechanically Enhanced Lamellar Materials.

    Science.gov (United States)

    Chen, Ke; Zhang, Shuhao; Li, Anran; Tang, Xuke; Li, Lidong; Guo, Lin

    2018-05-22

    Many biological organisms usually derived from the ordered assembly of heterogeneous, hierarchical inorganic/organic constituents exhibit outstanding mechanical integration, but have proven to be difficult to produce the combination of excellent mechanical properties, such as strength, toughness, and light weight, by merely mimicking their component and structural characteristics. Herein, inspired by biologically strong chelating interactions of phytic acid (PA) or IP6 in many biomaterials, we present a biologically interfacial chelating-like reinforcement (BICR) strategy for fabrication of a highly dense ordered "brick-and-mortar" microstructure by incorporating tiny amounts of a natural chelating agent ( e. g., PA) into the interface or the interlamination of a material ( e. g., graphene oxide (GO)), which shows joint improvement in hardness (∼41.0%), strength (∼124.1%), maximum Young's modulus (∼134.7%), and toughness (∼118.5%) in the natural environment. Besides, for different composite matrix systems and artificial chelating agents, the BICR strategy has been proven successful for greatly enhancing their mechanical properties, which is superior to many previous reinforcing approaches. This point can be mainly attributed to the stronger noncovalent cross-linking interactions such as dense hydrogen bonds between the richer phosphate (hydroxyl) groups on its cyclohexanehexol ring and active sites of GO, giving rise to the larger energy dissipation at its hybrid interfaces. It is also simple and environmentally friendly for further scale-up fabrication and can be readily extended to other material systems, which opens an advanced reinforcement route to construct structural materials with high mechanical performance in an efficient way for practical applications.

  6. Phosphinic acid functionalized polyazacycloalkane chelators for radiodiagnostics and radiotherapeutics: unique characteristics and applications.

    Science.gov (United States)

    Notni, Johannes; Šimeček, Jakub; Wester, Hans-Jürgen

    2014-06-01

    Given the wide application of positron emission tomography (PET), positron-emitting metal radionuclides have received much attention recently. Of these, gallium-68 has become particularly popular, as it is the only PET nuclide commercially available from radionuclide generators, therefore allowing local production of PET radiotracers independent of an on-site cyclotron. Hence, interest in optimized bifunctional chelators for the elaboration of (68) Ga-labeled bioconjugates has been rekindled as well, resulting in the development of improved triazacyclononane-triphosphinate (TRAP) ligand structures. The most remarkable features of these ligands are unparalleled selectivity for Ga(III) , rapid Ga(III) complexation kinetics, extraordinarily high thermodynamic stability, and kinetic inertness of the respective Ga(III) chelates. As a result, TRAP chelators exhibit very favorable (68) Ga-labeling properties. Based on the scaffolds NOPO (1,4,7-triazacyclononane-1,4-bis[methylene(hydroxymethyl)phosphinic acid]-7-[methylene(2-carboxyethyl)phosphinic acid]) and TRAP-Pr, tailored for convenient preparation of (68) Ga-labeled monomeric and multimeric bioconjugates, a variety of novel (68) Ga radiopharmaceuticals have been synthesized. These include bisphosphonates, somatostatin receptor ligands, prostate-specific membrane antigen (PSMA)-targeting peptides, and cyclic RGD pentapeptides, for in vivo PET imaging of bone, neuroendocrine tumors, prostate cancer, and integrin expression, respectively. Furthermore, TRAP-based (68) Ga-labeled gadolinium(III) complexes have been proposed as bimodal probes for PET/MRI, and a cyclen-based analogue of TRAP-Pr has been suggested for the elaboration of targeted radiotherapeutics comprising radiolanthanide ions. Thus, polyazacycloalkane-based polyphosphinic acid chelators are a powerful toolbox for pharmaceutical research, particularly for the development of (68) Ga radiopharmaceuticals. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Solution mining dawsonite from hydrocarbon containing formations with a chelating agent

    Science.gov (United States)

    Vinegar, Harold J [Bellaire, TX

    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.

  8. DFT study of the interaction between DOTA chelator and competitive alkali metal ions.

    Science.gov (United States)

    Frimpong, E; Skelton, A A; Honarparvar, B

    2017-09-01

    1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetracetic acid (DOTA) is an important chelator for radiolabeling of pharmaceuticals. The ability of alkali metals found in the body to complex with DOTA and compete with radio metal ions can alter the radiolabeling process. Non-covalent interactions between DOTA complexed with alkali metals Li + , Na + , K + and Rb + , are investigated with density functional theory using B3LYP and ωB97XD functionals. Conformational possibilities of DOTA were explored with a varying number of carboxylic pendant arms of DOTA in close proximity to the ions. It is found that the case in which four arms of DOTA are interacting with ions is more stable than other conformations. The objective of this study is to explore the electronic structure properties upon complexation of alkali metals Li + Na + , K + and Rb + with a DOTA chelator. Interaction energies, relaxation energies, entropies, Gibbs free energies and enthalpies show that the stability of DOTA, complexed with alkali metals decreases down the group of the periodic table. Implicit water solvation affects the complexation of DOTA-ions leading to decreases in the stability of the complexes. NBO analysis through the natural population charges and the second order perturbation theory, revealed a charge transfer between DOTA and alkali metals. Conceptual DFT-based properties such as HOMO/LUMO energies, ΔE HOMO-LUMO and chemical hardness and softness indicated a decrease in the chemical stability of DOTA-alkali metal complexes down the alkali metal series. This study serves as a guide to researchers in the field of organometallic chelators, particularly, radiopharmaceuticals in finding the efficient optimal match between chelators and various metal ions. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Preclinical evaluation of somatostatin analogs bearing two macrocyclic chelators for high specific activity labeling with radiometals

    International Nuclear Information System (INIS)

    Storch, D.; Schmitt, J.S.; Waldherr, C.; Maecke, H.R.; Waser, B.; Reubi, J.C.

    2007-01-01

    Radiometallated analogues of the regulatory peptide somatostatin are of interest in the in vivo localization and targeted radiotherapy of somatostatin receptor-overexpressing tumors. An important aspect of their use in vivo is a fast and efficient labeling (complexation) protocol for radiometals along with a high specific activity. We describe in this manuscript synthetic methods for the coupling of two chelators (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid = DOTA) to the bioactive peptide [Tyr 3 ,Thr 8 ]-octreotide (TATE) in order to increase the specific activity (radioactivity in Bq per mole peptide). The full chelator-linker-peptide conjugate was assembled on solid support using standard Fmoc chemistry. Two DOTA-chelators were linked to the peptide using lysine or N,N'-bis(3-aminopropyl)-glycine (Apg); in addition, pentasarcosine (Sar 5 ) was used as a spacer between the chelators and the peptide to probe its influence on biology and pharmacology. Complexation rates with In 3+ and Y 3+ salts and the corresponding radiometals were high, the bis-DOTA-derivatives showed higher complexation rates and gave higher specific activity than DOTA-TATE. Pharmacological and biological data of the complexed molecules did not show significant differences if compared to the parent peptide [ 111/nat In-DOTA]-TATE except for [( 111/nat In-DOTA) 2 -Apg]-TATE which showed a lower binding affinity and rate of internalization into tumor cells. The biodistribution of [( 111/nat In-DOTA)-Lys( 111/nat In-DOTA)]-TATE in the rat tumor model (AR4-2J) showed a high and specific (as shown by a blocking experiment) tracer uptake in somatostatin receptor-positive tissue but a lower tumor uptake compared to [ 111/nat In-DOTA]-TATE. (orig.)

  10. Exploiting the Metal-Chelating Properties of the Drug Cargo for In Vivo Positron Emission Tomography Imaging of Liposomal Nanomedicines

    DEFF Research Database (Denmark)

    Edmonds, Scott; Volpe, Alessia; Shmeeda, Hilary

    2016-01-01

    of a radiolabeled stealth liposomal nanomedicine containing alendronate that shows high uptake in primary tumors and metastatic organs. The versatility, efficiency, simplicity, and GMP compatibility of this method may enable submicrodosing imaging studies of liposomal nanomedicines containing chelating drugs...

  11. Advantages of gadolinium based ultrasmall nanoparticles vs molecular gadolinium chelates for radiotherapy guided by MRI for glioma treatment

    OpenAIRE

    Le Duc, G.; Roux, S.; Paruta-Tuarez, A.; Dufort, S.; Bräuer, E.; Marais, A.; Truillet, C.; Sancey, L.; Perriat, P.; Lux, F.; Tillement, O.

    2014-01-01

    AGuIX nanoparticles are formed of a polysiloxane network surrounded by gadolinium chelates. They present several characteristics. They are easy to produce, they present very small hydrodynamic diameters (

  12. New method for studying the efficiency of chelating agents of the polyamine acid series for internal decontamination

    International Nuclear Information System (INIS)

    Lafuma, J.; Nenot, J.C.; Morin, M.

    1968-01-01

    We followed the biological fate of a complex formed on one side with either a rare earth (cerium-144) or a transuranium element (plutonium-239), and on the other side with a chelating agent of the polyamino acid series (EDTA, BAETA, DTPA, TTHA). This method allowed to study: 1 - the in vivo stability of the various complexes and to compare them; 2 - the stability of the complexes as a function of the isotope - chelating agent weight relationships; 3 - the metabolism of the chelating agents resulting in stable complexes, i. e. DTPA and TTHA mainly. This simple method brought out the higher efficiency, of DTPA in chelating rare earths and plutonium and for therapeutic purposes. (authors) [fr

  13. Comparison of natural organic acids and synthetic chelates at enhancing phytoextraction of metals from a multi-metal contaminated soil

    International Nuclear Information System (INIS)

    Clistenes do Nascimento, Williams A.; Amarasiriwardena, Dula; Xing, Baoshan

    2006-01-01

    Chemically assisted phytoremediation has been developing to induce accumulation of metals by high biomass plants. Synthetic chelates have shown high effectiveness to reach such a goal, but they pose serious drawbacks in field application due to the excessive amount of metals solubilized. We compared the performance of synthetic chelates with naturally occurring low molecular weight organic acids (LMWOA) in enhancing phytoextraction of metals by Indian mustard (Brassica juncea) from multi-metal contaminated soils. Gallic and citric acids were able to induce removal of Cd, Zn, Cu, and Ni from soil without increasing the leaching risk. Net removal of these metals caused by LMWOA can be as much as synthetic chelates. A major reason for this is the lower phytotoxicity of LMWOA. Furthermore, supplying appropriate mineral nutrients increased biomass and metal removal. - Organic acids can be as efficient as synthetic chelates for use in phytoextraction of multi-metal contaminated soils

  14. Photo-Curable Metal-Chelating Coatings Offer a Scalable Approach to Production of Antioxidant Active Packaging.

    Science.gov (United States)

    Lin, Zhuangsheng; Goddard, Julie

    2018-02-01

    Synthetic metal chelators (for example, ethylenediaminetetraacetic acid, EDTA) are widely used as additives to control trace transition metal induced oxidation in consumer products. To enable removal of synthetic chelators in response to increasing consumer demand for clean label products, metal-chelating active food packaging technologies have been developed with demonstrated antioxidant efficacy in simulated food systems. However, prior work in fabrication of metal-chelating materials leveraged batch chemical reactions to tether metal-chelating ligands, a process with limited industrial translatability for large-scale fabrication. To improve the industrial translatability, we have designed a 2-step laminated photo-grafting process to introduce metal chelating functionality onto common polymeric packaging materials. Iminodiacetic acid (IDA) functionalized materials were fabricated by photo-grafting poly(acrylic acid) onto polypropylene (PP) films, followed by a second photo-grafting process to graft-polymerize an IDA functionalized vinyl monomer (GMA-IDA). The photo-grafting was conducted under atmospheric conditions and was completed in 2 min. The resulting IDA functionalized metal-chelating material was able to chelate iron and copper, and showed antioxidant efficacy against ascorbic acid degradation, supporting its potential to be used synergistically with natural antioxidants for preservation of food and beverage products. The 2-step photo-grafting process improves the throughput of active packaging coatings, enabling potential roll-to-roll fabrication of metal-chelating active packaging materials for antioxidant food packaging applications. To address consumer and retail demands for "clean label" foods and beverages without a corresponding loss in product quality and shelf life, producers are seeking next generation technologies such as active packaging. In this work, we will report the synthesis of metal-chelating active packaging films, which enable removal

  15. 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.

  16. Cathodic electrogenerated chemiluminescence of aromatic Tb(III) chelates at polystyrene-graphite composite electrodes

    International Nuclear Information System (INIS)

    Salminen, Kalle; Grönroos, Päivi; Tuomi, Sami; Kulmala, Sakari

    2017-01-01

    Tb(III) chelates exhibit intense hot electron-induced electrogenerated chemiluminescence during cathodic polarization of metal/polystyrene-graphite (M/PG) electrodes in fully aqueous solutions. The M/PG working electrode provides a sensitive means for the determination of aromatic Tb(III) chelates at nanomolar concentration levels with a linear log-log calibration curve spanning more than five orders of magnitude. The charge transport and other properties of these novel electrodes were studied by electrochemiluminescence measurements and cyclic voltammetry. The present composite electrodes can by utilized both under pulse polarization and DC polarization unlike oxide-coated metal electrodes which do not tolerate cathodic DC polarization. The present cost-effective electrodes could be utilized e.g. in immunoassays where polystyrene is extensively used as a solid phase for various bioaffinity assays by using electrochemiluminescent Tb(III) chelates or e.g. Ru(bpy) 3 2+ as labels. - Highlights: • Generation of hydrated electrons at Polystyrene-graphite electrodes. • The insulating polystyrene layer on the outer electrode surface seems necessary. • Hydrated electrons are able to produce chemiluminescence. • Strongest signal and lowest std. dev. achieved at same graphite weight fraction.

  17. Effects of iron(III)chelates on the solubility of heavy metals in calcareous soils

    Energy Technology Data Exchange (ETDEWEB)

    Ylivainio, Kari, E-mail: kari.ylivainio@mtt.f [Department of Applied Chemistry and Microbiology, FIN-00014 University of Helsinki (Finland)

    2010-10-15

    In this study I evaluated the effects of complexing agents on the solubility of heavy metals in an incubation experiment up to 56 days when complexing agents were applied as Fe-chelates (Fe-EDDS(S,S), Fe-EDDS(mix), Fe-EDTA and Fe-EDDHA) on calcareous soils at a level sufficient to correct Fe chlorosis (0.1 mmol kg{sup -1}). Of these ligands, EDDHA was the most efficient in keeping Fe in water-soluble form, and EDDS increased the solubility of Cu and Zn most, and only EDTA increased the solubility of Cd and Pb. EDTA increased the solubility of Ni steadily during the incubation period, equalling about 5-8% of the added EDTA concentration. [S,S]-EDDS was biodegraded within 56 days, whereas EDDS(mix) was less biodegradable. Ni-chelates were the most recalcitrant against biodegradation. The study shows that even a moderate input of chelates to soil increases the solubility of toxic heavy metals and their risk of leaching. - When correcting Fe chlorosis Fe-EDDS causes lower environmental concern than Fe-EDTA.

  18. Labeling of antibodies with a 67Ga-phenolic aminocarboxylic acid chelate. Pt. 1

    International Nuclear Information System (INIS)

    Schuhmacher, J.; Matys, R.; Hauser, H.; Maier-Borst, W.; Matzku, S.

    1986-01-01

    As a chelating agent for labeling antibodies (Abs) with metallic radionuclides, a propionic acid substituted ethylenediamine N, N'-di-[(o-hydroxyphenyl) acetic acid] (P-EDDHA), which tighly complexes 67 Ga, was synthetized. The 67 Ga-P-EDDHA chelate was coupled in aqueous solution to IgG at a molar ratio of 1:1 via carbodiimide. The average coupling yield was 15%. A specific activity of 4 mCi/mg IgG could be obtained with commercially supplied 67 Ga. In vitro stability was evaluated in human serum at 37 0 C and showed a half-life of about 120 h for the release of 67 Ga from the labeled Ab during the initial phase of incubation. This in vitro halflife is similar to that measured for 111 In-DTPA labeled Abs. Because of the high stability of the 67 Ga-P-EDDHA chelate, the in vivo formation of radioactive lebeled transferrin by transchelation, as described for 111 In-DTPA labeled Abs, should, however, be reduced by this labeling technique. (orig.)

  19. Effects of iron(III)chelates on the solubility of heavy metals in calcareous soils

    International Nuclear Information System (INIS)

    Ylivainio, Kari

    2010-01-01

    In this study I evaluated the effects of complexing agents on the solubility of heavy metals in an incubation experiment up to 56 days when complexing agents were applied as Fe-chelates (Fe-EDDS(S,S), Fe-EDDS(mix), Fe-EDTA and Fe-EDDHA) on calcareous soils at a level sufficient to correct Fe chlorosis (0.1 mmol kg -1 ). Of these ligands, EDDHA was the most efficient in keeping Fe in water-soluble form, and EDDS increased the solubility of Cu and Zn most, and only EDTA increased the solubility of Cd and Pb. EDTA increased the solubility of Ni steadily during the incubation period, equalling about 5-8% of the added EDTA concentration. [S,S]-EDDS was biodegraded within 56 days, whereas EDDS(mix) was less biodegradable. Ni-chelates were the most recalcitrant against biodegradation. The study shows that even a moderate input of chelates to soil increases the solubility of toxic heavy metals and their risk of leaching. - When correcting Fe chlorosis Fe-EDDS causes lower environmental concern than Fe-EDTA.

  20. Effects of iron(III)chelates on the solubility of heavy metals in calcareous soils.

    Science.gov (United States)

    Ylivainio, Kari

    2010-10-01

    In this study I evaluated the effects of complexing agents on the solubility of heavy metals in an incubation experiment up to 56 days when complexing agents were applied as Fe-chelates (Fe-EDDS(S,S), Fe-EDDS(mix), Fe-EDTA and Fe-EDDHA) on calcareous soils at a level sufficient to correct Fe chlorosis (0.1 mmol kg(-1)). Of these ligands, EDDHA was the most efficient in keeping Fe in water-soluble form, and EDDS increased the solubility of Cu and Zn most, and only EDTA increased the solubility of Cd and Pb. EDTA increased the solubility of Ni steadily during the incubation period, equalling about 5-8% of the added EDTA concentration. [S,S]-EDDS was biodegraded within 56 days, whereas EDDS(mix) was less biodegradable. Ni-chelates were the most recalcitrant against biodegradation. The study shows that even a moderate input of chelates to soil increases the solubility of toxic heavy metals and their risk of leaching. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  1. Potassium fulvate-modified graft copolymer of acrylic acid onto cellulose as efficient chelating polymeric sorbent.

    Science.gov (United States)

    Mohamed, Magdy F; Essawy, Hisham A; Ammar, Nabila S; Ibrahim, Hanan S

    2017-01-01

    Acrylic acid (AA) was graft copolymerized from cellulose (Cell) in presence of potassium fulvate (KF) in order to enhance the chemical activity of the resulting chelating polymer and the handling as well. Fourier transform infrared (FTIR) proved that KF was efficiently inserted and became a permanent part of the network structure of the sorbent in parallel during the grafting copolymerization. Scanning electron microscopy (SEM) revealed intact homogeneous structure with uniform surface. This indicates improvement of the handling, however, it was not the case for the graft copolymer of acrylic acid onto cellulose in absence of KF, which is known to be brittle and lacks mechanical integrity. Effective insertion of this co-interpenetrating agent provided more functional groups, such as OH and COOH, which improved the chelating power of the produced sorbent as found for the removal of Cu 2+ ions from its aqueous solutions (the removal efficiency reached ∼98.9%). Different models were used to express the experimental data. The results corroborated conformity of the pseudo-second order kinetic model and Langmuir isotherm model to the sorption process, which translates into dominance of the chemisorption. Regeneration of the chelating polymers under harsh conditions did not affect the efficiency of copper ions uptake up to three successive cycles. A thermodynamic investigation ensured exothermic nature of the adsorption process that became less favourable at higher temperatures. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Gd (III) chelates adsorbed on TiO2 nanoparticles - promising MRI contrast agent

    International Nuclear Information System (INIS)

    Rehor, Ivan; Lukes, Ivan; Peters, Joop A.; Jirak, Daniel

    2009-01-01

    Full text: The project deals with a new contrast agent (CA) for magnetic resonance imaging (MRI). The CA consists of two main parts - diamagnetic core (TiO 2 nanoparticle) and Gd (III) chelates grafted on its surface. The presence of the nanoparticle core is responsible for significant increase of r1 millimolar relaxivity (which corresponds to the efficiency of the CA) due to the slowing down the rotation of the complex in solution. It also affects the biodistribution characteristics of the CA - the ability to penetrate through cell membranes is well known for nanoparticles, making them useful for cell labeling. The structure of the chelate is derived from DOTA ligand, whose Gd (III) complexes are commercially used as MRI CA in human medicine. The connection of the complex to the surface is realized via penylphosphonate, which is attached to the pendant arm of the ligand. Strong interaction of the phosphonate with the TiO 2 surface results in the full surface coverage. The complexation and MRI properties of Gd chelate were studied and exhibit analogy to the complexes of DOTA, The millimolar relaxivity (r1) of the Gd (III) complex significantly increases upon adsorption on the TiO 2 nanoparticles. PVA was added to the colloidal solutions of CA to stabilize them under biological conditions and such stabilized CA was utilized for MRI visualization of rat pancreatic islets (P1). The labeled islets were detected on MR images as hyperintense area and therefore our CA seems to be promising material for cellular MRI

  3. Direct nanoimprint lithography of Al2O3 using a chelated monomer-based precursor

    International Nuclear Information System (INIS)

    Ganesan, Ramakrishnan; Dinachali, Saman Safari; Lim, Su Hui; Saifullah, M S M; He, Chaobin; Low, Hong Yee; Chong, Wee Tit; Lim, Andrew H H; Yong, Jin Jie; Thian, Eng San

    2012-01-01

    Nanostructuring of Al 2 O 3 is predominantly achieved by the anodization of aluminum film and is limited to obtaining porous anodized aluminum oxide (AAO). One of the main restrictions in developing approaches for direct fabrication of various types of Al 2 O 3 patterns, such as lines, pillars, holes, etc, is the lack of a processable aluminum-containing resist. In this paper, we demonstrate a stable precursor prepared by reacting aluminum tri-sec-butoxide with 2-(methacryloyloxy)ethyl acetoacetate, a chelating monomer, which can be used for large area direct nanoimprint lithography of Al 2 O 3 . Chelation in the precursor makes it stable against hydrolysis whilst the presence of a reactive methacrylate group renders it polymerizable. The precursor was mixed with a cross-linker and their in situ thermal free-radical co-polymerization during nanoimprinting rigidly shaped the patterns, trapped the metal atoms, reduced the surface energy and strengthened the structures, thereby giving a ∼100% yield after demolding. The imprinted structures were heat-treated, leading to the loss of organics and their subsequent shrinkage. Amorphous Al 2 O 3 patterns with line-widths as small as 17 nm were obtained. Our process utilizes the advantages of sol–gel and methacrylate routes for imprinting and at the same time alleviates the disadvantages associated with both these methods. With these benefits, the chelating monomer route may be the harbinger of the universal scheme for direct nanoimprinting of metal oxides. (paper)

  4. A Powerful Mitochondria-Targeted Iron Chelator Affords High Photoprotection against Solar Ultraviolet A Radiation.

    Science.gov (United States)

    Reelfs, Olivier; Abbate, Vincenzo; Hider, Robert C; Pourzand, Charareh

    2016-08-01

    Mitochondria are the principal destination for labile iron, making these organelles particularly susceptible to oxidative damage on exposure to ultraviolet A (UVA, 320-400 nm), the oxidizing component of sunlight. The labile iron-mediated oxidative damage caused by UVA to mitochondria leads to necrotic cell death via adenosine triphosphate depletion. Therefore, targeted removal of mitochondrial labile iron via highly specific tools from these organelles may be an effective approach to protect the skin cells against the harmful effects of UVA. In this work, we designed a mitochondria-targeted hexadentate (tricatechol-based) iron chelator linked to mitochondria-homing SS-like peptides. The photoprotective potential of this compound against UVA-induced oxidative damage and cell death was evaluated in cultured primary skin fibroblasts. Our results show that this compound provides unprecedented protection against UVA-induced mitochondrial damage, adenosine triphosphate depletion, and the ensuing necrotic cell death in skin fibroblasts, and this effect is fully related to its potent iron-chelating property in the organelle. This mitochondria-targeted iron chelator has therefore promising potential for skin photoprotection against the deleterious effects of the UVA component of sunlight. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Synthesis and spectroscopic investigations of hydroxyapatite using a green chelating agent as template

    Science.gov (United States)

    Gopi, D.; Bhuvaneshwari, N.; Indira, J.; Kavitha, L.

    2013-03-01

    Hydroxyapatite [Ca10(PO4)6(OH)2, HAP] particles have been successfully synthesized by a cost-effective, eco-friendly green template method using natural and commercially available sucrose as a chelating agent. The sucrose used in this method has been extracted from various sources, three from natural and one from commercially available sources are exploited in our study to achieve a controlled crystallinity, particle size as well as uniform morphology. Spectral characterizations involving Fourier transform infrared spectroscopy (FT-IR) for the functional group analysis of sucrose and HAP; carbon-13 nuclear magnetic resonance spectroscopy (13C NMR) for the identification of the carbon atoms in sucrose and in HAP; liquid chromatography/mass spectrometry (LC-MS) for the determination of the hydrolyzed products of sucrose; and X-ray diffraction (XRD) techniques for the phase identification of the HAP particles were performed. The morphology of the HAP particles were assessed thoroughly using a scanning electron microscope (SEM) equipped with energy dispersive X-ray analysis (EDAX). The experimental results indicate that the obtained HAP using the natural sucrose as a chelating agent is of phase pure, with a well defined morphology having discrete particles without any agglomeration than the HAP from commercially available sucrose. Further, the reduced particle size can be achieved from the stem sugarcane extract as the source of the chelating agent.

  6. Synthesis and spectroscopic investigations of hydroxyapatite using a green chelating agent as template.

    Science.gov (United States)

    Gopi, D; Bhuvaneshwari, N; Indira, J; Kavitha, L

    2013-03-01

    Hydroxyapatite [Ca(10)(PO(4))(6)(OH)(2), HAP] particles have been successfully synthesized by a cost-effective, eco-friendly green template method using natural and commercially available sucrose as a chelating agent. The sucrose used in this method has been extracted from various sources, three from natural and one from commercially available sources are exploited in our study to achieve a controlled crystallinity, particle size as well as uniform morphology. Spectral characterizations involving Fourier transform infrared spectroscopy (FT-IR) for the functional group analysis of sucrose and HAP; carbon-13 nuclear magnetic resonance spectroscopy ((13)C NMR) for the identification of the carbon atoms in sucrose and in HAP; liquid chromatography/mass spectrometry (LC-MS) for the determination of the hydrolyzed products of sucrose; and X-ray diffraction (XRD) techniques for the phase identification of the HAP particles were performed. The morphology of the HAP particles were assessed thoroughly using a scanning electron microscope (SEM) equipped with energy dispersive X-ray analysis (EDAX). The experimental results indicate that the obtained HAP using the natural sucrose as a chelating agent is of phase pure, with a well defined morphology having discrete particles without any agglomeration than the HAP from commercially available sucrose. Further, the reduced particle size can be achieved from the stem sugarcane extract as the source of the chelating agent. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Soft chelating irrigation protocol optimizes bonding quality of Resilon/Epiphany root fillings.

    Science.gov (United States)

    De-Deus, Gustavo; Namen, Fátima; Galan, João; Zehnder, Matthias

    2008-06-01

    This study was designed to test the impact of either a strong (MTAD) or a soft (1-hydroxyethylidene-1, 1-bisphosphonate [HEPB]) chelating solution on the bond strength of Resilon/Epiphany root fillings. Both 17% EDTA and the omission of a chelator in the irrigation protocol were used as reference treatments. Forty extracted human upper lateral incisors were prepared using different irrigation protocols (n = 10): G1: NaOCl, G2: NaOCl + 17% EDTA, G3: NaOCl + BioPure MTAD (Dentsply/Tulsa, Tulsa, OK), and G4: NaOCl + 18% HEPB. The teeth were obturated and then prepared for micropush-out assessment using root slices of 1 mm thickness. Loading was performed on a universal testing machine at a speed of 0.5 mm/min. One-way analysis of variance and Tukey multiple comparisons were used to compare the results among the experimental groups. EDTA- and MTAD-treated samples revealed intermediate bond strength (0.3-3.6 MPa). The lowest bond strengths were achieved in NaOCl-treated samples (0.3-1.2 MPa, p < 0.05). The highest bond strength was reached in the HEBP-treated samples (3.1-6.1 MPa, p < 0.05). Under the present in vitro conditions, the soft chelating irrigation protocol (18% HEBP) optimized the bonding quality of Resilon/Epiphany (Resilon Research LLC, Madison, CT) root fillings.

  8. [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.

  9. Effects of hydroxycinnamic acids on blue color expression of cyanidin derivatives and their metal chelates.

    Science.gov (United States)

    Sigurdson, G T; Robbins, R J; Collins, T M; Giusti, M M

    2017-11-01

    Mechanisms to recreate many anthocyanin blue hues in nature are not fully understood, but interactions with metal ions and phenolic compounds are thought to play important roles. Bluing effects of hydroxycinnamic acids on cyanidin and chelates were investigated by addition of the acids to triglycosylated cyanidin (0-50×[anthocyanin]) and by comparison to hydroxycinnamic acid monoacylated and diacylated Cy fractions by spectrophotometry (380-700nm) and colorimetry in pH 5-8. With no metal ions, λ max and absorbance was greatest for cyanidin with diacylation>monoacylation>increasing [acids]. Hydroxycinnamic acids added to cyanidin solutions weakly impacted color characteristics (ΔEacid attachment) resulted in ΔE 5-15. Triglycosylated cyanidin expressed blue color (pH 7-8), suggesting glycosylation pattern also plays a role. Al 3+ chelation increased absorbance 2-42× and λ max ≳40nm (pH 5-6) compared to added hydroxycinnamic acids. Metal chelation and aromatic diacylation resulted in the most blue hues. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. XAS studies of the effectiveness of iron chelating treatments of Mary Rose timbers

    International Nuclear Information System (INIS)

    Berko, A; Schofield, E J; Chadwick, A V; Smith, A D; Jones, A M; Mosselmans, J F W

    2009-01-01

    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.

  11. Effect of chelators and nisin produced in situ on inhibition and inactivation of gram negatives.

    Science.gov (United States)

    Boziaris, I S; Adams, M R

    1999-12-15

    The ability of chelators and nisin generated in situ to inhibit and inactivate E. coli and other gram negatives in a model substrate was investigated. The effect of various chelators and different concentrations of exogenous nisin on inhibition of E. coli in broth medium showed that only EDTA and pyrophosphates were able to cause appreciable inhibition of E. coli by nisin. In a broth where L. lactis NCFB 497 produced nisin in a concentration of 250-300 IU/ml, pyrophosphates were unable to inactivate E. coli. Under the same conditions, addition of EDTA led to inactivation of E. coli at neutral and slightly acidic pH only. A cocktail of strains of E. coli was less sensitive than E. coli ATCC 25922 alone. Pseudomonas aeruginosa was more sensitive and salmonellae more resistant. EDTA also caused a slight reduction in the L. lactis population and its biochemical activity as regards pH drop and acid production. Some of the inhibition of E. coli could be ascribed to the physical presence of Lactococcus cells rather than their metabolites excreted into the medium. Failure to observe any inhibition in fermented broths at their natural pH (4.0) was ascribed to the poor chelating power of EDTA under acid conditions.

  12. Effect of the Alkyl Chain Length on the Adsorption Properties of Malonamide Chelating Resins

    International Nuclear Information System (INIS)

    Ismail, I.M.; Nogami, M.; Suzuki, K.

    2004-01-01

    In order to investigate the effect of the alkyl chain length of malonamide chelating resins on the rate of uptake of U(VI) ions and Ce(III) Ions, lV,N,N',N'-tetraethyl malonamide (TEMA), N,N,N',N'-tetra-n-propyl malonamide (TPrMA), lV,lV,N',N'-tetra-n-butyl malonamide (TBMA) and N,l V,N',N'-tetra-n-pentyl malonamide (Tamp) chelating resins were synthesized by chemically bonding these function groups to CMS-DVB co-polymer beads. N,lV,N',N'-tetraphenyl malonamide (TPhMA) chelating resin was also investigated and the results of these resins were compared with those of N,lY,N',N-tetra methylmalonamide (TMMA) previously reported. The batch technique was used to study the thermodynamic equilibrium, in terms of distribution coefficient, and the kinetics of the adsorption U(VI) and Ce(III) ions from 3 M HNO 3 , Acid, and 3 M NaNO 3 + 0.05 M HNO 3 , Salt, media. The introduction ratio of the function group into the polymer base and the uptake of U(VI) ions and C(III) ions were found to decrease with the increase in the alkyl chain length. The uptake was found to diminish in case of TPhMA resin due to the decrease of the function group ratio and the steric-hinder effect

  13. 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.)

  14. Separation and recovery of uranium ore by chlorinating, chelate resin and molten salt treatment

    International Nuclear Information System (INIS)

    Taki, Tomohiro

    2000-12-01

    Three fundamental researches of separation and recovery of uranium from uranium ore are reported in this paper. Three methods used the chloride pyrometallurgy, sodium containing molten salts and chelate resin. When uranium ore is mixed with activated carbon and reacted for one hour under the mixed gas of chlorine and oxygen at 950 C, more than 90% uranium volatilized and vaporization of aluminum, silicone and phosphorus were controlled. The best activated carbon was brown coal because it was able to control the large range of oxygen concentration. By blowing oxygen into the molten sodium hydroxide, the elution rate of uranium attained to about 95% and a few percent of uranium was remained in the residue. On the uranium ore of unconformity-related uranium deposits, a separation method of uranium, molybdenum, nickel and phosphorus from the sulfuric acid elusion solution with U, Ni, As, Mo, Fe and Al was developed. Methylene phosphonic acid type chelate resin (RCSP) adsorbed Mo and U, and then 100 % Mo was eluted by sodium acetate solution and about 100% U by sodium carbonate solution. Ni and As in the passing solution were recovered by imino-diacetic acid type chelate resin and iron hydroxide, respectively. (S.Y.)

  15. DNA demethylation by 5-aza-2-deoxycytidine treatment abrogates 17 beta-estradiol-induced cell growth and restores expression of DNA repair genes in human breast cancer cells.

    Science.gov (United States)

    Singh, Kamaleshwar P; Treas, Justin; Tyagi, Tulika; Gao, Weimin

    2012-03-01

    Prolonged exposure to elevated levels of estrogen is a risk factor for breast cancer. Though increased cell growth and loss of DNA repair capacity is one of the proposed mechanisms for estrogen-induced cancers, the mechanism through which estrogen induces cell growth and decreases DNA repair capacity is not clear. DNA hypermethylation is known to inactivate DNA repair genes and apoptotic response in cancer cells. Therefore, the objective of this study was to determine the role of DNA hypermethylation in estrogen-induced cell growth and regulation of DNA repair genes expression in breast cancer cells. To achieve this objective, the estrogen-responsive MCF-7 cells either pretreated with 5-aza-2-deoxycytidine (5-aza-dC) or untreated (as control) were exposed to 17 beta-estradiol (E2), and its effect on cell growth and expression of DNA repair genes were measured. The result revealed that 5-aza-dC abrogates the E2-induced growth in MCF-7 cells. An increased expression of OGG1, MSH4, and MLH1 by 5-aza-dC treatment alone, suggest the DNA hypermethylation as a potential cause for decreased expression of these genes in MCF-7 cells. The decreased expression of ERCC1, XPC, OGG1, and MLH1 by E2 alone and its restoration by co-treatment with 5-aza-dC further suggest that E2 reduces the expression of these DNA repair genes potentially through promoter hypermethylation. Reactivation of mismatch repair (MMR) gene MLH1 and abrogation of E2-induced cell growth by 5-aza-dC treatment suggest that estrogen causes increased growth in breast cancer cells potentially through the inhibition of MMR-mediated apoptotic response. In summary, this study suggests that estrogen increases cell growth and decreases the DNA repair capacity in breast cancer cells, at least in part, through epigenetic mechanism. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Inhibition of Hb Binding to GP1bα Abrogates Hb-Mediated Thrombus Formation on Immobilized VWF and Collagen under Physiological Shear Stress.

    Science.gov (United States)

    Annarapu, Gowtham K; Singhal, Rashi; Peng, Yuandong; Guchhait, Prasenjit

    2016-01-01

    Reports including our own describe that intravascular hemolysis increases the risk of thrombosis in hemolytic disorders. Our recent study shows that plasma Hb concentrations correlate directly with platelet activation in patients with paroxysmal nocturnal hemoglobinuria (PNH). The binding of Hb to glycoprotein1bα (GP1bα) increases platelet activation. A peptide AA1-50, designed from N-terminal amino acid sequence of GP1bα significantly inhibits the Hb binding to GP1bα as well as Hb-induced platelet activation. This study further examined if the Hb-mediated platelet activation plays any significant role in thrombus formation on subendothelium matrix under physiological flow shear stresses and the inhibition of Hb-platelet interaction can abrogate the above effects of Hb. Study performed thrombus formation assay in vitro by perfusing whole blood over immobilized VWF or collagen type I in presence of Hb under shear stresses simulating arterial or venous flow. The Hb concentrations ranging from 5 to 10 μM, commonly observed level in plasma of the hemolytic patients including PNH, dose-dependently increased thrombus formation on immobilized VWF under higher shear stress of 25 dyne/cm2, but not at 5 dyne/cm2. The above Hb concentrations also increased thrombus formation on immobilized collagen under both shear stresses of 5 and 25 dyne/cm2. The peptide AA1-50 abrogated invariably the above effects of Hb on thrombus formation. This study therefore indicates that the Hb-induced platelet activation plays a crucial role in thrombus formation on immobilized VWF or collagen under physiological flow shear stresses. Thus suggesting a probable role of this mechanism in facilitating thrombosis under hemolytic conditions.

  17. Development of Iron-Chelating Poly(ethylene terephthalate) Packaging for Inhibiting Lipid Oxidation in Oil-in-Water Emulsions.

    Science.gov (United States)

    Johnson, David R; Tian, Fang; Roman, Maxine J; Decker, Eric A; Goddard, Julie M

    2015-05-27

    Foods such as bulk oils, salad dressings, and nutritionally fortified beverages that are susceptible to oxidative degradation are often packaged in poly(ethylene terephthalate) (PET) bottles with metal chelators added to the food to maintain product quality. In the present work, a metal-chelating active packaging material is designed and characterized, in which poly(hydroxamic acid) (PHA) metal-chelating moieties were grafted from the surface of PET. Biomimetic PHA groups were grafted in a two-step UV-initiated process without the use of a photoinitiator. Surface characterization of the films by attenuated total reflective Fourier transform infrared spectroscopy (ATR-FTIR) and scanning electron microscopy (SEM) suggested successful grafting and conversion of poly(hydroxyethyl acrylate) (PHEA) to PHA chelating moieties from the surface of PET. Colorimetric (ferrozine) and inductively coupled plasma mass spectroscopy (ICP-MS) assays demonstrated the ability of PET-g-PHA to chelate iron in a low-pH (3.0) environment containing a competitive metal chelator (citric acid). Lipid oxidation studies demonstrated the antioxidant activity of PET-g-PHA films in inhibiting iron-promoted oxidation in an acidified oil-in-water (O/W) emulsion model system (pH 3.0). Particle size and ζ-potential analysis indicated that the addition of PET-g-PHA films did not affect the physical stability of the emulsion system. This work suggests that biomimetic chelating moieties can be grafted from PET and effectively inhibit iron-promoted degradation reactions, enabling removal of metal-chelating additives from product formulations.

  18. Leach studies of chelating agents and influence on radionuclide leaching from simulated LLW/ILW cement waste forms

    International Nuclear Information System (INIS)

    Vejmelka, P.; Koester, R.; Ferrara, D.; Wacks, M.E.

    1990-01-01

    Leach studies were performed on cemented waste forms containing sodium nitrate, trace amounts of cesium-137, and cobalt-60, and a chelating agent (ethylene diamine tetraacetic acid (EDTA), nitrilotriacetic acid (NTA), or citric acid). Leaching of the chelates was measured in water and the effect of the chelates on the release of the Cs-137 and Co-60 was studied. The time dependence of the release rate of the chelates is comparable but the chelate concentration in solution and the released fractions are different. EDTA shows the highest release rate followed by NTA and citrate. The release of the non complex forming cesium is not affected by the presence of the chelates. Independent from the strong complex formation of cobalt with EDTA, NTA, and citrate in the alkaline region the cobalt release is also not affected by the presence of the chelates. The high calcium content of the system decreases the stability of the Co complexes in the high pH region (12-13). Experiments were performed to determine the equilibrium concentration of the chelates between liquid and solid phases. The liquid phases were deionized water, saturated sodium chloride, 24 percent magnesium chloride and Q-brine. The equilibrium studies are based on the assumption that in time a stable final condition is to be established in the near field of the waste form in which each compound is at chemical equilibrium between the dissolved and the various solid phases. The total release may be assessed from the concentration in solution and flow rate out of the near field. The fraction of EDTA released from the cement ranged from 0.2 in the Q-brine to 0.5 in the saturated sodium chloride. The concentration of EDSA in solution was dependent on the original amount in the cement sample, but the released fraction was independent of the initial loading. Indicating, EDTA concentration is not affected by solubility limits. 11 refs., 3 figs., 2 tabs

  19. 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.

  20. Heavy Metal Displacement in Chelate-Assisted Phytoremediation of Biosolids Soil

    Science.gov (United States)

    Kirkham, M. B.; Liphadzi, M. S.

    2005-05-01

    Heavy metals in biosolids (sewage sludge) applied to land contaminate the soil. Phytoremediation, the use of plants to clean up toxic heavy metals, might remove them. Chelating agents are added to soil to solubilize the metals for enhanced phytoextraction. Yet no studies follow the displacement and leaching of heavy metals in soil with biosolids following solubilization with chelates. The objective of this work was to determine the mobility of heavy metals, as affected by a chelate, in soil (Haynie very fine sandy loam) from a 25-year old sludge farm. Soil columns (105 cm long; 39 cm in diameter) either had a plant (hybrid poplar; Populus deltoides Marsh. x P. nigra L.) or no plant. When the poplars were 144 days old, the tetrasodium salt of the chelating agent EDTA (ethylenediamine-tetraacetic acid) was irrigated onto the soil at a rate of 1 g per kg of soil. Drainage water, soil, and plants were analyzed for three toxic heavy metals (Cd, Ni, Pb) and four essential heavy metals (Cu, Fe, Mn, Zn). Without EDTA, concentrations of the seven heavy metals in the leachate from columns with or without plants were low or below detection limits. With or without plants, the EDTA mobilized all heavy metals and increased their concentration in drainage water. Without plants, the concentrations of Cd, Cu, Fe, Pb, and Zn in the leachate from columns with EDTA were above drinking-water standards. (There is no drinking-water standard for Ni.) The presence of poplar plants in the soil reduced the concentrations of Cu, Fe, and Zn in the leachate so it fell within drinking-water standards. Concentrations of Cd and Pb in the leachate remained above drinking-water standards with or without plants. At harvest (124 days after the EDTA application), total concentration of each heavy metal in the soil at different depths in the columns with EDTA was similar to that in the columns without EDTA. The chelate did not affect the concentration of heavy metals in the roots, stems, or leaves

  1. Repurposing of Copper(II)-chelating Drugs for the Treatment of Neurodegenerative Diseases.

    Science.gov (United States)

    Lanza, Valeria; Milardi, Danilo; Di Natale, Giuseppe; Pappalardo, Giuseppe

    2018-02-12

    There is mounting urgency to find new drugs for the treatment of neurodegenerative disorders. A large number of reviews have exhaustively described either the molecular or clinical aspects of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD). Conversely, reports outlining how known drugs in use for other diseases can also be effective as therapeutic agents in neurodegenerative diseases are less reported. This review focuses on the current uses of some copper(II) chelating molecules as potential drug candidates in neurodegeneration. Starting from the well-known harmful relationships existing between the dyshomeostasis and mis-management of metals and AD onset, we surveyed the experimental work reported in the literature, which deals with the repositioning of metal-chelating drugs in the field of neurodegenerative diseases. The reviewed papers were retrieved from common literature and their selection was limited to those describing the biomolecular aspects associated with neuroprotection. In particular, we emphasized the copper(II) coordination abilities of the selected drugs. Copper, together with zinc and iron, are known to play a key role in regulating neuronal functions. Changes in copper homeostasis are crucial for several neurodegenerative disorders. The studies included in this review may provide an overview on the current strategies aimed at repurposing copper (II) chelating drugs for the treatment of neurodegenerative disorders. Starting from the exemplary case of clioquinol repurposing, we discuss the challenge and the opportunities that repurposing of other metal-chelating drugs may provide (e.g. PBT-2, metformin and cyclodipeptides) in the treatment of neurodegenerative disease. In order to improve the success rate of drug repositioning, comprehensive studies on the molecular mechanism and therapeutic efficacy are still required. The present review upholds that drug repurposing makes significant advantages over drug discovery since

  2. 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.

  3. Curcumin induces apoptosis and protective autophagy in castration-resistant prostate cancer cells through iron chelation

    Directory of Open Access Journals (Sweden)

    Yang C

    2017-02-01

    Full Text Available Chunguang Yang,1,* Xueyou Ma,1,* Zhihua Wang,1 Xing Zeng,1 Zhiquan Hu,1 Zhangqun Ye,1 Guanxin Shen2 1Department of Urology, Tongji Hospital, 2Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China *These authors contributed equally to this work 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

  4. Bill project aiming at abrogating exclusive search permits for unconventional hydrocarbon searches, and at prohibiting their exploration and exploitation of the national territory; Proposition de Loi visant a abroger les permis exclusifs de recherches d'hydrocarbures non conventionnels et a interdire leur exploration et leur exploitation sur le territoire national

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-01

    After having briefly recalled the origin of shale gases, their extraction process and the evolution of their production in the USA, the authors outline the extremely negative environmental impacts of the fracking technique (hydraulic fracturing): water pollution, air pollution, soil pollution, existence of numerous drilling sites which would degrade landscapes, water and soil contamination risks. As some search permits have already been awarded, and while taking these negative consequences into account, the authors propose a bill project to prohibit these explorations, to abrogate the existing permits, and to ensure public information before bestowing such search permits and exploitation concessions

  5. Bill project aiming at abrogating exclusive search permits for unconventional hydrocarbon searches, and at prohibiting their exploration and exploitation of the national territory; Proposition de Loi visant a abroger les permis exclusifs de recherches d'hydrocarbures non conventionnels et a interdire leur exploration et leur exploitation sur le territoire national

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-01

    After having briefly recalled the origin of shale gases, their extraction process and the evolution of their production in the USA, the authors outline the extremely negative environmental impacts of the fracking technique (hydraulic fracturing): water pollution, air pollution, soil pollution, existence of numerous drilling sites which would degrade landscapes, water and soil contamination risks. As some search permits have already been awarded, and while taking these negative consequences into account, the authors propose a bill project to prohibit these explorations, to abrogate the existing permits, and to ensure public information before bestowing such search permits and exploitation concessions

  6. Characterization of the effect of serum and chelating agents on Staphylococcus aureus biofilm formation; chelating agents augment biofilm formation through clumping factor B

    Science.gov (United States)

    Abraham, Nabil Mathew

    Staphylococcus aureus is the causative agent of a diverse array of acute and chronic infections, and some these infections, including infective endocarditis, joint infections, and medical device-associated bloodstream infections, depend upon its capacity to form tenacious biofilms on surfaces. Inserted medical devices such as intravenous catheters, pacemakers, and artificial heart valves save lives, but unfortunately, they can also serve as a substrate on which S. aureus can form a biofilm, attributing S. aureus as a leading cause of medical device-related infections. The major aim of this work was take compounds to which S. aureus would be exposed during infection and to investigate their effects on its capacity to form a biofilm. More specifically, the project investigated the effects of serum, and thereafter of catheter lock solutions on biofilm formation by S. aureus. Pre-coating polystyrene with serum is frequently used as a method to augment biofilm formation. The effect of pre-coating with serum is due to the deposition of extracellular matrix components onto the polystyrene, which are then recognized by MSCRAMMs. We therefore hypothesized that the major component of blood, serum, would induce biofilm formation. Surprisingly, serum actually inhibited biofilm formation. The inhibitory activity was due to a small molecular weight, heat-stable, non-proteinaceous component/s of serum. Serum-mediated inhibition of biofilm formation may represent a previously uncharacterized aspect of host innate immunity that targets the expression of a key bacterial virulence factor: the ability to establish a resistant biofilm. Metal ion chelators like sodium citrate are frequently chosen to lock intravenous catheters because they are regarded as potent inhibitors of bacterial biofilm formation and viability. We found that, while chelating compounds abolished biofilm formation in most strains of S. aureus, they actually augmented the phenotype in a subset of strains. We

  7. Extrafibrillar collagen demineralization-based chelate-and-rinse technique bridges the gap between wet and dry dentin bonding.

    Science.gov (United States)

    Mai, Sui; Wei, Chin-Chuan; Gu, Li-Sha; Tian, Fu-Cong; Arola, Dwayne D; Chen, Ji-Hua; Jiao, Yang; Pashley, David H; Niu, Li-Na; Tay, Franklin R

    2017-07-15

    Limitations associated with wet-bonding led to the recent development of a selective demineralization strategy in which dentin was etched with a reduced concentration of phosphoric acid to create exclusive extrafibrillar demineralization of the collagen matrix. However, the use of acidic conditioners removes calcium via diffusion of very small hydronium ions into the intrafibrillar collagen water compartments. This defeats the purpose of limiting the conditioner to the extrafibrillar space to create a collagen matrix containing only intrafibrillar minerals to prevent collapse of the collagen matrix. The present work examined the use of polymeric chelators (the sodium salt of polyacrylic acid) of different molecular weights to selectively demineralize extrafibrillar dentin. These polymeric chelators exhibit different affinities for calcium ions (isothermal titration calorimetry), penetrated intrafibrillar dentin collagen to different extents based on their molecular sizes (modified size-exclusion chromatography), and preserve the dynamic mechanical properties of mineralized dentin more favorably compared with completely demineralized phosphoric acid-etched dentin (nanoscopical dynamic mechanical analysis). Scanning and transmission electron microscopy provided evidence for retention of intrafibrillar minerals in dentin surfaces conditioned with polymeric chelators. Microtensile bond strengths to wet-bonded and dry-bonded dentin conditioned with these polymeric chelators showed that the use of sodium salts of polyacrylic acid for chelating dentin prior to bonding did not result in significant decline in resin-dentin bond strength. Taken together, the findings led to the conclusion that a chelate-and-rinse conditioning technique based on extrafibrillar collagen demineralization bridges the gap between wet and dry dentin bonding. The chelate-and-rinse dental adhesive bonding concept differentiates from previous research in that it is based on the size

  8. The effect of macrocyclic chelators on the targeting properties of the 68Ga-labeled gastrin releasing peptide receptor antagonist PEG2-RM26

    International Nuclear Information System (INIS)

    Varasteh, Zohreh; Mitran, Bogdan; Rosenström, Ulrika; Velikyan, Irina; Rosestedt, Maria; Lindeberg, Gunnar; Sörensen, Jens; Larhed, Mats; Tolmachev, Vladimir; Orlova, Anna

    2015-01-01

    Introduction: Overexpression of gastrin-releasing peptide receptors (GRPR) has been reported in several cancers. Bombesin (BN) analogs are short peptides with a high affinity for GRPR. Different BN analogs were evaluated for radionuclide imaging and therapy of GRPR-expressing tumors. We have previously investigated an antagonistic analog of BN (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH 2 , RM26) conjugated to NOTA via a PEG 2 spacer (NOTA-PEG 2 -RM26) labeled with 68 Ga, 111 In and Al 18 F. 68 Ga-labeled NOTA-PEG 2 -RM26 showed high tumor-to-organ ratios. Methods: The influence of different macrocyclic chelators (NOTA, NODAGA, DOTA and DOTAGA) on the targeting properties of 68 Ga-labeled PEG 2 -RM26 was studied in vitro and in vivo. Results: All conjugates were labeled with generator-produced 68 Ga with high yields and demonstrated high stability and specific binding to GRPR. The IC 50 values of nat Ga-X-PEG 2 -RM26 (X = NOTA, DOTA, NODAGA, DOTAGA) were 2.3 ± 0.2, 3.0 ± 0.3, 2.9 ± 0.3 and 10.0 ± 0.6 nM, respectively. The internalization of the conjugates by PC-3 cells was low. However, the DOTA-conjugated analog demonstrated a higher internalization rate compared to other analogs. GRPR-specific uptake was found in receptor-positive normal tissues and PC-3 xenografts for all conjugates. The biodistribution of the conjugates was influenced by the choice of the chelator moiety. Although all radiotracers cleared rapidly from the blood, [ 68 Ga]Ga-NOTA-PEG 2 -RM26 showed significantly lower uptake in lung, muscle and bone compared to the other analogs. The uptake in tumors (5.40 ± 1.04 %ID/g at 2 h p.i.) and the tumor-to-organ ratios (25 ± 3, 157 ± 23 and 39 ± 4 for blood, muscle and bone, respectively) were significantly higher for the NOTA-conjugate than the other analogs. Conclusions: Chelators had a clear influence on the biodistribution and targeting properties of 68 Ga-labeled antagonistic BN analogs. Positively charged [ 68 Ga]Ga-NOTA-PEG 2 -RM26 provided

  9. 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 < .001) and 3.1 ± 7.9 mg Fe/g dw (n = 68; P < .001) in the deferasirox and crossover cohorts, respectively. Median serum ferritin significantly decreased by 706 ng/mL (n = 196; P < .001) and 371 ng/mL (n = 147; P < .001), respectively, after ≥ 4 years' exposure. Investigator-assessed, drug-related adverse events, including increased blood creatinine (11.2%), abdominal pain (9.0%), and nausea (7.4%), were generally mild to moderate, transient, and reduced in frequency over time. No adverse effect was observed on pediatric growth or adolescent sexual development. This first prospective study of long-term 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.

  10. A Novel Iron Chelator-Radical Scavenger Ameliorates Motor Dysfunction and Improves Life Span and Mitochondrial Biogenesis in SOD1G93A ALS Mice.

    Science.gov (United States)

    Golko-Perez, Sagit; Amit, Tamar; Bar-Am, Orit; Youdim, Moussa B H; Weinreb, Orly

    2017-02-01

    The aim of the present study was to evaluate the therapeutic effect of the novel neuroprotective multitarget brain permeable monoamine oxidase inhibitor/iron chelating-radical scavenging drug, VAR10303 (VAR), co-administered with high-calorie/energy-supplemented diet (ced) in SOD1 G93A transgenic amyotrophic lateral sclerosis (ALS) mice. Administration of VAR-ced was initiated after the appearance of disease symptoms (at day 88), as this regimen is comparable with the earliest time at which drug therapy could start in ALS patients. Using this rescue protocol, we demonstrated in the current study that VAR-ced treatment provided several beneficial effects in SOD1 G93A mice, including improvement in motor performance, elevation of survival time, and attenuation of iron accumulation and motoneuron loss in the spinal cord. Moreover, VAR-ced treatment attenuated neuromuscular junction denervation and exerted a significant preservation of myofibril regular morphology, associated with a reduction in the expression levels of genes related to denervation and atrophy in the gastrocnemius (GNS) muscle in SOD1 G93A mice. These effects were accompanied by upregulation of mitochondrial DNA and elevated activities of complexes I and II in the GNS muscle. We have also demonstrated that VAR-ced treatment upregulated the mitochondrial biogenesis master regulator, peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) and increased PGC-1α-targeted metabolic genes and proteins, such as, PPARγ, UCP1/3, NRF1/2, Tfam, and ERRα in GNS muscle. These results provide evidence of therapeutic potential of VAR-ced in SOD1 G93A mice with underlying molecular mechanisms, further supporting the importance role of multitarget iron chelators in ALS treatment.

  11. Psychological therapies for thalassaemia.

    Science.gov (United States)

    Anie, Kofi A; Massaglia, Pia

    2014-03-06

    Thalassaemia is a group of genetic blood disorders characterised by the absence or reduction in the production of haemoglobin. Severity is variable from less severe anaemia, through thalassaemia intermedia, to profound severe anaemia (thalassaemia major). In thalassaemia major other complications include growth retardation, bone deformation, and enlarged spleen. Blood transfusion is required to treat severe forms of thalassaemia, but this results in excessive accumulation of iron in the body (iron overload), removed mostly by a drug called desferrioxamine through 'chelation therapy'. Non-routine treatments are bone marrow transplantation (which is age restricted), and possibly hydroxyurea, designed to raise foetal haemoglobin level, thus reducing anaemia. In addition, psychological therapies seem appropriate to improving outcome and adherence to medical treatment. To examine the evidence that in people with thalassaemia, psychological treatments improve the ability to cope with the condition, and improve both medical and psychosocial outcomes. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Searches on the Internet were also performed.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 11 November 2013. All randomised or quasi-randomised controlled trials comparing the use of psychological intervention to no (psychological) intervention in people with thalassaemia. No trials of psychological therapies have been found in the literature for inclusion in this review. There are currently no results to be reported. As a chronic disease with a considerable role for self-management, psychological support seems appropriate for managing thalassaemia. However, from the information currently available, no conclusions

  12. The implication of decorporation therapy for contaminated persons

    International Nuclear Information System (INIS)

    Matsuoka, Osamu

    1989-01-01

    The procedures of removal on internally deposited radionuclides from accidentally contaminated individual are divided for two different category such as 1) Physical procedure, and 2) Chemical procedure. Physical procedures include surgical excision and lung lavage. Both procedures are very effective for decorporation but are slight unsafe in procedure itself. Therefore, it is difficult to judge to apply these procedures under balance of risk and benefit. Chemical procedure include 1) Inhibition of intestinal absorption, such as production of insoluble compounds. 2) Capture of radionuclides in entero-hepatic circulation such as Cs-137 by Prussian Blue, 3) Blocking of deposition to target organs or competitive acceleration of excretion by excess administration of stable isotope or analogous element such as stable iodine for thyroid blocking and 4) Acceleration of excretion by chelating agent such as Pb by EDTA, Hg by BAL, Fe by DFOA. Chelation therapy is major procedure of most practical sense. For the removal of transuranic element, Ca-DTPA and Zn-DTPA (1g/day/person) are the most effective agents in conventional use and new developing agent such as TTHA, Puchel and LICAMS are still not in routine use. The advantage and disadvantage of each agent for decorporation therapy were reviewed. The future research trends expected were discussed related with current difficulties on the application of chelating therapy. (author)

  13. Knockdown of platinum-induced growth differentiation factor 15 abrogates p27-mediated tumor growth delay in the chemoresistant ovarian cancer model A2780cis

    International Nuclear Information System (INIS)

    Meier, Julia C; Haendler, Bernard; Seidel, Henrik; Groth, Philip; Adams, Robert; Ziegelbauer, Karl; Kreft, Bertolt; Beckmann, Georg; Sommer, Anette; Kopitz, Charlotte

    2015-01-01

    Molecular mechanisms underlying the development of resistance to platinum-based treatment in patients with ovarian cancer remain poorly understood. This is mainly due to the lack of appropriate in vivo models allowing the identification of resistance-related factors. In this study, we used human whole-genome microarrays and linear model analysis to identify potential resistance-related genes by comparing the expression profiles of the parental human ovarian cancer model A2780 and its platinum-resistant variant A2780cis before and after carboplatin treatment in vivo. Growth differentiation factor 15 (GDF15) was identified as one of five potential resistance-related genes in the A2780cis tumor model. Although A2780-bearing mice showed a strong carboplatin-induced increase of GDF15 plasma levels, the basal higher GDF15 plasma levels of A2780cis-bearing mice showed no further increase after short-term or long-term carboplatin treatment. This correlated with a decreased DNA damage response, enhanced AKT survival signaling and abrogated cell cycle arrest in the carboplatin-treated A2780cis tumors. Furthermore, knockdown of GDF15 in A2780cis cells did not alter cell proliferation but enhanced cell migration and colony size in vitro. Interestingly, in vivo knockdown of GDF15 in the A2780cis model led to a basal-enhanced tumor growth, but increased sensitivity to carboplatin treatment as compared to the control-transduced A2780cis tumors. This was associated with larger necrotic areas, a lobular tumor structure and increased p53 and p16 expression of the carboplatin-treated shGDF15-A2780cis tumors. Furthermore, shRNA-mediated GDF15 knockdown abrogated p27 expression as compared to control-transduced A2780cis tumors. In conclusion, these data show that GDF15 may contribute to carboplatin resistance by suppressing tumor growth through p27. These data show that GDF15 might serve as a novel treatment target in women with platinum-resistant ovarian cancer

  14. Polyaminoquinoline iron chelators for vectorization of antiproliferative agents: design, synthesis, and validation.

    Science.gov (United States)

    Corcé, Vincent; Morin, Emmanuelle; Guihéneuf, Solène; Renault, Eric; Renaud, Stéphanie; Cannie, Isabelle; Tripier, Raphaël; Lima, Luís M P; Julienne, Karine; Gouin, Sébastien G; Loréal, Olivier; Deniaud, David; Gaboriau, François

    2012-09-19

    Iron chelation in tumoral cells has been reported as potentially useful during antitumoral treatment. Our aim was to develop new polyaminoquinoline iron chelators targeting tumoral cells. For this purpose, we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, which we named Quilamines, based on an 8-hydroxyquinoline (8-HQ) scaffold linked to linear polyamine vectors. These were designed to target tumor cells expressing an overactive polyamine transport system (PTS). A set of Quilamines bearing variable polyamine chains was designed and assessed for their ability to interact with iron. Quilamines were also screened for their cytostatic/cytotoxic effects and their selective uptake by the PTS in the CHO cell line. Our results show that both the 8-HQ moiety and the polyamine part participate in the iron coordination. HQ1-44, the most promising Quilamine identified, presents a homospermidine moiety and was shown to be highly taken up by the PTS and to display an efficient antiproliferative activity that occurred in the micromolar range. In addition, cytotoxicity was only observed at concentrations higher than 100 μM. We also demonstrated the high complexation capacity of HQ1-44 with iron while much weaker complexes were formed with other cations, indicative of a high selectivity. We applied the density functional theory to study the binding energy and the electronic structure of prototypical iron(III)-Quilamine complexes. On the basis of these calculations, Quilamine HQ1-44 is a strong tridentate ligand for iron(III) especially in the form of a 1:2 complex.

  15. 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)

  16. Water-soluble chelating polymers for removal of actinides from wastewater

    International Nuclear Information System (INIS)

    Jarvinen, G.D.

    1997-01-01

    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

  17. Improving the efficiency of phytoremediation using electrically charged plant and chelating agents.

    Science.gov (United States)

    Tahmasbian, Iman; Safari Sinegani, Ali Akbar

    2016-02-01

    The low efficiency of phytoremediation is a considerable problem that limits the application of this environmentally friendly method on heavy metal-polluted soils. The combination of chelate-assisted phytoextraction and electrokinetic remediation could offer new opportunities to improve the effectiveness of phytoextraction. The current experiment aims to investigate the effects of electrical fields and chelating agents on phytoremediation efficiency. In a pot experiment using mine soil, poultry manure extract (PME), cow manure extract (CME), and ethylenediaminetetraacetic acid (EDTA) were applied to soil as chelating agents (2 g kg(-1)) at the beginning of the flowering stage. A week later, Helianthus annuus (sunflower) was negatively charged by inserting a stainless steel needle with 10 and 30 V DC electricity in the lowest part of the stems for 1 h each day for a 14-day period. At the end of the experiment, the shoot and root dry weight, lead (Pb) concentration in plant organs, translocation factor (TF), metal uptake index (UI), and soil available Pb (diethylene triamine pentaacetic acid (DTPA) extractable) were detected. Results indicated that the application of electrical fields had no significant impact on the shoot and root dry weights, while Pb concentration and UI increased in the 10-V EDTA treatment by 500 % compared to control. There was no significant difference between UI in 30- and 10-V EDTA treatments. Soil available Pb significantly increased in the 30-V treated soil. A positive correlation was observed between the available Pb in soil near the root and Pb concentration in shoot, its TF, and UI. In conclusion, a negatively charged plant along with the application of EDTA significantly increased the phytoremediation efficiency.

  18. Transition Metal Chelator Induces Progesterone Production in Mouse Cumulus-Oocyte Complexes and Corpora Lutea.

    Science.gov (United States)

    Tian, X; Anthony, K; Diaz, Francisco J

    2017-04-01

    Progesterone production is upregulated in granulosa cells (cumulus and mural) after the LH surge, but the intra-follicular mechanisms regulating this transition are not completely known. Recent findings show that the transition metal chelator, N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN), impairs ovarian function. In this study, we provide evidence that chelating transition metals, including zinc, enhances progesterone production. The findings show that TPEN (transition metal chelator) increases abundance of Cyp11a1 and Star messenger RNA (mRNA) between 8- and 20-fold and progesterone production more than 3-fold in cultured cumulus-oocyte complexes (COC). Feeding a zinc-deficient diet for 10 days, but not 3 days, increased Star, Hsd3b, and prostaglandin F2 alpha receptor (Ptgfr) mRNA ~2.5-fold, suggesting that the effect of TPEN is through modulation of zinc availability. Progesterone from cumulus cells promotes oocyte developmental potential. Blocking progesterone production with epostane during maturation reduced subsequent blastocyst formation from 89 % in control to 18 % in epostane-treated complexes, but supplementation with progesterone restored blastocyst developmental potential to 94 %. Feeding a zinc-deficient diet for 5 days before ovulation did not affect the number of CL, STAR protein, or serum progesterone. However, incubating luteal tissue with TPEN increased abundance of Star, Hsd3b, and Ptgfr mRNA 2-3-fold and increased progesterone production 3-fold. TPEN is known to abolish SMAD2/3 signaling in cumulus cells. However, treatment of COC with the SMAD2/3 phosphorylation inhibitor, SB421542, did not by itself induce steroidogenic transcripts but did potentiate EGF-induced Star mRNA expression. Collectively, the results show that depletion of transition metals with TPEN acutely enhances progesterone biosynthesis in COC and luteal tissue.

  19. Assessment of a gel-type chelating preparation containing 1-hydroxyethylidene-1, 1-bisphosphonate.

    Science.gov (United States)

    Girard, S; Paqué, F; Badertscher, M; Sener, B; Zehnder, M

    2005-11-01

    To test an aqueous gel containing 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) regarding its interactions with sodium hypochlorite, its calcium binding capacity, and its potential in preventing the formation of a smear layer when used in conjunction with rotary root canal preparation. The experimental aqueous gel consisted of (w/v) 2% alginate, 3% aerosil, 10% Tween 80 and 18% HEBP. Interactions of gel components with hypochlorite were assessed using iodometric titration and monochromatic ultraviolet spectrometry. Two commercial paste-type chelators containing ethylenediaminetetraacetic acid (EDTA) and peroxide (RC-Prep and Glyde) served as controls. Calcium-binding capacities were measured in mixtures with a Ca2+ standard solution buffered at pH 10 using a calcium-selective measuring chain. Finally, root canals of 16 extracted single-rooted premolars per group were instrumented using ProFile instruments dipped in the experimental gel, RC-Prep, or nothing. Additionally, canals were rinsed with 10 mL of a 1% NaOCl solution during/after preparation. Smear scores in instrumented teeth were monitored using scanning electron microscopy. None of the experimental gel components showed short-term interactions with hypochlorite, whilst EDTA, peroxide, RC-Prep and Glyde immediately reduced the hypochlorite in solution. The experimental gel chelated 30 mg Ca2+ g-1, compared with 16 mg Ca2+ g-1 and 11 mg Ca2+ g-1 chelated by RC-Prep and Glyde respectively. Smear scores obtained with the experimental gel were significantly (P<0.05) lower than with RC-Prep in coronal and middle root thirds, whilst no differences were observed in apical root thirds. Under the conditions of this study, an HEBP gel appeared advantageous over currently available products.

  20. 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

  1. Preparation of Ga-67 labeled monoclonal antibodies using deferoxamine as a bifunctional chelating agent

    International Nuclear Information System (INIS)

    Endo, K.; Furukawa, T.; Ohmomo, Y.

    1984-01-01

    Ga-67 labeled monoclonal IgG or F(ab')/sub 2/ fragments against α-fetoprotein and β-subunit of human choriogonadotropin (HCG), were prepared using Deferoxamine (DFO) as a bifunctional chelating agent. DFO, a well-known iron chelating agent, was conjugated with monoclonal antibodies (Ab) by a glutaraldehyde two step method and the effect of conjugation on the Ab activities was examined by RIA and Scatchard plot analysis. In both monoclonal Ab preparations, the conjugation reaction was favored as the pH increased. However, Ab-binding activities decreased as the molecular ratios of DFO to Ab increased. Preserved Ab activities were observed when Ab contained DFO per Ab molecule less than 2.1. At a ratio of over 3.3 DFO molecules per Ab, the maximal binding capacity rather than the affinity constant decreased. The inter-molecular cross linkage seemed to be responsible for the deactivation of binding activities. The obtained DFO-Ab conjugates, were then easily labeled with high efficiency and reproducibility and Ga-67 DFO-Ab complexes were highly stable both in vitro and in vivo. Thus, biodistribution of Ga-67 labeled F(ab')/sub 2/ fragments of monoclonal Ab to HCG β-subunit was attempted in nude mice transplanted with HCG-producing human teratocarcinoma. Tumor could be visualized, in spite of relatively high background imaging of liver, kidney and spleen. The use of DFO as a bifunctional chelating agent provided good evidence for its applicability to labeling monoclonal Ab with almost full retention of Ab activities. Further, availability of Ga-68 will make Ga-68 DFO-monoclonal Ab a very useful tool for positron tomography imaging of various tumors

  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. SYNTHESIS OF N- ACETONITRIL AND N- ETHYLAMINE- 3- HYDROXYPYRIDINONES AS IRON (III CHELATORS

    Directory of Open Access Journals (Sweden)

    L.A. SAGHAEI

    2000-12-01

    Full Text Available Background. The need of iron-chelating agents as orally active alternatives to desferal for the treatment of iron overload in thalassaemic patients, has stimulated considerable research efforts in the synthesis of new metal chelators. One of the member of hydroxypyridinones (2,3- dimethyl-3- hydroxypyridinones has so far received the most attention. This compound is rapidly glucuronidated into a non-chelating metabolite, which partly explains why high doses of the compound has to be used in order to achieve negative balance. This metabolic behavior has led the medicinal chemists to design compounds such as N-hydroxyalkyl derivatives which do not undergo extensive metabolism. The objective of the present work was to further synthesis and design new derivatives of hydroxypyridinones (N- acetonitril and N-ethylamine derivatives Methods. The synthesis route involves the benzylation of hydroxyl group of maltol (ethyl maltol using benzyl chloride conversion of the benazylated maltol (ethyl maltol to the N-acetonitril bezylated pyridinone derivatives by introducing the aminoacetonitril in pyridine solvent and cleavage of benzyl group by hydrogenation method or using the bromodimethyl borane to form the N-acetonitril or N- ethylamine- 3- hydroxypyridinones respectively.
    Results. In this work three final compounds such as 1- (2- aminoethyl- 2- methyl- 3-hydroxypyridin- 4- one, 1- (2- aminoethyl- 2- ethyl- 3- hydroxypyridin-4- one and 1- cyanomethyl -2- methyl- 3- hydroxypyridin- 4- one were synthesized.
    Discussion. Identification and structural elucidation of compounds were achieved by IH NMR and Mass spectra, elemental analysis and through physical constants. The biological effects of compounds will be studied in the near future.

  4. Iron Chelation

    Science.gov (United States)

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  5. Moessbauer and EPR studies on iron-dihydroxybenzoic acid and iron-itoic acid chelate complexes

    International Nuclear Information System (INIS)

    Bagyinka, Cs.; Horvath, L.I.; Keszthelyi, L.

    1984-01-01

    Low molecular weight iron-dihydroxybenzoic acid and iron-itoic acid complexes were investigated by Moessbauer and EPR spectroscopy. In strong acidic medium the iron is chelated in high spin ferrous form. By varying the pH of the medium a (S=2)Fesup(2+)→(S=5/2)Fesup(3+) transition was found with a midpoint pH value of 4. From the g'-tensor anisotropy it is concluded that the metal atom is coordinated by six oxygen atoms in rhombically distorted octahedral configuration. The biological significance of these structural data is briefly discussed. (author)

  6. Chelating extractants of improved selectivity. Progress report, 1 August 1979-31 July 1980

    International Nuclear Information System (INIS)

    1980-01-01

    During the current contract year, mixed ligand chelate extraction systems for separating lanthanides was extended to elucidating the underlying reasons for the observed enhancement by quaternary ammonium salts. Equilibrium studies reveal the formation of anionic complexes (LnL 4 .HL - ) (where HL is 8-quinolinol) that was extracted when paired with a quaternary ammonium ion. Lathanum, as a lone exception was extracted as R 4 N + , LaL 4 - . Work is underway in the application of similar extractants, 5,7-dibromo-8-quinolinol and Kelex 100 (a 7-alkenyl-8-quinolinol) to the separation of lanthanides

  7. Chelating agents improve enzymatic solubilization of pectinaceous co-processing streams

    DEFF Research Database (Denmark)

    Ravn, Helle Christine; Meyer, Anne S.

    2014-01-01

    of different levels of ethylene-diaminetetraacetic acid (EDTA), citric acid, oxalic acid, and phosphate was assessed in relation to enzymatic solubilization of isopropanol precipitatable oligo- and polysaccharides from sugar beet pulp, citrus peel, and two types of potato pulp. The two types of potato pulp...... solubilization yields. The effect of the chelating agents correlated to their dissociation constants (pKa values) and calcium binding constants and citric acid and EDTA exerted highest effects. Maximum polysaccharide yield was obtained for FiberBind 400 where the enzymatic treatment in presence of citric acid...

  8. Chromatographic methods for determination of metals as chelate compounds with heterocyclic azo reagents

    International Nuclear Information System (INIS)

    Basova, E.M.; Bol'shova, T.A.; Shpigun, O.A.; Ivanov, V.M.

    1993-01-01

    Methods for separation and concentration of transition metals as well as cadmium in form of chelates with heterocyclic azo compounds namely, PAN(1-(2-pyridylaso)-2-naphthol), PAR(4-(2-pyridylazo)-resorcin), Br-PAAP (2-(5-bromine-2-pyridylazo)-5-diethyl aminophenol) are considered. The Br-PAAP reagent is the most sensitive and widely-applied one in extraction and highly-efficient liquid chromatography. Methods of sorption concentration with subsequent element determination directly on the sorbent without microelements separation or destruction are the most promissing ones

  9. 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.

  10. Sequestration of chelated copper by structural Fe(II): Reductive decomplexation and transformation of Cu{sup II}-EDTA

    Energy Technology Data Exchange (ETDEWEB)

    He, Hongping [State Key Laboratory of Pollution Control and Resources Reuse, School of Environmental Science & Engineering, Tongji University, Shanghai 200092 (China); Wu, Deli, E-mail: wudeli@tongji.edu.cn [State Key Laboratory of Pollution Control and Resources Reuse, School of Environmental Science & Engineering, Tongji University, Shanghai 200092 (China); Zhao, Linghui [State Key Laboratory of Pollution Control and Resources Reuse, School of Environmental Science & Engineering, Tongji University, Shanghai 200092 (China); Luo, Cong [School of Civil and Environmental Engineering, Georgia Institute of Technology, GA 30332 (United States); Dai, Chaomeng; Zhang, Yalei [State Key Laboratory of Pollution Control and Resources Reuse, School of Environmental Science & Engineering, Tongji University, Shanghai 200092 (China)

    2016-05-15

    Highlights: • Structural Fe(II) was found to reveal high sequestration potential in various chelated copper. • Chelated copper was reduced to Cu(0) and Cu{sub 2}O by =Fe(II), whcih was oxidized to Fe{sub 2}O{sub 3}·H{sub 2}O. • Both electron transfer and surface =Fe(II) were found to be crucial during chelated copper reduction. • The indispensible role of reductive decomplexation was identified in chelated copper sequestration. - Abstract: Chelated coppers, such as Cu{sup II}-EDTA, are characteristically refractory and difficult to break down because of their high stability and solubility. Cu{sup II}–EDTA sequestration by structural Fe(II) (=Fe(II)) was investigated intensively in this study. Up to 101.21 mgCu(II)/gFe(II) was obtained by =Fe(II) in chelated copper sequestration under near neutral pH condition (pH 7.70). The mechanism of Cu{sup II}-EDTA sequestration by =Fe(II) was concluded as follows: 3Cu{sup II}–EDTA + 7=Fe(II) + 9H{sub 2}O → Cu(0) ↓ + Cu{sub 2}O ↓ (the major product) + 2Fe{sub 2}O{sub 3}·H{sub 2}O ↓ + 3Fe{sup II}–EDTA +14H{sup +} Novel results strongly indicate that Cu{sup II} reductive transformation induced by surface =Fe(II) was mainly responsible for chelated copper sequestration. Cu(0) generation was initially facilitated, and subsequent reduction of Cu(II) into Cu(I) was closely combined with the gradual increase of ORP (Oxidation-Reduction Potential). Cu-containing products were inherently stable, but Cu{sub 2}O would be reoxidized to Cu(II) with extra-aeration, resulting in the release of copper, which was beneficial to Cu reclamation. Concentration diminution of Cu{sup II}–EDTA within the electric double layer and competitive adsorption were responsible for the negative effects of Ca{sup 2+}, Mg{sup 2+}. By generating vivianite, PO{sub 4}{sup 3−} was found to decrease surface =Fe(II) content. This study is among the first ones to identify the indispensible role of reductive decomplexation in chelated copper

  11. Metal chelates of some transition and non-transition metal ions with Schiff base derived from isatin with o-phenylenediamine

    International Nuclear Information System (INIS)

    Hassaan, A.M.A.; Khalifa, M.A.

    1993-01-01

    New Cr(III), Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Pb(II) chelates of the Schiff base derived from isatin with o-phenylenediamine have been synthesized and characterized on the basis of elemental analyses, electronic, IR and 1 H NMR spectra, and also by aid of molar conductivity and magnetic moment measurements. It has been found that the Schiff base behaves as ONNO tetradentate dibasic ligand forming chelates with 1:1 (metal:ligand) stoichiometry. Square planar environment is suggested for nickel(II) chelate. All the metal chelates show non-electrolytic behaviour

  12. Synthesis, spectroscopic studies and antimicrobial activity of chelates 2-(acetyloxy)-benzoic acid with transition metals (CR+3, MN+2, NI+2 AND CU+2)

    International Nuclear Information System (INIS)

    Khan, B.; Mateen, B.; Ahmed, F.; Ahmed, F.

    2007-01-01

    2-(acetyloxy)-Benzoic acid chelates with Cr+3, Mn+2, Ni+2 and Cu+2 were synthesized and characterized by the melting point, solubility, Fourier Transform Infrared (FT-IR) Spectroscopy, Atomic Absorption Spectroscopy (AAS), X-Ray Diffraction (XRD) method and evaluated by antimicrobial activity. The functional group present in the chelates was determined by Fourier Transform Infrared Spectroscopy, by X-Ray Diffraction analysis crystal data of chelates, their inter-atomic and inter-planer spacing was also determined. The amount of metal in the chelates was estimated by Atomic Absorption Spectroscopy and their Antimicrobial Activity was studied against Pseudomonas aeruginosa, Escherisha coli and Staphylococcus aureus. (author)

  13. High-performance lithium-rich layered oxide materials: Effects of chelating agents on microstructure and electrochemical properties

    International Nuclear Information System (INIS)

    Li, Lingjun; Xu, Ming; Chen, Zhaoyong; Zhou, Xiang; Zhang, Qiaobao; Zhu, Huali; Wu, Chun; Zhang, Kaili

    2015-01-01

    The mechanisms and effects of three typical chelating agents, namely glucose, citric acid and sucrose on the sol-gel synthesis process, electrochemical degradation and structural evolution of 0.5Li 2 MnO 3 ·0.5LiNi 0.5 Co 0.2 Mn 0.3 O 2 (LLMO) materials are systematically compared for the first time. X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy and high-resolution transmission electron microscopy analysis indicate that the sample synthesized from sucrose owns well structure, homogenous distribution, low Ni 3+ concentration and good surface structural stability during cycling, respectively. Electrochemical tests further prove that the LLMO material obtained from sucrose maintains 258.4 mAh g −1 with 94.8% capacity retention after 100 cycles at 0.2 C. The superior electrochemical performance can be ascribed to the exceptional complexing mechanism of sucrose, compared to those of the glucose and citric acid. Namely, one mole sucrose can be hydrolyzed into two different monosaccharides and further chelates three M (Li, Ni, Co and Mn) ions to form a more uniform ion-chelated matrix during sol-gel process. This discovery is an important step towards understanding the selection criterion of chelating agents for sol-gel method, that chelating agent with excellent complexing capability is beneficial to the distribution, structural stability and electrochemical properties of advanced lithium-rich layered materials

  14. Monitoring the effects of chelating agents and electrical fields on active forms of Pb and Zn in contaminated soil.

    Science.gov (United States)

    Tahmasbian, Iman; Safari Sinegani, Ali Akbar

    2013-11-01

    The application of electrical fields and chelating agents is an innovative hybrid technology used for the decontamination of soil polluted by heavy metals. The effects of four center-oriented electrical fields an