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Sample records for assess chelation therapy

  1. 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.

  2. 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...

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

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    Tamil Selvan

    2014-01-01

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

  4. Combination therapies in iron chelation

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    Raffaella Origa

    2014-12-01

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

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

    Science.gov (United States)

    Budimir, Ana

    2011-03-01

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

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

    Science.gov (United States)

    Frizzell, Norma; Baynes, John W

    2014-01-01

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

  7. Importance of iron chelation therapy

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    A. Varoğlu

    2011-12-01

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

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

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    Zvi Ioav Cabantchik

    2013-12-01

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

  9. 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

  10. Myelodysplastic Syndromes and Iron Chelation Therapy

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

    2017-01-01

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

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

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    Monica Pinheiro de Almeida Verissimo

    2013-01-01

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

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

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

    2010-01-01

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

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

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

    2014-08-01

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

  15. Μethods of iron chelation therapy: a bibliographic review

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    Maria Agapiou

    2012-01-01

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

  16. Efficacy of chelation therapy to remove aluminium intoxication.

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

    2015-11-01

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

  17. Iron Chelation

    Science.gov (United States)

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  19. Combined Chelation Therapy with Deferasirox and Deferoxamine in Thalassemia

    OpenAIRE

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

    2012-01-01

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

  20. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-11-01

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

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

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

    2014-10-01

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

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

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    Saliba AN

    2015-06-01

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

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

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    Delangle, Pascale; Mintz, Elisabeth

    2012-06-01

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

  5. 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.

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

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    Kontoghiorghe, Christina N; Kontoghiorghes, George J

    2016-03-26

    Iron is essential for all organisms including microbial, cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overload. Iron also plays an important role in free radical pathology and oxidative damage which is observed in almost all major diseases, cancer and ageing. New developments include the complete treatment of iron overload and reduction of morbidity and mortality in thalassaemia using deferiprone and selected deferiprone/deferoxamine combinations and also the use of the maltol iron complex in the treatment of iron deficiency anaemia. There is also a prospect of using deferiprone as a universal antioxidant in non iron overloaded diseases such as neurodegenerative, cardiovascular, renal, infectious diseases and cancer. New regulatory molecules of iron metabolism such as endogenous and dietary chelating molecules, hepcidin, mitochondrial ferritin and their role in health and disease is under evaluation. Similarly, new mechanisms of iron deposition, removal, distribution and toxicity have been identified using new techniques such as magnetic resonance imaging increasing our understanding of iron metabolic processes and the targeted treatment of related diseases. The uniform distribution of iron in iron overload between organs and within each organ is no longer valid. Several other controversies such as the toxicity impact of non transferrin bound iron vs injected iron, the excess levels of iron in tissues causing toxicity and the role of chelation on iron absorption need further investigation. Commercial interests of pharmaceutical companies and connections to leading journals are playing a crucial role in shaping worldwide medical opinion on drug sales and use but also patients' therapeutic outcome and safety. Major controversies include the selection criteria and risk/benefit assessment in the use of deferasirox in thalassaemia and more so in idiopathic

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

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    Amira A.M. Adly

    2014-10-01

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

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

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Adriana Ceci

    2011-01-01

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

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

    Science.gov (United States)

    McKay, Charles A

    2013-12-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

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

    Science.gov (United States)

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

    2014-08-01

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

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

    Science.gov (United States)

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

    1986-02-01

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

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

    Science.gov (United States)

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

    2013-10-01

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

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

    OpenAIRE

    2009-01-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-11-01

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

  19. Oral iron chelators.

    Science.gov (United States)

    Kwiatkowski, Janet L

    2010-02-01

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

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

    Science.gov (United States)

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

    2001-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

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

    Science.gov (United States)

    Kontoghiorghes, George J

    2009-01-01

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

  4. 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

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

    Science.gov (United States)

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

    2014-04-21

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

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

    Directory of Open Access Journals (Sweden)

    Marcus W. Brazier

    2014-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Maria Concetta Renda

    2014-09-01

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

  8. 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.

  9. Beliefs about chelation among thalassemia patients

    Directory of Open Access Journals (Sweden)

    Trachtenberg Felicia L

    2012-12-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Elena Maria Elli

    2014-05-01

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

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

    Science.gov (United States)

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

    2007-05-01

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

  13. Performance of standard media in toxicological assessments with Daphnia magna: chelators and ionic composition versus metal toxicity.

    Science.gov (United States)

    Loureiro, Cláudia; Castro, Bruno B; Pereira, Joana Luísa; Gonçalves, Fernando

    2011-01-01

    Fully artificial test media can increase reproducibility and standardization in ecotoxicological assessments, but there is still a lack of convergence among ecotoxicology laboratories in aquatic test media with respect to ionic composition, chelators, and organic supplements. We compared the performance of Daphnia magna in three widely-used reconstituted media. The tested media differed in composition: (a) ADaM, an artificial medium based in a synthetic sea salt, with no a priori known chelating properties; (b) ASTM hard water supplemented with algal extract, a semi-artificial medium with unknown chelating properties; and (c) M7, a complex artificial medium containing EDTA as a chelator. All three media were suitable for rearing D. magna (although performance in M7 was suboptimal) and acute EC(50) values for reference substances (3,4-DCA, K(2)Cr(2)O(7)) were similar between media. In acute exposures to Cu and Cd, daphniids were least sensitive when reared in M7, as expected due to metal chelation by EDTA. Daphnia sensitivity to Cd was low in ADaM. Thus, these two media were suboptimal for assessing the toxicity of some metals to D. magna in acute tests. We suggest that both the ionic composition of the medium and the presence of chelators should be taken into account when metal toxicity is concerned. Chronic toxicity profiles for Cu suggested a mild chelating effect of the algal extract in ASTM medium. Still, ASTM hard water persists as one of the most suitable media for acute toxicity assessments of metals and metal-contaminated samples.

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

    Science.gov (United States)

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

    1994-04-01

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

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

    Science.gov (United States)

    Šömen Joksić, Agnes; Katz, Sidney A

    2015-01-01

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

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

    Science.gov (United States)

    Chakravarty, Rubel; Chakraborty, Sudipta; Dash, Ashutosh

    2014-02-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Harpreet Kochhar

    2015-01-01

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

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

    Science.gov (United States)

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

    2011-04-01

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

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

    Science.gov (United States)

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

    2002-03-01

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

  2. 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.

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

    Science.gov (United States)

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

    2015-11-18

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

  4. Music therapy assessment

    DEFF Research Database (Denmark)

    Wigram, Tony

    2007-01-01

    Når klienter henvises til musikterapi, gennemgår de en assessment-procedure (en klinisk vurdering), som kræver terapeutens ekspertise inden for forskellige områder - med henblik på at stille en en diagnose og identificere klientens behov og potentialer, samt at opstille realistiske forventninger ...

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

    Science.gov (United States)

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

    2015-12-01

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

  6. Spiritual Assessments in Occupational Therapy

    Directory of Open Access Journals (Sweden)

    Barbara Hemphill

    2015-07-01

    Full Text Available Spirituality is recognized as an important concept in the study and practice of medicine, including occupational therapy. This aligns with occupational therapy’s core value of treating people holistically—mind, body, and spirit. Currently, the Joint Commission for the Accreditation of Hospital Organizations ( JCAHO requires that a spiritual assessment be given to patients on admission. To conduct effective spiritual assessments, occupational therapists must distinguish between religion and spirituality. They also must be aware of their own spiritual beliefs and practices and how those might influence their clinical interactions. This article presents spiritual assessment tools that occupational therapists can use in clinical practice; they range from history taking, to questionnaires, to observation scales. Guidelines are presented for selecting among several spiritual assessments. A case study is presented in which a patient’s faith tradition is being challenged, which could affect the outcome of therapy. Finally, treatment and intervention planning and ethical considerations are discussed.

  7. Electroconvulsive Therapy: A Comprehensive Assessment

    Directory of Open Access Journals (Sweden)

    Tayfun Zeren

    2003-08-01

    Full Text Available Electroconvulsive therapy (ECT is one of the most important discoveries of psychiatric treatments. This article comprehensively assesses historical progress, mechanism of actions, practical methods, indications, side effects, complications, drug interactions of ECT and attitudes towards ECT. [Archives Medical Review Journal 2003; 12(4.000: 340-377

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

    Directory of Open Access Journals (Sweden)

    Taher AT

    2016-12-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yasuo Miura

    2010-01-01

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

  11. Molecular Docking Assessment of Efficacy of Different Clinically Used Arsenic Chelator Drugs

    Directory of Open Access Journals (Sweden)

    Durjoy Majumder

    2013-01-01

    Full Text Available Arsenic contamination of ground water has become a global problem affecting specially, south-east Asian countries like Bangladesh and eastern parts of India. It also affects South America and some parts of the US. Different organs of the physiological system are affected due to contamination of inorganic arsenic in water. Animal studies with different chelators are not very conclusive as far as the multi/differential organ effect(s of arsenic is concerned. Our docking study establishes the molecular rationale of blood test for early detection of arsenic toxicity; as arsenic has a high affinity to albumin, a plasma protein and actin, a structural protein of all cells including Red Blood Cells. This study also shows that there is a little possibility of male reproductive organs toxicity by different forms of inorganic arsenic; however, female reproductive system is very much susceptible to sodium-arsenite. Through comparative analysis regarding the chelating effectiveness among the available arsenic chelator drugs, meso-2,3 dimercaptosuccinic acid (DMSA and in some cases lipoic acid is the most preferred choice of drug for removing of arsenic deposits. This computational method actually reinforces the clinical finding regarding DMSA as the most preferred drug in removal of arsenic deposits from majority of the human tissues.

  12. Colour and stability assessment of blue ferric anthocyanin chelates in liquid pectin-stabilised model systems.

    Science.gov (United States)

    Buchweitz, M; Brauch, J; Carle, R; Kammerer, D R

    2013-06-01

    The formation of blue coloured ferric anthocyanin chelates and their colour stability during storage and thermal treatment were monitored in a pH range relevant to food (3.6-5.0). Liquid model systems were composed of different types of Citrus pectins, juices (J) and the respective phenolic extracts (E) from elderberry (EB), black currant (BC), red cabbage (RC) and purple carrot (PC) in the presence of ferric ions. For EB, BC and PC, pure blue colours devoid of a violet tint were exclusively observed for the phenolic extracts and at pH values ≥ 4.5 in model systems containing high methoxylated and amidated pectins, respectively. Colour and its stability strongly depended on the amount of ferric ions and the plant source; however, colour decay could generally be described as a pseudo-first-order kinetics. Despite optimal colour hues for RC-E and RC-J, storage and heat stabilities were poor. Highest colour intensities and best stabilities were observed for model systems containing PC-E at a molar anthocyanin:ferric ion ratio of 1:2. Ascorbic and lactic acids interfered with ferric ions, thus significantly affecting blue colour evolution and stability. Colour loss strongly depended on heat exposure with activation energies ranging between 60.5 and 78.4 kJ/mol. The comprehensive evaluation of the interrelationship of pigment source, pH conditions and pectin type on chelate formation and stability demonstrated that ferric anthocyanin chelates are promising natural blue food colourants.

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

    Science.gov (United States)

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

    2016-03-01

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

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

    Science.gov (United States)

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

    1983-05-01

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

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

    Science.gov (United States)

    Rose, Frisco; Hodak, Miroslav; Bernholc, Jerry

    2011-03-01

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

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

    Science.gov (United States)

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

    2014-11-01

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

  17. Bioavailability assessment of metals chelated as proteinates using the Ussing Chamber Model

    Directory of Open Access Journals (Sweden)

    G. Piva

    2011-03-01

    Full Text Available Preparation of proteinates by hydrolysis of organic matter produces a blend of different proteins, and may likely result in the chelation of trace elements. Often this process results in an increased bioavailability of minerals, leading to a higher absorption rate than inorganic salts (Cao et al., 2000; Uchida et al., 2001; Bailey et al., 2001; Guo et al., 2001. Usually trace elements uptake takes place along the small intestine, mainly jejunum (Tapia et al., 1996; Arredondo et al., 2000, even if the precise mechanisms underlying transport are not well understood. If these complexes are formed among metals and amino acids, they could be easily transported across the intestinal membrane by amino acids carriers..............

  18. [Risk assessment in pain therapy].

    Science.gov (United States)

    Schoeffel, D; Casser, H R; Bach, M; Kress, H G; Likar, R; Locher, H; Steinleitner, W; Strohmeier, M; Brunner, H; Treede, R D; Zieglgänsberger, W; Sandkühler, J

    2008-10-01

    Analgesic therapy is not without risk. However, the risk of most analgesic interventions is minor compared to the risk of the inadequate treatment of pain and insufficient treatment may lead to chronic pain.A correct diagnosis should be the basis of any specific treatment of pain disorders. Only a diagnosis which implicates a multi-disciplinary assessment and which considers both the pathoanatomical, functional and biopsychosocial dysfunctions can lead to an adequate therapeutic intervention. Furthermore, therapeutic planning should include the personal needs of the patient and should have realistic aims.Pharmacological treatment is guided by the WHO pain ladder. The risks of the relevant substance groups must be considered. NSAIDs (non-steroidal anti-inflammatory drugs) which are included in all steps of the WHO pain ladder carry specific risks for the gastrointestinal, cardiovascular and renal systems and are contraindicated in many patients in need of analgesic therapy, e.g. in many elderly patients. Opioids which are recommended at steps 2 and 3 of the WHO pain ladder have less organ toxicity but they are still used reluctantly. Coanalgetics, especially antidepressants bear specific risks and the discussion on suicide rates under antidepressant medication is ongoing.Invasive methods such as the intrathecal application of analgesics are valuable procedures if the indication is correct and the treating physician has sufficient experience. Pain therapy is essential and the risks of the procedures are manageable. Considering the current knowledge on the mechanisms of pain sensitisation, the lack of adequate pain control can lead to chronic pain with severe consequences for the patient.

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

    Directory of Open Access Journals (Sweden)

    Kontoghiorghe CN

    2016-01-01

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

  20. 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...

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

    Directory of Open Access Journals (Sweden)

    Banu Kaya

    2014-12-01

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

  2. Material interaction in art therapy assessment

    NARCIS (Netherlands)

    Penzes-Driessen, I.J.N.J.; Hooren, S. van; Dokter, D.; Smeijsters, H.; Hutschemaekers, G.J.M.

    2014-01-01

    Diverse approaches to art therapy assessment agree that art materials should play a central role. However, relatively little research is done on the role of different art materials. This article describes the results of a qualitative study on the use of art materials by art therapists in art therapy

  3. Assessment and therapy of vitiligo

    NARCIS (Netherlands)

    Komen, L.

    2016-01-01

    Vitiligo is a common skin disorder causing depigmented macules that can alter a patient's appearance and impair a patient's quality of life. This thesis contains studies on different methods of assessment of vitiligo and their quality as well as studies assessing repigmentation and depigmentation th

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

    Directory of Open Access Journals (Sweden)

    Jasmine L Hamilton

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

  5. Complexation of labile aluminium species by chelating resins Iontosorb--a new method for Al environmental risk assessment.

    Science.gov (United States)

    Matús, Peter; Kubová, Jana

    2005-09-01

    The utilization of chelating ion-exchange by the method based on binding strength and kinetic discrimination for aluminium fractionation was studied. Two chelating cellulose resins, Iontosorb Oxin (IO) and Iontosorb Salicyl (IS), were used for the determination of quickly reacting labile aluminium species. The possibilities of aluminium fractionation on these chelating resins were investigated by a solid phase extraction technique. The study of the pH (2.5-6.0) influence on the Al complexation by both resins indicates that at low pH the IS has lower sorption capacity but better adsorptive kinetic properties than IO. The optimal resin complexation time for reactive Al species was experimentally found after aluminium sorption study at pH 4.0 in synthetic solutions containing some inorganic and organic ligands, which simulate the composition of analysed acid soil and water samples. The negative influence of sulphate and iron on the Al complexation by IS resin was found and investigated. The flame atomic absorption spectrometry was used for the aluminium quantification.

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

    Science.gov (United States)

    Smith, Donald; Strupp, Barbara J

    2013-12-01

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

  7. Iron Chelation and Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Kelsey J. Weigel

    2014-01-01

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

  8. 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

  9. Assessing the Impact of EDTA Chelating Effect on some Macro- and Microminerals in Prussian Carp (Carassius Gibelio Tissues

    Directory of Open Access Journals (Sweden)

    Marioara Nicula

    2011-10-01

    Full Text Available Chelators are used in chemical analysis, in medical aplications, as water softeners, as decontamination agents on radioactive surfaces and they are ingredients in many commercial products such as shampoos and food preservatives. Such a synthetic chelator is EDTA (ethylenediaminetetraacetic acid. It is considered one of the tools that promises to control the heavy metal pollution in aquaculture. EDTA attaches itself to heavy metals and carries the metals from the fish body. EDTA can also slow free-radical activity produced by heavy metals in the body. Because its ability to sequester metal ions, we tried to estimate the potential risks of a chronic exposure to EDTA on tissue mobilization of some metals which have an essential role in realization of different cell functions in Prussian carp specimens. Ca, Mg, Fe, Zn. Mn and Cu, were the mineral elements we have targeted in this study. It was found that these minerals have a trend of their tissues distribution and concentration in the body of the control specimens (higher or lower related to other similar works and EDTA presence in water led to a significant decreasing of their level in all tissues analyzed in a dose-dependent manner.

  10. Assessments in outcome evaluation in aphasia therapy

    DEFF Research Database (Denmark)

    Isaksen, Jytte; Brouwer, Catherine E.

    2015-01-01

    Abstract Outcomes of aphasia therapy in Denmark are documented in evaluation sessions in which both the person with aphasia and the speech-language therapist take part. The participants negotiate agreements on the results of therapy. By means of conversation analysis, we study how such agreements...... on therapy outcome are reached interactionally. The sequential analysis of 34 video recordings focuses on a recurrent method for reaching agreements in these outcome evaluation sessions. In and through a special sequence of conversational assessment it is claimed that the person with aphasia has certain...... communicative skills. Such claims are systematically substantiated by invoking examples of the person with aphasia performing this skill either outside or inside the therapeutic setting. Substantiation can be seen as a form of validation of the claim and thereby a basis is set for agreement. The findings...

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

    Science.gov (United States)

    Kwiatkowski, Janet L

    2016-03-01

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

  12. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  14. The Chelate Effect Redefined.

    Science.gov (United States)

    da Silva, J. J. R. Frausto

    1983-01-01

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

  15. Preparation and assessment cytotoxic and hemolytic activities of Complexes from “Chelating Kojic–Lipid Conjugate”

    Directory of Open Access Journals (Sweden)

    Antônio S. C. Carvalho

    2012-06-01

    Full Text Available Complex bis (2-Oleicoyloxymethyl-5-hydroxy-gamma-pyrone copper (II and tris (2-Oleicoyloxymethyl-5-hydroxy-gamma-pyrone iron (III were prepared in ethanol using the structure "chelator conjugate kojic -lipid". This ester was obtained from kojic acid by improving their lipophilicity of obtaining metalobioactives with application in Medicinal Bioinorganic Chemistry. Through the technique ATR/FTIR, the values ​​of the infrared kojic acid has been updated and it was possible to characterize      the complex 1567m, 1511w (Cu (II←[O=C]2, and 1540m, 1519m (Fe(III←[O=C]3. These compounds no showed cytotoxic potential against B16 (melanoma and ACP02 (gastric adenocarcinoma (IC50> 5 μg mL-1 and low hemolytic activity (EC50> 250 μg mL-1.The preparation of these new molecules by structural modification techniques and these interesting biological results confirm the continuity of this studies related to these coordination complexes to glimpse the possibility of obtaining other derivatives/ analogues with significant biological potential of this metallo-bioactive.

  16. 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

  17. Assessing parents' attitudes towards ketogenic dietary therapies.

    Science.gov (United States)

    Schoeler, Natasha E; MacDonald, Lindsay; Champion, Helena; Cross, J Helen; Sander, Josemir W; Sisodiya, Sanjay M; Horne, Rob

    2014-10-01

    We aimed to assess and quantify parental beliefs regarding ketogenic dietary therapies (KDTs). We also aimed to determine whether beliefs were related to response to KDTs. Adapted versions of the Beliefs about Medicine Questionnaire were completed by parents of children following KDTs for epilepsy. Demographic and clinical data were collected from hospital records. Ketogenic dietary therapy response was defined as ≥50% seizure reduction compared to baseline. Many parents had a positive perception of KDTs and were convinced of the necessity of KDTs for their children, although beliefs were wide-ranging. Over half of parents reported concerns about the potential long-term effects of KDTs. Parental beliefs about KDTs were significantly correlated with patient response. This was an attempt to quantify parents' beliefs regarding the use of KDTs for their child's epilepsy. The questionnaire may be used to identify individuals with a less positive attitude towards KDTs and who may be less likely to report a favorable response to KDTs. It is unknown whether people who have positive beliefs about KDTs engage in less nonadherent behavior or whether beliefs regarding KDTs simply reflect outcomes. The evidence behind the long-term side effects of KDTs should be emphasized when counseling patients and their families.

  18. Chelating polymeric membranes

    KAUST Repository

    Peinemann, Klaus-Viktor

    2015-01-22

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

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

    Science.gov (United States)

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

    1983-08-25

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

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

    Science.gov (United States)

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

    2004-06-01

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

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

    Science.gov (United States)

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

    2016-06-15

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

  2. 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

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

    Directory of Open Access Journals (Sweden)

    Vikram Bhardwaj

    2016-01-01

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

  4. Assessment of antioxidative, chelating, and DNA-protective effects of selected essential oil components (eugenol, carvacrol, thymol, borneol, eucalyptol) of plants and intact Rosmarinus officinalis oil.

    Science.gov (United States)

    Horvathova, Eva; Navarova, Jana; Galova, Eliska; Sevcovicova, Andrea; Chodakova, Lenka; Snahnicanova, Zuzana; Melusova, Martina; Kozics, Katarina; Slamenova, Darina

    2014-07-16

    Selected components of plant essential oils and intact Rosmarinus officinalis oil (RO) were investigated for their antioxidant, iron-chelating, and DNA-protective effects. Antioxidant activities were assessed using four different techniques. DNA-protective effects on human hepatoma HepG2 cells and plasmid DNA were evaluated with the help of the comet assay and the DNA topology test, respectively. It was observed that whereas eugenol, carvacrol, and thymol showed high antioxidative effectiveness in all assays used, RO manifested only antiradical effect and borneol and eucalyptol did not express antioxidant activity at all. DNA-protective ability against hydrogen peroxide (H2O2)-induced DNA lesions was manifested by two antioxidants (carvacrol and thymol) and two compounds that do not show antioxidant effects (RO and borneol). Borneol was able to preserve not only DNA of HepG2 cells but also plasmid DNA against Fe(2+)-induced damage. This paper evaluates the results in the light of experiences of other scientists.

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

    Science.gov (United States)

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

    2016-01-01

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

  6. Scatter factors assessment in microbeam radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Prezado, Y.; Martinez-Rovira, I.; Sanchez, M. [Laboratoire Imagerie et Modelisation en Neurobiologie et Cancerologie IMNC-UMR 8165, Centre National de la Recherche Scientifique (CNRS), Campus Universitaire, Bat. 440, 15 rue Georges Clemenceau, 91406 Orsay Cedex (France); Institut de Tecniques Energetiques, Universitat Politecnica de Catalunya, Diagonal 647, E-08028 Barcelona (Spain) and ID17 Biomedical Beamline, European Synchrotron Radiation Facility (ESRF), 6 Rue Jules Horowitz, B.P. 220, 38043 Grenoble Cedex (France); Servicio de Radiofisica, Complejo Hospitalario de Santiago de Compostela, Rua Choupana S/N, 15706 Santiago de Compostela (Spain)

    2012-03-15

    Purpose: The success of the preclinical studies in Microbeam Radiation Therapy (MRT) paved the way to the clinical trials under preparation at the Biomedical Beamline of the European Synchrotron Radiation Facility. Within this framework, an accurate determination of the deposited dose is crucial. With that aim, the scatter factors, which translate the absolute dose measured in reference conditions (2 x 2 cm{sup 2} field size at 2 cm-depth in water) to peak doses, were assessed. Methods: Monte Carlo (MC) simulations were performed with two different widely used codes, PENELOPE and GEANT4, for the sake of safety. The scatter factors were obtained as the ratio of the doses that are deposited by a microbeam and by a field of reference size, at the reference depth. The calculated values were compared with the experimental data obtained by radiochromic (ISP HD-810) films and a PTW 34070 large area chamber. Results: The scatter factors for different microbeam field sizes assessed by the two MC codes were in agreement and reproduced the experimental data within uncertainty bars. Those correction factors were shown to be non-negligible for the future MRT clinical settings: an average 30% lower dose was deposited by a 50 {mu}m microbeam with respect to the reference conditions. Conclusions: For the first time, the scatter factors in MRT were systematically studied. They constitute an essential key to deposit accurate doses in the forthcoming clinical trials in MRT. The good agreement between the different calculations and the experimental data confirms the reliability of this challenging micrometric dose estimation.

  7. Iron chelating agents for iron overload diseases

    Directory of Open Access Journals (Sweden)

    Guido Crisponi

    2014-09-01

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

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

    Science.gov (United States)

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

    2005-09-25

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

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

    Directory of Open Access Journals (Sweden)

    Berdoussi Eleni

    2009-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-03-21

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

  11. The music therapy assessment tool in Alzheimer's patients.

    Science.gov (United States)

    Glynn, N J

    1992-01-01

    1. Empirical research is needed to evaluate immediate and sustained physiological, psychological, and psychosocial therapeutic effects, if any, of music therapy on behavioral patterns of elderly institutionalized Alzheimer's patients. 2. The Music Therapy Assessment Tool (MTAT) was specifically designed and developed to assess the effects of music therapy on behavioral patterns of Alzheimer's disease patients. 3. Preliminary testing of the MTAT suggests that it has fairly high internal consistency and inter-rater reliability and warrants consideration as a research tool. 4. Musical intervention included familiar music to facilitate communication and socialization, ethnic and nostalgic music to stimulate reminiscence, and melodies with distinctive rhythmic patterns to enhance movement and behavioral repatterning.

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

    OpenAIRE

    I. Portioli

    2013-01-01

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

  13. 78 FR 70307 - Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy...

    Science.gov (United States)

    2013-11-25

    ... Investigational Cellular and Gene Therapy Products; Availability AGENCY: Food and Drug Administration, HHS. ACTION... entitled ``Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy... and Gene Therapies (OCTGT). The product areas covered by this guidance are cellular therapy,...

  14. Chelated minerals for poultry

    Directory of Open Access Journals (Sweden)

    SL Vieira

    2008-06-01

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

  15. Using iron chelating agents to enhance dermatological PDT

    Science.gov (United States)

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

    2009-06-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  17. A customisable framework for the assessment of therapies in the solution of therapy decision tasks.

    Science.gov (United States)

    Manjarrés Riesco, A; Martínez Tomás, R; Mira Mira, J

    2000-01-01

    In current medical research, a growing interest can be observed in the definition of a global therapy-evaluation framework which integrates considerations such as patients preferences and quality-of-life results. In this article, we propose the use of the research results in this domain as a source of knowledge in the design of support systems for therapy decision analysis, in particular with a view to application in oncology. We discuss the incorporation of these considerations in the definition of the therapy-assessment methods involved in the solution of a generic therapy decision task, described in the context of AI software development methodologies such as CommonKADS. The goal of the therapy decision task is to identify the ideal therapy, for a given patient, in accordance with a set of objectives of a diverse nature. The assessment methods applied are based either on data obtained from statistics or on the specific idiosyncrasies of each patient, as identified from their responses to a suite of psychological tests. In the analysis of the therapy decision task we emphasise the importance, from a methodological perspective, of using a rigorous approach to the modelling of domain ontologies and domain-specific data. To this aim we make extensive use of the semi-formal object oriented analysis notation UML to describe the domain level.

  18. Macroreticular chelating ion-exchangers.

    Science.gov (United States)

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

    1970-06-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  20. The Music Therapy assessment tool for Advanced Huntington's Disease

    DEFF Research Database (Denmark)

    O'Kelly, Julian; Bodak, R.

    2013-01-01

    in respiration rate with decreases in respiration variability. Similar findings within EEG data for controls and both VS and MCS cohorts, combined with significant findings for behavioral measures across the VS cohort, indicate music therapy is able to increase arousal levels for DOC patients, optimising...... is limited, is a challenging process. With awareness often masked by perceptual or motor impairments, misdiagnosis rates remain high. Music therapy assessment holds the potential to elicit responses despite damage to verbal or visual processing faculties, although robust empirical studies are lacking...... the conditions for accurate assessment. Research is indicated to explore both the use of bio-markers of awareness and longer term effects upon neuroplasticity in response to music therapy within this population....

  1. Iron chelation therapy in thalassemia major: a systematic review with meta-analyses of 1520 patients included on randomized clinical trials

    DEFF Research Database (Denmark)

    Maggio, Aurelio; Filosa, Aldo; Vitrano, Angela

    2011-01-01

    The effectiveness of deferoxamine (DFO), deferiprone (DFP), or deferasirox (DFX) in thalassemia major was assessed. Outcomes were reported as means±SD, mean differences with 95% CI, or standardized mean differences. Statistical heterogeneity was tested using χ2 (Q) and I2. Sources of bias...

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

    Science.gov (United States)

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

    2015-10-01

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

  3. Research into the Development of Voice Assessment in Music Therapy

    DEFF Research Database (Denmark)

    Storm, Sanne

    This study was a research into the development of a voice assessment profile (VOIAS). Already a preliminary literature search showed that no such profile within music therapy existed, and only very sparse research within music therapy focusing on and involving the human voice. The development...... of VOIAS is based on vocal parameters extracted from the literature review and my clinical approach “Psychodynamic Voice Therapy”. The parameters’ relevance is based on clinical practice and the focus of population in this study, clients suffering from depression....

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-07-01

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

  9. Ab initio coordination chemistry for nickel chelation motifs.

    Science.gov (United States)

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

    2015-01-01

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

  10. Ab initio coordination chemistry for nickel chelation motifs.

    Directory of Open Access Journals (Sweden)

    R Jesu Jaya Sudan

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

  11. HElmet therapy Assessment in infants with Deformed Skulls (HEADS): protocol for a randomised controlled trial

    NARCIS (Netherlands)

    Wijk, R.M. van; Boere-Boonekamp, M.M.; Groothuis-Oudshoorn, C.G.; Vlimmeren, L.A. van; MJ, I.J.

    2012-01-01

    BACKGROUND: In The Netherlands, helmet therapy is a commonly used treatment in infants with skull deformation (deformational plagiocephaly or deformational brachycephaly). However, evidence of the effectiveness of this treatment remains lacking. The HEADS study (HElmet therapy Assessment in Deformed

  12. HElmet therapy Assessment in infants with Deformed Skulls (HEADS): protocol for a randomised controlled trial

    NARCIS (Netherlands)

    Wijk, van R.M.; Boonekamp, M.M.; Groothuis-Oudshoorn, C.G.M.; Vlimmeren, van L.A.; IJzerman, M.J.

    2012-01-01

    Background In The Netherlands, helmet therapy is a commonly used treatment in infants with skull deformation (deformational plagiocephaly or deformational brachycephaly). However, evidence of the effectiveness of this treatment remains lacking. The HEADS study (HElmet therapy Assessment in Deformed

  13. 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.

  14. Objective assessment of image quality VI: imaging in radiation therapy

    Science.gov (United States)

    Barrett, Harrison H.; Kupinski, Matthew A.; Müeller, Stefan; Halpern, Howard J.; Morris, John C., III; Dwyer, Roisin

    2013-11-01

    Earlier work on objective assessment of image quality (OAIQ) focused largely on estimation or classification tasks in which the desired outcome of imaging is accurate diagnosis. This paper develops a general framework for assessing imaging quality on the basis of therapeutic outcomes rather than diagnostic performance. By analogy to receiver operating characteristic (ROC) curves and their variants as used in diagnostic OAIQ, the method proposed here utilizes the therapy operating characteristic or TOC curves, which are plots of the probability of tumor control versus the probability of normal-tissue complications as the overall dose level of a radiotherapy treatment is varied. The proposed figure of merit is the area under the TOC curve, denoted AUTOC. This paper reviews an earlier exposition of the theory of TOC and AUTOC, which was specific to the assessment of image-segmentation algorithms, and extends it to other applications of imaging in external-beam radiation treatment as well as in treatment with internal radioactive sources. For each application, a methodology for computing the TOC is presented. A key difference between ROC and TOC is that the latter can be defined for a single patient rather than a population of patients.

  15. Physical Therapy Observation and Assessment in the Neonatal Intensive Care Unit

    Science.gov (United States)

    Byrne, Eilish; Campbell, Suzann K.

    2013-01-01

    This article presents the elements of the Observation and Assessment section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy assessments presented in this path are evidence-based and the suggested timing of these assessments is primarily based on practice knowledge from expert…

  16. Assessment of the effects of massage therapy on premenstrual syndrome

    Directory of Open Access Journals (Sweden)

    Leily Ghaedi

    2011-05-01

    Full Text Available Background: Premenstrual syndrome is characterized by the cyclic occurrence physical, psychological and behavioral symptoms during the luteal phase of the menstruation cycle and will be disappear within a few days of the onset of menstruation. The aim of this research was to assess the effect of massage therapy on premenstrual syndrome. Materials and Method: A randomized clinical trial was carried out on 30 volunteer students of Tehran University with PMS diagnosis. After surveying two menstruation cycles and confirming PMS existence, subjects were randomly assigned into massage and control group. Massage protocol was performed for eight weeks. Volunteers completed Daily Symptom Rating (DSR during 2 cycles before and 2 cycles after intervention. Data collected via data gathering form, criteria for PMS (DSM- IV, DSR and Beck test. Data were analyzed by descriptive and analytic statistics (χ2, Fischer's exact test, paired and independent t tests.Results: In comparison between before and after intervention, massage group showed significant decrease averagely in mean of somatic (56.7%, psychological (64.8% (p<0.001.This is while, in control group only mean of somatic symptoms (averagely 21.2% relieved obviously (p=0.02. comparing two groups often intervention, we did not found any significant difference in mean of somatic symptoms while psychological (p=0.01 and total symptoms (p=0.03 in massage group was significantly less than controls.Conclusion: The authors concluded that massage therapy is an effective method for relieving symptoms of premenstrual syndrome

  17. Neurodegenerative diseases and therapeutic strategies using iron chelators.

    Science.gov (United States)

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

    2015-01-01

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

  18. Luminescent lanthanide chelates and methods of use

    Science.gov (United States)

    Selvin, Paul R.; Hearst, John

    1997-01-01

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

  19. Chelators for investigating zinc metalloneurochemistry.

    Science.gov (United States)

    Radford, Robert J; Lippard, Stephen J

    2013-04-01

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

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

    Science.gov (United States)

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

    2012-03-01

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

  1. 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.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2006-10-09

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

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

    Science.gov (United States)

    Saljooghi, Amir Shokooh

    2012-09-01

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

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

    OpenAIRE

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kwiatkowski JL

    2011-09-01

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

  7. Assessing Competencies in Couples and Family Therapy/Counseling: A Call to the Profession

    Science.gov (United States)

    Perosa, Linda M.; Perosa, Sandra L.

    2010-01-01

    Psychometrically sound measures of family therapy competencies are necessary to assess the effectiveness of training on student performance. This article critiques the self-report and observer rating measures developed to date to assess the clinical skills of trainees in the individual and in the family therapy fields. Suggestions are made to…

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

    Institute of Scientific and Technical Information of China (English)

    赵国阳; 徐又佳

    2015-01-01

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

  9. Role of chelates in treatment of cancer

    Directory of Open Access Journals (Sweden)

    Tripathi Laxmi

    2007-01-01

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

  10. Tumor targeting of radiolabeled antibodies using HYNIC chelate

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-07-01

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

  11. 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.

  12. Non-Viral Ocular Gene Therapy: Assessment and Future Directions

    OpenAIRE

    2008-01-01

    The purpose of this review is to give the general reader a brief overview of the current state of the field of non-viral ocular gene therapy. For multiple reasons the eye is an excellent organ for gene therapy application and while non-viral gene therapy modalities have been around for quite some time; they have only been applied to the eye in the last few years. This review will cover the exciting current trends in non-viral gene therapy and their application to the eye in addition to a brie...

  13. Iron chelator daphnetin against Pneumocystis carinii in vitro

    Institute of Scientific and Technical Information of China (English)

    叶彬; 郑玉强; 武卫华; 张静

    2004-01-01

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

  14. Assessment of the Evolution of Cancer Treatment Therapies

    Directory of Open Access Journals (Sweden)

    Mónica Valladares

    2011-08-01

    Full Text Available Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.. In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine. We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present.

  15. Assessment of the Evolution of Cancer Treatment Therapies

    Energy Technology Data Exchange (ETDEWEB)

    Arruebo, Manuel [Instituto de Nanociencia de Aragón (INA), Mariano Esquillor, Edif. I+D, University of Zaragoza, Zaragoza 50018 (Spain); CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza 50018 (Spain); Vilaboa, Nuria [CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza 50018 (Spain); Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, Madrid 28046 (Spain); Sáez-Gutierrez, Berta; Lambea, Julio; Tres, Alejandro [Instituto de Nanociencia de Aragón (INA), Mariano Esquillor, Edif. I+D, University of Zaragoza, Zaragoza 50018 (Spain); Servicio de Oncología Médica, Hospital Clínico Universitario Lozano Blesa, Avda. San Juan Bosco 50009, Zaragoza (Spain); Instituto Aragonés de Ciencias de la Salud (I-CS), Avda. Gómez Laguna, 25, Zaragoza 50009 (Spain); Valladares, Mónica [Lonza Biologics Porriño, A relva s/n, Porriño (Pontevedra) 36410 (Spain); González-Fernández, África, E-mail: africa@uvigo.es [Immunology Department, Biomedical Research Center (CINBIO), University of Vigo, Campus Lagoas Marcosende, Vigo (Pontevedra) 36310 (Spain)

    2011-08-12

    Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.). In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine). We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present.

  16. Material interaction and art product in art therapy assessment in adult mental health

    NARCIS (Netherlands)

    Penzé s, I.; Hooren, S. van; Dokter, D.; Smeijsters, H.; Hutschemaekers, G.J.M.

    2016-01-01

    Background: Art materials have a central role in art therapy. The way a client interacts with art materials - material interaction - is an important source of information in art therapy assessment in adult mental health. The aim of this study was to develop the categories of material interaction and

  17. HElmet therapy Assessment in infants with Deformed Skulls (HEADS): protocol for a randomised controlled trial

    NARCIS (Netherlands)

    Wijk, R.M. van; Boere-Boonekamp, M.M.; Groothuis-Oudshoorn, C.G. van; Vlimmeren, L.A. van; IJzerman, M.J.

    2012-01-01

    In The Netherlands helmet therapy is a commonly used treatment in infants with skull deformation (deformational plagiocephaly or deformational brachycephaly). However, evidence on the effectiveness of this treatment is lacking. The HEADS study (Helmet therapy Assessment in Deformed Skulls) aims to d

  18. Assessment and Therapeutic Application of the Expressive Therapies Continuum: Implications for Brain Structures and Functions

    Science.gov (United States)

    Lusebrink, Vija B.

    2010-01-01

    The Expressive Therapies Continuum (ETC) provides a theoretical model for art-based assessments and applications of media in art therapy. The three levels of the ETC (Kinesthetic/Sensory, Perceptual/Affective, and Cognitive/Symbolic) appear to reflect different functions and structures in the brain that process visual and affective information.…

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

    Institute of Scientific and Technical Information of China (English)

    李仙松; 杜娟; 李伟平

    2014-01-01

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

  20. [Multidisciplinary assessment for multimodal pain therapy. Indications and range of performance].

    Science.gov (United States)

    Casser, H-R; Arnold, B; Brinkschmidt, T; Gralow, I; Irnich, D; Klimczyk, K; Nagel, B; Pfingsten, M; Sabatowski R; Schiltenwolf, M; Sittl, R; Söllner, W

    2013-08-01

    According to evidence-based German national guidelines for non-specific low back pain, a broad multidisciplinary assessment is indicated after persisting pain experience of 6 weeks in order to check the indications for an multi- and interdisciplinary pain therapy program. In this paper the necessary topics, the content and the disciplines involved as well as the extent of the multidisciplinary assessment are described as developed by the ad hoc commission on multimodal pain therapy of the German Pain Society.

  1. Quantitative Assessment of Dance Therapy Infulence on the Parkinson’s Disease Patients’ Lower Limb Biomechanics

    Directory of Open Access Journals (Sweden)

    Donatas Lukšys

    2017-01-01

    Full Text Available Parkinson’s disease – progressive neurologic disorder that damages a variety of motor function and reduces the quality of life. Patients with PD are subject to various physical therapy exercises, but recently is applied more often the dance – music therapy. This study aims assessing the therapeutic effect of the modified Lindy Hop dance therapy on lower extremity biomechanics. The experimental study was performed using inertial sensors that registered lower extremity biomechanical parameters during gait. Several spatio-temporal parameters of lower limb were calculated and were found statistically significant between groups, which allows quantifying the influence of dance therapy.

  2. Dosage assessment for radioiodine therapy in benign thyroid disorders

    NARCIS (Netherlands)

    Isselt, J.W. van

    2001-01-01

    The general aim of this thesis was to investigate the value and the shortcomings of the becquerel-per-gram method for radioiodine therapy in various benign thyroid disorders. The history of this treatment form, which goes back to the late 1940s, is described in Chapter 1. Almost fifty years after th

  3. Individual risk assessment for intracranial haemorrhage during thrombolytic therapy

    NARCIS (Netherlands)

    M.L. Simoons (Maarten); A.P. Maggioni; G. Knatterud; J.D. Leimberger; P.P.T. de Jaegere (Peter); R.T. van Domburg (Ron); H. Boersma (Eric); M. Grazia Franzosi (M.); R.M. Califf (Robert); R. Schroder; E. Braunwald (Eugene)

    1993-01-01

    textabstractThrombolytic therapy improves outcome in patients with myocardial infarction but is associated with an increased risk of intracranial haemorrhage. For some patients, this risk may outweigh the potential benefits of thrombolytic treatment. Using data from other studies, we developed a mod

  4. After the Assessment: Introducing Adolescents to Cognitive-Behavioural Therapy

    Science.gov (United States)

    Cosgrave, Elizabeth; Keating, Vanessa

    2006-01-01

    The objective of this article is to describe the practical aspects involved in adapting cognitive-behavioural therapy (CBT) to an adolescent population in Australia. Some effective ways to use CBT with adolescents include preparing them for CBT by providing a thorough cognitive-behavioural formulation, describing the cognitive-behavioural approach…

  5. 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.

  6. Training needs assessment for clinicians at antiretroviral therapy clinics: evidence from a national survey in Uganda

    Directory of Open Access Journals (Sweden)

    Namagala Elizabeth

    2009-08-01

    Full Text Available Abstract Background To increase access to antiretroviral therapy in resource-limited settings, several experts recommend "task shifting" from doctors to clinical officers, nurses and midwives. This study sought to identify task shifting that has already occurred and assess the antiretroviral therapy training needs among clinicians to whom tasks have shifted. Methods The Infectious Diseases Institute, in collaboration with the Ugandan Ministry of Health, surveyed health professionals and heads of antiretroviral therapy clinics at a stratified random sample of 44 health facilities accredited to provide this therapy. A sample of 265 doctors, clinical officers, nurses and midwives reported on tasks they performed, previous human immunodeficiency virus training, and self-assessment of knowledge of human immunodeficiency virus and antiretroviral therapy. Heads of the antiretroviral therapy clinics reported on clinic characteristics. Results Thirty of 33 doctors (91%, 24 of 40 clinical officers (60%, 16 of 114 nurses (14% and 13 of 54 midwives (24% who worked in accredited antiretroviral therapy clinics reported that they prescribed this therapy (p Conclusion Training initiatives should be an integral part of the support for task shifting and ensure that antiretroviral therapy is used correctly and that toxicity or drug resistance do not reverse accomplishments to date.

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

    Science.gov (United States)

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

    2009-05-22

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

  8. Questions and Answers on Unapproved Chelation Products

    Science.gov (United States)

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

  9. Functional assessment in mental health: lessons from occupational therapy

    Science.gov (United States)

    Rogers, Joan C.; Holm, Margo B.

    2016-01-01

    Occupational therapists have been conducting functional assessments since World War I, and this accumulated experience has taught us several critical lessons. First, a comprehensive profile of a patient's functioning requires multiple assessment methods. Second, assessment content and measurement constructs must change with the times. Third, technology can enhance and extend functional assessment. Fourth, performance-based assessments of everyday activities can also be used to measure body functions/impairments. However, while deconstructing activities into body functions/impairments is possible, the results do not reflect patients' abilities to integrate the cognitive, motor, sensory and affective functions necessary to complete a complex activity. Finally, the differential complexity of everyday activities that a patient can master or successfully complete can also provide a ruler with which to measure progress. PMID:27489454

  10. Functional assessment in mental health: lessons from occupational therapy.

    Science.gov (United States)

    Rogers, Joan C; Holm, Margo B

    2016-06-01

    Occupational therapists have been conducting functional assessments since World War I, and this accumulated experience has taught us several critical lessons. First, a comprehensive profile of a patient's functioning requires multiple assessment methods. Second, assessment content and measurement constructs must change with the times. Third, technology can enhance and extend functional assessment. Fourth, performance-based assessments of everyday activities can also be used to measure body functions/impairments. However, while deconstructing activities into body functions/impairments is possible, the results do not reflect patients' abilities to integrate the cognitive, motor, sensory and affective functions necessary to complete a complex activity. Finally, the differential complexity of everyday activities that a patient can master or successfully complete can also provide a ruler with which to measure progress.

  11. SYNTHESIS AND APPLICATION OF IMINOCARBOXYLIC CHELATING FIBERS

    Institute of Scientific and Technical Information of China (English)

    LiHangqiu; ZhouShaoji

    1997-01-01

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

  12. Persistence on prostaglandin ocular hypotensive therapy: an assessment using medication possession and days covered on therapy

    Directory of Open Access Journals (Sweden)

    Schwartz Gail F

    2010-03-01

    Full Text Available Abstract Background Prior research has demonstrated that medication persistence (continued acquisition of therapy over time is far from optimal among patients with glaucoma. The purpose of the present study was to evaluate persistence with prostaglandin analogs among glaucoma patients in the first therapy year using a modification of a previously published technique. Methods This retrospective analysis of medical and pharmacy claims database included treatment-naive patients dispensed bimatoprost, latanoprost, or travoprost between 1/1/04-12/31/04. "Index agent" was defined as the first agent filled; "index date" was defined as the fill date. Follow-up continued for 358 days. Persistence measures for first therapy year were: (1 whether last fill had sufficient days supply to achieve medication possession at year's end, and (2 number of days for which the index agent was available (days covered. Associations between index agent and medication possession (logistic regression and days covered (linear regression were evaluated. Models were adjusted for gender, age, and previous ocular hypertension diagnosis. Results 7873 patients met inclusion criteria (bimatoprost, n = 1464; latanoprost, n = 4994; travoprost, n = 1415. Medication possession was 28% and days covered was 131 when using the unadjusted (pharmacy-reported days supply estimates and rose to 47-48% and days covered to 228-236 days when days supply was imputed. Compared to latanoprost, odds of achieving medication possession at first year's end were 26-34% lower for bimatoprost and 34-36% lower for travoprost (p ≤ 0.001 for all comparisons. Days covered in the first year were 21-29 days lower for bimatoprost and 33-42 days lower for travoprost (p ≤ 0.001 for all comparisons. Failure to refill the index agent within the initial 90 days was a strong predictor of poor persistence. Conclusions Persistence with ocular prostaglandin therapy remains a problem. Latanoprost users had greater

  13. A Review of the Principles for Culturally Appropriate Art Therapy Assessment Tools

    Science.gov (United States)

    Betts, Donna

    2013-01-01

    In an increasingly diverse society, and with the broadening scope of art therapy, the duty of art therapists to ensure responsible and appropriate assessment is ever more important. This article discusses considerations that are necessary for the successful adaptation and use of drawing-based assessments in cross-cultural and multicultural…

  14. In vivo assessment of antiretroviral therapy-associated side effects

    Directory of Open Access Journals (Sweden)

    Eduardo Milton Ramos-Sanchez

    2014-07-01

    Full Text Available Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs.

  15. 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

  16. Dyslipidemia therapy update: the importance of full lipid profile assessment.

    LENUS (Irish Health Repository)

    Menown, I B A

    2009-07-01

    Lipid guidelines typically focus on total cholesterol +\\/- low-density lipoprotein cholesterol levels with less emphasis on high-density lipoprotein cholesterol (HDL-C) or triglyceride assessment, thus potentially underestimating cardiovascular (CV) risk and the need for lifestyle or treatment optimization. In this article, we highlight how reliance on isolated total cholesterol assessment may miss prognostically relevant lipid abnormalities; we describe from the European Systematic COronary Risk Evaluation (SCORE) data set how incorporation of HDL-C may improve estimation of CV risk; and, finally, we critically evaluate the evidence base surrounding triglycerides and CV risk.

  17. A VALIDATION STUDY OF THE FACIAL-ORAL TRACT THERAPY SWALLOWING ASSESSMENT OF SALIVA

    DEFF Research Database (Denmark)

    Mortensen, Jesper; Jensen, Ditte; Kjærsgaard, Annette

    Introduction Facial-Oral Tract Therapy (F.O.T.T.) (1) is an approach that provides both clinical assessment and treatment of oropharyngeal dysphagia. In the F.O.T.T. approach, a prerequisite for the initiation of oral intake is safe swallowing of saliva. A recent randomized controlled trial (2......) showed that patients assessed for initiation of oral intake with an F.O.T.T. based clinical assessment, hereinafter referred to as the Swallowing Assessment of Saliva (SAS), were no more likely to develop aspiration pneumonia that patients who were assessed with an endoscopic evaluation. The objective...

  18. Intensive Stuttering Modification Therapy: A Multidimensional Assessment of Treatment Outcomes

    Science.gov (United States)

    Blomgren, Michael; Roy, Nelson; Callister, Thomas; Merrill, Ray M.

    2005-01-01

    Nineteen adults who stutter participated in a 3-week intensive stuttering modification treatment program (the Successful Stuttering Management Program [SSMP]). A series of 14 fluency and affective-based measures were assessed before treatment, immediately after treatment, and 6 months after treatment. Measures included stuttering frequency; the…

  19. Motor Response Deficits of Unilateral Neglect: Assessment, Therapy, and Neuroanatomy.

    Science.gov (United States)

    Saevarsson, Styrmir

    2013-04-16

    The clinical impact of the motor deficits of unilateral neglect is indisputable. The diagnosis criteria are confusing and complicated, and assessment has been extended and modified gradually during the last few decades, which has led to inconsistency and confusion. Many different attempts have been made to overcome various assessment shortcomings. In this article, different examinations of previous studies and analyses are discussed in a systematic and critical way. Research databases were used to identify 254 reports, including 26 different empirical studies on motor neglect and 44 studies on premotor neglect. Most of the studies address the gross neuroanatomical location of lesions. The main findings indicate that frontal lesions are more common in motor neglect than in premotor neglect, and parietal lesions are more common in premotor neglect than in motor neglect. Few studies have evaluated therapeutic programs for the motor deficits of neglect. Unfortunately, most studies suffer from various diagnostic problems that result in inconsistent and controversial findings. Different assessment issues need to be addressed systematically in future studies in light of current findings to increase our understanding and awareness of these important neuropsychological motor deficits. Implications of and possible solutions to the current assessment shortcomings are discussed.

  20. Music Therapy Assessment and Development of Parental Competences in Families Where Children Have Experienced Emotional Neglect

    DEFF Research Database (Denmark)

    Jacobsen, Stine Lindahl

    2012-01-01

    In trying to aid difficulties within social services of assessing families at risk, the thesis sat out to strengthen, further develop, and test a music therapy assessment tool, Assessment of Parenting Competencies (APC). The study also aimed to examine the effect of music therapy on parenting...... competencies and parent-child interaction measured by scores from APC and by the Parenting Stress Index and Parent-Child Relationship-Inventory. The study had a multiple strategy sequential design. The fixed design was a between and within groups design to test the APCs reliability and validity in a clinical...... group of 18 parents with neglected children and a nonclinical group of 34 parents with non-neglected children. The study also included an experimental design with a randomized controlled trial only applied to the clinical group. In the experimental design there were two conditions: a music therapy...

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

    Directory of Open Access Journals (Sweden)

    Talba T

    2011-04-01

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

  2. Construction of an Occupational Therapy Screenings Assessment for elderly medical patients

    DEFF Research Database (Denmark)

    Holsbæk, Jonas

    Background: Occupational Therapist working with Elderly Medical inpatients at hospitals in Denmark, are under pressure due to an increasing patients, demands for validated interventions and best practice and economically effectually solutions at the same time. Occupational Therapists in Denmark...... there for demands a validated Occupational Therapy Screening Assessment, that fast and easy can tell if more Occupational Therapy is needed. Aim: The aim of the study is to develop a Screening Assessment which can be used in the Occupational Therapist practice screening Hospitalized Elderly medical inpatients...

  3. Development of the music therapy assessment Tool for advanced Huntington’s disease: A pilot validation study

    DEFF Research Database (Denmark)

    O'Kelly, Julian; Bodak, Rebeka

    2016-01-01

    Background: Case studies of people with Huntington's disease (HD) report that music therapy provides a range of benefits that may improve quality of life; however, no robust music therapy assessment tools exist for this population. Objective: Develop and conduct preliminary psychometric testing o...... patient responses to music therapy interventions across psychological, physical, social, and communication domains of functioning in patients with advanced HD.......Background: Case studies of people with Huntington's disease (HD) report that music therapy provides a range of benefits that may improve quality of life; however, no robust music therapy assessment tools exist for this population. Objective: Develop and conduct preliminary psychometric testing...... of a music therapy assessment tool for patients with advanced HD. Methods: First, we established content and face validity of the Music Therapy Assessment Tool for Advanced HD (MATA-HD) through focus groups and field testing. Second, we examined psychometric properties of the resulting MATA-HD in terms...

  4. 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.

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

    Science.gov (United States)

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

    2007-04-01

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

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

    Science.gov (United States)

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

    2007-04-15

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

  7. A music therapy tool for assessing parent-child interaction in cases of emotional neglect

    DEFF Research Database (Denmark)

    Jacobsen, Stine Lindahl; H. McKinney, Cathy

    2015-01-01

    Using a music therapy approach to assess emotional communication and parent–child interaction is new to the field of child protection. However, musical improvisations in music therapy has long been known as an analogue to affect attunement and early non-verbal communication between parent...... of the APC-R (revised version) in a quantitative study including a small, embedded qualitative component. A total of 52 dyads of children and their parents participated of whom 18 were in residential center to address emotional neglect and 33 functioned as a non-clinical comparison (children aged 5–12). All...... dyads underwent two video recorded music therapy assessment sessions. Video analyses focused on autonomy relationship, turns, and parental response types producing scores on Mutual Attunement, Nonverbal Communication Skills and Emotional Parental Response. Psychometric analyses of the APC-R included...

  8. An Occupational Therapy Work Skills Assessment for Individuals with Head Injury.

    Science.gov (United States)

    Chappell, Irene; Higham, Julie; McLean, Alison M.

    2003-01-01

    Describes an occupational therapy skills assessment protocol developed and used to evaluate physical, cognitive, and behavioral abilities for persons seeking to return to work following head injuries. It measures them within the framework of productivity, interpersonal skills, and safety. (Contains 48 references.) (Author/JOW)

  9. Cross-modality grief therapy : description and assessment of a new program

    NARCIS (Netherlands)

    Schut, H A; de Keijser, J; van den Bout, J; Stroebe, M S

    1996-01-01

    A recently developed program for extensive inpatient grief therapy in groups, administered on a time-limited basis, is outlined, an illustrative case study is described, and empirical assessment of the program's efficacy is provided. During a 3-month stay in a Dutch Health Care Centre, a combined tr

  10. An Automatic Framework for Assessing Breast Cancer Risk Due to Various Hormone Replacement Therapies (HRT)

    DEFF Research Database (Denmark)

    Karemore, Gopal Raghunath; brandt, sami; Nielsen, Mads

    It is well known that menopausal hormone therapy increases mammographic density. Increase in breast density may relate to breast cancer risk. Several computer assisted automatic methods for assessing mammographic density have been suggested by J.W. Byng (1996), N. Karssemeijer (1998), J.M. Boone...

  11. Music Therapy for children with special needs - clinical practice and assessment in the light of developmental psychology and communicative musicality

    DEFF Research Database (Denmark)

    Holck, Ulla

    for patterns in clinical work, e.g. analyzing the way members act in the group or towards the therapist. The practices will continuously be connected with a focus on how the music therapy research as well as developmental psychology can inform the assessment. Literature for further reading: Holck, U. (2007......Assessment or evaluation is a continuing part of clinical music therapy, both in the beginning, in the continuous process, and in the evaluation of the music therapy – and sometimes even for a diagnostic assessment (Wigram, Pedersen and Bonde, 2002). After an overall introduction to music therapy...... assessment, the focus is on clinical use of an assessment approach in everyday work, followed by ways of using video recordings in assessing music therapy processes. The way you ask musically, the way the child can answer you! Therefore, it is the therapist’s responsibility to ask in many ways...

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

    Directory of Open Access Journals (Sweden)

    I. Portioli

    2013-05-01

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

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

    Science.gov (United States)

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

    2014-10-01

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

  14. HElmet therapy Assessment in infants with Deformed Skulls (HEADS: protocol for a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    van Wijk Renske M

    2012-07-01

    Full Text Available Abstract Background In The Netherlands, helmet therapy is a commonly used treatment in infants with skull deformation (deformational plagiocephaly or deformational brachycephaly. However, evidence of the effectiveness of this treatment remains lacking. The HEADS study (HElmet therapy Assessment in Deformed Skulls aims to determine the effects and costs of helmet therapy compared to no helmet therapy in infants with moderate to severe skull deformation. Methods/design Pragmatic randomised controlled trial (RCT nested in a cohort study. The cohort study included infants with a positional preference and/or skull deformation at two to four months (first assessment. At 5 months of age, all children were assessed again and infants meeting the criteria for helmet therapy were asked to participate in the RCT. Participants were randomly allocated to either helmet therapy or no helmet therapy. Parents of eligible infants that do not agree with enrolment in the RCT were invited to stay enrolled for follow up in a non-randomisedrandomised controlled trial (nRCT; they were then free to make the decision to start helmet therapy or not. Follow-up assessments took place at 8, 12 and 24 months of age. The main outcome will be head shape at 24 months that is measured using plagiocephalometry. Secondary outcomes will be satisfaction of parents and professionals with the appearance of the child, parental concerns about the future, anxiety level and satisfaction with the treatment, motor development and quality of life of the infant. Finally, compliance and costs will also be determined. Discussion HEADS will be the first study presenting data from an RCT on the effectiveness of helmet therapy. Outcomes will be important for affected children and their parents, health care professionals and future treatment policies. Our findings are likely to influence the reimbursement policies of health insurance companies. Besides these health outcomes, we will be able to

  15. Application of iron chelates in hydrodesulphurisation

    NARCIS (Netherlands)

    Wubs, Harm Jan

    1994-01-01

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

  16. Recent developments centered on orally active iron chelators

    Directory of Open Access Journals (Sweden)

    Robert Hider

    2014-09-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

  18. An audit about music therapy assessments and recommendations for adult patients suspected to be in a low awareness state.

    Science.gov (United States)

    Daveson, Barbara

    2010-01-01

    In neuro-rehabilitation, the role of music therapy is expanding to include assessment of patients with severely-altered states of consciousness. Diagnosis of these conditions is a complex task for all, and cases of misdiagnosis have been reported. Aggregated findings from 33 music therapy assessments of patients suspected of being in a low awareness state are described and discussed here. The Music Therapy Assessment Tool for Low Awareness States (MATLAS) was used during these assessments. All assessments were offered as part of a specialist multidisciplinary assessment package. A brief description of the patient group is supplied, along with details regarding the assessment tool and the recommendations that followed. In summary, a difference in the time it took to assess patients in vegetative state (VS) as compared to those in minimally conscious state (MCS) was found and, on average, the assessment of those in VS took less time to complete than for those in MCS. A greater range in session length was found for patients in VS, as compared to those in MCS. Generally after the assessments, patients in VS were likely to be admitted to a sensory regulation group administered by a music therapy assistant, supervised by a qualified music therapist, to enable the continued collection of behavioral responses to stimuli. Patients in MCS were admitted to a music therapy treatment program offered by a qualified music therapist. Ongoing work is recommended to advance the assessment and treatment of this patient population, and to consolidate the role of music therapy with this population.

  19. Synergistic Activities of an Efflux Pump Inhibitor and Iron Chelators against Pseudomonas aeruginosa Growth and Biofilm Formation

    DEFF Research Database (Denmark)

    Liu, Yang; Yang, Liang; Molin, Søren

    2010-01-01

    The efflux pump inhibitor phenyl-arginine-beta-naphthylamide (PA beta N) was paired with iron chelators 2,2'-dipyridyl, acetohydroxamic acid, and EDTA to assess synergistic activities against Pseudomonas aeruginosa growth and biofilm formation. All of the tested iron chelators synergistically...... inhibited P. aeruginosa growth and biofilm formation with PA beta N. PA beta N-EDTA showed the most promising activity against P. aeruginosa growth and biofilm formation....

  20. Music therapy for the Assessment of Parental Competencies for Children in need of Care

    DEFF Research Database (Denmark)

    Jacobsen, Stine; Wigram, Tony

    2007-01-01

    using the autonomy profile of the Improvisation Assessment Profiles. Results demonstrate the strengths, weaknesses, and potential in the parent, and quantifiable observed musical events in the gradients of autonomy provide evidence of positive and/or negative interactional behaviour. The therapist has......The assessment for parenting competencies for parents of children potentially in need of care involves an evaluation of their relationship with their child, and the interaction that underpins that relationship. The "Assessment of Parenting Competences" (APC) music therapy assessment provides...... a structured series of interactional exercises that allow the therapist to explore the nature of the relationship both as a tool in every day clinical work and as a research method. The method of the assessment involves free improvisation, turn-taking exercises, and following leading exercises and is evaluated...

  1. 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.

  2. Increased Uptake of Chelated Copper Ions by Lolium perenne Attributed to Amplified Membrane and Endodermal Damage.

    Science.gov (United States)

    Johnson, Anthea; Singhal, Naresh

    2015-10-23

    The contributions of mechanisms by which chelators influence metal translocation to plant shoot tissues are analyzed using a combination of numerical modelling and physical experiments. The model distinguishes between apoplastic and symplastic pathways of water and solute movement. It also includes the barrier effects of the endodermis and plasma membrane. Simulations are used to assess transport pathways for free and chelated metals, identifying mechanisms involved in chelate-enhanced phytoextraction. Hypothesized transport mechanisms and parameters specific to amendment treatments are estimated, with simulated results compared to experimental data. Parameter values for each amendment treatment are estimated based on literature and experimental values, and used for model calibration and simulation of amendment influences on solute transport pathways and mechanisms. Modeling indicates that chelation alters the pathways for Cu transport. For free ions, Cu transport to leaf tissue can be described using purely apoplastic or transcellular pathways. For strong chelators (ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA)), transport by the purely apoplastic pathway is insufficient to represent measured Cu transport to leaf tissue. Consistent with experimental observations, increased membrane permeability is required for simulating translocation in EDTA and DTPA treatments. Increasing the membrane permeability is key to enhancing phytoextraction efficiency.

  3. Inhibitor Ranking Through QM based Chelation Calculations for Virtual Screening of HIV-1 RNase H inhibition

    DEFF Research Database (Denmark)

    Poongavanam, Vasanthanathan; Svendsen, Casper Steinmann; Kongsted, Jacob

    2014-01-01

    . Furthermore, full protein fragment molecular orbital (FMO) calculations were conducted and subsequently analysed for individual residue stabilization/destabilization energy contributions to the overall binding affinity in order to better understand the true and false predictions. After a successful assessment......Quantum mechanical (QM) calculations have been used to predict the binding affinity of a set of ligands towards HIV-1 RT associated RNase H (RNH). The QM based chelation calculations show improved binding affinity prediction for the inhibitors compared to using an empirical scoring function...... of the methods based on the use of a training set of molecules, QM based chelation calculations were used as filter in virtual screening of compounds in the ZINC database. By this, we find, compared to regular docking, QM based chelation calculations to significantly reduce the large number of false positives...

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

    Directory of Open Access Journals (Sweden)

    Arun John Baksi

    2014-09-01

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

  5. Influence of Chelating Agents on Chromium Fate in Sediment

    Institute of Scientific and Technical Information of China (English)

    WANGXIAOCHANG; SUNJINHE; 等

    1996-01-01

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

  6. 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.

  7. An Automatic Framework for Assessing Breast Cancer Risk Due to Various Hormone Replacement Therapies (HRT)

    DEFF Research Database (Denmark)

    Karemore, Gopal Raghunath; Brandt, Sami; Nielsen, Mads

    measurements of breast density changes related to HRT. 2) To investigate whether transdermal low dose estradiol treatment induces changes in mammographic density compared to raloxifene and if these findings indicate elevation of breast cancer risk by treatment. Material and Methods: Digitised mammographies......Background: It is well known that Menopausal Hormone therapy increases mammographic density. Increase in breast density may relate to breast cancer risk. Several computer assisted automatic methods for assessing mammographic density have been suggested by J.W. Byng (1996), N. Karssemeijer (1998), J...... of 2x135 completers of a two year, randomised, trial formed the base of the present analysis. Active treatments were transdermal estradiol releasing 0.014mg E2/week and orally administered raloxifene hydrochloride, 60mg/day respectively. Influence of the therapies on breast density was assessed...

  8. High Risk Suicidal Behavior in Veterans - Assessment of Predictors and Efficacy of Dialectical Behavioral Therapy

    Science.gov (United States)

    2015-12-01

    Award Number: W81XWH-09-1-0722 TITLE: High Risk Suicidal Behavior in Veterans- Assessment of Predictors and Efficacy of Dialectical Behavioral ...first project is a randomized clinical trial of 120 veterans identified with high-risk suicidal behavior comparing the efficacy of Dialectical... Behavioral Therapy (DBT) vs. treatment as usual (TAU) on suicidal behavior as a primary outcome measure. A second aim of the project is to examine group

  9. Federal regulation of unapproved chelation products.

    Science.gov (United States)

    Lee, Charles E

    2013-12-01

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

  10. Clinical application of music therapy assessment within the field of child protection

    DEFF Research Database (Denmark)

    Jacobsen, Stine Lindahl; Killén, Kari

    2015-01-01

    The focus of this article is the theoretical understanding behind, and the clinical application of, a newly developed music-therapy assessment tool, Assessment of Parenting Competencies (APC). While the psychometric properties have been analyzed successfully in prior publications, the advantages...... and challenges of a nonverbal and emotional interactional medium such as music in assessing parent–child interaction and parental capacity are presented and discussed. The assessment model relates to theories of attunement, autonomy, and attachment, and clinical relevance for practice within the field of child......-service professions within the field of child protection, including level of mutual attunement, nonverbal communication skills, emotional parental response, and possibly indications of attachment behavior in the child. APC can thereby help indicate the severity of the situation and the possible therapeutic direction...

  11. How people with HIV/AIDS manage and assess their use of complementary therapies: a qualitative analysis.

    Science.gov (United States)

    Gillett, James; Pawluch, Dorothy; Cain, Roy

    2002-01-01

    The objective of this article is to provide a qualitative analysis of the practical concerns that people with HIV/AIDS have with regard to their use of complementary therapies. In-depth semistructured interviews were conducted with a diverse range of people with HIV/AIDS (N = 46). An inductive grounded approach was used to collect and analyze the data. There were five central concerns: (a) selecting which therapies to use, (b) judging which therapies work, (c) combining Western medicine with complementary therapies, (d) assessing the safety of complementary therapies, and (e) dealing with the barriers to the use of complementary therapies. A better understanding of the practical dimensions of complementary therapy use highlights the treatment and care issues that people with HIV/AIDS face and offers insights into the role that nurses might play in addressing some of these issues.

  12. Thermography Improves Clinical Assessment in Patients with Systemic Sclerosis Treated with Ozone Therapy.

    Science.gov (United States)

    Nowicka, Danuta

    2017-01-01

    Objective. Treatment of scleroderma is challenging and limited. The aim of our study was to evaluate the usefulness of thermography in assessment of the clinical condition (joints movability and skin thickness) in clinically advanced patients with systemic sclerosis before and after ozone therapy. Method. The study included 42 patients aged 32 to 73 years with advanced systemic sclerosis hospitalized in the university clinic between 2003 and 2006. Thermography and clinical examinations were conducted at baseline and after two series of bath in water with ozone. Results. The comparison of results showed significant increase in skin temperature by 2.5°C, significant increase in interphalangeal joints movability by 18 degrees, and significant decrease in skin score by 14.7 points. The skin temperature was correlated with skin score (r = -0.59) and joints movability (r = +0.8). Conclusions. Ozone therapy shows positive effect on clinical parameters and skin temperature as measured with thermography. The study indicated possibility of introducing ozonotherapy as an independent therapy in cases with low level of progression or during remission periods and as additional treatment in patients with advanced disease requiring immunosuppressive treatment. Thermography is useful in assessment of skin condition showing strong correlation between skin temperature and clinical parameters.

  13. Thermography Improves Clinical Assessment in Patients with Systemic Sclerosis Treated with Ozone Therapy

    Science.gov (United States)

    2017-01-01

    Objective. Treatment of scleroderma is challenging and limited. The aim of our study was to evaluate the usefulness of thermography in assessment of the clinical condition (joints movability and skin thickness) in clinically advanced patients with systemic sclerosis before and after ozone therapy. Method. The study included 42 patients aged 32 to 73 years with advanced systemic sclerosis hospitalized in the university clinic between 2003 and 2006. Thermography and clinical examinations were conducted at baseline and after two series of bath in water with ozone. Results. The comparison of results showed significant increase in skin temperature by 2.5°C, significant increase in interphalangeal joints movability by 18 degrees, and significant decrease in skin score by 14.7 points. The skin temperature was correlated with skin score (r = −0.59) and joints movability (r = +0.8). Conclusions. Ozone therapy shows positive effect on clinical parameters and skin temperature as measured with thermography. The study indicated possibility of introducing ozonotherapy as an independent therapy in cases with low level of progression or during remission periods and as additional treatment in patients with advanced disease requiring immunosuppressive treatment. Thermography is useful in assessment of skin condition showing strong correlation between skin temperature and clinical parameters.

  14. An end-to-end assessment of range uncertainty in proton therapy using animal tissues

    Science.gov (United States)

    Zheng, Yuanshui; Kang, Yixiu; Zeidan, Omar; Schreuder, Niek

    2016-11-01

    Accurate assessment of range uncertainty is critical in proton therapy. However, there is a lack of data and consensus on how to evaluate the appropriate amount of uncertainty. The purpose of this study is to quantify the range uncertainty in various treatment conditions in proton therapy, using transmission measurements through various animal tissues. Animal tissues, including a pig head, beef steak, and lamb leg, were used in this study. For each tissue, an end-to-end test closely imitating patient treatments was performed. This included CT scan simulation, treatment planning, image-guided alignment, and beam delivery. Radio-chromic films were placed at various depths in the distal dose falloff region to measure depth dose. Comparisons between measured and calculated doses were used to evaluate range differences. The dose difference at the distal falloff between measurement and calculation depends on tissue type and treatment conditions. The estimated range difference was up to 5, 6 and 4 mm for the pig head, beef steak, and lamb leg irradiation, respectively. Our study shows that the TPS was able to calculate proton range within about 1.5% plus 1.5 mm. Accurate assessment of range uncertainty in treatment planning would allow better optimization of proton beam treatment, thus fully achieving proton beams’ superior dose advantage over conventional photon-based radiation therapy.

  15. Phd study of reliability and validity: One step closer to a standardized music therapy assessment model

    DEFF Research Database (Denmark)

    Jacobsen, Stine Lindahl

    The paper will present a phd study concerning reliability and validity of music therapy assessment model “Assessment of Parenting Competences” (APC) in the area of families with emotionally neglected children. This study had a multiple strategy design with a philosophical base of critical realism...... and pragmatism. The fixed design for this study was a between and within groups design in testing the APCs reliability and validity. The two different groups were parents with neglected children and parents with non-neglected children. The flexible design had a multiple case study strategy specifically...... of the theoretical understanding of the clientgroup. Furthermore, a short describtion of the specific assessment protocol and analysis procedures of APC will be a part of the presentation. The phd study sought to explore how to develop measures of parenting competences in looking at autonomy relationship...

  16. Therapy evaluation and diagnostic accuracy in neuroendocrine tumours: assessment of radiological methods

    Energy Technology Data Exchange (ETDEWEB)

    Elvin, A.

    1993-01-01

    The diagnostic accuracy of ultrasonically guided biopsy-gun biopsies was assessed in a group of 47 patients with suspected pancreatic carcinoma. A correct diagnosis was obtained in 44 of the 47 patients (94%). Twenty-five patients with known neuroendocrine tumour disease were biopsied with 1.2 mm and 0.9 mm biopsy-gun needles. The influence of treatment-related fibrosis was also evaluated. The overall diagnostic accuracy with the 0.9 mm needle was 69% as compared to 92% with the 1.2 mm needle. In order to assess the diagnostic accuracy rate for radiologists with different experience of biopsy procedures 175 cases of renal biopsy-gun biopsies were evaluated. No statistical significant difference was found between the different operators. The role of duplex Doppler ultrasound in monitoring interferon treatment-related changes in carcinoid metastases was evaluated. It present duplex Doppler ultrasound does not seem to play a role in the evaluation of tumour therapy in carcinoid patients. Therapy response evaluation was performed with MR imaging in a group of 17 patients with neuroendocrine liver metastases. A significant difference was found between patients responding to and patients with failure of treatment in terms of tumour T1, contrast enhancement and signal intensity ratio. This indicates that MR investigation may be used in therapy monitoring of patients with neuroendocrine metastases. The neuroendocrine-differentiated colonic carcinoma cell line (LCC-18) was transplanted to 29 mice to establish a tumour/animal model that would allow the monitoring of changes with MR imaging induced by interferon therapy and to evaluate whether the therapeutic response could be modulated by different interferon dosages. Interferon does not seem to have any prolonged anti-proliferative effect on the LCC-18 tumour cell line when transplanted to nude mice.

  17. A pilot study assessing art therapy as a mental health intervention for subfertile women.

    Science.gov (United States)

    Hughes, Edward G; da Silva, Alicia Mann

    2011-03-01

    BACKGROUND Subfertility is a common but hidden source of anxiety, depressive symptoms and hopelessness. Counselling reduces this emotional burden and may even enhance the likelihood of pregnancy. Art therapy may be a useful intervention, because it facilitates the expression of feelings, both visually and verbally, and may ease emotional distress. METHODS Weekly 2-h art therapy group courses were held for a total of 21 subfertile women. The impact of subfertile women's support systems and barriers to coping were all explored. The effectiveness of art therapy was assessed using Beck Hopelessness, Depression and Anxiety Inventories, administered before and after participation, as well as a qualitative exit questionnaire. RESULTS The mean age of participants was 35.7 (SD 2.1) years and duration of infertility was 64 (12.0) months. Mean Beck Hopelessness Scale fell from 6.1 (3.8) to 3.5 (3.1, P = 0.01) after therapy. Beck Depression Inventory-II Score fell from 19.8 (11.0) to 12.5 (10.2, P = 0.01) and Beck Anxiety Inventory Score changed from 12.4 (8.4) to 8.4 (5.2, P = 0.3). Based on the exit questionnaire, women felt the course was insightful, powerful and enjoyable. CONCLUSIONS Art therapy is an inexpensive, non-pharmacological intervention, which was associated with decreased levels of hopelessness and depressed mood in subfertile women. It also provides insight into the meaning and emotional implications of subfertility for patients and caregivers. This pilot study highlights the need for further research in this field.

  18. Novel Terbium Chelate Doped Fluorescent Silica Nanoparticles

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  19. Cerebral blood flow assessment of preterm infants during respiratory therapy with the expiratory flow increase technique

    Directory of Open Access Journals (Sweden)

    Mariana Almada Bassani

    2016-06-01

    Full Text Available Abstract Objective: To assess the impact of respiratory therapy with the expiratory flow increase technique on cerebral hemodynamics of premature newborns. Methods: This is an intervention study, which included 40 preterm infants (≤34 weeks aged 8-15 days of life, clinically stable in ambient air or oxygen catheter use. Children with heart defects, diagnosis of brain lesion and/or those using vasoactive drugs were excluded. Ultrasonographic assessments with transcranial Doppler flowmetry were performed before, during and after the increase in expiratory flow session, which lasted 5min. Cerebral blood flow velocity and resistance and pulsatility indices in the pericallosal artery were assessed. Results: Respiratory physical therapy did not significantly alter flow velocity at the systolic peak (p=0.50, the end diastolic flow velocity (p=0.17, the mean flow velocity (p=0.07, the resistance index (p=0.41 and the pulsatility index (p=0.67 over time. Conclusions: The expiratory flow increase technique did not affect cerebral blood flow in clinically-stable preterm infants.

  20. Relationship Between Cognitive Assessment and Balance Measures in Adolescents Referred for Vestibular Physical Therapy After Concussion

    Science.gov (United States)

    Alsalaheen, Bara A.; Whitney, Susan L.; Marchetti, Gregory F.; Furman, Joseph M.; Kontos, Anthony P.; Collins, Michael W.; Sparto, Patrick J.

    2016-01-01

    Objective To examine the relationship between cognitive and balance performance in adolescents with concussion. Design Retrospective case series. Setting Tertiary. Patients Sixty patients. Interventions Correlation analyses were performed to describe the relationship between symptoms, cognitive measure, and balance measure at the time of initiation of vestibular physical therapy. Main Outcome Measures Cognitive performance was assessed using the Immediate Post-concussion Assessment and Cognitive Testing (ImPACT). The dizziness and balance function measures included dizziness severity rating, Activities-specific Balance Confidence scale (ABC), Dizziness Handicap Inventory (DHI), Functional Gait Assessment, gait speed, Timed “UP and GO,” Five Times Sit to Stand, and Sensory Organization Test (SOT). To account for multiple comparisons, the False Discovery Rate method was used. Results Performance measures of balance were significantly correlated with cognitive measures. Greater total symptom scores were related to greater impairment in the ABC and DHI (r = 0.35-0.39, P ≤ 0.008) and worse performance in condition 2 of the SOT (r = −0.48, P = 0.004). Among the ImPACT composite scores, lower memory scores were correlated with impaired balance performance measures (r = 0.37-0.59, P ≤ 0.012). Lower visual memory was also correlated with worse ABC scores. Conclusions The significant relationships reported between the cognitive performance scores and balance measures may reflect that similar levels of functioning exist across domains in individuals with protracted recovery who receive vestibular physical therapy. PMID:25706663

  1. ASSESSMENT OF MICRONEEDLING THERAPY IN THE MANAGEMENT OF ATROPHIC FACIAL ACNE SCARS

    Directory of Open Access Journals (Sweden)

    Ajay

    2015-12-01

    Full Text Available STUDY BACKGROUND Post acne scars are always a challenge to treat, especially the ones which are deep seated. There are many treatment options like laser resurfacing, dermabrasion, microdermabrasion and non-ablative laser resurfacing but with considerable morbidity and interference with the daily activities of the patient in the post-treatment period. Microneedling or dermaroller therapy is one of the new treatment options in the management of acne scars with satisfactory improvement and no significant side effect. The aim of the present study is to perform an objective evaluation the efficacy of microneedling in the treatment of atrophic acne scars. MATERIALS AND METHODS Thirty patients of skin type III-V having atrophic facial acne scars presenting to our dermatology OPD. were received multiple sittings of microneedling (dermaroller treatment with an interval of 6 weeks between each session. Goodman & Baron’s acne scar grading system was used for assessment of their scars and was evaluated clinically by serial photography at the start as well as at two months after the conclusion of the treatment. Patients on anticoagulant therapy, of keloidal tendency, with bleeding disorders, vitiligo patients, pregnant and lactating mothers and patients with active acne lesions were excluded from the study. The duration of this study was for ten months-from January 2014 to October 2014. RESULTS Any change in the grading of scars after the end of treatment and follow-up period was noted down. The efficacy and improvement of dermaroller treatment was assessed by Goodman and Baron’s Global Acne Scarring System. Out of 30 patients, 26(80.64% patients achieved a reduction in the severity of their scarring by one or two grades. Quantitative assessment showed that 13.3% of patients had minimal, 16.6% had good and 70% showed very good improvement. Adverse effects were limited to transient pain, erythema and edema. CONCLUSION Microneedling therapy seems to be

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2000-07-01

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

  3. Transformation of paper-based occupational therapy assessment forms to a digital format

    DEFF Research Database (Denmark)

    Bang, Marie Bangsgaard; Lunn, Tine Bieber Kirkegaard; Helle, Tina

    2016-01-01

    Background The growing digitalization process serves to modernize the health care systems, to improve documentation and the efficiency of the public sector. Consequently, the adoption of digitalization at large is critical for the development of occupational therapy (OT). Yet, most OT assessment...... by means of individual online diaries followed by a focus group interview. The interview was transcribed verbatim. A qualitative content analysis was performed to systemize and analyse all data. Results The HE app is easy to use in clinical OT and the app permits new valuable functions such as photo...

  4. Computed tomography assessment of early response to neoadjuvant therapy in colon cancer

    DEFF Research Database (Denmark)

    Dam, Claus; Lund-Rasmussen, Vera; Pløen, John;

    2015-01-01

    INTRODUCTION: Using multidetector computed tomography, we aimed to assess the early response of neoadjuvant drug therapy for locally advanced colon cancer. METHODS: Computed tomography with IV contrast was acquired from 67 patients before and after up to three cycles of preoperative treatment. All...... patients had histologically confirmed colon cancer, a T4 or T3 tumour with extramural invasion ≥ 5 mm and no distant metastases or peritoneal nodules. The patients were treated with oxaliplatin and capecitabine. In addition, those with no mutations in the KRAS, BRAF and PIK3CA genes were also treated...

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

    Institute of Scientific and Technical Information of China (English)

    杨燕生; 安保礼; 龚孟濂; 史华红; 雷衡毅; 孟建新

    2002-01-01

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

  6. 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.

  7. 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...

  8. Radiation therapy for nasopharyngeal carcinoma: the predictive value of interim survival assessment.

    Science.gov (United States)

    Toya, Ryo; Murakami, Ryuji; Saito, Tetsuo; Murakami, Daizo; Matsuyama, Tomohiko; Baba, Yuji; Nishimura, Ryuichi; Hirai, Toshinori; Semba, Akiko; Yumoto, Eiji; Yamashita, Yasuyuki; Oya, Natsuo

    2016-09-01

    Pretreatment characteristics are suggested as predictive and/or prognostic factors for nasopharyngeal carcinoma (NPC); however, individual tumor radiosensitivities have previously not been considered. As boost planning is recommended for NPC, we performed interim assessments of magnetic resonance (MR) images for boost planning and retrospectively evaluated their predictive value for the survival of NPC patients. Radiation therapy via elective nodal irradiation (median dose: 39.6 Gy) with/without chemotherapy was used to treat 63 NPC patients. Boost irradiation (median total dose: 70 Gy) was performed based on the interim assessment. The largest lymph node (LN) was measured on MR images acquired at the time of interim assessment. The site of first failure was local in 8 (12.7%), regional in 7 (11.1%), and distant in 12 patients (19.0%). All 7 patients with regional failure harbored LNs ≥15 mm at interim assessment. We divided the 63 patients into two groups based on LN size [large (≥15 mm), n = 10 and small (interim assessment could predict survival in NPC patients.

  9. Assessing adherence factors in patients under topical treatment: development of the Topical Therapy Adherence Questionnaire (TTAQ).

    Science.gov (United States)

    Zschocke, Ina; Mrowietz, Ulrich; Lotzin, Annett; Karakasili, Eleni; Reich, Kristian

    2014-04-01

    Medication adherence rates strongly depend on favorable disease outcomes. It is known that medication adherence rates are lower for topical treatment than for systemic treatment. However, to date no validated instrument for the assessment of adherence factors in topical treatment is available. The aim of this study was to develop a new questionnaire to assess adherence risk factors in topical treatment. The development of the Topical Therapy Adherence Questionnaire (TTAQ) and Patient Preference Questionnaire (PPQ) was based on a systematic literature review, and qualitative patient focus interviews and expert focus groups' input. The psychometric properties and comprehensibility of the TTAQ and PPQ were assessed in a feasibility study with 59 psoriasis patients. Our first preliminary results indicate that the TTAQ and PPQ are psychometrically sound and reliable measures for the assessment of factors influencing topical treatment adherence. The questionnaires are currently being further developed and various parameters (e.g., time point of assessment) are currently being tested in an exploratory pilot study with ca. 2,000 psoriasis patients receiving topical treatment in a European clinical trial. The use of the final versions of TTAQ and PPQ in clinical practice may facilitate the early identification of specific non-adherence factors in patients under topical treatment, which could enable designing and applying adherence-enhancing interventions according to the patient's individual needs.

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

    Science.gov (United States)

    Gateau, Christelle; Delangle, Pascale

    2014-05-01

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

  11. Challenge models to assess new therapies in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    van der Merwe R

    2012-09-01

    Full Text Available René van der Merwe,1 Nestor A Molfino2,31Respiratory Clinical Development, MedImmune Ltd, Cambridge, UK; 2Respiratory Clinical Development, MedImmune, LLC, Gaithersburg, MD, USA, 3KaloBios Pharmaceuticals, South San Francisco, CA, USAAbstract: Chronic obstructive pulmonary disease (COPD is a major cause of morbidity and mortality. Current therapies confer partial benefits either by incompletely improving airflow limitation or by reducing acute exacerbations, hence new therapies are desirable. In the absence of robust early predictors of clinical efficacy, the potential success of novel therapeutic agents in COPD will not entirely be known until the drugs enter relatively large and costly clinical trials. New predictive models in humans, and new study designs are being sought to allow for confirmation of pharmacodynamic and potentially clinically meaningful effects in early development. This review focuses on human challenge models with lipopolysaccharide endotoxin, ozone, and rhinovirus, in the early clinical development phases of novel therapeutic agents for the treatment and reduction of exacerbations in COPD.Keywords: chronic obstructive pulmonary disease, challenge models, therapy assessment

  12. Objective assessment of biomagnetic devices and alternative clinical therapies using infrared thermal imaging

    Science.gov (United States)

    Rockley, Graham J.

    2001-03-01

    The overwhelming introduction of magnetic devices and other alternative therapies into the health care market prompts the need for objective evaluation of these techniques through the use of infrared thermal imaging. Many of these therapies are reported to promote the stimulation of blood flow or the relief of pain conditions. Infrared imaging is an efficient tool to assess such changes in the physiological state. Therefore, a thermal imager can help document and substantiate whether these therapies are in fact providing an effective change to the local circulation. Thermal images may also indicate whether the change is temporary or sustained. As a specific case example, preliminary findings will be presented concerning the use of magnets and the effect they have on peripheral circulation. This will include a discussion of the recommended protocols for this type of infrared testing. This test model can be applied to the evaluation of other devices and therapeutic procedures which are reputed to affect circulation such as electro acupuncture, orthopedic footwear and topical ointments designed to relieve pain or inflammation.

  13. Music Therapy in Special Schools: The Assessment of the Quality of Relationship

    Directory of Open Access Journals (Sweden)

    Aspasia Fragkouli

    2013-12-01

    Full Text Available This qualitative scientific study – by means of analysing recorded therapeutic sessions with children with autism or mental disability in a special school – examines the process of creating a relationship between the therapist and the child in the context of music-therapeutic moments. The analysis of therapeutic moments was carried out through the AQR-instrument (Assessment of the Quality of Relationship and led to a the evaluation of the quality of relationship between the therapist and the child with autism or mental disability during therapy, b the evaluation of the correspondence of the therapeutic intervention to each child’s developmental level (modus, and c the appreciation of the differentiation in the relationship between the therapist and the child with autism or mental disability, as well as the size of that differentiation. Regardless of the pathology, it was observed that music therapy with children is advisable when the child shows disorders in his/her emotional development and in the ability to create a relationship. Music-therapeutic interventions that use the child itself as a starting point and follow the concept of elemental music, succeed in mobilising children’s healthy part and promote their development, in many areas. Research data are based on the author’s dissertation thesis: “Music therapy for children with psychological disorders in special education” (Fragkouli 2012.

  14. Assessing disease activity in psoriasis and psoriatic arthritis: impact on management and therapy.

    Science.gov (United States)

    Chandran, Vinod; Maharaj, Ajesh B

    2016-01-01

    The management of psoriatic arthritis (PsA) and psoriasis has undergone major advancements over the last decade. This has been made possible, in part, due to the introduction of new therapies for their management, as well as global collaboration in the development of outcome measures and "treat- to- target" paradigms. In this review article, we discuss how disease activity is measured and the outcome measures that have been recently developed for the management of PsA. The importance of assessing the individual domains as well as global assessments both from the physician and patient perspective, and the development of composite measures are discussed. The newer PsA specific measures are expected to be more commonly used in clinical trials as well as clinical practice.

  15. Utility of Ultrasonography in Assessing the Effectiveness of Extracorporeal Shock Wave Therapy in Insertional Achilles Tendinopathy

    Directory of Open Access Journals (Sweden)

    Yi Cheng

    2016-01-01

    Full Text Available Introduction. The aim of this study was to investigate the utility of ultrasonography (US for predicting and assessing the effectiveness of extracorporeal shock wave therapy (ESWT in insertional Achilles tendinopathy (IAT. Methods. A total of 42 patients with an established diagnosis of chronic IAT were examined by US before ESWT and at 4 weeks and 12 weeks after ESWT. The thickness and cross-sectional area (CSA of the Achilles tendon, size of calcific plaques, tendon structure score, and neovascularization score were measured at each time point. Results. After therapy, Victorian Institute of Sport Assessment-Achilles (VISA-A scores increased significantly, and the size of calcific plaques decreased (P<0.05. Neovascularization scores increased at the 4th week and then decreased at the 12th week (P<0.05. The thickness, CSA, and structure of the Achilles tendon did not change. Variables observed by US at baseline were not associated with changes in VISA-A scores at follow-up. However, the changes in calcific plaque size and neovascularization scores were related to the improvement of VISA-A scores between pre- and posttherapy (P<0.01. Conclusion. Ultrasonography can reveal some changes in the insertion of the Achilles tendon after ESWT, but the outcome of ESWT in IAT cannot be predicted by the variables observed by US.

  16. Utility of Ultrasonography in Assessing the Effectiveness of Extracorporeal Shock Wave Therapy in Insertional Achilles Tendinopathy

    Science.gov (United States)

    Zhang, Jian

    2016-01-01

    Introduction. The aim of this study was to investigate the utility of ultrasonography (US) for predicting and assessing the effectiveness of extracorporeal shock wave therapy (ESWT) in insertional Achilles tendinopathy (IAT). Methods. A total of 42 patients with an established diagnosis of chronic IAT were examined by US before ESWT and at 4 weeks and 12 weeks after ESWT. The thickness and cross-sectional area (CSA) of the Achilles tendon, size of calcific plaques, tendon structure score, and neovascularization score were measured at each time point. Results. After therapy, Victorian Institute of Sport Assessment-Achilles (VISA-A) scores increased significantly, and the size of calcific plaques decreased (P < 0.05). Neovascularization scores increased at the 4th week and then decreased at the 12th week (P < 0.05). The thickness, CSA, and structure of the Achilles tendon did not change. Variables observed by US at baseline were not associated with changes in VISA-A scores at follow-up. However, the changes in calcific plaque size and neovascularization scores were related to the improvement of VISA-A scores between pre- and posttherapy (P < 0.01). Conclusion. Ultrasonography can reveal some changes in the insertion of the Achilles tendon after ESWT, but the outcome of ESWT in IAT cannot be predicted by the variables observed by US. PMID:28004000

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

    Science.gov (United States)

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

    2016-01-01

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

  18. Virtual reality and motor imagery: promising tools for assessment and therapy in Parkinson's disease.

    Science.gov (United States)

    Mirelman, Anat; Maidan, Inbal; Deutsch, Judith E

    2013-09-15

    Motor imagery (MI) and virtual reality (VR) are two evolving therapeutic approaches that make use of cognitive function to study and enhance movement, in particular, balance and mobility of people with Parkinson's disease (PD). This review examines the literature on the use of VR and MI in the assessment of mobility and as a therapeutic intervention to improve balance and gait in patients with PD. A study was eligible for inclusion if MI or VR were used to assess motor or cognitive function to improve gait, balance, or mobility in patients with PD. Data were extracted on the following categories: participants; study design; intervention (type, duration, and frequency); and outcomes. Intervention studies were evaluated for quality using the Physiotherapy Evidence Database scale. Sixteen studies were identified; 4 articles used MI and 12 used VR for assessment and treatment of gait impairments in PD. The studies included small samples and were diverse in terms of methodology. Quality of the intervention trials varied from fair for VR to good for MI. The benefits of using MI and VR for assessment and treatment were noted. Encouraging findings on the potential benefits of using MI and VR in PD were found, although further good-quality research is still needed. Questions remain on the optimal use, content of interventions, and generalizability of findings across the different stages of the disease. The possible mechanisms underlying MI and VR and recommendations for future research and therapy are also presented.

  19. 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…

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

    NARCIS (Netherlands)

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

    2002-01-01

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

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

    Science.gov (United States)

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

    2013-12-01

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

  2. Assessment of cognitive impairment in long-term oxygen therapy-dependent COPD patients

    Directory of Open Access Journals (Sweden)

    Karamanli H

    2015-09-01

    Full Text Available Harun Karamanli,1 Faik Ilik,2 Fatih Kayhan,3 Ahmet Cemal Pazarli4 1Department of Pulmonology, 2Department of Neurology, ³Department of Psychiatry, Faculty of Medicine, Mevlana University, Konya, Turkey; 4Department of Pulmonology, Elbistan State Hospital, Elbistan, Turkey Background: A number of studies have shown that COPD, particularly in its later and more severe stages, is associated with various cognitive deficits. Thus, the primary goal of the present study was to elucidate the extent of cognitive impairment in patients with long-term oxygen therapy-dependent (LTOTD COPD. In addition, this study aimed to determine the effectiveness of two cognitive screening tests, the Mini-Mental State Examination (MMSE and the Montreal Cognitive Assessment (MoCA, for COPD patients and the ability of oxygen therapy to mitigate COPD-related deficits in cognitive function. Methods: The present study enrolled 45 subjects: 24 nonuser and 21 regular-user LTOTD-COPD patients. All subjects had a similar grade of education, and there were no significant differences regarding age or sex. The MoCA (cutoff: <26 points and MMSE (cutoff: ≤24 points scores were compared between these two groups.Results: The nonuser LTOTD-COPD group had a significantly lower MoCA score than that of the regular-user LTOTD-COPD group (19.38±2.99 vs 21.68±2.14, respectively as well as a significantly lower MMSE score. Moreover, the absence of supplemental oxygen therapy increased the risk of cognitive impairment (MoCA, P=0.007 and MMSE, P=0.014, and the MoCA and MMSE scores significantly correlated with the number of emergency admissions and the number of hospitalizations in the last year.Conclusion: In the present study, the nonuser LTOTD-COPD group exhibited a significant decrease in cognitive status compared with the regular-user LTOTD-COPD group. This suggests that the assessment of cognitive function in nonuser LTOTD-COPD patients and the use of protective strategies, such as

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Monika E. Miller

    2015-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-12-15

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

  6. 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.

  7. Assessing Adverse Events of Postprostatectomy Radiation Therapy for Prostate Cancer: Evaluation of Outcomes in the Regione Emilia-Romagna, Italy

    Energy Technology Data Exchange (ETDEWEB)

    Showalter, Timothy N., E-mail: tns3b@virginia.edu [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Hegarty, Sarah E. [Center for Research in Medical Education and Health Care, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Rabinowitz, Carol [Center for Research in Medical Education and Health Care, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Maio, Vittorio [Jefferson School of Population Health, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Hyslop, Terry [Department of Biostatistics & Bioinformatics, Duke University School of Medicine, Durham, North Carolina (United States); Dicker, Adam P. [Department of Radiation Oncology, Kimmel Cancer Center & Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Louis, Daniel Z. [Center for Research in Medical Education and Health Care, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2015-03-15

    Purpose: Although the likelihood of radiation-related adverse events influences treatment decisions regarding radiation therapy after prostatectomy for eligible patients, the data available to inform decisions are limited. This study was designed to evaluate the genitourinary, gastrointestinal, and sexual adverse events associated with postprostatectomy radiation therapy and to assess the influence of radiation timing on the risk of adverse events. Methods: The Regione Emilia-Romagna Italian Longitudinal Health Care Utilization Database was queried to identify a cohort of men who received radical prostatectomy for prostate cancer during 2003 to 2009, including patients who received postprostatectomy radiation therapy. Patients with prior radiation therapy were excluded. Outcome measures were genitourinary, gastrointestinal, and sexual adverse events after prostatectomy. Rates of adverse events were compared between the cohorts who did and did not receive postoperative radiation therapy. Multivariable Cox proportional hazards models were developed for each class of adverse events, including models with radiation therapy as a time-varying covariate. Results: A total of 9876 men were included in the analyses: 2176 (22%) who received radiation therapy and 7700 (78%) treated with prostatectomy alone. In multivariable Cox proportional hazards models, the additional exposure to radiation therapy after prostatectomy was associated with increased rates of gastrointestinal (rate ratio [RR] 1.81; 95% confidence interval [CI] 1.44-2.27; P<.001) and urinary nonincontinence events (RR 1.83; 95% CI 1.83-2.80; P<.001) but not urinary incontinence events or erectile dysfunction. The addition of the time from prostatectomy to radiation therapy interaction term was not significant for any of the adverse event outcomes (P>.1 for all outcomes). Conclusion: Radiation therapy after prostatectomy is associated with an increase in gastrointestinal and genitourinary adverse events. However

  8. Chelating ionic liquids for reversible zinc electrochemistry.

    Science.gov (United States)

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

    2013-05-21

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

  9. Relationship between conformational flexibility and chelate cooperativity.

    Science.gov (United States)

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

    2011-04-15

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

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

    Science.gov (United States)

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

    2011-11-01

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

  11. MO-DE-303-03: Session on quantitative imaging for assessment of tumor response to radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Bowen, S. [University of Washington, School of Medicine: PET/CT and SPECT/CT for Lung and Liver Radiation Therapy Response Assessment of Tumor and Normal Tissue (United States)

    2015-06-15

    This session will focus on quantitative imaging for assessment of tumor response to radiation therapy. This is a technically challenging method to translate to practice in radiation therapy. In the new era of precision medicine, however, delivering the right treatment, to the right patient, and at the right time, can positively impact treatment choices and patient outcomes. Quantitative imaging provides the spatial sensitivity required by radiation therapy for precision medicine that is not available by other means. In this Joint ESTRO -AAPM Symposium, three leading-edge investigators will present specific motivations for quantitative imaging biomarkers in radiation therapy of esophageal, head and neck, locally advanced non-small cell lung cancer, and hepatocellular carcinoma. Experiences with the use of dynamic contrast enhanced (DCE) MRI, diffusion- weighted (DW) MRI, PET/CT, and SPECT/CT will be presented. Issues covered will include: response prediction, dose-painting, timing between therapy and imaging, within-therapy biomarkers, confounding effects, normal tissue sparing, dose-response modeling, and association with clinical biomarkers and outcomes. Current information will be presented from investigational studies and clinical practice. Learning Objectives: Learn motivations for the use of quantitative imaging biomarkers for assessment of response to radiation therapy Review the potential areas of application in cancer therapy Examine the challenges for translation, including imaging confounds and paucity of evidence to date Compare exemplary examples of the current state of the art in DCE-MRI, DW-MRI, PET/CT and SPECT/CT imaging for assessment of response to radiation therapy Van der Heide: Research grants from the Dutch Cancer Society and the European Union (FP7) Bowen: RSNA Scholar grant.

  12. 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

  13. Sequence diversity and enzyme activity of ferric-chelate reductase LeFRO1 in tomato.

    Science.gov (United States)

    Kong, Danyu; Chen, Chunlin; Wu, Huilan; Li, Ye; Li, Junming; Ling, Hong-Qing

    2013-11-20

    Ferric-chelate reductase which functions in the reduction of ferric to ferrous iron on root surface is a critical protein for iron homeostasis in strategy I plants. LeFRO1 is a major ferric-chelate reductase involved in iron uptake in tomato. To identify the natural variations of LeFRO1 and to assess their effect on the ferric-chelate reductase activity, we cloned the coding sequences of LeFRO1 from 16 tomato varieties collected from different regions, and detected three types of LeFRO1 (LeFRO1(MM), LeFRO1(Ailsa) and LeFRO1(Monita)) with five amino acid variations at the positions 21, 24, 112, 195 and 582. Enzyme activity assay revealed that the three types of LeFRO1 possessed different ferric-chelate reductase activity (LeFRO1(Ailsa) > LeFRO1(MM) > LeFRO1(Monita)). The 112th amino acid residue Ala of LeFRO1 is critical for maintaining the high activity of ferric-chelate reductase, because modification of this amino acid resulted in a significant reduction of enzyme activity. Further, we showed that the combination of the amino acid residue Ile at the site 24 with Lys at the site 582 played a positive role in the enzyme activity of LeFRO1. In conclusion, the findings are helpful to understand the natural adaptation mechanisms of plants to iron-limiting stress, and may provide new knowledge to select and manipulate LeFRO1 for improving the iron deficiency tolerance in tomato.

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

    Energy Technology Data Exchange (ETDEWEB)

    Paine, R.T.

    2000-12-12

    A large body of data has been collected over the last fifty years on the chemical behavior of f-element ions. The ions undergo rapid hydrolysis reactions in neutral or basic aqueous solutions that produce poorly understood oxide-hydroxide species; therefore, most of the fundamental f-element solution chemistry has allowed synthetic and separations chemists to rationally design advanced organic chelating ligands useful for highly selective partitioning and separation of f-element ions from complex acidic solution matrices. These ligands and new examples under development allow for the safe use and treatment of solutions containing highly radioactive species. This DOE/EMSP project was undertaken to address the following fundamental objectives: (1) study the chemical speciation of Sr and lanthanide (Ln) ions in basic aqueous media containing classical counter anions found in waste matrices; (2) prepare pyridine N-oxide phosphonates and phosphonic acids that might act as selective chelator s for Ln ions in model basic pH waste streams; (3) study the binding of the new chelators toward Ln ions and (4) examine the utility of the chelators as decontamination and dissolution agents under basic solution conditions. The project has been successful in attacking selected aspects of the very difficult problems associated with basic pH solution f-element waste chemistry. In particular, the project has (1) shed additional light on the initial stages of Ln ion sol-gel-precipitate formulation under basic solution conditions; (2) generated new families of pyridine phosphonic acid chelators; (3) characterized the function of the chelators and (4) examined their utility as oxide-hydroxide dissolution agents. These findings have contributed significantly to an improved understanding of the behavior of Ln ions in basic media containing anions found in typical waste sludges as well as to the development of sludge dissolution agents. The new chelating reagents are easily made and could be

  15. Assessment of the Effectiveness of Extracorporeal Shock Wave Therapy (ESWT) For Soft Tissue Injuries (ASSERT): An Online Database Protocol

    OpenAIRE

    Maffulli, G; Hemmings, Steph; Maffulli, Nicola

    2014-01-01

    Background Soft tissue injuries and tendinopathies account for large numbers of chronic musculoskeletal disorders. Extracorporeal shockwave therapy (ESWT) is popular, and effective in the management of chronic tendon conditions in the elbow, shoulder, and pain at and around the heel. Methods/Design Ethical approval was granted from the South East London Research Ethics Committee to implement a database for the Assessment of Effectiveness of Extracorporeal Shock Wave Therapy for Soft Tis...

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

    Science.gov (United States)

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

    2016-07-01

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

  17. Intraoperative optical assessment of photodynamic therapy response of superficial oral squamous cell carcinoma

    Science.gov (United States)

    Rohrbach, Daniel J.; Rigual, Nestor; Arshad, Hassan; Tracy, Erin C.; Cooper, Michelle T.; Shafirstein, Gal; Wilding, Gregory; Merzianu, Mihai; Baumann, Heinz; Henderson, Barbara W.; Sunar, Ulas

    2016-01-01

    This study investigated whether diffuse optical spectroscopy (DOS) measurements could assess clinical response to photodynamic therapy (PDT) in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the correlation between parameters measured with DOS and the crosslinking of signal transducer and activator of transcription 3 (STAT3), a molecular marker for PDT-induced photoreaction, was investigated. Thirteen patients with early stage HNSCC received the photosensitizer 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) and DOS measurements were performed before and after PDT in the operating room (OR). In addition, biopsies were acquired after PDT to assess the STAT3 crosslinking. Parameters measured with DOS, including blood volume fraction, blood oxygen saturation (StO2), HPPH concentration (cHPPH), HPPH fluorescence, and blood flow index (BFI), were compared to the pathologic response and the STAT3 crosslinking. The best individual predictor of pathological response was a change in cHPPH (sensitivity=60%, specificity=100%), while discrimination analysis using a two-parameter classifier (change in cHPPH and change in StO2) classified pathological response with 100% sensitivity and 100% specificity. BFI showed the best correlation with the crosslinking of STAT3. These results indicate that DOS-derived parameters can assess the clinical response in the OR, allowing for earlier reintervention if needed.

  18. Lumbar segmental instability: a criterion-related validity study of manual therapy assessment

    Directory of Open Access Journals (Sweden)

    Chapple Cathy

    2005-11-01

    Full Text Available Abstract Background Musculoskeletal physiotherapists routinely assess lumbar segmental motion during the clinical examination of a patient with low back pain. The validity of manual assessment of segmental motion has not, however, been adequately investigated. Methods In this prospective, multi-centre, pragmatic, diagnostic validity study, 138 consecutive patients with recurrent or chronic low back pain (R/CLBP were recruited. Physiotherapists with post-graduate training in manual therapy performed passive accessory intervertebral motion tests (PAIVMs and passive physiological intervertebral motion tests (PPIVMs. Consenting patients were referred for flexion-extension radiographs. Sagittal angular rotation and sagittal translation of each lumbar spinal motion segment was measured from these radiographs, and compared to a reference range derived from a study of 30 asymptomatic volunteers. Motion beyond two standard deviations from the reference mean was considered diagnostic of rotational lumbar segmental instability (LSI and translational LSI. Accuracy and validity of the clinical assessments were expressed using sensitivity, specificity, and likelihood ratio statistics with 95% confidence intervals (CI. Results Only translation LSI was found to be significantly associated with R/CLBP (p Conclusion This study provides the first evidence reporting the concurrent validity of manual tests for the detection of abnormal sagittal planar motion. PAIVMs and PPIVMs are highly specific, but not sensitive, for the detection of translation LSI. Likelihood ratios resulting from positive test results were only moderate. This research indicates that manual clinical examination procedures have moderate validity for detecting segmental motion abnormality.

  19. Elimination of hand-wrist radiographs for maturity assessment in children needing orthodontic therapy

    Energy Technology Data Exchange (ETDEWEB)

    Al Khal, Hessa A.; Wong, Ricky W.K.; Rabie, A.B.M. [University of Hong Kong, Orthodontics, Faculty of Dentistry, Prince Philip Dental Hospital, Hong Kong (China)

    2008-03-15

    Our aim was to evaluate the validity of the cervical vertebra maturation (CVM) method as an indicator of skeletal age during the circumpubertal period by correlating the CVM method with the hand-wrist maturation (HWM) method in an attempt to eliminate the need for hand-wrist radiographs for maturity assessment. Hand-wrist and lateral cephalometric radiographs of 400 Chinese were randomly selected. The age for girls was between 10 years and 15 years and for boys it was between 12 years and 17 years, so that they were within the circumpubertal period. The CVM was assessed by a method developed by Baccetti and co-workers, whereas hand-wrist maturation was assessed by Fishman's method. The CVM was significantly correlated with HWM skeletal age. (Spearman's r boys = 0.9206, girls = 0.9363). All the patients in cervical vertebra stage 3 (CVS3) of CVM corresponded to skeletal maturation indicator 2 (SMI2) or SMI3 stages of HWM (around the peak of the growth spurt). The method error was insignificant. CVM is a valid indicator of skeletal growth during the circumpubertal period. This work will provide dental practitioners with information on jaw growth modification therapy. (orig.)

  20. Functional Assessment of Cancer Therapy-Brain questionnaire: translation and linguistic adaptation to Brazilian Portuguese

    Directory of Open Access Journals (Sweden)

    Mariana Rodrigues Gazzotti

    Full Text Available CONTEXT AND OBJECTIVE: Quality of life assessment among patients with brain tumors is important, given that new treatments have increased patient survival. The aim of this study was to translate the Functional Assessment of Cancer Therapy-Brain (FACT-Br questionnaire (version 4 into Portuguese, carry out cross-cultural adaptation and assess its reproducibility. DESIGN AND SETTING: Cohort at the Universidade Federal de São Paulo (Unifesp. METHODS: Forty patients with a brain tumor seen at the neuro-oncology outpatient clinic participated in the study. The process of translation and back-translation was carried out, along with adaptation to the Portuguese language and Brazilian culture. The intraclass correlation coefficient (ICC was used to test the reproducibility of the FACT-Br (version 4. RESULTS: The reproducibility of the questionnaire was excellent (ICC = 0.95; 95% confidence interval, CI: 0.89-0.97. The ICC with a mean interval of 15 days between applications of the questionnaire was very good in all domains (ICC = 0.87 to 0.95. The mean time taken to answer the questionnaire was 6.27 ± 2.26 minutes, ranging from 3 to 11 minutes. CONCLUSION: The translated version of the FACT-Br questionnaire (version 4 adapted to the Portuguese language and Brazilian culture proved to be easily understood and achieved very good reproducibility among patients with diagnoses of brain tumors.

  1. 患者中心疗法疗效评估%Patient-centered Therapy Efficacy Assessment

    Institute of Scientific and Technical Information of China (English)

    卢雅; 王欢; 苗银宁

    2014-01-01

    Patient-centered therapy (CCT) was created by the famous American Humanism psychologist Carl o Rogers. This therapy is based on the characteristics of the patient as the center, the entire treatment process of creating a suitable environ-ment for the atmosphere and the patient to alleviate the patient's anxiety. This article will be based on collecting and collating documents, to assess the efficacy of CCT.%患者中心疗法(CCT)由美国著名人本主义心理学家卡尔·罗杰斯倡导创立。这种疗法的特点是以患者为中心,在整个治疗过程中为患者创造适宜的气氛和环境,以减轻患者的焦虑。本文将在文献搜集和整理的基础上,对CCT的疗效进行评估。

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

    Science.gov (United States)

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

    2012-06-07

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

  3. 77 FR 71194 - Draft Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy...

    Science.gov (United States)

    2012-11-29

    ... Investigational Cellular and Gene Therapy Products; Availability AGENCY: Food and Drug Administration, HHS. ACTION... for Biologics Research and Evaluation (CBER), Office of Cellular, Tissue, and Gene Therapies (OCTGT). The product areas covered by this guidance are cellular therapy, gene therapy, therapeutic...

  4. Computed tomography assessment of early response to neoadjuvant therapy in colon cancer

    DEFF Research Database (Denmark)

    Dam, Claus; Lund-Rasmussen, Vera; Pløen, John;

    2015-01-01

    INTRODUCTION: Using multidetector computed tomography, we aimed to assess the early response of neoadjuvant drug therapy for locally advanced colon cancer. METHODS: Computed tomography with IV contrast was acquired from 67 patients before and after up to three cycles of preoperative treatment. All...... patients had histologically confirmed colon cancer, a T4 or T3 tumour with extramural invasion ≥ 5 mm and no distant metastases or peritoneal nodules. The patients were treated with oxaliplatin and capecitabine. In addition, those with no mutations in the KRAS, BRAF and PIK3CA genes were also treated.......1, 45% (95% CI: 34-57) of the patients had a response and 55% (95% CI: 43-67) had stable disease. None of the patients showed progressive disease. CONCLUSION: Using CT, we demonstrated a significant reduction in tumour size, extramural tumour invasion, number and size of enlarged lymph nodes following...

  5. Methodology for assessment of low level laser therapy (LLLT) irradiation parameters in muscle inflammation treatment

    Science.gov (United States)

    Mantineo, M.; Pinheiro, J. P.; Morgado, A. M.

    2013-11-01

    Several studies in human and animals show the clinical effectiveness of low level laser therapy (LLLT) in reducing some types of pain, treating inflammation and wound healing. However, more scientific evidence is required to prove the effectiveness of LLLT since many aspects of the cellular and molecular mechanisms triggered by irradiation of injured tissue with laser remain unknown. Here, we present a methodology that can be used to evaluate the effect of different LLLT irradiation parameters on the treatment of muscle inflammation on animals, through the quantification of four cytokines (TNF-α, IL-1β, IL-2 and IL-6) in systemic blood and histological analysis of muscle tissue. We have used this methodology to assess the effect of LLLT parameters (wavelength, dose, power and type of illumination) in the treatment of inflammation induced in the gastrocnemius muscle of Wistar rats. Results obtained for laser dose evaluation with continuous illumination are presented.

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

    Science.gov (United States)

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

    2007-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-09-15

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

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

    Science.gov (United States)

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

    2017-02-01

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

  9. Face Validity of the Functional Assessment of Cancer Therapy-Breast Symptom Index (FACT- B into Formal Arabic

    Directory of Open Access Journals (Sweden)

    Loulou Kobeissi

    2014-06-01

    Full Text Available Background: Breast cancer affects over one million women annually and is the most common global malignancy among women. Extensive improvements have taken place in the management of breast cancer in recent years and a higher percentage of women are cured from this disease. A proper assessment of the quality of life of women with breast cancer is an essential component in disease management. The Functional Assessment of Cancer Therapy- Breast Symptom Index has been commonly used and well-validated among English speaking populations as well as other populations. To date, no formal translation and evaluation of the Functional Assessment of Cancer Therapy-Breast System Index exists in Arabic. Therefore, this study intends to translate, adapt and face-validate the Functional Assessment of Cancer Therapy-Breast System Index into Arabic, specifically in the context of the Lebanese culture. Methods: We conducted forward and backward translation in Arabic, combined with face validity by clinicians. This was followed by pre-testing to ensure the instrument’s adequacy and cultural sensitivity conducted by the administration of face-to-face interviews with individual breast cancer patients (n=33 and two focus groups (4 women/group to evaluate the relevance and appropriateness of each item and words used in the questionnaire. Results: Study results reinforced the value of the Arabic translated version of the Functional Assessment of Cancer Therapy-Breast System Index in capturing the quality of life of women with breast cancer in Lebanon. Conclusion: The instrument was perceived to be adequate, appropriate for use, culturally sensitive, simple as well as exhaustive. Suggestions have been made to enrich the instruments’ ability to incorporate other quality of life dimensions not captured, as well to enhance the cultural specificity of the Functional Assessment of Cancer Therapy-Breast System Index, when administered among Lebanese women diagnosed with

  10. Preliminary assessment of one-dimensional MR elastography for use in monitoring focused ultrasound therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yuan Le [Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, MN 55905 (United States); Glaser, Kevin J [Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic Foundation, 200 1st St. SW, Rochester, MN 55905, Rochester, MN 55905 (United States); Rouviere, Olivier [Department of GenitoUrinary Radiology, Hopital E Herriot, 5, place d' Arsonval, 69003 Lyon (France); Gorny, Krzysztof R [Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic Foundation, 200 1st St. SW, Rochester, MN 55905, Rochester, MN 55905 (United States); Chen, Shigao [Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic Foundation, 200 1st St. SW, Rochester, MN 55905, Rochester, MN 55905 (United States); Manduca, Armando [Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic Foundation, 200 1st St. SW, Rochester, MN 55905, Rochester, MN 55905 (United States); Ehman, Richard L [Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic Foundation, 200 1st St. SW, Rochester, MN 55905, Rochester, MN 55905 (United States); Felmlee, Joel P [Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic Foundation, 200 1st St. SW, Rochester, MN 55905, Rochester, MN 55905 (United States)

    2007-09-21

    The purpose of this work is to assess a fast technique that measures tissue stiffness and temperature during focused ultrasound thermal therapy (FUS). A one-dimensional (1D) MR elastography (MRE) pulse sequence was evaluated for the purpose of obtaining rapid measurements of thermally induced changes in tissue stiffness and temperature for monitoring FUS treatments. The accuracy of the 1D measurement was studied by comparing tissue displacements measured by 1D MRE with those measured by the well-established 2D MRE pulse sequence. The reproducibility of the 1D MRE measurement was assessed, in gel phantoms and ex vivo porcine tissue, for varied FUS intensity levels (31.5-199.9 W cm{sup -2}) and over a range of displacements at the focus (0.1-1 {mu}m). Temperature elevations in agarose gel phantoms were measured using 1D MRE and calibrated using fiberoptic-thermometer-based measurements. The 1D MRE displacement measurements are highly correlated with those obtained with the 2D technique (R{sup 2} = 0.88-0.93), indicating that 1D MRE can successfully measure tissue displacement. Ten repeated trials at each FUS power level yielded a minimum detectable displacement change of 0.2 {mu}m in phantoms and 0.4 {mu}m in tissue (at 95% confidence level). The 1D MRE temperature measurements correlated well with temperature changes measured simultaneously with fiberoptic thermometers (R{sup 2} = 0.97). The 1D MRE technique is capable of detecting tissue displacements as low as 0.4 {mu}m, which is an order of magnitude smaller than 5 {mu}m displacements expected during FUS therapy (Le et al 2005 AIP Conf. Proc.: Ther. Ultrasound 829 186-90). Additionally, 1D MRE was shown to provide adequate measurements of temperature elevations in tissue. These findings indicate that 1D MRE may be an effective tool for monitoring FUS treatments.

  11. Curcumin induces apoptosis and protective autophagy in castration-resistant prostate cancer cells through iron chelation

    Science.gov (United States)

    Yang, Chunguang; Ma, Xueyou; Wang, Zhihua; Zeng, Xing; Hu, Zhiquan; Ye, Zhangqun; Shen, Guanxin

    2017-01-01

    Background Curcumin induces apoptosis and autophagy in different cancer cells. Moreover, chemical and biological experiments have evidenced that curcumin is a biologically active iron chelator and induces cytotoxicity through iron chelation. We thus hypothesized that curcumin may induce apoptosis and autophagy in castration-resistant prostate cancer (CRPC) cells through its iron-chelating properties. Materials and methods CRPC cells were loaded with curcumin alone or in combination with ferric ammonium citrate (FAC). Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was assessed by flow cytometry, terminal deoxynucleotidyl transferase nick end labeling (TUNEL) assay and caspase activity. Autophagy status was analyzed by the detection of autophagosomes and light chain 3-II (LC3-II) using transmission electron microscopy and Western blot. Iron-binding activity of curcumin was assessed by spectrophotometry and MTT assay. The expression levels of transferrin receptor 1 (TfR1) and iron regulatory protein 1 (IRP1) were examined by Western blot. Results Curcumin induced apoptosis and autophagy in CRPC cells. Combining curcumin with autophagy inhibitors (3-methyladenine [3-MA]) synergized the apoptotic effect of curcumin. Moreover, curcumin bound to FAC at a ratio of ~1:1, as assessed by spectrophotometry and MTT assay. Apoptosis and autophagy induced by curcumin were counteracted by equal amounts of FAC. At apoptosis- and autophagy-inducing concentrations, curcumin enhanced the expression levels of TfR1 and IRP1, indicative of iron deprivation induced by curcumin. Conclusion Together, our results indicate that curcumin induces apoptosis and protective autophagy in CRPC cells, which are at least partially dependent on its iron-chelating properties. PMID:28243065

  12. 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.

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

    Science.gov (United States)

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

    2007-05-16

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

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

    Institute of Scientific and Technical Information of China (English)

    HU Binghuan; CHEN Riyao; LIN Jinhuo; CHEN Wending

    1994-01-01

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

  15. A calcium-collagen chelate dietary supplement attenuates bone loss in postmenopausal women with osteopenia: a randomized controlled trial.

    Science.gov (United States)

    Elam, Marcus L; Johnson, Sarah A; Hooshmand, Shirin; Feresin, Rafaela G; Payton, Mark E; Gu, Jennifer; Arjmandi, Bahram H

    2015-03-01

    Menopause leads to an increased risk for osteoporosis in women. Although drug therapies exist, increasing numbers of people prefer alternative therapies such as dietary supplements, for example, calcium, vitamin D, and collagen hydrolysates for the prevention and treatment of osteoporosis. We have previously shown that a 3-month intervention using a calcium-collagen chelate (CC) dietary supplement was efficacious in improving bone mineral density (BMD) and blood biomarkers of bone turnover in osteopenic postmenopausal women. This study reports the long-term efficacy of CC in reducing bone loss in postmenopausal women with osteopenia. Thirty-nine women were randomly assigned to one of two groups: 5 g of CC containing 500 mg of elemental calcium and 200 IU vitamin D (1,25-dihydroxyvitamin D3) or control (500 mg of calcium and 200 IU vitamin D) daily for 12 months. Total body, lumbar, and hip BMD were evaluated at baseline, 6 and 12 months using dual-energy X-ray absorptiometry. Blood was collected at baseline, 6 and 12 months to assess levels of blood biomarkers of bone turnover. Intent-to-treat (ITT) analysis was performed using repeated measures analysis of variance pairwise comparisons and multivariate analysis to assess time and group interactions. The loss of whole body BMD in women taking CC was substantially lower than that of the control group at 12 months in those who completed the study and the ITT analysis, respectively (CC: -1.33% and -0.33% vs. control: -3.75% and -2.17%; P=.026, P=.035). The CC group had significantly reduced levels of sclerostin and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) (P<.05), and higher bone-specific alkaline phosphatase/TRAP5b ratio (P<.05) than control at 6 months. These results support the use of CC in reducing bone loss in osteopenic postmenopausal women.

  16. Synergistic effect of chelators and Herbaspirillum sp. GW103 on lead phytoextraction and its induced oxidative stress in Zea mays.

    Science.gov (United States)

    Govarthanan, Muthusamy; Kamala-Kannan, Seralathan; Kim, Seol Ah; Seo, Young-Seok; Park, Jung-Hee; Oh, Byung-Taek

    2016-10-01

    Phytoremediation is an in situ, low-cost strategy for cleanup of the sites contaminated with heavy metals. Experiments were conducted to assess the impact of synthetic chelators and plant growth-promoting rhizosphere bacteria (Herbaspirillum sp. GW103) on heavy metal lead (Pb) uptake in Z. mays cultivated in Pb-contaminated soil. The present study investigated the Pb phytoaccumulation rate and plant antioxidant enzyme activities in Z. mays exposed to 100 mg/kg of PbNO3. The combination of gluconic acid (GA) with Herbaspirillum sp. GW103 treatment showed higher Pb solubility (18.9 mg/kg) compared with other chelators. The chemical chelators showed the significant difference in phytoaccumulation as well as antioxidant enzyme activities. The antioxidant enzymes such as catalase, peroxidase and superoxide dismutase activities changed under Pb stress. The study indicated that increased activity of antioxidant enzymes may play as signal inducers to fight against Pb.

  17. Assessing treatment motivation among patients receiving antiretroviral therapy: a multidimensional approach.

    Science.gov (United States)

    Houston, Eric; McKirnan, David J; Cervone, Daniel; Johnson, Matthew S; Sandfort, Theo G M

    2012-01-01

    Using multidimensional scaling (MDS) analysis, this study examined how patient conceptualisations of treatment motivation compare with theoretically based assumptions used in current assessment approaches. Patients undergoing antiretroviral therapy for HIV/AIDS (n=39) rated for similarity between all possible pairings of 23 treatment descriptions, including descriptors of intrinsic, extrinsic, approach and avoidance motivation. MDS analyses revealed that patient perceptions of intrinsic and extrinsic motivations often differ from those based on definitions derived from common interpretations of self-determination theory. Findings also showed that patients reported motivation for avoiding treatment when they associated their medication regimens with side effects and other negatively valenced outcomes. The study describes new applications of MDS in assessing how patients perceive the relationship between treatment behaviours and specific forms of motivation, such as intrinsic and extrinsic motivations. In addition, the study suggests how MDS may be used to develop behavioural strategies aimed at helping patients follow their regimens consistently by identifying treatment conceptualisations and contexts that facilitate or impede adherence.

  18. Longitudinal liver stiffness assessment in patients with chronic hepatitis C undergoing antiviral therapy.

    Directory of Open Access Journals (Sweden)

    Stella M Martinez

    Full Text Available BACKGROUND/AIMS: Liver stiffness (LS measurement by means of transient elastography (TE is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC. METHODS: TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. RESULTS: 323 treated (62.7% and 192 untreated patients (37.3% were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001. The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥ 9.5 and ≥ 7.1 kPa vs lower values, respectively. Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change -16%, -10% and -2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR. In multivariate analysis, high baseline LS (P<0.0001 and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. CONCLUSIONS: LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS and suggests an improvement in liver damage.

  19. Longitudinal Liver Stiffness Assessment in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy

    Science.gov (United States)

    Martinez, Stella M.; Foucher, Juliette; Combis, Jean-Marc; Métivier, Sophie; Brunetto, Maurizia; Capron, Dominique; Bourlière, Marc; Bronowicki, Jean-Pierre; Dao, Thong; Maynard-Muet, Marianne; Lucidarme, Damien; Merrouche, Wassil; Forns, Xavier; de Lédinghen, Victor

    2012-01-01

    Background/Aims Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC). Methods TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. Results 323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001). The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥9.5 and ≥7.1 kPa vs lower values, respectively). Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change −16%, −10% and −2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR). In multivariate analysis, high baseline LS (P<0.0001) and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. Conclusions LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS) and suggests an improvement in liver damage. PMID:23082200

  20. A randomized prospective study to assess the efficacy of two cold-therapy treatments following carpal tunnel release.

    Science.gov (United States)

    Hochberg, J

    2001-01-01

    A prospective randomized study was performed comparing the efficacy of controlled cold therapy (CCT) with the efficacy of ice therapy in the postoperative treatment of 72 patients with carpal tunnel syndrome. Immediately after surgery, patients applied either a temperature-controlled cooling blanket (CCT) or a standard ice pack over their surgical dressings. Pain was assessed by visual analog scale and swelling by wrist circumference preoperatively, immediately after surgery, and on postoperative day 3. Patients kept log books of daily treatment times. Narcotic use (of Vicodin ES) was determined by pill count at day 3 and by daily log book recordings. Patients who used CCT showed significantly greater reduction in pain, edema (wrist circumference), and narcotic use at postoperative day 3 than did those using ice therapy. This study indicates that after carpal tunnel surgery, the use of CCT, compared with traditional ice therapy, provides patients with greater comfort and lessens the need for narcotics.

  1. Approaching low liver iron burden in chelated patients with non-transfusion-dependent thalassemia: the safety profile of deferasirox

    Science.gov (United States)

    Taher, Ali T; Porter, John B; Viprakasit, Vip; Kattamis, Antonis; Chuncharunee, Suporn; Sutcharitchan, Pranee; Siritanaratkul, Noppadol; Origa, Raffaella; Karakas, Zeynep; Habr, Dany; Zhu, Zewen; Cappellini, M Domenica

    2014-01-01

    Objective Patients with non-transfusion-dependent thalassemia (NTDT) often develop iron overload and related complications, and may require iron chelation. However, the risk of over-chelation emerges as patients reach low, near-normal body iron levels and dose adjustments may be needed. In the THALASSA study, the threshold for chelation interruption was LIC <3 mg Fe/g dw (LIC<3); 24 patients receiving deferasirox for up to 2 yr reached this target. A post hoc analysis was performed to characterize the safety profile of deferasirox as these patients approached LIC<3. Methods THALASSA was a randomized, double-blind, placebo-controlled study of two deferasirox regimens (5 and 10 mg/kg/d) versus placebo in patients with NTDT. Patients randomized to deferasirox or placebo in the core could enter a 1-yr extension, with all patients receiving deferasirox (extension starting doses based on LIC at end-of-core and prior chelation response). The deferasirox safety profile was assessed between baseline and 6 months before reaching LIC<3 (Period 1), and the 6 months immediately before achieving LIC<3 (Period 2). Results Mean ± SD deferasirox treatment duration up to reaching LIC<3 was 476 ± 207 d, and deferasirox dose was 9.7 ± 3.0 mg/kg/d. The exposure-adjusted AE incidence regardless of causality was similar in periods 1 (1.026) and 2 (1.012). There were no clinically relevant differences in renal and hepatic laboratory parameters measured close to the time of LIC<3 compared with measurements near the previous LIC assessment. Conclusions The deferasirox safety profile remained consistent as patients approached the chelation interruption target, indicating that, with appropriate monitoring and dose adjustments in relation to iron load, low iron burdens may be reached with deferasirox with minimal risk of over-chelation. PMID:24460655

  2. Low Impact of Urinary Cortisol in the Assessment of Hydrocortisone Replacement Therapy.

    Science.gov (United States)

    Haas, C S; Rahvar, A-H; Danneberg, S; Lehnert, H; Moenig, H; Harbeck, B

    2016-09-01

    Hydrocortisone replacement therapy is a cornerstone in the treatment of adrenal insufficiency (AI). While urinary cortisol has been used as a diagnostic tool for AI, it remains unclear whether it is a useful parameter to monitor hydrocortisone replacement therapy. Aim of this study was to evaluate possible differences in cortisol metabolism between adrenal insufficient patients and healthy subjects and to assess the value of urinary cortisol in AI management. In a case-control study, urinary cortisol excretion was determined in 14 patients with primary and secondary AI receiving hydrocortisone infusions from midnight to 8:00 AM. Results were correlated with serum cortisol levels and compared to urinary values obtained from 53 healthy volunteers. Urinary cortisol excretion in healthy subjects was 14.0±7.8 μg/8 h (range: 0.24-35.4), levels did not differ between 3 groups aged 20-34 years, 35-49 years, and ≥50 years. Patients with AI receiving hydrocortisone infusions demonstrated significantly higher rates of urinary cortisol excretion (51.6±37.8 μg/8 h; range 17.1-120.0, pcortisol levels (r(2)=0.98). Of interest, patients with secondary AI showed significantly higher serum cortisol levels after hydrocortisone infusion than those with primary AI, conceivably due to residual adrenal function. In conclusion, we showed that: (i) there is a wide inter-individual variability in urinary cortisol excretion rates; (ii) cortisol metabolism in adrenal insufficient patients differs when compared to controls; (iii) there is a strong correlation between urinary and serum cortisol levels; and (iv) urinary cortisol levels despite their variability may help to discriminate between secondary and primary adrenal insufficiency.

  3. Assessing Morphological Awareness as a Predictor of Academic Performance and Performance on the National Physical Therapy Examination

    Science.gov (United States)

    Moran, Kelley A.

    2012-01-01

    The primary purpose of this study was to validate a method for assessing Morphological Awareness (MA) using multimorphemic words commonly used in the academic and clinical practice settings of physical therapy. The Medical Morphology Test (MMT) was developed for this study and was compared to scores on the Nelson-Denny Reading Test (NDRT©). The…

  4. Can virtual reality exposure therapy gains be generalized to real life? A meta-analysis of studies applying behavioral assessments

    NARCIS (Netherlands)

    Morina, N.; Ijntema, H.; Meyerbröker, K.; Emmelkamp, P.M.G.

    2015-01-01

    In virtual reality exposure therapy (VRET), patients are exposed to virtual environments that resemble feared real-life situations. The aim of the current study was to assess the extent to which VRET gains can be observed in real-life situations. We conducted a meta-analysis of clinical trials apply

  5. Assessment of the Prerequisite Skills for Cognitive Behavioral Therapy in Children with and without Autism Spectrum Disorders

    Science.gov (United States)

    Lickel, Athena; MacLean, William E., Jr.; Blakeley-Smith, Audrey; Hepburn, Susan

    2012-01-01

    The purpose of this study was to assess the cognitive skills of children with autism spectrum disorders (ASD) thought to be necessary for Cognitive Behavioral Therapy (CBT). Forty children with ASD and forty age-matched typically developing children between the ages of 7-12 years participated. Groups were comparable with regard to nonverbal IQ,…

  6. Assessment of the effectiveness of yoga therapy as an adjunct in patients with alcohol dependence syndrome

    Directory of Open Access Journals (Sweden)

    Dipesh Bhagabati

    2017-01-01

    Full Text Available Introduction: Substance use disorders, alcohol use in particular, are among the leading disorders in psychiatry in terms of prevalence. They put a lot of burden on health as well as family, society, and economic status of the patient. What more challenging is that such patients often suffer from comorbid anxiety and depression, which has the potential to perpetuate the alcohol use. Yoga is an alternative and complementary therapy which is widely practiced by people in India. However, its effectiveness in alcohol use disorders is not tested systematically. Aims and objectives: To study the effectiveness of yoga as an adjunctive therapy in patients of alcohol use disorders and to evaluate its ability to reduce comorbid depression, anxiety, and craving. Materials and methods: Hundred patients of alcohol use disorders as per the tenth revision of the International Classification of Diseases and Related Health Problems (ICD-10 were selected and were divided into two groups each containing 50 patients. The case group received structured yoga session in addition to standard pharmacotherapy while the control group received only pharmacotherapy. Assessment of depression (Hamilton depression rating scale [HAM-D], anxiety (Hamilton anxiety rating scale [HAM-A], and craving (Obsessive-compulsive drinking scale [OCDS] was done at baseline, two weeks, and at one month. Results were compared between the two groups and statistical analysis was done. Results: Both the case and control groups were similar in HAM-D (p=0.9634, HAM-A (p=0.7744, and OCDS (p= 0.8626 scores at baseline. There was significant reduction in HAM-A score at one month (p=0.0091, and OCDS score at two weeks (p=0.0428 and one month (p<0.0001 respectively in yoga group as compared to control group. Within case group, only reduction in HAM-A (p<0.001 and p<0.01 and OCDS (p<0.0001 and p<0.0001 scores were progressively better statistically at two weeks and one month while reduction in HAM-D score

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

    Science.gov (United States)

    1992-09-15

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

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

    Directory of Open Access Journals (Sweden)

    Shuanglong Liu

    2014-04-01

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

  9. Metal chelate process to remove pollutants from fluids

    Science.gov (United States)

    Chang, Shih-Ger T.

    1994-01-01

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

  10. A Brief Review of Chelators for Radiolabeling Oligomers

    Directory of Open Access Journals (Sweden)

    Yuxia Liu

    2010-05-01

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

  11. 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.

  12. Effect of Ionic and Chelate Assisted Hexavalent Chromium on Mung Bean Seedlings (Vigna radiata L. wilczek. var k-851 During Seedling Growth

    Directory of Open Access Journals (Sweden)

    Mohanty, Monalisa

    2013-04-01

    Full Text Available The effect of Cr+6 with and without chelating agents were assessed in mung bean seedlings grown hydroponically. It was noted that the growth parameters showed a declining trend with increasing Cr+6 concentrations without chelate application. Among the seedlings grown with chelated chromium complexes, Cr+6–DTPA (10µM showed highest growth rate of roots as well as shoots. At higher concentration of Chromium i.e. Cr+6 (100µM, there exhibited high chlorophyll content in mung bean leaves where the seedlings showed stunted growth. The seedlings treated without and with chelated chromium complexes showed increased proline content as compared to control. The enzymatic study showed that, the catalase activity was maximum in shoots as compared to roots and the reverse is true in the case of peroxidase activity i.e. the roots showed higher value than that of the shoots.

  13. Chelated Ruthenium Catalysts for Z-Selective Olefin Metathesis

    Science.gov (United States)

    Endo, Koji; Grubbs, Robert H.

    2011-01-01

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

  14. Iron Chelation Adherence to Deferoxamine and Deferasirox in Thalassemia

    OpenAIRE

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

    2011-01-01

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

  15. Radiation binary targeted therapy for HER-2 positive breast cancers: assumptions, theoretical assessment and future directions

    Energy Technology Data Exchange (ETDEWEB)

    Mundy, Daniel W [School of Nuclear Engineering, Purdue University, 400 Central Drive, West Lafayette, IN 47909 (United States); Harb, Wael [Horizon Oncology, The Care Group, Unity Medical Center, Lafayette, IN 47901 (United States); Jevremovic, Tatjana [School of Nuclear Engineering, Purdue University, 400 Central Drive, West Lafayette, IN 47909 (United States)

    2006-03-21

    A novel radiation targeted therapy is investigated for HER-2 positive breast cancers. The proposed concept combines two known approaches, but never used together for the treatment of advanced, relapsed or metastasized HER-2 positive breast cancers. The proposed radiation binary targeted concept is based on the anti HER-2 monoclonal antibodies (MABs) that would be used as vehicles to transport the nontoxic agent to cancer cells. The anti HER-2 MABs have been successful in targeting HER-2 positive breast cancers with high affinity. The proposed concept would utilize a neutral nontoxic boron-10 predicting that anti HER-2 MABs would assure its selective delivery to cancer cells. MABs against HER-2 have been a widely researched strategy in the clinical setting. The most promising antibody is Trastuzumab (Herceptin (registered) ). Targeting HER-2 with the MAB Trastuzumab has been proven to be a successful strategy in inducing tumour regression and improving patient survival. Unfortunately, these tumours become resistant and afflicted women succumb to breast cancer. In the proposed concept, when the tumour region is loaded with boron-10 it is irradiated with neutrons (treatment used for head and neck cancers, melanoma and glioblastoma for over 40 years in Japan and Europe). The irradiation process takes less than an hour producing minimal side effects. This paper summarizes our recent theoretical assessments of radiation binary targeted therapy for HER-2 positive breast cancers on: the effective drug delivery mechanism, the numerical model to evaluate the targeted radiation delivery and the survey study to find the neutron facility in the world that might be capable of producing the radiation effect as needed. A novel method of drug delivery utilizing Trastuzumab is described, followed by the description of a computational Monte Carlo based breast model used to determine radiation dose distributions. The total flux and neutron energy spectra of five currently available

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  17. Iron Chelation Adherence to Deferoxamine and Deferasirox in Thalassemia

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Wai, Chien M.; Laintz, Kenneth E.

    1998-01-01

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

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

    Science.gov (United States)

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

    1998-03-24

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

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

    Science.gov (United States)

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

    2011-05-01

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

  1. Objective Assessment of Vergence and Accommodation After Vision Therapy for Convergence Insufficiency in a Child: A Case Report

    Directory of Open Access Journals (Sweden)

    Mitchell Scheiman, OD

    2014-01-01

    Full Text Available Background: To evaluate objective changes in vergence and accommodation after treatment of symptomatic convergence insufficiency (CI with office-based optometric vision therapy in a pediatric patient. Case Report: A 10-year, 10-month-old child with symptomatic CI was treated with 16 visits of office-based vision therapy with home reinforcement. Pre- and post-therapy testing included both traditional clinical measures and objective laboratory measures of vergence and accommodation. The main clinical outcome measures were the CI Symptom Survey (CISS, near point of convergence (NPC, positive fusional vergence range at near (PFV, accommodative amplitude, and accommodative facility. The objective vergence range outcome measures were peak velocity, time constant, total response time, and steady-state response variability as assessed with the Power Refractor II. The objective accommodative outcome measures were peak velocity, time constant, total response time, steady-state response variability, and steady-state level, as assessed with the Grand Seiko WAM-5500. Most accommodative and vergence objective laboratory parameters improved/normalized following the vision therapy. Gains were greater for vergence than for accommodation. These objective measures confirmed the concurrent improvements in the clinical tests and markedly reduced symptom levels. Conclusions: This is the first study to document, objectively, improvements in laboratory-based dynamic measures of both accommodation and vergence following conventional office-based optometric vision therapy for CI in a child. Objective oculomotor measures can and should be performed in similar future studies in children, as well as in adults

  2. Flattening filter-free accelerators: a report from the AAPM Therapy Emerging Technology Assessment Work Group.

    Science.gov (United States)

    Xiao, Ying; Kry, Stephen F; Popple, Richard; Yorke, Ellen; Papanikolaou, Niko; Stathakis, Sotirios; Xia, Ping; Huq, Saiful; Bayouth, John; Galvin, James; Yin, Fang-Fang

    2015-05-08

    This report describes the current state of flattening filter-free (FFF) radiotherapy beams implemented on conventional linear accelerators, and is aimed primarily at practicing medical physicists. The Therapy Emerging Technology Assessment Work Group of the American Association of Physicists in Medicine (AAPM) formed a writing group to assess FFF technology. The published literature on FFF technology was reviewed, along with technical specifications provided by vendors. Based on this information, supplemented by the clinical experience of the group members, consensus guidelines and recommendations for implementation of FFF technology were developed. Areas in need of further investigation were identified. Removing the flattening filter increases beam intensity, especially near the central axis. Increased intensity reduces treatment time, especially for high-dose stereotactic radiotherapy/radiosurgery (SRT/SRS). Furthermore, removing the flattening filter reduces out-of-field dose and improves beam modeling accuracy. FFF beams are advantageous for small field (e.g., SRS) treatments and are appropriate for intensity-modulated radiotherapy (IMRT). For conventional 3D radiotherapy of large targets, FFF beams may be disadvantageous compared to flattened beams because of the heterogeneity of FFF beam across the target (unless modulation is employed). For any application, the nonflat beam characteristics and substantially higher dose rates require consideration during the commissioning and quality assurance processes relative to flattened beams, and the appropriate clinical use of the technology needs to be identified. Consideration also needs to be given to these unique characteristics when undertaking facility planning. Several areas still warrant further research and development. Recommendations pertinent to FFF technology, including acceptance testing, commissioning, quality assurance, radiation safety, and facility planning, are presented. Examples of clinical

  3. Assessing client self-narrative change in emotion-focused therapy of depression: an intensive single case analysis.

    Science.gov (United States)

    Angus, Lynne E; Kagan, Fern

    2013-12-01

    Personality researchers use the term self-narrative to refer to the development of an overall life story that places life events in a temporal sequence and organizes them in accordance to overarching themes. In turn, it is often the case that clients seek out psychotherapy when they can no longer make sense of their life experiences, as a coherent story. Angus and Greenberg (L. Angus and L. Greenberg, 2011, Working with narrative in emotion-focused therapy: Changing stories, healing lives. Washington, DC: American Psychological Association Press) view the articulation and consolidation of an emotionally integrated self-narrative account as an important part of the therapeutic change process that is essential for sustained change in emotion-focused therapy of depression. The purpose of the present study was to investigate client experiences of change, and self-narrative reconstruction, in the context of one good outcome emotion-focused therapy dyad drawn from the York II Depression Study. Using the Narrative Assessment Interview (NAI) method, client view of self and experiences of change were assessed at three points in time--after session one, at therapy termination, and at 6 months follow-up. Findings emerging from an intensive narrative theme analyses of the NAI transcripts--and 1 key therapy session identified by the client--are reported and evidence for the contributions of narrative and emotion processes to self-narrative change in emotion-focused therapy of depression are discussed. Finally, the implications of assessing clients' experiences of self-narrative change for psychotherapy research and practice are addressed.

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

    Institute of Scientific and Technical Information of China (English)

    LINWeiping; LUYun; 等

    1992-01-01

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

  5. Systemic Cyclosporine Therapy for Scleritis: A Proposal of a Novel System to Assess the Activity of Scleritis

    Directory of Open Access Journals (Sweden)

    Haruka Aoki

    2015-05-01

    Full Text Available In the present study, two female patients with unilateral scleritis without systemic complications were examined. Both patients were suffering from ocular pain and received corticosteroid therapy. The first patient, a 45-year-old woman, was diagnosed with scleritis and iritis in her right eye. Topical corticosteroid treatment could eradicate the iritis but not the scleritis. Oral corticosteroid administration and corticosteroid pulse therapy were applied with little effect. The application of systemic cyclosporine had a satisfactory effect in controlling the scleritis. The other patient, a 60-year-old woman, was suffering from scleritis and lid swelling in her right eye. Not only did topical and systemic corticosteroid therapy prove insufficient, they also resulted in the elevation of her intraocular pressure. After termination of corticosteroid therapy, the systemic cyclosporine was applied orally. Subsequently, the patient's scleritis improved without any severe side effects. Scleritis is a painful and destructive inflammatory disease of the sclera that causes congestion of the scleral venous plexus. In this study, we have established a new grading system for assessing activity in scleritis that can score the extent of ocular pain and the area of congestion. This system provides a practical method for following the clinical course and monitoring the outcome of therapy. We report two cases of unilateral scleritis that were resistant to corticosteroid therapy but responsive to systemic administration of cyclosporine. Findings from these cases indicate that cyclosporine is an effective drug for controlling severe scleritis.

  6. Systemic Cyclosporine Therapy for Scleritis: A Proposal of a Novel System to Assess the Activity of Scleritis.

    Science.gov (United States)

    Aoki, Haruka; Hiraoka, Miki; Hashimoto, Masato; Ohguro, Hiroshi

    2015-01-01

    In the present study, two female patients with unilateral scleritis without systemic complications were examined. Both patients were suffering from ocular pain and received corticosteroid therapy. The first patient, a 45-year-old woman, was diagnosed with scleritis and iritis in her right eye. Topical corticosteroid treatment could eradicate the iritis but not the scleritis. Oral corticosteroid administration and corticosteroid pulse therapy were applied with little effect. The application of systemic cyclosporine had a satisfactory effect in controlling the scleritis. The other patient, a 60-year-old woman, was suffering from scleritis and lid swelling in her right eye. Not only did topical and systemic corticosteroid therapy prove insufficient, they also resulted in the elevation of her intraocular pressure. After termination of corticosteroid therapy, the systemic cyclosporine was applied orally. Subsequently, the patient's scleritis improved without any severe side effects. Scleritis is a painful and destructive inflammatory disease of the sclera that causes congestion of the scleral venous plexus. In this study, we have established a new grading system for assessing activity in scleritis that can score the extent of ocular pain and the area of congestion. This system provides a practical method for following the clinical course and monitoring the outcome of therapy. We report two cases of unilateral scleritis that were resistant to corticosteroid therapy but responsive to systemic administration of cyclosporine. Findings from these cases indicate that cyclosporine is an effective drug for controlling severe scleritis.

  7. Quantitative assessment of the response to therapy in achalasia of the cardia.

    Science.gov (United States)

    Robertson, C S; Hardy, J G; Atkinson, M

    1989-06-01

    Radionuclide oesophageal transit studies and manometry have been carried out in 15 patients with achalasia of the cardia, before treatment, after a course of nifedipine and after pneumatic bag dilatation. Transit studies were also done in 10 patients after cardiomyotomy and in 10 normal subjects. Images were recorded with the subjects seated in front of a gamma camera while swallowing a 10 ml bolus of 99Tcm-tin colloid and then after a further drink of 50 ml water. There was marked retention of tracer in the oesophagus in patients with achalasia compared with rapid clearance in control subjects. Bag dilatation significantly reduced lower oesophageal sphincter pressure but there was no significant difference in the 50% clearance time or percentage dose retained at 100s before and after the treatments. Oesophageal clearance of tracer after the additional drink of water, was improved by bag dilatation. Oesophageal transit in the patients after cardiomyotomy was similar to that in patients who had undergone bag dilatation. There was considerable retention of the tracer in the oesophagus overnight, but this did not result in pulmonary aspiration. Radionuclide oesophageal transit studies provided a quantitative assessment of therapy in achalasia and the proportion of tracer retained after the additional drink proved to be a sensitive measure of response to treatment. Nifedipine proved ineffective as a treatment for achalasia. Bag dilatation and cardiomyotomy were of similar value.

  8. Photodynamic therapy induces epidermal thickening in hairless mice skin: an optical coherence tomography assessment

    Science.gov (United States)

    Jorge, Ana Elisa S.; Campos, Carolina P.; Freitas, Anderson Z.; Bagnato, Vanderlei S.

    2014-03-01

    Photodynamic therapy (PDT) promotes skin improvement according to many practitioners, however the immediately in vivo assessment of its response remains clinically inaccessible. As a non-invasive modality, optical coherence tomography (OCT) has been shown a feasible optical diagnostic technique that provides images in real time, avoiding tissue biopsies. For this reason, our investigation focused on evaluates the PDT effect on a rodent model by means of OCT. Therefore, a normal hairless mouse skin has undergone a single-session PDT, which was performed with topical 5- aminolevulinic acid (ALA) cream using a red (630 nm) light emitting diode (LED) which reached the light dose of 75 J/cm2. As the optical imaging tool, an OCT (930 nm) with axial resolution of 6.0 microns in air was used, generating images with contact to the mouse skin before, immediately after, 24 hours, and 2 weeks after the correspondent procedure. Our result demonstrates that, within 24 hours after ALA-PDT, the mouse skin from the PDT group has shown epidermal thickness (ET), which has substantially increased after 2 weeks from the treatment day. Moreover, the skin surface has become evener after ALA-PDT. Concluding, this investigation demonstrates that the OCT is a feasible and reliable technique that allows real-time cross-sectional imaging of skin, which can quantify an outcome and predict whether the PDT reaches its goal.

  9. Influence of shoulder pain on muscle function: implications for the assessment and therapy of shoulder disorders.

    Science.gov (United States)

    Struyf, Filip; Lluch, Enrique; Falla, Deborah; Meeus, Mira; Noten, Suzie; Nijs, Jo

    2015-02-01

    Shoulder pain is often a challenging clinical phenomenon because of the potential mismatch between pathology and the perception of pain. Current evidence clearly emphasizes an incomplete understanding of the nature of shoulder pain. Indeed, the effective diagnosis and treatment of shoulder pain should not only rely upon a detailed knowledge of the peripheral pathologies that may be present in the shoulder, but also on current knowledge of pain neurophysiology. To assess and treat shoulder pain, a comprehensive understanding of the way in which pain is processed is essential. This review reflects modern pain neurophysiology to the shoulder and aims to answer the following questions: why does my shoulder hurt? What is the impact of shoulder pain on muscle function? What are the implications for the clinical examination of the shoulder? And finally, what are the clinical implications for therapy? Despite the increasing amount of research in this area, an in-depth understanding of the bidirectional nociception-motor interaction is still far from being achieved. Many questions remain, especially related to the treatment of nociception-motor interactions.

  10. Clinical Assessment of Intraventricular Blood Transport in Patients Undergoing Cardiac Resynchronization Therapy

    Science.gov (United States)

    Rossini, Lorenzo; Martinez-Legazpi, P.; Benito, Y.; Perez Del Villar, C.; Gonzalez-Mansilla, A.; Barrio, A.; Yotti, R.; Kahn, A. M.; Shadden, S. C.; Fernandez-Aviles, F.; Bermejo, J.; Del Alamo, J. C.

    2015-11-01

    In the healthy heart, left ventricular (LV) filling generates flow patterns which have been proposed to optimize blood transport by coupling diastole and systole phases. We present a novel image-based method to assess how flow patterns influence LV blood transport in patients undergoing cardiac resynchronization therapy (CRT). Solving the advection equation with time-varying inflow boundary conditions allows to track the transport of blood entering the LV in the different filling waves, as well as the transport barriers which couple filling and ejection. The velocity fields were obtained using echocardiographic color Doppler velocimetry, which provides two-dimensional time-resolved flow maps in the apical long axis three-chamber view of the LV. We analyze flow transport in a group of patients with CRT devices as well as in healthy volunteers. In the patients under CRT, the device programming was varied to analyze flow transport under different values of the atrioventricular (AV) conduction delay and to model tachycardia. This analysis illustrates how CRT influences the transit of blood inside the LV, contributes to conserving kinetic energy and favors the generation of hemodynamic forces that accelerate blood in the direction of the LV outflow tract.

  11. Influence of human nail etching for the assessment of topical onychomycosis therapies.

    Science.gov (United States)

    Repka, Michael A; Mididoddi, Praveen K; Stodghill, Steven P

    2004-09-10

    The purpose of this investigation was to study the physico-chemical properties of hot-melt extruded films containing ketoconazole and to determine the influence of 'nail etching' on film bioadhesion and drug permeability for the assessment of topical onychomycosis therapies. Hot-melt extrusion (HME) was used to prepare films containing 20% w/w ketoconazole. Ketoconazole 0.125% gel was also prepared using Carbopol 974P NF. Films were processed at a temperature range of 115-120 degrees C utilizing a Killion extruder (KLB-100), and were evaluated for post-extrusion drug content, content uniformity, bioadhesion, thermal behavior and nail drug permeation. The extruded films demonstrated excellent content uniformity and post-processing drug content. Tensile and peel tests were recorded to determine the bioadhesive profiles. In this study, work of adhesion and peak adhesive force determinations using the peel tests provided more sensitive results for evaluating the bioadhesivity of the HME films than the tensile tests. The in vitro permeability profiles have demonstrated, that nail samples treated with an 'etchant' demonstrated a significant increase in drug permeability compared to control. Differential scanning calorimetry (DSC) thermograms indicated that ketoconazole was in solid solution within the HME films. These findings are encouraging for the future design and formulation of novel drug delivery systems for the topical treatment of onychomycosis.

  12. Assessing barriers to care and readiness for cognitive behavioral therapy in early acute care PTSD interventions.

    Science.gov (United States)

    Trusz, Sarah Geiss; Wagner, Amy W; Russo, Joan; Love, Jeff; Zatzick, Douglas F

    2011-01-01

    Cognitive Behavioral Therapy (CBT) interventions are efficacious in reducing posttraumatic stress disorder (PTSD) but are challenging to implement in acute care and other non-specialty mental health settings. This investigation identified barriers impacting CBT delivery through a content analysis of interventionist chart notes from an acute care PTSD prevention trial. Only 8.5% of all intervention patients were able to complete CBT. Lack of engagement, clinical and logistical barriers had the greatest impact on CBT entry. Treatment preferences and stigma only prevented entry when more primary barriers resolved. Patients with prior diagnosis of alcohol abuse or dependence were able to enter CBT after six months of sobriety. Based on the first trial, we developed a CBT readiness assessment tool. We implemented and evaluated the tool in a second early intervention trial. Lack of engagement emerged again as the primary impediment to CBT entry. Patients who were willing to enter CBT treatment but demonstrated high rates of past trauma or diagnosis of PTSD were also the least likely to engage in any PTSD treatment one month post-discharge. Findings support the need for additional investigations into engagement and alternative delivery strategies, including those which dismantle traditional office-based, multi-session CBT into stepped, deliverable components.

  13. Longitudinal assessment of carotid atherosclerosis after Radiation Therapy using Computed Tomography: A case control Study

    Energy Technology Data Exchange (ETDEWEB)

    Anzidei, Michele [Rome Univ. ' ' La Sapienza' ' (Italy). Dept. of Radiology; Suri, Jasjit S.; Piga, Mario [AtheroPoint TM LLC, Roseville, CA (United States). Monitoring and Diagnostic Div.; Global Biomedical Technologies, Inc., CA (United States). Point of Care Devices; Idaho Univ., Moscow, ID (United States). Electrical Engineering Dept.; Saba, Luca [Azienda Ospedaliero Universitaria (A.O.U.), Cagliari (Italy). Dept. of Radiology; Sanfilippo, Roberto; Montisci, Roberto [Azienda Ospedaliero Universitaria (A.O.U.), Cagliari (Italy). Dept. of Vascular Surgery; Laddeo, Giancarlo [New York Univ. Langone Medical Center, New York, NY (United States). Dept. of Radiology; Argiolas, Giovanni Maria [Azienda Ospedaliera Brotzu, Cagliari (Italy). Dept. of Radiology; Raz, Eytan [Rome Univ. ' ' La Sapienza' ' (Italy). Dept. of Radiology; New York Univ. Langone Medical Center, New York, NY (United States). Dept. of Radiology

    2016-01-15

    To study the carotid artery plaque composition and its volume changes in a group of patients at baseline and 2 years after head and neck radiation therapy treatment (HNXRT). In this retrospective study, 62 patients (41 males; mean age 63 years; range 52-81) who underwent HNXRT and 40 patients (24 males; mean age 65) who underwent surgical resection of neoplasm and did not undergo HNXRT were assessed, with 2-year follow-up. The carotid artery plaque volumes, as well as the volume of the sub-components (fatty-mixed-calcified), were semiautomatically quantified. Mann-Whitney and Wilcoxon tests were used to test the hypothesis. In the HNXRT group, there was a statistically significant increase in the total volume of the carotid artery plaques (from 533 to 746 mm{sup 3}; p = 0.001), in the fatty plaques (103 vs. 202 mm{sup 3}; p = 0.001) and mixed plaque component volume (328 vs. 419 mm{sup 3}; p = 0.034). A statistically significant variation (from 21.8 % to 27.6 %) in the percentage of the fatty tissue was found. of this preliminary study suggest that HNXRT promotes increased carotid artery plaque volume, particularly the fatty plaque component. (orig.)

  14. Longitudinal assessment of thrombin generation potential in response to alteration of antiplatelet therapy after TIA or ischaemic stroke.

    LENUS (Irish Health Repository)

    Tobin, W O

    2013-02-01

    The impact of changing antiplatelet therapy on thrombin generation potential in patients with ischaemic cerebrovascular disease (CVD) is unclear. We assessed patients within 4 weeks of TIA or ischaemic stroke (baseline), and then 14 days (14d) and >90 days (90d) after altering antiplatelet therapy. Thrombin generation was assessed in platelet poor plasma. Ninety-one patients were recruited. Twenty-four were initially assessed on no antiplatelet therapy, and then after 14d (N = 23) and 90d (N = 8) on aspirin monotherapy; 52 were assessed on aspirin monotherapy, and after 14 and 90 days on aspirin and dipyridamole combination therapy; 21 patients were assessed on aspirin and after 14 days (N = 21) and 90 days (N = 19) on clopidogrel. Peak thrombin generation and endogenous thrombin potential were reduced at 14 and 90 days (p ≤ 0.04) in the overall cohort. We assessed the impact of individual antiplatelet regimens on thrombin generation parameters to investigate the cause of this effect. Lag time and time-to-peak thrombin generation were unchanged at 14 days, but reduced 90 days after commencing aspirin (p ≤ 0.009). Lag time, peak thrombin generation and endogenous thrombin potential were reduced at both 14 and 90 days after adding dipyridamole to aspirin (p ≤ 0.01). Lag time was reduced 14 days after changing from aspirin to clopidogrel (p = 0.045), but this effect was not maintained at 90 days (p = 0.2). This pilot study did not show any consistent effects of commencing aspirin, or of changing from aspirin to clopidogrel on thrombin generation potential during follow-up. The addition of dipyridamole to aspirin led to a persistent reduction in peak and total thrombin generation ex vivo, and illustrates the diverse, potentially beneficial, newly recognised \\'anti-coagulant\\' effects of dipyridamole in ischaemic CVD.

  15. Inhibitor ranking through QM based chelation calculations for virtual screening of HIV-1 RNase H inhibition.

    Directory of Open Access Journals (Sweden)

    Vasanthanathan Poongavanam

    Full Text Available Quantum mechanical (QM calculations have been used to predict the binding affinity of a set of ligands towards HIV-1 RT associated RNase H (RNH. The QM based chelation calculations show improved binding affinity prediction for the inhibitors compared to using an empirical scoring function. Furthermore, full protein fragment molecular orbital (FMO calculations were conducted and subsequently analysed for individual residue stabilization/destabilization energy contributions to the overall binding affinity in order to better understand the true and false predictions. After a successful assessment of the methods based on the use of a training set of molecules, QM based chelation calculations were used as filter in virtual screening of compounds in the ZINC database. By this, we find, compared to regular docking, QM based chelation calculations to significantly reduce the large number of false positives. Thus, the computational models tested in this study could be useful as high throughput filters for searching HIV-1 RNase H active-site molecules in the virtual screening process.

  16. Reliability and accuracy assessment of radiation therapy oncology group-endorsed guidelines for brachial plexus contouring

    Energy Technology Data Exchange (ETDEWEB)

    Velde, Joris van de [Ghent University, Department of Anatomy, Ghent (Belgium); Ghent University, Department of Radiotherapy, Ghent (Belgium); Vercauteren, Tom; Gersem, Werner de; Vandecasteele, Katrien; Vuye, Philippe; Vanpachtenbeke, Frank; Neve, Wilfried de [Ghent University, Department of Radiotherapy, Ghent (Belgium); Wouters, Johan; Herde, Katharina d' ; Kerckaert, Ingrid; Hoof, Tom van [Ghent University, Department of Anatomy, Ghent (Belgium)

    2014-07-15

    The goal of this work was to validate the Radiation Therapy Oncology Group (RTOG)-endorsed guidelines for brachial plexus (BP) contouring by determining the intra- and interobserver agreement. Accuracy of the delineation process was determined using anatomically validated imaging datasets as a gold standard. Five observers delineated the right BP on three cadaver computed tomography (CT) datasets. To assess intraobserver variation, every observer repeated each delineation three times with a time interval of 2 weeks. The BP contours were divided into four regions for detailed analysis. Inter- and intraobserver variation was verified using the Computerized Environment for Radiation Research (CERR) software. Accuracy was measured using anatomically validated fused CT-magnetic resonance imaging (MRI) datasets by measuring the BP inclusion of the delineations. The overall kappa (κ) values were rather low (mean interobserver overall κ: 0.29, mean intraobserver overall κ: 0.45), indicating poor inter- and intraobserver reliability. In general, the κ coefficient decreased gradually from the medial to lateral BP regions. The total agreement volume (TAV) was much smaller than the union volume (UV) for all delineations, resulting in a low Jaccard index (JI; interobserver agreement 0-0.124; intraobserver agreement 0.004-0.636). The overall accuracy was poor, with an average total BP inclusion of 38 %. Inclusions were insufficient for the most lateral regions (region 3: 21.5 %; region 4: 12.6 %). The inter- and intraobserver reliability of the RTOG-endorsed BP contouring guidelines was poor. BP inclusion worsened from the medial to lateral regions. Accuracy assessment of the contours showed an average BP inclusion of 38 %. For the first time, this was assessed using the original anatomically validated BP volume. The RTOG-endorsed BP guidelines have insufficient accuracy and reliability, especially for the lateral head-and-neck regions. (orig.) [German] Ziel der Studie war

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

    Science.gov (United States)

    Risher, John F; Amler, Sherlita N

    2005-08-01

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

  18. 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.

  19. Early response assessment in patients with multiple myeloma during anti-angiogenic therapy using arterial spin labelling: first clinical results

    Energy Technology Data Exchange (ETDEWEB)

    Fenchel, Michael [Eberhard-Karls University, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany); Eberhard-Karls University, Department of Diagnostic and Interventional Neuroradiology, Tuebingen (Germany); Konaktchieva, Marina [Eberhard-Karls University, Department of Internal Medicine, Gastroenterology, Tuebingen (Germany); Weisel, Katja; Kraus, Sabina [Eberhard-Karls University, Department of Internal Medicine, Hematology, Tuebingen (Germany); Brodoefel, Harald; Claussen, Claus D.; Horger, Marius [Eberhard-Karls University, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany)

    2010-12-15

    To determine if arterial-spin-labelling (ASL) MRI can reliably detect early response to anti-angiogenic therapy in patients with multiple myeloma by comparison with clinical/haematological response. Nineteen consecutive patients (10 men; mean age 63.5 {+-} 9.1 years) were included in the present study. Inclusion criteria were diagnosis of stage III multiple myeloma and clinical indication for therapeutical administration of bortezomib or lenalidomide. We performed MRI on 3.0T MR in the baseline setting, 3 weeks after onset of therapy and after 8 weeks. Clinical responses were determined on the basis of international uniform response criteria in correlation with haematological parameters and medium-term patient outcome. MRI studies were performed after approval by the local institutional review board. Fifteen patients responded to anti-myeloma therapy; 4/19 patients were non-responders to therapy. Mean tumour perfusion assessed by ASL-MRI in a reference lesion was 220.7 {+-} 132.5 ml min{sup -1} 100 g{sup -1} at baseline, and decreased to 125.7 {+-} 86.3 (134.5 {+-} 150.9) ml min{sup -1} 100 g{sup -1} 3 (8) weeks after onset of therapy (P < 0.02). The mean decrease in paraproteinaemia at week 3 (8) was 52.3 {+-} 47.7% (58.2 {+-} 58.7%), whereas {beta}2-microglobulinaemia decreased by 20.3 {+-} 53.1% (23.3 {+-} 57.0%). Correlation of ASL perfusion with outcome was significant (P = 0.0037). ASL tumour perfusion measurements are a valuable surrogate parameter for early assessment of response to novel anti-angiogenic therapy. (orig.)

  20. Assessing Treatment Integrity in Acceptance and Commitment Therapy: Strategies and Suggestions

    Science.gov (United States)

    Plumb, Jennifer C.; Vilardaga, Roger

    2010-01-01

    In this paper, we briefly review the current literature on treatment integrity and discuss the relevance of this procedure for detecting, measuring and ensuring that the proposed mechanisms of change in cognitive behavior therapy, in this case of acceptance and commitment therapy (ACT; S.C. Hayes, Strosahl, & Wilson, 1999), take place. We discuss…

  1. National Survey Assessing Perceived Multicultural Competence in Art Therapy Graduate Students

    Science.gov (United States)

    Robb, Megan

    2014-01-01

    Multicultural competence is essential to contemporary art therapy practice. Current education standards require that culturally sound theories and practices be taught along with self-awareness, but there is little research on the effects of such training in art therapy. The current study examined data from the Multicultural Awareness, Knowledge,…

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

    Science.gov (United States)

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

    2017-03-04

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

  3. Assessment of secondary radiation and radiation protection in laser-driven proton therapy

    Energy Technology Data Exchange (ETDEWEB)

    Faby, Sebastian; Wilkens, Jan J. [Technische Univ. Muenchen Klinikum rechts der Isar (Germany). Dept. of Radiation Oncology; Technische Univ. Muenchen (Germany). Physik-Dept.

    2015-09-01

    This work is a feasibility study of a radiation treatment unit with laser-driven protons based on a state-of-the-art energy selection system employing four dipole magnets in a compact shielded beamline. The secondary radiation emitted from the beamline and its energy selection system and the resulting effective dose to the patient are assessed. Further, it is evaluated whether or not such a compact system could be operated in a conventional treatment vault for clinical linear accelerators under the constraint of not exceeding the effective dose limit of 1 mSv per year to the general public outside the treatment room. The Monte Carlo code Geant4 is employed to simulate the secondary radiation generated while irradiating a hypothetical tumor. The secondary radiation inevitably generated inside the patient is taken into account as well, serving as a lower limit. The results show that the secondary radiation emanating from the shielded compact therapy system would pose a serious secondary dose contamination to the patient. This is due to the broad energy spectrum and in particular the angular distribution of the laser-driven protons, which make the investigated beamline together with the employed energy selection system quite inefficient. The secondary radiation also cannot be sufficiently absorbed in a conventional linear accelerator treatment vault to enable a clinical operation. A promising result, however, is the fact that the secondary radiation generated in the patient alone could be very well shielded by a regular treatment vault, allowing the application of more than 100 fractions of 2 Gy per day with protons. It is thus theoretically possible to treat patients with protons in such treatment vaults. Nevertheless, the results show that there is a clear need for alternative more efficient energy selection solutions for laser-driven protons.

  4. Assessment of the changes in alveolar bone quality after fixed orthodontic therapy: A trabecular structure analysis

    Science.gov (United States)

    Haghnegahdar, Abdolaziz; Zarif Najafi, Hooman; Sabet, Maryam; Saki, Maryam

    2016-01-01

    Background. Tooth displacement changes the periodontium. The aim of orthodontic treatment is desired tooth movement with minimum side effects on the alveolar bone quality. The aim of the present study was to assess changes of alveolar trabeculation in children, young adults and adults and the two genders. Methods. In this cross-sectional study, 63 patients who had been treated in Department of Orthodontics, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran, were chosen with convenient sampling method. They were divided into three groups based on their age. Their digitized panoramic radiographs (PRs) were evaluated at six interdental sites from the mesial aspect of the mandibular second molars to the distal aspect of the mandibular first premolars using a visual index. The trabeculation pattern was assigned as either dense (score 3), dense-sparse (score 2) or sparse (score 1). Data were imported to SPSS. Mean of the scores before treatment (score B) and mean of them after treatment (score A) were compared for each group with paired t-test. Changes between score B and sore A of the groups were compared using one-way ANOVA and post hoc tests. Results. Mean score A was significantly higher than mean score B in children (P = 0.001). In contrast, mean score A was significantly lower than mean score B in young adults (P = 0.003). Conclusion. Orthodontists should be cautious when treating young adults and adults regarding the probable, yet possibly temporary, negative effects of orthodontic therapy on the alveolar bone quality. PMID:28096944

  5. Significant and sustaining elevation of blood oxygen induced by Chinese cupping therapy as assessed by near-infrared spectroscopy

    OpenAIRE

    Li, Ting; Li, Yaoxian; Lin, Yu; Li, Kai

    2016-01-01

    Cupping therapy has been used in traditional Chinese medicine for thousands of years to relieve muscle pain/tendency/fatigue and to cure or reduce symbols of other diseases. However, its therapeutic effect is sparsely interpreted in the language of modern physiology. To objectively evaluate its therapeutic effect, we focused on dry cupping treatment and utilized near-infrared spectroscopy (NIRS) to assess the concentration change in oxy-hemoglobin ([HbO2]), deoxy-hemoglobin ([Hb]), and blood ...

  6. Assessment of the Prerequisite Skills for Cognitive Behavioral Therapy in Children with and Without Autism Spectrum Disorders

    OpenAIRE

    Lickel, Athena; MacLean, William E.; Blakeley-Smith, Audrey; Hepburn, Susan

    2012-01-01

    The purpose of this study was to assess the cognitive skills of children with autism spectrum disorders (ASD) thought to be necessary for Cognitive Behavioral Therapy (CBT). Forty children with ASD and forty age-matched typically developing children between the ages of 7–12 years participated. Groups were comparable with regard to nonverbal IQ, but children with ASD had significantly lower verbal IQ. Children completed three CBT-related tasks requiring emotion recognition, discrimination amon...

  7. Preparation and Properties of Iminodiacetic Acid Chelate Fiber

    Directory of Open Access Journals (Sweden)

    QIAN Jin-xin

    2016-07-01

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

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

    Science.gov (United States)

    Hnatowich, D J; Schlegel, P

    1981-07-01

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

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

    Institute of Scientific and Technical Information of China (English)

    LIU Zhuannian; SONG Yejing; HAN Xiaogang

    2012-01-01

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

  10. Chelation of heavy metals by potassium butyl dithiophosphate

    Institute of Scientific and Technical Information of China (English)

    Ying Xu; Zhigang Xie; Lu Xue

    2011-01-01

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

  11. The Metal Chelators, Trientine and Citrate, Inhibit the Development of Cardiac Pathology in the Zucker Diabetic Rat

    Directory of Open Access Journals (Sweden)

    John W. Baynes

    2009-01-01

    Full Text Available Purpose. The objective of this study was to determine the efficacy of dietary supplementation with the metal chelators, trientine or citric acid, in preventing the development of cardiomyopathy in the Zucker diabetic rat. Hypothesis. We hypothesized that dietary chelators would attenuate metal-catalyzed oxidative stress and damage in tissues and protect against pathological changes in ventricular structure and function in type II diabetes. Methods. Animals (10 weeks old included lean control (LC, fa/+, untreated Zucker diabetic fatty (ZDF, fa/fa, and ZDF rats treated with either trientine (triethylenetetramine or citrate at 20 mg/d in drinking water, starting when rats were frankly diabetic. Cardiac functional assessment was determined using a Millar pressure/volume catheter placed in the left ventricle at 32 weeks of age. Results. End diastolic volume for the ZDF animals increased by 36% indicating LV dilatation (P<.05 and was accompanied by a 30% increase in the end diastolic pressure (P≤.05. Both trientine and citric acid prevented the increases in EDV and EDP (P<.05. Ejection fraction and myocardial relaxation were also significantly improved with chelator treatment. Conclusion. Dietary supplementation with trientine and citric acid significantly prevented structural and functional changes in the diabetic heart, supporting the merits of mild chelators for prevention of cardiovascular disease in diabetes.

  12. Dynamic contrast-enhanced micro-CT on mice with mammary carcinoma for the assessment of antiangiogenic therapy response

    Energy Technology Data Exchange (ETDEWEB)

    Eisa, Fabian [University of Erlangen-Nuremberg, Institute of Medical Physics, Erlangen (Germany); University of Erlangen-Nuremberg, Graduate School in Advanced Optical Technologies (SAOT), Erlangen (Germany); Brauweiler, Robert; Hupfer, Martin; Nowak, Tristan; Kalender, Willi A. [University of Erlangen-Nuremberg, Institute of Medical Physics, Erlangen (Germany); Lotz, Laura; Hoffmann, Inge; Dittrich, Ralf; Beckmann, Matthias W. [University of Erlangen-Nuremberg, OB/GYN, University Hospital Erlangen, Erlangen (Germany); Wachter, David [University Hospital Erlangen, Institute of Pathology, Erlangen (Germany); Jost, Gregor; Pietsch, Hubertus [Bayer Pharma AG, Berlin (Germany)

    2012-04-15

    To evaluate the potential of in vivo dynamic contrast-enhanced micro-computed tomography (DCE micro-CT) for the assessment of antiangiogenic drug therapy response of mice with mammary carcinoma. 20 female mice with implanted MCF7 tumours were split into control group and therapy group treated with a known effective antiangiogenic drug. All mice underwent DCE micro-CT for the 3D analysis of functional parameters (relative blood volume [rBV], vascular permeability [K], area under the time-enhancement curve [AUC]) and morphology. All parameters were determined for total, peripheral and central tumour volumes of interest (VOIs). Immunohistochemistry was performed to characterise tumour vascularisation. 3D dose distributions were determined. The mean AUCs were significantly lower in therapy with P values of 0.012, 0.007 and 0.023 for total, peripheral and central tumour VOIs. K and rBV showed significant differences for the peripheral (P{sub per}{sup K} = 0.032, P{sub per}{sup rBV} = 0.029), but not for the total and central tumour VOIs (P{sub total}{sup K} = 0.108, P{sub central}{sup K} = 0.246, P{sub total}{sup rBV} = 0.093, P{sub central}{sup rBV} = 0.136). Mean tumour volume was significantly smaller in therapy (P{sub in} {sub vivo} = 0.001, P{sub ex} {sub vivo} = 0.005). Histology revealed greater vascularisation in the controls and central tumour necrosis. Doses ranged from 150 to 300 mGy. This study indicates the great potential of DCE micro-CT for early in vivo assessment of antiangiogenic drug therapy response. (orig.)

  13. Quantitative assessment of barriers to the clinical development and adoption of cellular therapies: A pilot study

    Directory of Open Access Journals (Sweden)

    Benjamin M Davies

    2014-09-01

    Full Text Available There has been a large increase in basic science activity in cell therapy and a growing portfolio of cell therapy trials. However, the number of industry products available for widespread clinical use does not match this magnitude of activity. We hypothesize that the paucity of engagement with the clinical community is a key contributor to the lack of commercially successful cell therapy products. To investigate this, we launched a pilot study to survey clinicians from five specialities and to determine what they believe to be the most significant barriers to cellular therapy clinical development and adoption. Our study shows that the main concerns among this group are cost-effectiveness, efficacy, reimbursement, and regulation. Addressing these concerns can best be achieved by ensuring that future clinical trials are conducted to adequately answer the questions of both regulators and the broader clinical community.

  14. Salivary cortisol day curves in assessing glucocorticoid replacement therapy in Addison's disease

    NARCIS (Netherlands)

    Smans, L.; Lentjes, E.G.W.M.; Hermus, A.R.; Zelissen, P.

    2013-01-01

    OBJECTIVE: Patients with Addison's disease require lifelong treatment with glucocorticoids. At present, no glucocorticoid replacement therapy (GRT) can exactly mimic normal physiology. As a consequence, under- and especially overtreatment can occur. Suboptimal GRT may lead to various side effects. T

  15. Chelation in metal intoxication—Principles and paradigms

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  16. Safety Assessment of Anticoagulation therapy in Patients with Hemorrhagic Cerebral Venous Thrombosis

    Directory of Open Access Journals (Sweden)

    Kavian Ghandehari

    2013-07-01

    Full Text Available Background: Anticoagulation therapy is a routine treatment in patients with hemorrhagic cerebral venous thrombosis (CVT. However, fear of hemorrhagic complications and deterioration course following anticoagulation often disturbs the responsible physician.Methods: This was a Prospective observational study on consecutive CVT patients with hemorrhagic venous infarction or subarachnoid hemorrhage (SAH admitted in Ghaem Hospital, Mashhad, Iran, during 2006-2012. The diagnosis of CVT in suspected cases was confirmed by magnetic resonance imaging/magnetic resonance venography (MRI/MRV, and computerized tomography (CT angiography following established diagnostic criteria. Demographic data, clinical manifestations from onset to end of the observation period, location of thrombus, location and size of infarction and hemorrhage, and clinical course during treatment were recorded. Choice of the treatment was left to the opinion of the treating physician. Clinical course during 1 week of treatment was assessed based on the baseline modified National Institute of Health Stroke Scale (NIHSS score. Three or more points decrease or increase of modified NIHSS after 1 week of treatment was considered as improvement or deterioration courses, respectively. Other clinical courses were categorized as stabilization course.Results: 102 hemorrhagic CVT patients (80 females,22 males with mean age of 38.6 ± 8 years were prospectively investigated. Of the 102 hemorrhagic CVT patients in the acute phase, 52 patients (50.9% were anticoagulated with adjusted dose intravenous heparin infusion and 50 cases (49.1% received subcutaneous enoxaparin 1mg/Kg twice daily. Decreased consciousness had a significant effect on the clinical course of the patients (X2 = 9.493, df = 2, P = 0.009. Presence of SAH had no significant effect on the clinical course of our anticoagulated hemorrhagic CVT cases (X2 = 0.304, df = 2,P = 0.914. Extension of Infarction in more than two thirds of a

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

    Science.gov (United States)

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

    2015-11-01

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

  18. Prospective assessment of pituitary size and shape on MR imaging after suppressive hormonal therapy in central precocious puberty

    Energy Technology Data Exchange (ETDEWEB)

    Beek, J.T. van; Sharafuddin, M.J.A.; Kao, S.C.S. [Department of Radiology-JPP 3889, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52246 (United States); Luisiri, A. [Cardinal Glennon Children' s Hospital, St. Louis, Missouri (United States); Garibaldi, L.R. [Children' s Hospital of New Jersey, Newark Beth Israel Medical Center, Newark, New Jersey (United States); St. Barnabas Medical Center, Livingston, New Jersey (United States)

    2000-07-01

    Objective. The diagnostic significance of an enlarged pituitary gland regarding both shape and size parameters on MR imaging has previously been demonstrated in children with central precocious puberty. This study was designed to assess changes in these parameters following successful suppressive therapy of central precocious puberty with the gonadotropin-releasing hormone (GnRH) analogue. Materials and methods. Twelve girls (mean age 7.3 years) with central precocious puberty were prospectively enrolled in our study protocol. Sagittal and coronal MR images of the pituitary region were obtained in all patients before treatment and after at least 6 months of GnRH analogue therapy (mean 18.0 months). Parameters measured included pituitary gland height, length, width, sagittal cross-sectional area, and volume. Results. All patients had excellent clinical response to treatment with arrest of secondary sexual development, normalization of serum estradiol levels, and complete obliteration of the LH response to diagnostic GnRH stimulation. No significant change occurred in any pituitary size or shape parameter following GnRH analogue therapy. Conclusion. Favorable clinical response to GnRH analogue therapy in central precocious puberty is not accompanied by significant a change in pituitary gland size and shape. (orig.)

  19. Assessment of potential advantages of relevant ions for particle therapy: A model based study

    Energy Technology Data Exchange (ETDEWEB)

    Grün, Rebecca, E-mail: r.gruen@gsi.de [Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt 64291 (Germany); Institute of Medical Physics and Radiation Protection, University of Applied Sciences Gießen, Gießen 35390 (Germany); Medical Faculty of Philipps-University Marburg, Marburg 35032 (Germany); Friedrich, Thomas; Krämer, Michael; Scholz, Michael [Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt 64291 (Germany); Zink, Klemens [Institute of Medical Physics and Radiation Protection, University of Applied Sciences Gießen, Gießen 35390, Germany and Department of Radiotherapy and Radiation Oncology, University Medical Center Giessen and Marburg, Marburg 35043 (Germany); Durante, Marco [Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt 64291, Germany and Department of Condensed Matter Physics, Darmstadt University of Technology, Darmstadt 64289 (Germany); Engenhart-Cabillic, Rita [Medical Faculty of Philipps-University Marburg, Marburg 35032, Germany and Department of Radiotherapy and Radiation Oncology, University Medical Center Giessen and Marburg, Marburg 35043 (Germany)

    2015-02-15

    Purpose: Different ion types offer different physical and biological advantages for therapeutic applications. The purpose of this work is to assess the advantages of the most commonly used ions in particle therapy, i.e., carbon ({sup 12}C), helium ({sup 4}He), and protons ({sup 1}H) for different treatment scenarios. Methods: A treatment planning analysis based on idealized target geometries was performed using the treatment planning software TRiP98. For the prediction of the relative biological effectiveness (RBE) that is required for biological optimization in treatment planning the local effect model (LEM IV) was used. To compare the three ion types, the peak-to-entrance ratio (PER) was determined for the physical dose (PER{sub PHY} {sub S}), the RBE (PER{sub RBE}), and the RBE-weighted dose (PER{sub BIO}) resulting for different dose-levels, field configurations, and tissue types. Further, the dose contribution to artificial organs at risk (OAR) was assessed and a comparison of the dose distribution for the different ion types was performed for a patient with chordoma of the skull base. Results: The study showed that the advantages of the ions depend on the physical and biological properties and the interplay of both. In the case of protons, the consideration of a variable RBE instead of the clinically applied generic RBE of 1.1 indicates an advantage in terms of an increased PER{sub RBE} for the analyzed configurations. Due to the fact that protons show a somewhat better PER{sub PHY} {sub S} compared to helium and carbon ions whereas helium shows a higher PER{sub RBE} compared to protons, both protons and helium ions show a similar RBE-weighted dose distribution. Carbon ions show the largest variation of the PER{sub RBE} with tissue type and a benefit for radioresistant tumor types due to their higher LET. Furthermore, in the case of a two-field irradiation, an additional gain in terms of PER{sub BIO} is observed when using an orthogonal field configuration

  20. Decorporation approach following rat lung contamination with a moderately soluble compound of plutonium using local and systemic Ca-DTPA combined chelation.

    Science.gov (United States)

    Grémy, Olivier; Tsapis, Nicolas; Bruel, Sylvie; Renault, Daniel; Van der Meeren, Anne

    2012-09-01

    Decorporation efficacy of prompt pulmonary delivery of DTPA dry powder was assessed following lung contamination with plutonium nitrate and compared to an intravenous injection of DTPA solution and a combined administration of both DTPA compounds. In addition, efficacy of a delayed treatment was assessed. In case of either early or late administration, insufflated DTPA was more efficient than intravenously injected DTPA in reducing the plutonium lung burden due to its high local concentration. Prompt treatment with DTPA powder was also more effective in limiting extrapulmonary deposits by removing the early transportable fraction of plutonium from lungs prior its absorption into blood. Translocation of DTPA from lungs to blood may also contribute to the decrease in extrapulmonary retention, as shown by reduced liver deposit after delayed pulmonary administration of DTPA. Efficacy of DTPA dry powder was further increased by the combined intravenous administration of DTPA solution for reducing extrapulmonary deposits of plutonium and promoting its urinary excretion. According to our results, the most effective treatment protocol for plutonium decorporation was the early pulmonary delivery of DTPA powder supplemented by an intravenous injection of DTPA solution. Following inhalation of plutonium as nitrate chemical form, this combined chelation therapy should provide a more effective method of treatment than conventional intravenous injection alone. At later stages following lung contamination, pulmonary administration of DTPA should also be considered as the treatment of choice for decreasing the lung burden.

  1. Clinical Assessment of the Efficiency of Low Level Laser Therapy in the Treatment of Oral Lichen Planus

    Directory of Open Access Journals (Sweden)

    Hanaa M. Elshenawy

    2015-10-01

    Full Text Available BACKGROUND: Oral lichen planus (OLP is a chronic inflammatory disease of the oral mucosa of uncertain etiology. AIM: To evaluate the effect of using low level laser therapy (LLLT (970 nm Siro laser Advance for the treatment of symptomatic (OLP. SUBJECTS AND METHODS: The present study was conducted on ten patients suffering from persistent oral lichen planus (OLP.Patients were treated with diode laser (970nm for the symptomatic relief of pain and burning sensation. The patients were assessed before, during and after the completion of the laser treatment which was done twice weekly for two successive months with maximum of ten sessions. The assessment was performed using visual analogue scale (VAS and clinical investigation for each patient. RESULTS: Detailed significant reduction in lesion size and showed complete remission of burning sensation and pain. No reported complications or therapy side effects were observed in any of the treated patients. CONCLUSION: Diode laser therapy seems to be an effective adjunctive treatment modality for relieving pain and clinical symptoms of OLP.

  2. Anxiety and Depression in Tinnitus Patients: 5-Year Follow-Up Assessment after Completion of Habituation Therapy

    Directory of Open Access Journals (Sweden)

    Eva-Signe Falkenberg

    2012-01-01

    Full Text Available Treatment programs based on a neurophysiological model have shown a positive effect on anxiety and depression in tinnitus patients. The aim of this paper was to assess the long-term effect of tinnitus habituation therapy. Sixty-eight individuals were treated with a comprehensive therapy program. The degree of anxiety and depression was assessed before, after, and five years after intervention using the Hospital Anxiety and Depression Scale. The positive and significant changes achieved after habituation therapy (pre = 1.10, post = 0.92 for anxiety and pre = 0.77, post = 0.62 for depression were maintained five years after treatment ended (0.87 for anxiety and 0.52 for depression. A regression analysis revealed that individual evaluation of the treatment lectures, self-reported health condition, individual experiences of hyperacusis, and hearing loss could explain 44.3% of the variation in anxiety and 30.5% of the variation in depression posttreatment. Five years after, individual evaluation of the treatment lectures and self-reported health condition explained 22.2% of the variation in anxiety. These factors and individual experiences of hyperacusis could further explain 34.9% of the variation in depression. The effect of a neurophysiologic-based management treatment was maintained five years after treatment ended, indicating that the patients continued the improvement process without becoming dependent on professionals.

  3. Risk Assessment of Hepatocellular Carcinoma Using Transient Elastography Vs. Liver Biopsy in Chronic Hepatitis B Patients Receiving Antiviral Therapy.

    Science.gov (United States)

    Seo, Yeon Seok; Kim, Mi Na; Kim, Seung Up; Kim, Sang Gyune; Um, Soon Ho; Han, Kwang-Hyub; Kim, Young Seok

    2016-03-01

    Liver stiffness (LS) assessed using transient elastography (TE) can assess the risk of developing hepatocellular carcinoma (HCC). We evaluated whether TE, when compared with histological data as a reference standard, can predict the risk of HCC development in chronic hepatitis B (CHB) patients starting antiviral therapy.Observational cohort database of 381 patients with CHB who underwent liver biopsy (LB) and TE were reviewed. All patients underwent surveillance for HCC development using ultrasonography and alpha-fetoprotein.During the median follow-up period of 48.1 (interquartile range 30.3-69.3) months, HCC developed in 34 (8.9%) patients. In patients with HCC development, age, proportion of diabetes mellitus, histological fibrosis stage, and LS value were significantly higher than those in patients without (all P 13 kPa; log-rank test, P 0.05).TE predicted HCC development independently in patients with CHB starting antiviral therapy. However, further investigation is needed to determine whether the current surveillance strategy can be optimized based on the LS value at the time of starting antiviral therapy.

  4. Anxiety and depression in tinnitus patients: 5-year follow-up assessment after completion of habituation therapy.

    Science.gov (United States)

    Falkenberg, Eva-Signe; Wie, Ona Bø

    2012-01-01

    Treatment programs based on a neurophysiological model have shown a positive effect on anxiety and depression in tinnitus patients. The aim of this paper was to assess the long-term effect of tinnitus habituation therapy. Sixty-eight individuals were treated with a comprehensive therapy program. The degree of anxiety and depression was assessed before, after, and five years after intervention using the Hospital Anxiety and Depression Scale. The positive and significant changes achieved after habituation therapy (pre = 1.10, post = 0.92 for anxiety and pre = 0.77, post = 0.62 for depression) were maintained five years after treatment ended (0.87 for anxiety and 0.52 for depression). A regression analysis revealed that individual evaluation of the treatment lectures, self-reported health condition, individual experiences of hyperacusis, and hearing loss could explain 44.3% of the variation in anxiety and 30.5% of the variation in depression posttreatment. Five years after, individual evaluation of the treatment lectures and self-reported health condition explained 22.2% of the variation in anxiety. These factors and individual experiences of hyperacusis could further explain 34.9% of the variation in depression. The effect of a neurophysiologic-based management treatment was maintained five years after treatment ended, indicating that the patients continued the improvement process without becoming dependent on professionals.

  5. CT in the assessment of early response to neoadjuvant therapy of colon

    DEFF Research Database (Denmark)

    Rafaelsen, Søren Rafael; Dam, Claus; Lund-Rasmussen, Vera;

    tumour invasion and number and size of enlarged lymph nodes were measured before and after the therapy. Results: Mean tumour length was 7.8 cm (95% CI: 5.3–10.4) at baseline and 4.34 cm (95%, CI: 4.0–4.9) after therapy. Mean extramural tumour invasion was 10.6 mm (95% CI: 9.5–11.8) at baseline and 5.7 mm...... (95% CI: 4.7–6.7) after therapy. Mean number of enlarged lymph nodes was 4.1 (95% CI: 3.4– 4.9) at baseline and 2.1 (95% CI: 1.4–2.7) after therapy. According to the RECIST criteria 45% (95% CI: 34–57) of the patients had response and 55% (95% CI: 43–67) had stable disease. No one showed progressive...... disease. Conclusion: Using MDCT we demonstrate a significant reduction in tumour size, extramural tumour invasion, number and size of enlarged lymph nodes following neoadjuvant therapy for colon cancer. Using the RESIST criteria 45% had a response....

  6. Assessment of response to endocrine therapy using FDG PET/CT in metastatic breast cancer: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Mortazavi-Jehanno, Nina; Giraudet, Anne-Laure; Champion, Laurence; Edeline, Veronique; Madar, Olivier; Pecking, Alain Paul [Institut Curie, Hopital Rene Huguenin, Service de Medecine Nucleaire, Saint-Cloud (France); Lerebours, Florence [Institut Curie, Hopital Rene Huguenin, Service d' Oncologie Medicale, Saint-Cloud (France); Stanc, Elise Le [Hopital Foch, Service de Medecine Nucleaire, Suresnes (France); Bellet, Dominique [Institut Curie, Hopital Rene Huguenin, Service de Medecine Nucleaire, Saint-Cloud (France); Universite Paris Descartes, Pharmacologie Chimique et Genetique and Imagerie, Inserm U1022 CNRS UMR 8151, Faculte des sciences pharmaceutiques et biologiques, Paris (France); Alberini, Jean-Louis [Institut Curie, Hopital Rene Huguenin, Service de Medecine Nucleaire, Saint-Cloud (France); Universite Versailles Saint-Quentin, Faculte de Medecine, Versailles (France)

    2012-03-15

    The purpose of this pilot study was to assess whether outcome in metastatic or recurrent breast cancer patients is related to metabolic response to endocrine therapy determined by {sup 18}F-FDG PET/CT. The study group comprised 22 patients with breast cancer (age 58 {+-} 11 years, mean {+-} SD) who were scheduled to receive endocrine therapy. They were systematically assessed by PET/CT at baseline and after a mean of 10 {+-} 4 weeks for evaluation of response after induction. All patients demonstrated FDG-avid lesions on the baseline PET/CT scan. The metabolic response was assessed according to EORTC criteria and based on the mean difference in SUV{sub max} between the two PET/CT scans, and the patients were classified into four groups: complete or partial metabolic response, or stable or progressive metabolic disease (CMR, PMR, SMD and PMD, respectively). All patients were followed in our institution. Metastatic sites were localized in bone (n = 15), lymph nodes (n = 11), chest wall (n = 3), breast (n = 5), lung (n = 3), soft tissue (n = 1) and liver (n = 1). PMR was observed in 11 patients (50%), SMD in 5 (23%) and PMD in 6 (27%). The median progression-free survival (PFS) times were 20, 27 and 6 months in the PMR, SMD and PMD groups, respectively. PFS in the SMD group differed from that in the PMR and SMD groups (p < 0.0001). Metabolic response assessed by FDG PET/CT imaging in patients with metastatic breast cancer treated with endocrine therapy is predictive of the patients' PFS. (orig.)

  7. 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.

  8. 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...

  9. Two percent ethylenediaminetetraacetic acid chelation treatment for band-shaped keratopathy, without blunt scratching after removal of the corneal epithelium

    Directory of Open Access Journals (Sweden)

    Kobayashi W

    2015-02-01

    Full Text Available Wataru Kobayashi,1 Shunji Yokokura,1 Takehiro Hariya,1 Toru Nakazawa1–3 1Department of Ophthalmology, 2Department of Retinal Disease Control, Ophthalmology, 3Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Background: The purpose of this study was to assess the effectiveness of 2% ethylenediaminetetraacetic acid (EDTA for the treatment of band-shaped keratopathy.Methods: We studied 24 eyes of 16 patients with band-shaped keratopathy who underwent EDTA chelation treatment from April 1, 2011 to December 31, 2012. We compared preoperative and 1 month postoperative logarithm of the minimum angle of resolution (logMAR best corrected visual acuity, intraocular pressure, and corneal curvature radius (K1, horizontal meridian; K2, vertical meridian; Km, average of K1 and K2. The Mann-Whitney U-test was used to determine the significance of differences.Results: There was a significant difference in preoperative and postoperative logMAR best corrected visual acuity (P=0.01. There were no significant differences in preoperative and postoperative intraocular pressure (P=0.24 or corneal curvature radius (K1, P=0.54; K2, P=0.49; Km, P=0.45.Conclusion: After 2% EDTA chelation treatment, post-operative logMAR best corrected visual acuity improved significantly. Moreover, since there was no significant difference in corneal curvature radius, there was little influence on corneal surface form. We believe that the results of our 2% EDTA chelation treatment were comparable with results obtained with 3.75% EDTA chelation treatment in previous reports. Two percent EDTA chelation is an effective treatment for band-shaped keratopathy and a useful method for any institution. Keywords: ethylenediaminetetraacetic acid, band-shaped keratopathy, phototherapeutic keratectomy, cornea

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

    Science.gov (United States)

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

    2016-04-01

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

  11. Assessment of the cardiovascular effects of electroconvulsive therapy in individuals older than 50 years

    Directory of Open Access Journals (Sweden)

    Takada J.Y.

    2005-01-01

    Full Text Available To evaluate the impact of electroconvulsive therapy on arterial blood pressure, heart rate, heart rate variability, and the occurrence of ischemia or arrhythmias, 38 (18 men depressive patients free from systemic diseases, 50 to 83 years old (mean: 64.7 ± 8.6 underwent electroconvulsive therapy. All patients were studied with simultaneous 24-h ambulatory blood pressure and Holter monitoring, starting 18 h before and continuing for 3 h after electroconvulsive therapy. Blood pressure, heart rate, heart rate variability, arrhythmias, and ischemic episodes were recorded. Before each session of electroconvulsive therapy, blood pressure and heart rate were in the normal range; supraventricular ectopic beats occurred in all patients and ventricular ectopic beats in 27/38; 2 patients had non-sustained ventricular tachycardia. After shock, systolic, mean and diastolic blood pressure increased 29, 25, and 24% (P < 0.001, respectively, and returned to baseline values within 1 h. Maximum, mean and minimum heart rate increased 56, 52, and 49% (P < 0.001, respectively, followed by a significant decrease within 5 min; heart rate gradually increased again thereafter and remained elevated for 1 h. Analysis of heart rate variability showed increased sympathetic activity during shock with a decrease in both sympathetic and parasympathetic drive afterwards. No serious adverse effects occurred; electroconvulsive therapy did not trigger any malignant arrhythmias or ischemia. In middle-aged and elderly people free from systemic diseases, electroconvulsive therapy caused transitory increases in blood pressure and heart rate and a decrease in heart rate variability but these changes were not associated with serious adverse clinical events.

  12. Behavioural Assessment of Wilderness Therapy Participants: Exploring the Consistency of Observational Data

    Science.gov (United States)

    Lariviere, Michel; Couture, Roger; Ritchie, Stephen D.; Cote, Daniel; Oddson, Bruce; Wright, Jesse

    2012-01-01

    Wilderness therapy (WT) provides an alternative treatment modality for a number of mental health issues. It holds particular appeal for at-risk youth, a population that is often less responsive to traditional psychotherapeutic interventions. Anecdotal accounts on the effectiveness of WT often show positive outcomes. Still, some researchers have…

  13. Assessing Outcome in Cognitive Behavior Therapy for Child Depression: An Illustrative Case Series

    Science.gov (United States)

    Eckshtain, Dikla; Gaynor, Scott T.

    2009-01-01

    Recent meta-analytic data suggest a need for ongoing evaluation of treatments for youth depression. The present article calls attention to a number of issues relevant to the empirical evaluation of if and how cognitive behavior therapy for child depression works. A case series of 6 children and a primary caregiver received treatment--individual…

  14. Use of Standardized Assessment Instruments in Couple Therapy: The Role of Attitudes and Professional Factors

    Science.gov (United States)

    Lavee, Yoav; Avisar, Yitzhak

    2006-01-01

    The study examined therapeutic approach, professional affiliation, training, seniority, and work setting as predictors of attitudes toward standardized instruments and their use in couple therapy. Data were gathered from 163 certified marriage and family therapists in Israel. Results showed that 27.6% of marital therapists used standardized…

  15. Development and Safety Assessment of Lentiviral Vector Gene Therapy for SCID-X1

    NARCIS (Netherlands)

    M.W. Huston (Marshall W.)

    2013-01-01

    markdownabstract__Abstract__ This thesis work focuses on exploring ways to improve hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency disease (SCID-X1) using lentiviral vectors and a mouse model of the disease. This involved 3-part approach: modifying some components

  16. Assessment of radiation-induced second cancer risks in proton therapy and IMRT for organs inside the primary radiation field.

    Science.gov (United States)

    Paganetti, Harald; Athar, Basit S; Moteabbed, Maryam; A Adams, Judith; Schneider, Uwe; Yock, Torunn I

    2012-10-07

    There is clinical evidence that second malignancies in radiation therapy occur mainly within the beam path, i.e. in the medium or high-dose region. The purpose of this study was to assess the risk for developing a radiation-induced tumor within the treated volume and to compare this risk for proton therapy and intensity-modulated photon therapy (IMRT). Instead of using data for specific patients we have created a representative scenario. Fully contoured age- and gender-specific whole body phantoms (4 year and 14 year old) were uploaded into a treatment planning system and tumor volumes were contoured based on patients treated for optic glioma and vertebral body Ewing's sarcoma. Treatment plans for IMRT and proton therapy treatments were generated. Lifetime attributable risks (LARs) for developing a second malignancy were calculated using a risk model considering cell kill, mutation, repopulation, as well as inhomogeneous organ doses. For standard fractionation schemes, the LAR for developing a second malignancy from radiation therapy alone was found to be up to 2.7% for a 4 year old optic glioma patient treated with IMRT considering a soft-tissue carcinoma risk model only. Sarcoma risks were found to be below 1% in all cases. For a 14 year old, risks were found to be about a factor of 2 lower. For Ewing's sarcoma cases the risks based on a sarcoma model were typically higher than the carcinoma risks, i.e. LAR up to 1.3% for soft-tissue sarcoma. In all cases, the risk from proton therapy turned out to be lower by at least a factor of 2 and up to a factor of 10. This is mainly due to lower total energy deposited in the patient when using proton beams. However, the comparison of a three-field and four-field proton plan also shows that the distribution of the dose, i.e. the particular treatment plan, plays a role. When using different fractionation schemes, the estimated risks roughly scale with the total dose difference in%. In conclusion, proton therapy can

  17. Value of subtraction MRI in assessing treatment response following image-guided loco-regional therapies for hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Winters, S.D. [Department of Radiology and Diagnostic Imaging, Royal Alexandra Hospital, Edmonton (Canada); Department of Radiology and Diagnostic Imaging, University of Alberta Hospital, Edmonton (Canada); 1 Canadian Field Hospital, Department of National Defence, Government of Canada (Canada); Jackson, S. [Department of Radiology and Diagnostic Imaging, University of Alberta Hospital, Edmonton (Canada); Armstrong, G.A. [Department of Radiology and Diagnostic Imaging, Royal Alexandra Hospital, Edmonton (Canada); Department of Radiology and Diagnostic Imaging, University of Alberta Hospital, Edmonton (Canada); Birchall, I.W. [Department of Radiology and Diagnostic Imaging, University of Alberta Hospital, Edmonton (Canada); Lee, K.H.Y. [Department of Radiology and Diagnostic Imaging, Royal Alexandra Hospital, Edmonton (Canada); Low, G., E-mail: timgy@yahoo.com [Department of Radiology and Diagnostic Imaging, University of Alberta Hospital, Edmonton (Canada)

    2012-07-15

    Aim: To compare contrast-enhanced subtraction magnetic resonance imaging (MRI) with contrast-enhanced standard MRI in assessing treatment response following loco-regional therapies for hepatocellular carcinoma (HCC). Method and materials: Institutional review board approval was obtained and informed consent was waived for this retrospective study. All patients were analysed from our institution's liver tumour database that had loco-regional HCC therapy and the following: (1) a contrast-enhanced MRI {<=}6 weeks post-treatment, (2) an unenhanced T1-weighted high-signal treatment zone (TZ) {>=}1 cm, (3) follow-up contrast-enhanced MRI performed {>=}6 months post-treatment. Randomized standard and subtraction TZ datasets were independently assessed by three blinded radiology readers for either complete treatment necrosis or residual disease. The standard of reference (SOR) comprised a consensus read by two radiologists with knowledge of the follow-up MRI and all available clinical data. Statistical analyses were performed using receiver operating characteristics (ROC), t-test, and kappa statistic. Results: Twenty-six patients (19 male and seven female patients; mean age 60 years, standard deviation 10.9 years, range 46-88 years) had a total of 45 corresponding HCCs and TZs. For ROC, the area under the curve (AUC) was 0.93 (subtraction protocol) versus 0.90 (standard protocol; p = 0.49). For the t-test, the mean reader confidence level was 4.4, 3.6, and 4.4 (subtraction protocol) versus 3, 3, and 3.7 (standard protocol; p {<=} 0.011). The kappa statistic for reader-to-SOR agreement was 0.83, 0.63, and 0.71 (subtraction protocol) versus 0.51, 0.36, and 0.64 (standard protocol). Conclusion: Subtraction MRI significantly improves the reader confidence level in the assessment of treatment response following loco-regional therapies for HCC.

  18. Randomised controlled trial of cognitive-motivational therapy program for the initial phase of schizophrenia: a 6-month assessment

    Directory of Open Access Journals (Sweden)

    Carol Palma-Sevillano

    2011-06-01

    Full Text Available Background and Objectives: The aim of this study is to investigate the relative effectiveness of routine care (RC in addition to a specific early intervention program (PIPE compared to routine care alone. Methods: A total of 34 participants in the initial phase of schizophrenia took part in randomized, single-blind controlled trial. Participants were randomized to receive either routine care (RC; n = 13 or routine integrated with Cognitive-Motivational Therapy (PIPE; n = 21. PIPE comprised individual and family Cognitive-Motivational therapy plus routine care for 12 months. In this paper we present preliminary results at 6 months after the beginning of the intervention. Clinical assessments were carried out at pre-treatment, and in this manuscript the results at 3 and 6 months after starting the intervention by external raters are presented, using the Positive and Negative Syndrome Scale, Brief Psychiatry Rating Scale, the Clinical Global Impression Scale, the Global Assessment of Functioning scale, and relapses. Mann-Whitney test and MANOVAs analysis for variance effects were used for the statistical analysis. Results: Significant greater clinical effects were observed in those patients treated in RC+PIPE at three months from baseline assessment and at six months in PANSS scale (Mann-Whitney test; p < 0.000. Other benefits of the program included increase in global activity, reduced relapse rates, and reduction of the pharmacological treatment. Conclusions: These findings show the effectiveness of a program of routine care integrated with cognitive-motivational interventions (individual and family therapy over routine psychiatric care alone for patients who are in the initial phase of schizophrenia.

  19. Dynamic three-dimensional echocardiography combined with semi-automated border detection offers advantages for assessment of resynchronization therapy

    Directory of Open Access Journals (Sweden)

    Voormolen Marco M

    2003-10-01

    Full Text Available Abstract Simultaneous electrical stimulation of both ventricles in patients with interventricular conduction disturbance and advanced heart failure improves hemodynamics and results in increased exercise tolerance, quality of life. We have developed a novel technique for the assessment and optimization of resynchronization therapy. Our approach is based on transthoracic dynamic three-dimensional (3D echocardiography and allows determination of the most delayed contraction site of the left ventricle (LV together with global LV function data. Our initial results suggest that fast reconstruction of the LV is feasible for the selection of the optimal pacing site and allows identifying LV segments with dyssynchrony.

  20. 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.

  1. 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)

  2. Flow cytometric assessment of circulating platelet and erythrocytes microparticles in young thalassemia major patients: relation to pulmonary hypertension and aortic wall stiffness.

    Science.gov (United States)

    Tantawy, Azza A G; Adly, Amira A M; Ismail, Eman A R; Habeeb, Nevin M

    2013-06-01

    Heart disease is the leading cause of mortality and morbidity in β-thalassemia major (β-TM). Aggregability of abnormal red cells and membrane-derived microparticles (MPs) stemming from activated platelets and erythrocytes are responsible for thrombotic risk. We measured platelet and erythrocyte MPs (PMPs and ErMPs) in 60 young β-TM patients compared with 40 age- and sex-matched healthy controls and assessed their relation to clinicopathological characteristics and aortic elastic properties. Patients were studied stressing on transfusion history, splenectomy, thrombotic events, chelation therapy, hematological and coagulation profiles, flow cytometric measurement of PMPs (CD41b(+) ) and ErMPs (glycophorin A(+) ) as well as echocardiographic assessment of aortic elastic properties. Aortic stiffness index and pulmonary artery pressure were significantly higher, whereas aortic strain and distensibility were lower in TM patients than controls (P 2500 μg/L (P < 0.001). Compliant patients on chelation therapy had lower MPs levels than non-compliant patients (P < 0.001). PMPs and ErMPs were positively correlated to markers of hemolysis, serum ferritin, D-dimer, vWF Ag, and aortic stiffness, whereas negatively correlated to hemoglobin level and aortic distensibility (P < 0.05). We suggest that increased MPs may be implicated in vascular dysfunction, pulmonary hypertension risk, and aortic wall stiffness observed in thalassemia patients. Their quantification could provide utility for early detection of cardiovascular abnormalities and monitoring the biological efficacy of chelation therapy.

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

    Science.gov (United States)

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

    2016-02-01

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

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

    Science.gov (United States)

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

    2016-01-20

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

  5. Assessing visual attention using eye tracking sensors in intelligent cognitive therapies based on serious games.

    Science.gov (United States)

    Frutos-Pascual, Maite; Garcia-Zapirain, Begonya

    2015-05-12

    This study examines the use of eye tracking sensors as a means to identify children's behavior in attention-enhancement therapies. For this purpose, a set of data collected from 32 children with different attention skills is analyzed during their interaction with a set of puzzle games. The authors of this study hypothesize that participants with better performance may have quantifiably different eye-movement patterns from users with poorer results. The use of eye trackers outside the research community may help to extend their potential with available intelligent therapies, bringing state-of-the-art technologies to users. The use of gaze data constitutes a new information source in intelligent therapies that may help to build new approaches that are fully-customized to final users' needs. This may be achieved by implementing machine learning algorithms for classification. The initial study of the dataset has proven a 0.88 (±0.11) classification accuracy with a random forest classifier, using cross-validation and hierarchical tree-based feature selection. Further approaches need to be examined in order to establish more detailed attention behaviors and patterns among children with and without attention problems.

  6. Pharmacy adherence measures to assess adherence to antiretroviral therapy: review of the literature and implications for treatment monitoring.

    Science.gov (United States)

    McMahon, James H; Jordan, Michael R; Kelley, Karen; Bertagnolio, Silvia; Hong, Steven Y; Wanke, Christine A; Lewin, Sharon R; Elliott, Julian H

    2011-02-15

    Prescription or pill-based methods for estimating adherence to antiretroviral therapy (ART), pharmacy adherence measures (PAMs), are objective estimates calculated from routinely collected pharmacy data. We conducted a literature review to evaluate PAMs, including their association with virological and other clinical outcomes, their efficacy compared with other adherence measures, and factors to consider when selecting a PAM to monitor adherence. PAMs were classified into 3 categories: medication possession ratio (MPR), pill count (PC), and pill pick-up (PPU). Data exist to recommend PAMs over self-reported adherence. PAMs consistently predicted patient outcomes, but additional studies are needed to determine the most predictive PAM parameters. Current evidence suggests that shorter duration of adherence assessment (≤ 6 months) and use of PAMs to predict future outcomes may be less accurate. PAMs which incorporate the number of days for which ART was prescribed without the counting of remnant pills, are reasonable minimum-resource methods to assess adherence to ART.

  7. Esophageal Cancer: Role of Imaging in Primary Staging and Response Assessment Post Neoadjuvant Therapy.

    Science.gov (United States)

    Griffin, Yvette

    2016-08-01

    Advances in the early detection and treatment of esophageal cancer have meant improved survival rates for patients with esophageal cancer. Accurate pretreatment and post-neoadjuvant treatment staging of esophageal cancer is essential for assessing operability and determining the optimum treatment plan. This article reviews the multimodality imaging approach in the diagnosis, staging, and assessment of treatment response in esophageal cancer.

  8. Geometric and chelation influences on the electronic structure and optical properties of tetra(carboxylic acid)phenyleneethynylene dyes.

    Science.gov (United States)

    Berlin, Asher; Risko, Chad; Ratner, Mark A

    2008-05-08

    A quantum-chemical study on the consequences of geometric modification and chelation on the electronic structure and optical properties of a tetra(carboxylic acid)phenyleneethynylene dye, of interest for chemical sensing applications, is presented. Rotation within the central biphenylene and complexation with divalent metal ions--in particular Cu2+--lead to notable changes in the absorption and emission profiles. Calculations at both the density functional theory (DFT) and Hartree-Fock (HF) levels are used to evaluate geometric potential energy surfaces for rotation within the central biphenylene unit; HF coupled with configuration interaction singles (HF-CIS) is used to investigate the first excited state of the dye. Time-dependent DFT (TDDFT) calculations are employed to assess changes in optical absorption and fluorescence as a function of geometry and chelation.

  9. A Pilot Study to Assess the Feasibility of Group Exercise and Animal-Assisted Therapy in Older Adults.

    Science.gov (United States)

    Grubbs, Brandon; Artese, Ashley; Schmitt, Karla; Cormier, Eileen; Panton, Lynn

    2016-04-01

    This pilot study assessed the feasibility of incorporating animal-assisted therapy teams (ATT) into a 6-week group exercise program for older adults (77 ± 6 years). Fifteen participants were randomly assigned to an exercise with ATT (E+ATT; n = 8) or exercise only (E; n = 7) group. Groups exercised 3x/week for 45 min. Feasibility was assessed by three objectives: (1) ATT will not need extensive preparation beyond their original therapy training; (2) the study will require minimal cost; and (3) ATT must not impair the effectiveness of the exercise program. By the study conclusion, all objectives were met. Time and cost were minimal for ATT, and adherence was 93% and 90% for E+ATT and E, respectively. There were significant improvements in both groups (p ≤ .05) for arm curls, get-up and go, and 6-min walk. The results of this pilot study suggest that it is feasible to incorporate ATT into group exercise programming for older adults.

  10. Integration of imaging into clinical practice to assess the delivery and performance of macromolecular and nanotechnology-based oncology therapies.

    Science.gov (United States)

    Spence, Tara; De Souza, Raquel; Dou, Yannan; Stapleton, Shawn; Reilly, Raymond M; Allen, Christine

    2015-12-10

    Functional and molecular imaging has become increasingly used to evaluate interpatient and intrapatient tumor heterogeneity. Imaging allows for assessment of microenvironment parameters including tumor hypoxia, perfusion and proliferation, as well as tumor metabolism and the intratumoral distribution of specific molecular markers. Imaging information may be used to stratify patients for targeted therapies, and to define patient populations that may benefit from alternative therapeutic approaches. It also provides a method for non-invasive monitoring of treatment response at earlier time-points than traditional cues, such as tumor shrinkage. Further, companion diagnostic imaging techniques are becoming progressively more important for development and clinical implementation of targeted therapies. Imaging-based companion diagnostics are likely to be essential for the validation and FDA approval of targeted nanotherapies and macromolecular medicines. This review describes recent clinical advances in the use of functional and molecular imaging to evaluate the tumor microenvironment. Additionally, this article focuses on image-based assessment of distribution and anti-tumor effect of nano- and macromolecular systems.

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

    Science.gov (United States)

    Smentek, Lidia

    2011-04-13

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

  12. 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.

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

    Science.gov (United States)

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

    1986-01-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

  15. 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.

  16. Molecular imaging for assessment of mesenchymal stem cells mediated breast cancer therapy.

    Science.gov (United States)

    Leng, Liang; Wang, Yuebing; He, Ningning; Wang, Di; Zhao, Qianjie; Feng, Guowei; Su, Weijun; Xu, Yang; Han, Zhongchao; Kong, Deling; Cheng, Zhen; Xiang, Rong; Li, Zongjin

    2014-06-01

    The tumor tropism of mesenchymal stem cells (MSCs) makes them an excellent delivery vehicle used in anticancer therapy. However, the exact mechanisms of MSCs involved in tumor microenvironment are still not well defined. Molecular imaging technologies with the versatility in monitoring the therapeutic effects, as well as basic molecular and cellular processes in real time, offer tangible options to better guide MSCs mediated cancer therapy. In this study, an in situ breast cancer model was developed with MDA-MB-231 cells carrying a reporter system encoding a double fusion (DF) reporter gene consisting of firefly luciferase (Fluc) and enhanced green fluorescent protein (eGFP). In mice breast cancer model, we injected human umbilical cord-derived MSCs (hUC-MSCs) armed with a triple fusion (TF) gene containing the herpes simplex virus truncated thymidine kinase (HSV-ttk), renilla luciferase (Rluc) and red fluorescent protein (RFP) into tumor on day 13, 18, 23 after MDA-MB-231 cells injection. Bioluminescence imaging of Fluc and Rluc provided the real time monitor of tumor cells and hUC-MSCs simultaneously. We found that tumors were significantly inhibited by hUC-MSCs administration, and this effect was enhanced by ganciclovir (GCV) application. To further demonstrate the effect of hUC-MSCs on tumor cells in vivo, we employed the near infrared (NIR) imaging and the results showed that hUC-MSCs could inhibit tumor angiogenesis and increased apoptosis to a certain degree. In conclusion, hUC-MSCs can inhibit breast cancer progression by inducing tumor cell death and suppressing angiogenesis. Moreover, molecular imaging is an invaluable tool in tracking cell delivery and tumor response to hUC-MSCs therapies as well as cellular and molecular processes in tumor.

  17. [Long-term effects of combined therapy in patients with beta-thalassemia major].

    Science.gov (United States)

    Bagnulo, S; Giannini, A M; Moscatelli, F; Stragapede, L; Acquafredda, A; Dammacco, A

    1998-01-01

    We evaluated therapy complications in 19 beta-thalassemia major patients (mean age from 3 years/5 months and 1 years/6 months) who were followed at II Pediatric Department-University of Bari. 3 out of 19 patients underwent allogenic BMT from matched related donor; 2 out of 19 underwent splenectomy. All of them were receiving hypertransfusion therapy and continuous chelation with DFO. In all patients we performed physical examination, laboratory assays, cardiac and endocrinologic function tests, serum HBV-HCV-HIV antibodies, otoscopy and audiometric test, fundus oculi, skeletal x-ray. 1 out of 19 patients, who was under 15, had a slight dilatation of left ventricle and arythmia. All patients were HBsAb positive. 4/19 patients were HCV Ab positive (ELISA test) with an increase in ALT-AST serum levels since at least 6 months. In 3 of them we assessed RIBA test, always positive. 3 of them underwent liver biopsy (1 iron overload 2 chronic active hepatitis). All patients were HIV Ab negative. 4/15 patients revealed low GH levels after Arginina test. 13 pre-pubescent patients had normal results with GNRH test but lower results after FSH test. 1 pubescent patient had gonadotropic hypophyseal deficit. 4 patients had subclinic hypothiroidism. We couldn't find any sequelas in bone-eyes-ears. Hypertransfusion therapy, chelation, profilaxis of infections improved length and quality of life in thalassemic patients. Hypogonadotropic hypogonadism remains a serious sequela and we think it needs to be treated.

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  19. 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.

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

    Science.gov (United States)

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

    2015-12-21

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

  1. The influence of comprehensive geriatric assessment on drug therapy in elderly patients

    DEFF Research Database (Denmark)

    Larsen, Michael Due; Rosholm, Jens Ulrik; Hallas, Jesper

    2014-01-01

    Comprehensive geriatric assessment of hospitalised patients implies optimising patients' medical treatment, and good coordination between hospital and general practice is essential for the quality of the drug treatment. Only a few studies have investigated the continuation of patients' medication...

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

    Science.gov (United States)

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

    2015-10-01

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

  3. FDG PET/CT response assessment criteria for patients with Hodgkin's and non-Hodgkin's lymphoma at end of therapy: A multiparametric approach

    Energy Technology Data Exchange (ETDEWEB)

    Metser, Ur; Mohan, Ravi; Beckley, Vaughan; Murphy, Grainne [Mount Sinai Hospital and Women' s College Hospital, University of Toronto, Toronto (Canada); Hodgson, David [Radiation Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto (Canada)

    2016-03-15

    Based on the International Harmonization Project (IHP) criteria, positron emission tomography (PET) response assessment of residual nodal masses in patients with lymphoma after completion of therapy is performed visually using mediastinal blood pool as the reference. The primary objective of this study was to define the optimal reference for PET response assessment. Secondary aim was to assess if morphological criteria on computed tomography (CT) may improve performance of PET. This institutional review board approved retrospective study included 137 patients, with Hodgkin's (n = 43) or non-Hodgkin's lymphoma (n = 94) assessed for residual masses (n = 180) after completion of therapy with pathology and clinical and imaging surveillance data (mean, 19 months) as the standard of reference. Two readers independently assessed response by IHP and Deauville criteria. The addition of morphological parameters on CT was assessed in relation to therapy response. Based on the standard of reference, 36 patients (26.3 %) had residual lymphoma. For IHP and Deauville criteria, sensitivity, specificity and accuracy were 97.2 %, 97.2 % (p = 1); 79.2 %, 92.1 % (p < 0.001); and 83.9 %, 93.4 % (p = 0.001), respectively. Of the morphological parameters assessed, only change in size over course of therapy was significant (p < 0.003) and improved specificity for IHP-based interpretation to 90.4 % (p = 0.008). Using liver as the visual reference to determine PET positivity for lymphoma patients being assessed for residual masses at the end of therapy improves specificity, yet maintains the high sensitivity of PET in identifying residual disease. The addition of change in size after therapy improves specificity of PET when using IHP-based but not Deauville-based interpretation.

  4. Monte Carlo assessment of boron neutron capture therapy for the treatment of breast cancer

    Directory of Open Access Journals (Sweden)

    Mundy Daniel W.

    2005-01-01

    Full Text Available For a large number of women who are diagnosed with breast cancer every year the avail able treatment options are effective, though physically and mentally taxing. This work is a starting point of a study of the efficacy of boron neutron capture therapy as an alternative treatment for HER-2+ breast tumors. Using HER-2-specific monoclonal anti bodies coupled with a boron-rich oligomeric phosphate diester, it may be possible to deliver sufficient amounts of 10B to a tumor of the breast to al low for selective cell destruction via irradiation by thermal neutrons. A comprehensive computational model (MCNP for thermal neutron irradiation of the breast is described, as well as the results of calculations made using this model, in order to determine the optimum boron concentration within the tumor for an effective boron neutron capture therapy treatment, as compared with traditional X-ray radiotherapy. The results indicate that a boron concentration of 50-60 mg per gram of tumor tissue is optimal when considering treatment times, dose distributions and skin sparing. How ever these results are based upon best-guess assumptions that must be experimentally verified.

  5. Nutritional and metabolic assessment of HIV patients in use of antiretroviral therapy at Northeastern Brazil

    Directory of Open Access Journals (Sweden)

    Liana Aguiar Braga

    2010-12-01

    Full Text Available Objective: To evaluate nutritional and metabolic changes in HIV infected (HIV+ patients on use of antiretroviral therapy. Methods:  A cross-sectional descriptive study involving HIV+ patients on use of Highly Active Antiretroviral Therapy (HAART. The demographic data studied were gender, birth date and time of use of antiretroviral medication. Anthropometric variables were weight and height with calculation of body mass index (BMI. Biochemical data were lipid profile, blood glucose, renal function, albumin, uric acid, oxalacetic and pyruvic transaminases and red blood cells count. Results: The study population comprised 70 patients, 36 (51.4% men and 34 (48.6% women with an average time of HAART-use of 34.5 + 16.5 months. We observed a prevalence of 42 (60% healthy weight for BMI, changes in lipid profile and reduction of lean mass in 18 (50% men and increased abdominal obesity in 23 (67.7% women. Conclusion: The studied subjects in use of HAART showed to have loss of subcutaneous fat, lipid changes and higher prevalence of abdominal obesity in women.

  6. Optogenetics-enabled assessment of viral gene and cell therapy for restoration of cardiac excitability.

    Science.gov (United States)

    Ambrosi, Christina M; Boyle, Patrick M; Chen, Kay; Trayanova, Natalia A; Entcheva, Emilia

    2015-12-01

    Multiple cardiac pathologies are accompanied by loss of tissue excitability, which leads to a range of heart rhythm disorders (arrhythmias). In addition to electronic device therapy (i.e. implantable pacemakers and cardioverter/defibrillators), biological approaches have recently been explored to restore pacemaking ability and to correct conduction slowing in the heart by delivering excitatory ion channels or ion channel agonists. Using optogenetics as a tool to selectively interrogate only cells transduced to produce an exogenous excitatory ion current, we experimentally and computationally quantify the efficiency of such biological approaches in rescuing cardiac excitability as a function of the mode of application (viral gene delivery or cell delivery) and the geometry of the transduced region (focal or spatially-distributed). We demonstrate that for each configuration (delivery mode and spatial pattern), the optical energy needed to excite can be used to predict therapeutic efficiency of excitability restoration. Taken directly, these results can help guide optogenetic interventions for light-based control of cardiac excitation. More generally, our findings can help optimize gene therapy for restoration of cardiac excitability.

  7. Current and emerging quantitative magnetic resonance imaging methods for assessing and predicting the response of breast cancer to neoadjuvant therapy

    Directory of Open Access Journals (Sweden)

    Abramson RG

    2012-10-01

    Full Text Available Richard G Abramson,1,2,9 Lori R Arlinghaus,1,2 Jared A Weis,1,2 Xia Li,1,2 Adrienne N Dula,1,2 Eduard Y Chekmenev,1–4,9 Seth A Smith,1–3,5 Michael I Miga,1–3,6 Vandana G Abramson,7,9 Thomas E Yankeelov1–3,5,8,91Institute of Imaging Science, 2Department of Radiology and Radiological Sciences, 3Department of Biomedical Engineering, 4Department of Biochemistry, 5Department of Physics, 6Department of Neurosurgery, 7Department of Medical Oncology, 8Department of Cancer Biology, 9Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville,TN, USAAbstract: Reliable early assessment of breast cancer response to neoadjuvant therapy (NAT would provide considerable benefit to patient care and ongoing research efforts, and demand for accurate and noninvasive early-response biomarkers is likely to increase. Response assessment techniques derived from quantitative magnetic resonance imaging (MRI hold great potential for integration into treatment algorithms and clinical trials. Quantitative MRI techniques already available for assessing breast cancer response to neoadjuvant therapy include lesion size measurement, dynamic contrast-enhanced MRI, diffusion-weighted MRI, and proton magnetic resonance spectroscopy. Emerging yet promising techniques include magnetization transfer MRI, chemical exchange saturation transfer MRI, magnetic resonance elastography, and hyperpolarized MR. Translating and incorporating these techniques into the clinical setting will require close attention to statistical validation methods, standardization and reproducibility of technique, and scanning protocol design.Keywords: treatment response, presurgical treatment, neoadjuvant chemotherapy

  8. Prospective Longitudinal Assessment of Quality of Life for Liver Cancer Patients Treated With Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Klein, Jonathan, E-mail: jonathan.klein@rmp.uhn.on.ca [Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Dawson, Laura A. [Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Jiang, Haiyan [Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Kim, John; Dinniwell, Rob; Brierley, James; Wong, Rebecca [Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Lockwood, Gina [Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Ringash, Jolie [Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada)

    2015-09-01

    Purpose: To evaluate quality of life (QoL), an important outcome owing to poor long-term survival, after stereotactic body radiation therapy (SBRT) to the liver. Methods and Materials: Patients (n=222) with hepatocellular carcinoma (HCC), liver metastases, or intrahepatic cholangiocarcinoma and Child-Pugh A liver function received 24-60 Gy of 6-fraction image-guided SBRT. Prospective QoL assessment was completed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) and/or Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep, version 4) questionnaires at baseline and 1, 3, 6, and 12 months after treatment. Ten HCC patients with Child-Pugh B liver function were also treated. Results: The QLQ-C30 was available for 205 patients, and 196 completed the FACT-Hep. No difference in baseline QoL (P=.17) or overall survival (P=.088) was seen between the HCC, liver metastases, and intrahepatic cholangiocarcinoma patients. Appetite loss and fatigue measured by the QLQ-C30 clinically and statistically worsened by 1 month after treatment but recovered by 3 months. At 3 and 12 months after treatment, respectively, the FACT-Hep score had improved relative to baseline in 13%/19%, worsened in 36%/27%, and remained stable in 51%/54%. Using the QLQ-C30 Global Health score, QoL improved in 16%/23%, worsened in 34%/39%, and remained stable in 50%/38% at 3 and 12 months, respectively. Median survival was 17.0 months (95% confidence interval [CI] 12.3-19.8 months). Higher baseline scores on both FACT-Hep and QLQ-C30 Global Health were associated with improved survival. Hazard ratios for death, per 10-unit decrease in QoL, were 0.90 (95% CI 0.83-0.98; P=.001) and 0.88 (95% CI 0.82-0.95; P=.001), respectively. Tumor size was inversely correlated with survival. Conclusions: Liver SBRT temporarily worsens appetite and fatigue, but not overall QoL. Stereotactic body radiation therapy is well tolerated and warrants

  9. Assessing the role of cognitive behavioral therapy in the management of chronic nonspecific back pain

    Directory of Open Access Journals (Sweden)

    Sveinsdottir V

    2012-10-01

    Full Text Available Vigdis Sveinsdottir,1 Hege R Eriksen,1,2 Silje Endresen Reme1,31Uni Health, Uni Research, Bergen, Norway; 2Department of Health Promotion and Development, University of Bergen, Bergen, Norway; 3Department of Environmental Health, Harvard School of Public Health, Boston, MA, USAPurpose: The aim of this study is to provide a narrative review of the current state of knowledge of the role of cognitive behavioral therapy (CBT in the management of chronic nonspecific back pain.Methods: A literature search on all studies published up until July 2012 (PubMed and PsycINFO was performed. The search string consisted of 4 steps: cognitive behavioral therapy/treatment/management/modification/intervention, chronic, back pain (MeSH term or low back pain (MeSH term, and randomized controlled trial (MeSH term. The conclusions are based on the results from randomized controlled trials (RCTs and reviews of RCTs. Interventions were not required to be pure CBT interventions, but were required to include both cognitive and behavioral components.Results: The search yielded 108 studies, with 46 included in the analysis. Eligible intervention studies were categorized as CBT compared to wait-list controls/treatment as usual, physical treatments/exercise, information/education, biofeedback, operant behavioral treatment, lumbar spinal fusion surgery, and relaxation training. The results showed that CBT is a beneficial treatment for chronic back pain on a wide range of relevant variables, especially when compared to wait-list controls/treatment as usual. With regards to the other comparison treatments, results were mixed and inconclusive.Conclusion: The results of this review suggest that CBT is a beneficial treatment for chronic nonspecific back pain, leading to improvements in a wide range of relevant cognitive, behavioral and physical variables. This is especially evident when CBT is compared to treatment as usual or wait-list controls, but mixed and inconclusive when

  10. Assessment of the expectancy, seriousness and severity of adverse drug reactions reported for chronic obstructive pulmonary disease therapy

    Science.gov (United States)

    Petrova, Guenka; Stoimenova, Assena; Dimitrova, Maria; Kamusheva, Maria; Petrova, Daniela; Georgiev, Ognian

    2017-01-01

    Introduction: Adverse drug reactions can cause increased morbidity and mortality, and therefore information needs to be studied systematically. Little is known about the adverse drug reactions for chronic obstructive pulmonary disease therapy. The goal of this study is to assess the expectedness, seriousness and severity of adverse drug reactions during chronic obstructive pulmonary disease therapy based on their reporting in the national pharmacovigilance system. Methods: This was a prospective, observational, 1-year, real-life study about the pharmacotherapy of a sample of 390 chronic obstructive pulmonary disease patients. Prescribed medicines were systematized and national pharmacovigilance databases were searched for reported adverse drug reactions. The expectedness was evaluated through the review of the summary of product characteristics, the seriousness was evaluated by the clinicians based on the life threatening nature of the adverse drug reactions, and the severity was evaluated through Hartwig’s Severity Assessment Scale. Descriptive statistics of the reported adverse drug reactions was performed and the relative risk of developing an adverse drug reaction with all international non-proprietary names included in the analysis was calculated. Results: Results confirm that the chronic obstructive pulmonary disease is a disease with high appearance of adverse drug reactions, and causes many additional costs to the healthcare system. Unexpected and severe adverse drug reactions are frequent. A total of 4.8% of adverse drug reactions were evaluated as life threatening. Majority of adverse drug reactions are classified in Levels 1 (32.6%), 2 (26.4%) and 3 (19%) according to Hartwig’s Severity Assessment Scale. Approximately 22% of reported adverse drug reactions affect people’s everyday life to a greater extent and require additional therapy which might further increase the risk. The relative risk of developing an adverse drug reaction was highest for

  11. Assessment of anticancer effect of chlorin e6 dimethyl ether for photodynamic therapy

    Directory of Open Access Journals (Sweden)

    M. A. Kaplan

    2014-01-01

    Full Text Available Results of the study for anticancer efficacy of photodynamic therapy with chlorin e6 dimethyl ether for treatment of outbread rats with sarcoma M-1 are represented. The drug was given intravenously or intraperitonealy at a dose of 1.25 mg/kg body weight (light dose – 300 J/cm2 or 2,5 mg/kg body weight (light dose – 150 J/cm2. The spectrometry showed that maximal drug accumulation in tumor was in 2 h after intravenous injection or 3 h after intraperitoneal injection of photosensitizer, thus, sensitized tumors were irradiated according to these time intervals. Intraperitoneal injection of chlorin е6 dimethyl ether at a dose of 1.25 mg/kg body weight with treatment session in 3 h and light dose of 300 J/cm2 was the most effective (the complete response in animals – 86%.

  12. Low level laser therapy on injured rat muscle: assessment of irradiation parameters

    Science.gov (United States)

    Mantineo, M.; Pinheiro, J. P.; Morgado, A. M.

    2013-11-01

    Although studies show the clinical effectiveness of low level laser therapy (LLLT) in facilitating the muscle healing process, scientific evidence is still required to prove the effectiveness of LLLT and to clarify the cellular and molecular mechanisms triggered by irradiation. Here we evaluate the effect of different LLLT wavelengths, using continuous coherent Laser illumination (830 nm and 980 nm) and non-coherent LED illumination (850 nm), in the treatment of inflammation induced in the gastrocnemius muscle of Wistar rats, through the quantification of cytokines in systemic blood. We verified that all applied doses of coherent radiation produce an effect on reducing the concentration of pro-inflammatory TNF-α and IL-1β cytokines, while no treatment effect was observed after irradiation with non-coherent radiation. The best results were obtained for 40 mW at 830 nm. The results may suggest an important role of coherence properties of laser in LLLT.

  13. Low-light-level therapy as a treatment for minimal hepatic encephalopathy: behavioural and brain assessment.

    Science.gov (United States)

    Arias, Natalia; Méndez, Marta; Arias, Jorge L

    2016-11-01

    Minimal hepatic encephalopathy (MHE) has been shown to affect daily functioning, quality of life, driving and overall mortality. However, little is known about treating or diagnosing early impairments involved in MHE. We studied one of its precipitating factors, portal hypertension. The purpose was to evaluate an enhancement in neuronal metabolism through low-light-level therapy (LLLT) and whether this therapy has effects on behavioural task acquisition. Rats were trained to perform a stimulus-response task using the Morris water maze. Three groups of animals were used: a SHAM (sham-operated) group (n = 7), a portal hypertension (PH) group (n = 7) and a PH + LLLT group (n = 7). The triple portal vein ligation method was used to create an animal model of the early developmental phase of HE, and then the animals were exposed to 670 + 10 nm LED light at a dose of 9 J/cm(2) once a day for 7 days. The metabolic activity of the brains was studied with cytochrome c oxidase histochemistry. There were differences in behavioural performance, with an improvement in the PH + LLLT group. Energetic brain metabolism revealed significant differences between the groups in all the brain structures analysed, except the anterodorsal thalamus. At the same time, in different brain networks, the PH group showed a more complicated relationship among the structures, while the SHAM and PH + LLLT groups had similar patterns. In this study, we provide the first preliminary insights into the validity of LLLT as a possible intervention to improve memory under minimal hepatic encephalopathy conditions.

  14. Confocal Fluorescence Imaging Enables Noninvasive Quantitative Assessment of Host Cell Populations In Vivo Following Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Soumya Mitra, Oleg Mironov, Thomas H. Foster

    2012-01-01

    Full Text Available We report the use of optical imaging strategies to noninvasively examine photosensitizer distribution and physiological and host responses to 2-[1-hexyloxyethyl]-2 devinyl pyropheophorbide-a (HPPH-mediated photodynamic therapy (PDT of EMT6 tumors established in the ears of BALB/c mice. 24 h following intravenous (IV administration of 1 μmol kg-1 HPPH, wide-field fluorescence imaging reveals tumor selectivity with an approximately 2-3-fold differential between tumor and adjacent normal tissue. Confocal microscopy demonstrates a relatively homogeneous intratumor HPPH distribution. Labeling of host cells using fluorophore-conjugated antibodies allowed the visualization of Gr1+/CD11b+ leukocytes and major histocompatibility complex class II (MHC-II+ cells in vivo. Imaging of the treated site at different time-points following irradiation shows significant and rapid increases in Gr1+ cells in response to therapy. The maximum accumulation of Gr1+ cells is found at 24 h post-irradiation, followed by a decrease at the 48 h time-point. Using IV-injected FITC-conjugated dextran as a fluorescent perfusion marker, we imaged tissue perfusion at different times post-irradiation and found that the reduced Gr1+ cell density at 48 h correlated strongly with functional damage to the vasculature as reported via decreased perfusion status. Dual color confocal imaging experiments demonstrates that about 90% of the anti-Gr1 cell population co-localized with anti-CD11b labeling, thus indicating that majority of the Gr1-labeled cells were neutrophils. At 24 h post-PDT, an approximately 2-fold increase in MHC-II+ cells relative to untreated control is also observed. Co-localization analysis reveals an increase in the fraction of Gr1+ cells expressing MHC-II, suggesting that HPPH-PDT is stimulating neutrophils to express an antigen-presenting phenotype.

  15. Prospective randomized trial to assess effects of continuing hormone therapy on cerebral function in postmenopausal women at risk for dementia.

    Directory of Open Access Journals (Sweden)

    Natalie L Rasgon

    Full Text Available The objective of this study was to examine the effects of estrogen-based hormone therapy (HT on regional cerebral metabolism in postmenopausal women (mean age = 58, SD = 5 at risk for development of dementia. The prospective clinical trial design included pre- and post-intervention neuroimaging of women randomized to continue (HT+ or discontinue (HT- therapy following an average of 10 years of use. The primary outcome measure was change in brain metabolism during the subsequent two years, as assessed with fluorodeoxyglucose-18 positron emission tomography (FDG-PET. Longitudinal FDG-PET data were available for 45 study completers. Results showed that women randomized to continue HT experienced relative preservation of frontal and parietal cortical metabolism, compared with women randomized to discontinue HT. Women who discontinued 17-β estradiol (17βE-based HT, as well as women who continued conjugated equine estrogen (CEE-based HT, exhibited significant decline in metabolism of the precuneus/posterior cingulate cortical (PCC area. Significant decline in PCC metabolism was additionally seen in women taking concurrent progestins (with either 17βE or CEE. Together, these findings suggest that among postmenopausal subjects at risk for developing dementia, regional cerebral cortical metabolism is relatively preserved for at least two years in women randomized to continue HT, compared with women randomized to discontinue HT. In addition, continuing unopposed 17βE therapy is associated specifically with preservation of metabolism in PCC, known to undergo the most significant decline in the earliest stages of Alzheimer's disease.ClinicalTrials.gov NCT00097058.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-08-01

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

  17. Potential of robots as next-generation technology for clinical assessment of neurological disorders and upper-limb therapy

    Directory of Open Access Journals (Sweden)

    Stephen H. Scott, PhD

    2011-05-01

    Full Text Available Robotic technologies have profoundly affected the identification of fundamental properties of brain function. This success is attributable to robots being able to control the position of or forces applied to limbs, and their inherent ability to easily, objectively, and reliably quantify sensorimotor behavior. Our general hypothesis is that these same attributes make robotic technologies ideal for clinically assessing sensory, motor, and cognitive impairments in stroke and other neurologi-cal disorders. Further, they provide opportunities for novel therapeutic strategies. The present opinionated review describes how robotic technologies combined with virtual/augmented reality systems can support a broad range of behavioral tasks to objectively quantify brain function. This information could potentially be used to provide more accurate diagnostic and prognostic information than is available from current clinical assessment techniques. The review also highlights the potential benefits of robots to provide upper-limb therapy. Although the capital cost of these technologies is substantial, it pales in comparison with the potential cost reductions to the overall healthcare system that improved assessment and therapeutic interventions offer.

  18. Deferasirox as adjunctive therapy for mucormycosis.

    NARCIS (Netherlands)

    Donnelly, J.P.; Lahav, M.

    2012-01-01

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

  19. Development of a locally advanced orthotopic prostate tumor model in rats for assessment of combined modality therapy.

    Science.gov (United States)

    Tumati, Vasu; Mathur, Sanjeev; Song, Kwang; Hsieh, Jer-Tsong; Zhao, Dawen; Takahashi, Masaya; Dobin, Timothy; Gandee, Leah; Solberg, Timothy D; Habib, Amyn A; Saha, Debabrata

    2013-05-01

    The purpose of this study was to develop an aggressive locally advanced orthotopic prostate cancer model for assessing high-dose image-guided radiation therapy combined with biological agents. For this study, we used a modified human prostate cancer (PCa) cell line, PC3, in which we knocked down a tumor suppressor protein, DAB2IP (PC3‑KD). These prostate cancer cells were implanted into the prostate of nude or Copenhagen rats using either open surgical implantation or a minimally invasive procedure under ultrasound guidance. We report that: i) these DAB2IP-deficient PCa cells form a single focus of locally advanced aggressive tumors in both nude and Copenhagen rats; ii) the resulting tumors are highly aggressive and are poorly controlled after treatment with radiation alone; iii) ultrasound-guided tumor cell implantation can be used successfully for tumor development in the rat prostate; iv) precise measurement of the tumor volume and the treatment planning for radiation therapy can be obtained from ultrasound and MRI, respectively; and v) the use of a fiducial marker for enhanced radiotherapy localization in the rat orthotopic tumor. This model recapitulates radiation-resistant prostate cancers which can be used to demonstrate and quantify therapeutic response to combined modality treatments.

  20. Emotional impact in β-thalassaemia major children following cognitive-behavioural family therapy and quality of life of caregiving mothers

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    Romeo Maria

    2009-02-01

    Full Text Available Abstract Background Cognitive-Behavioural Family Therapy (CBFT can be an effective psychological approach for children with β-thalassaemia major, increasing compliance to treatment, lessening the emotional burden of disease, and improving the quality of life of caregivers. Design and methods Twenty-eight β-thalassaemic major children that followed CBFT for one year were compared with twenty-eight age-matched healthy children, focusing particularly on behavioural, mood, and temperamental characteristics as well as compliance with chelation, assessed using the Child Behaviour Checklist (CBCL, Children's Depression Inventory (CDI, Multidimensional Anxiety Scale for Children (MASC, and Emotionality, Activity, Sociability and Shyness Scale (EAS. We also monitored the quality of life of caregiving mothers using the World Health Organization Quality Of Life (WHOQOL-BREF questionnaire. Data were analysed with non-parametric standard descriptive statistics. Results 90% of β-Thalassaemic children showed good compliance with chelation therapy; however they had significantly increased somatic complains, physical symptoms and separation panic. Moreover, temperamental assessment revealed high emotionality and poor sociability in treated thalassaemic children and in their mothers. Physical and psychological domains concerning individual's overall perception of quality of life resulted impaired in mothers of β-thalassaemic children. Conclusion CBFT can be a valid tool to increase the compliance with chelation therapy in β-thalassaemic children; however, treated children continue to show an important emotional burden; moreover, CBFT therapy seems not to have any positive impact on the quality of life of caregiving mothers, who may therefore need additional psychological support.

  1. Quantitative assessment of rat corneal thickness and morphology during stem cell therapy by high-speed optical coherence tomography

    Science.gov (United States)

    Lal, Cerine; McGrath, James; Subhash, Hrebesh; Rani, Sweta; Ritter, Thomas; Leahy, Martin

    2016-03-01

    Optical Coherence Tomography (OCT) is a non-invasive 3 dimensional optical imaging modality that enables high resolution cross sectional imaging in biological tissues and materials. Its high axial and lateral resolution combined with high sensitivity, imaging depth and wide field of view makes it suitable for wide variety of high resolution medical imaging applications at clinically relevant speed. With the advent of swept source lasers, the imaging speed of OCT has increased considerably in recent years. OCT has been used in ophthalmology to study dynamic changes occurring in the cornea and iris, thereby providing physiological and pathological changes that occur within the anterior segment structures such as in glaucoma, during refractive surgery, lamellar keratoplasty and corneal diseases. In this study, we assess the changes in corneal thickness in the anterior segment of the eye during wound healing process in a rat corneal burn model following stem cell therapy using high speed swept source OCT.

  2. [Recommendations for pediatric oxygen therapy in acute and chronic settings: Needs assessment, implementation criteria, prescription practices and follow-up].

    Science.gov (United States)

    Aubertin, G; Marguet, C; Delacourt, C; Houdouin, V; Leclainche, L; Lubrano, M; Marteletti, O; Pin, I; Pouessel, G; Rittié, J-L; Saulnier, J-P; Schweitzer, C; Stremler, N; Thumerelle, C; Toutain-Rigolet, A; Beydon, N

    2013-12-01

    Recommendations for acute and long-term oxygen therapy (needs assessment, implementation criteria, prescription practices, and follow-up) in children were produced by the Groupe de Recherche sur les Avancées en Pneumo-Pédiatrie (GRAPP) under the auspices of the French Paediatric Pulmonology and Allergology Society (SP2A). The Haute Autorité de Santé (HAS) methodology, based on the Formalized Consensus, was used. A first panel of experts analyzed the English and French literature to provide a second panel of experts with recommendations to validate. Only the recommendations are presented here, but the full text (arguments+recommendations) is available at the website of the French Paediatric Society: www.sfpediatrie.com.

  3. Serum ferritin levels, socio-demographic factors and desferrioxamine therapy in multi-transfused thalassemia major patients at a government tertiary care hospital of Karachi, Pakistan

    Directory of Open Access Journals (Sweden)

    Rehman Anis

    2011-08-01

    Full Text Available Abstract Background Beta thalassemia is the most frequent genetic disorder of haemoglobin synthesis in Pakistan. Recurrent transfusions lead to iron-overload manifested by increased serum Ferritin levels, for which chelation therapy is required. Findings The study was conducted in the Pediatric Emergency unit of Civil Hospital Karachi after ethical approval by the Institutional Review Board of Dow University of Health Sciences. Seventy nine cases of beta thalassemia major were included after a written consent. The care takers were interviewed for the socio-demographic variables and the use of Desferrioxamine therapy, after which a blood sample was drawn to assess the serum Ferritin level. SPSS 15.0 was employed for data entry and analysis. Of the seventy-nine patients included in the study, 46 (58.2% were males while 33 (41.8% were females. The mean age was 10.8 (± 4.5 years with the dominant age group (46.2% being 10 to 14 years. In 62 (78.8% cases, the care taker education was below the tenth grade. The mean serum Ferritin level in our study were 4236.5 ng/ml and showed a directly proportional relationship with age. Desferrioxamine was used by patients in 46 (58.2% cases with monthly house hold income significant factor to the use of therapy. Conclusions The mean serum Ferritin levels are approximately ten times higher than the normal recommended levels for normal individuals, with two-fifths of the patients not receiving iron chelation therapy at all. Use of iron chelation therapy and titrating the dose according to the need can significantly lower the iron load reducing the risk of iron-overload related complications leading to a better quality of life and improving survival in Pakistani beta thalassemia major patients. Conflicts of Interest: None

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

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    Sanjeeva

    2015-03-01

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

  5. Study to assess the effectiveness of modified constraint-induced movement therapy in stroke subjects: A randomized controlled trial

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    Priyanka Singh

    2013-01-01

    Full Text Available Background and Purpose: The purpose of this study was to assess the effectiveness of modified constraint induced movement therapy (m-CIMT in stroke subjects. Materials and Methods: A total of forty sub-acute stroke subjects were randomly assigned to either a m-CIMT (n = 20 or in a control group (n = 20. The m-CIMT group (14 men, 6 women; mean age = 55.2 years consisted of structured 2 h therapy sessions emphasizing affected arm use, occurring 5 times/week for 2 weeks. A mitt was used to restrain the unaffected arm for 10 h/day for 2 week. The control group (11 men, 9 women; mean age = 56.4 years consisted of conventional rehabilitation for time-matched exercise program. The outcome measures were evaluated at pre- and post-intervention by using the Wolf Motor Function Test (WMFT and Fugl-Meyer assessment (FMA of motor recovery after stroke. Results: After intervention significant effects were observed in m-CIMT group on WMFT (pre-test and post-test score was 28.04 ± 6.58, 13.59 ± 2.86; P =0.003. Similarly on FMA (pre- and post-test score was 31.15 ± 6.37, 55.7 ± 6.4; P = 0.00. Conclusion: There is a significant improvem ent in upper extremity function so it indicates that m-CIMT is effective in improving the motor function of the affected arm in stroke subjects. However, its long-term effect has not proved since there was no follow-up after intervention.

  6. Clinical assessment of the therapeutic effect of low-level laser therapy on chronic recurrent aphthous stomatitis

    Science.gov (United States)

    Lalabonova, Hristina; Daskalov, Hristo

    2014-01-01

    The aim of this study was to clinically assess the therapeutic effect of low-level laser therapy (LLLT) on chronic recurrent aphthous stomatitis (RAS) using a protocol we developed especially for the purpose. The study included 180 patients: group 1 (the study group) – 90 patients who received LLLT using a laser operating in the red spectrum (658 nm; in a non-contact mode; power output P = 27 mW; frequency f 1 = 5.8 Hz, f 2 – continuous waveform; time T = 1.14 min; dosage of 2 J/cm2 once daily); group 2 (controls) – 90 patients who received pharmacotherapy (Granofurin and solcoseryl given twice daily). The indices we assessed were pain intensity, erythema dynamics and epithelization time. Pain was completely managed in 55.6% of group 1 patients one day after therapy began, while it took three days to alleviate pain for 11.1% of the patients in group 2. The erythema was managed entirely in 24.4% of group 1 patients after the first session, while it did not change in any of the group 2 patients. Pain intensity and erythema had similar dynamics for both groups. In 5 days, 75.6% of group 1 patients showed complete epithelization, while in group 2 the process was completed in only 37.8% of patients. As a whole, the results we obtained using LLLT to treat chronic RAS were better than those obtained in the group receiving pharmacotherapy. Pain and inflammation were very effectively managed with LLLT with the parameters we used and epithelization was considerably accelerated. PMID:26019580

  7. A Needs Assessment of Marriage and Family Therapy Approved Supervision in Utah

    OpenAIRE

    2005-01-01

    This research presents data gathered through a needs assessment regarding approved supervision in Utah. A sample of ISO therapists in Utah gave descriptive facts about the current need for supervision in Utah as well as the number of therapists that are willing to provide supervision. Additionally, therapists that are not currently approved supervisors indicated whether or not they would be willing to become approved supervisors, what would make the designation more appealing, and what would ...

  8. Application of transtheoretical model to assess the compliance of chronic periodontitis patients to periodontal therapy

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    Shilpa Emani

    2016-01-01

    Full Text Available Background: The present cross-sectional survey study was conducted to assess whether the transtheoretical model for oral hygiene behavior was interrelated in theoretically consistent directions in chronic periodontitis patients and its applicability to assess the compliance of the chronic periodontitis patients to the treatment suggested. Materials and Methods: A total of 150 chronic periodontitis patients were selected for the proposed study. The selected patients were given four questionnaires that were constructed based on transtheoretical model (TTM, and the patients were divided subsequently into five different groups (precontemplation, contemplation, preparation, action, and maintenance groups based on their answers to the questionnaires. Then, each patient was given four appointments for their periodontal treatment spaced with a time gap of 10 days. The patients visit for each appointments scheduled to them was documented. The results obtained were assessed using TTM. Results: Higher mean pro scores of decisional balance, self-efficacy, and process of change scores was recorded in maintenance group followed by action group, preparation group, contemplation group, and precontemplation group, respectively, whereas higher mean cons score was recorded in precontemplation group followed by contemplation group, preparation group, action group, and maintenance group, respectively. The difference scores of TTM constructs were statistically highly significant between all the five groups. Furthermore, the number of appointment attended in were significantly more than maintenance group followed by action group, preparation group, contemplation group, and precontemplation group. Conclusion: Within the limitations of this study, it can be concluded that transtheoretical model can be successfully applied to chronic periodontitis patients to assess their compliance to the suggested periodontal treatment.

  9. In vivo small animal imaging for early assessment of therapeutic efficacy of photodynamic therapy for prostate cancer

    Science.gov (United States)

    Fei, Baowei; Wang, Hesheng; Chen, Xiang; Meyers, Joseph; Mulvilhill, John; Feyes, Denise; Edgehouse, Nancy; Duerk, Jeffrey L.; Pretlow, Thomas G.; Oleinick, Nancy L.

    2007-03-01

    We are developing in vivo small animal imaging techniques that can measure early effects of photodynamic therapy (PDT) for prostate cancer. PDT is an emerging therapeutic modality that continues to show promise in the treatment of cancer. At our institution, a new second-generation photosensitizing drug, the silicon phthalocyanine Pc 4, has been developed and evaluated at the Case Comprehensive Cancer Center. In this study, we are developing magnetic resonance imaging (MRI) techniques that provide therapy monitoring and early assessment of tumor response to PDT. We generated human prostate cancer xenografts in athymic nude mice. For the imaging experiments, we used a highfield 9.4-T small animal MR scanner (Bruker Biospec). High-resolution MR images were acquired from the treated and control tumors pre- and post-PDT and 24 hr after PDT. We utilized multi-slice multi-echo (MSME) MR sequences. During imaging acquisitions, the animals were anesthetized with a continuous supply of 2% isoflurane in oxygen and were continuously monitored for respiration and temperature. After imaging experiments, we manually segmented the tumors on each image slice for quantitative image analyses. We computed three-dimensional T2 maps for the tumor regions from the MSME images. We plotted the histograms of the T2 maps for each tumor pre- and post-PDT and 24 hr after PDT. After the imaging and PDT experiments, we dissected the tumor tissues and used the histologic slides to validate the MR images. In this study, six mice with human prostate cancer tumors were imaged and treated at the Case Center for Imaging Research. The T2 values of treated tumors increased by 24 +/- 14% 24 hr after the therapy. The control tumors did not demonstrate significant changes of the T2 values. Inflammation and necrosis were observed within the treated tumors 24 hour after the treatment. Preliminary results show that Pc 4-PDT is effective for the treatment of human prostate cancer in mice. The small animal MR

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

    Science.gov (United States)

    Theil, Elizabeth C

    2010-08-01

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

  11. Use of a risk assessment method to improve the safety of negative pressure wound therapy.

    Science.gov (United States)

    Lelong, Anne-Sophie; Martelli, Nicolas; Bonan, Brigitte; Prognon, Patrice; Pineau, Judith

    2014-06-01

    To conduct a risk analysis of the negative pressure wound therapy (NPWT) care process and to improve the safety of NPWT, a working group of nurses, hospital pharmacists, physicians and hospital managers performed a risk analysis for the process of NPWT care. The failure modes, effects and criticality analysis (FMECA) method was used for this analysis. Failure modes and their consequences were defined and classified as a function of their criticality to identify priority actions for improvement. By contrast to classical FMECA, the criticality index (CI) of each consequence was calculated by multiplying occurrence, severity and detection scores. We identified 13 failure modes, leading to 20 different consequences. The CI of consequences was initially 712, falling to 357 after corrective measures were implemented. The major improvements proposed included the establishment of 6-monthly training cycles for nurses, physicians and surgeons and the introduction of computerised prescription for NPWT. The FMECA method also made it possible to prioritise actions as a function of the criticality ranking of consequences and was easily understood and used by the working group. This study is, to our knowledge, the first to use the FMECA method to improve the safety of NPWT.

  12. Assessment of Geant4 prompt gamma emission yields in the context of proton therapy monitoring

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    Marco ePinto

    2016-01-01

    Full Text Available Monte Carlo tools have been long used to assist the research and development of solutions for proton therapy monitoring. The present work focuses on the prompt-gamma emission yields by comparing experimental data with the outcomes of the current version of Geant4 using all applicable proton inelastic models. For the case in study and using the binary cascade model, it was found that Geant4 overestimates the prompt-gamma emission yields by 40.2+/-0.3%, even though it predicts the prompt-gamma profile length of the experimental profile accurately. In addition, the default implementations of all proton inelastic models show an overestimation in the number of prompt gammas emitted. Finally, a set of built-in options and physically-sound Geant4 source code changes have been tested in order to try to improve the discrepancy observed. A satisfactory agreement was found when using the QMD model with a wave packet width equal to 1.3 fm2.

  13. Assessment of DNA Damage after Photodynamic Therapy Using a Metallophthalocyanine Photosensitizer

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    A. El-Hussein

    2012-01-01

    Full Text Available Photodynamic therapy (PDT is a chemotherapeutic approach that utilizes a bifunctional reagent, a photosensitizer (PS that localizes to the target tissue relative to the surrounding tissue and is toxic when exposed to laser light. PDT rapidly induces cell death, inflammatory and immune reactions, and damage of the microvasculature. DNA damage results from a variety of factors including UV-light, X-rays, ionizing radiation, toxins, chemicals, or reactive oxygen species. The aim of this study was to determine the effect of PDT as well as the influence of presensitization leading to the adaptive response (AR on the integrity of DNA. Lung (A549, breast (MCF-7, and esophageal (SNO cancer cells and Zn sulfophthalocyanine as PS with irradiation conditions of 10 J/cm2 at 636 nm were used. Subcellular localization of PS, cell morphology, and viability after PDT and DNA damage were determined. A significant decrease in viability and marked DNA damage was observed in all 3 cancer cell types in response to PDT while the adaptive response was demonstrated to significantly decrease the effectiveness of the PDT.

  14. A Rasch and factor analysis of the Functional Assessment of Cancer Therapy-General (FACT-G

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    Selby Peter J

    2007-04-01

    Full Text Available Abstract Background Although the Functional Assessment of Cancer Therapy – General questionnaire (FACT-G has been validated few studies have explored the factor structure of the instrument, in particular using non-sample dependent measurement techniques, such as Rasch Models. Furthermore, few studies have explored the relationship between item fit to the Rasch Model and clinical utility. The aim of this study was to investigate the dimensionality and measurement properties of the FACT-G with Rasch Models and Factor analysis. Methods A factor analysis and Rasch analysis (Partial Credit Model was carried out on the FACT-G completed by a heterogeneous sample of cancer patients (n = 465. For the Rasch analysis item fit (infit mean squares ≥ 1.30, dimensionality and item invariance were assessed. The impact of removing misfitting items on the clinical utility of the subscales and FACT-G total scale was also assessed. Results The factor analysis demonstrated a four factor structure of the FACT-G which broadly corresponded to the four subscales of the instrument. Internal consistency for these four scales was very good (Cronbach's alpha 0.72 – 0.85. The Rasch analysis demonstrated that each of the subscales and the FACT-G total scale had misfitting items (infit means square ≥ 1.30. All these scales with the exception of the Social & Family Well-being Scale (SFWB were unidimensional. When misfitting items were removed, the effect sizes and the clinical utility of the instrument were maintained for the subscales and the total FACT-G scores. Conclusion The results of the traditional factor analysis and Rasch analysis of the FACT-G broadly agreed. Caution should be exercised when utilising the Social & Family Well-being scale and further work is required to determine whether this scale is best represented by two factors. Additionally, removing misfitting items from scales should be performed alongside an assessment of the impact on clinical utility.

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

    Institute of Scientific and Technical Information of China (English)

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

    2002-01-01

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

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

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    Jin Hee Kim

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

  17. Clinical mentorship of nurse initiated antiretroviral therapy in Khayelitsha, South Africa: a quality of care assessment.

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    Ann Green

    Full Text Available INTRODUCTION: To combat the AIDS epidemic and increase HIV treatment access, the South African government implemented a nurse-based, doctor-supported model of care that decentralizes administration of antiretroviral treatment (ART for HIV positive patients through nurse initiated and managed ART. Médecins Sans Frontières (MSF implemented a mentorship programme to ensure successful task-shifting, subsequently assessing the quality of clinical care provided by nurses. METHODS: A before-after cross-sectional study was conducted on nurses completing the mentorship programme in Khayelitsha, South Africa, from February 2011-September 2012. Routine clinical data from 229 patient folders and 21 self-assessment questionnaires was collected to determine the number of patients initiated on ART by nurses; quality of ART management before-after mentorship; patient characteristics for doctor and nurse ART initiations; and nurse self-assessments after mentorship. RESULTS: Twenty one nurses were authorized by one nurse mentor with one part-time medical officer's support, resulting in nurses initiating 77% of ART eligible patients. Improvements in ART management were found for drawing required bloods (91% vs 99%, p = 0.03, assessing adherence (50% vs 78%, p<0.001 and WHO staging (63% vs 91%, p<0.001. Nurse ART initiation indicators were successfully completed at 95-100% for 11 of 16 indicators: clinical presentation; patient weight; baseline blood work (CD4, creatinine, haemoglobin; STI screening; WHO stage, correlating medical history; medications prescribed appropriately; ART start date; and documented return date. Doctors initiated more patients with TB/HIV co-infection and WHO Stage 3 and 4 disease than nurses. Nurse confidence improved for managing HIV-infected children and pregnant women, blood result interpretation and long-term side effects. CONCLUSIONS: Implementation of a clinical mentorship programme in Khayelitsha led to nurse initiation of a

  18. Complexation and Antimicrobial Studies of Some Divalent Metal Chelates

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    Suparna Ghosh

    2010-01-01

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

  19. Assessment of efficacy of bothropic antivenom therapy on microcirculatory effects induced by Bothrops jararaca snake venom.

    Science.gov (United States)

    Battellino, Carolina; Piazza, Roxane; da Silva, Ana M M; Cury, Yara; Farsky, Sandra H P

    2003-04-01

    Intravenous administration of antibothropic antivenom (BAv) neutralises the systemic effects, but does not efficiently reverse the local symptoms elicited by the Bothrops jararaca venom (BjV). The mechanisms involved in this poor protection have not been clarified. In this work, intravital microscopy studies were carried out to determine the efficacy of different schedules of BAv treatment on local effects evoked by topical application of BjV in the microcirculatory network of the internal spermatic fascia of Wistar rats. Results demonstrated that BAv administration 15 min before, simultaneously with, or 15 min after BjV application did not totally reverse the local symptoms, represented by disturbances of coagulation, development of haemorrhage lesions, vascular permeability increase and increment on leukocyte-endothelium interactions. This lack of effectiveness neither reflects an inadequate amount of specific antibodies in the antivenom against toxins responsible for local effects nor an insufficient dose of circulating BAv during the assays. Administration of fluorescein isothiocyanate (FITC) labelled-BAv showed the dynamics of distribution of the antivenom in the microcirculatory network. Images obtained from prior and simultaneously treated animals showed that the antivenom remains at luminal side of vessels before venom application, and the latency time to antivenom leakage is coincidental to that for local effects evoked by the venom. In addition, images from posterior treatment demonstrated that the intense alterations in the microcirculatory network impair antivenom distribution at the site of injection. Together, our data show that the lack of effectiveness of antivenom therapy is due to impaired and delayed venom and antivenom interaction at the site of injury.

  20. Development and assessment of a cutaneous tissue stretch device as a novel scar therapy

    Institute of Scientific and Technical Information of China (English)

    Jonathan Kanevsky; Joshua Vorstenbosch; Julian Diaz-Abele; Tyler Safran; Markus Prinz; Youssef Tahiri; Mirko Gilardino; Satya Prakash

    2016-01-01

    Aim: Scar prevention and reduction is an area of therapeutic opportunity and unmet medical need. With no current effective scar therapy, patients are often disappointed in their appearance post surgery and re-present to surgeons, only to be turned away. The purpose of this study was to develop and test a device that produces intermittent parallel stretch on new scars and to analyze its potential to reduce scarring.Methods: Mice were randomized into 5 scar stretch treatment groups: 1 control, 1 sham, and 3 stretch models (0.5×, 1×, or 2× device strength) and treated for 10 days. Scars were scored using the Vancouver Scar Scale. Scar tissue samples were compared by histology and transforming growth factor beta 1 (TGF-β1) expression between control and treatment groups.Results: Scar scores of 0.5× and 1× groups were signiifcantly lower than the control group (P < 0.05). Scar scores from the 1× treatment group were also signiifcantly lower than the 0.5× group (P < 0.05). Sham, control scar and 2× groups showed more collagen deposition and a thicker dermal scar than the 0.5× and 1× groups. Unstretched scars had fewer ifbroblasts with more collagen deposition than the 0.5× and 2× groups. TGF-β1 levels were signiifcantly lower in the 0.5× (342.1 ± 9.2) and 1× (254.1 ± 3.1) groups than in the control group (P < 0.05). TGF-β1 levels in the 1× treatment group were also signiifcantly lower than the 0.5× treatment group (P < 0.05).Conclusion:Intermittent cutaneous tissue stretch parallel to scars during the proliferative phase of wound healing decreases ifbrosis on a macroscopic, microscopic and biochemical level.

  1. Xenograft assessment of predictive biomarkers for standard head and neck cancer therapies.

    Science.gov (United States)

    Stein, Andrew P; Swick, Adam D; Smith, Molly A; Blitzer, Grace C; Yang, Robert Z; Saha, Sandeep; Harari, Paul M; Lambert, Paul F; Liu, Cheng Z; Kimple, Randall J

    2015-05-01

    Head and neck squamous cell carcinoma (HNSCC) remains a challenging cancer to treat with overall 5-year survival on the order of 50-60%. Therefore, predictive biomarkers for this disease would be valuable to provide more effective and individualized therapeutic approaches for these patients. While prognostic biomarkers such as p16 expression correlate with outcome; to date, no predictive biomarkers have been clinically validated for HNSCC. We generated xenografts in immunocompromised mice from six established HNSCC cell lines and evaluated response to cisplatin, cetuximab, and radiation. Tissue microarrays were constructed from pre- and posttreatment tumor samples derived from each xenograft experiment. Quantitative immunohistochemistry was performed using a semiautomated imaging and analysis platform to determine the relative expression of five potential predictive biomarkers: epidermal growth factor receptor (EGFR), phospho-EGFR, phospho-Akt, phospho-ERK, and excision repair cross-complementation group 1 (ERCC1). Biomarker levels were compared between xenografts that were sensitive versus resistant to a specific therapy utilizing a two-sample t-test with equal standard deviations. Indeed the xenografts displayed heterogeneous responses to each treatment, and we linked a number of baseline biomarker levels to response. This included low ERCC1 being associated with cisplatin sensitivity, low phospho-Akt correlated with cetuximab sensitivity, and high total EGFR was related to radiation resistance. Overall, we developed a systematic approach to identifying predictive biomarkers and demonstrated several connections between biomarker levels and treatment response. Despite these promising initial results, this work requires additional preclinical validation, likely involving the use of patient-derived xenografts, prior to moving into the clinical realm for confirmation among patients with HNSCC.

  2. Assessment of Arterial Oxygen Saturation by Pulse Oximetry Before, During and After Electroconvulsive Therapy

    Directory of Open Access Journals (Sweden)

    SH Tarig

    2006-07-01

    Full Text Available Introduction & Objective: Electroconvulsive therapy (ECT is used widely in psychiatric practice. The goal of anesthesia for ECT is the prevention of complications such as discomfort, fractures, aspiration of gastric contents and hypoxia. However, general anesthesia can cause some adverse effects as hypoxia. Prevention and treatment of hypoxia is important due to its undesirable effects on seizure duration and cardiovascular system. This study was designed to detect the incidence and probable times of desaturation in patients receiving ECT. Materials & Methods: This prospective randomized clinical trial was carried out on 100 patients (18-50 y/o with ASA I or II who were scheduled for ECT. After pre-oxygenation and similar anesthesia induction the patients received ECT. The patients were ventilated by oxygen and face masked until the return of their spontaneous respiration with adequate tidal volume and respiratory rate. Then they were transferred to recovery room where there was no oxygen supplementation. Oxygen saturation was measured by a Nell core pulse oximeter and was recorded at six stages: before and after anesthesia induction, during ECT, after ECT, 5 minutes after entering recovery room and before leaving there. The data were analyzed by standard statistical tests using SPSS software Results: Data analysis revealed that desaturation was not noticed at any stage except for the 5th stage (5 minutes after entering recovery room, when 13% of patients developed Sao2% less than 90%. Also there was a significant difference between Sao2% of patients between this stage (5th and other stages (p<0.001. Conclusion: According to our findings, appropriate oxygen supplementation and pulse oximetry monitoring during recovery period after ECT can be recommend

  3. Clinical considerations for an effective medical therapy in Wilson's disease.

    Science.gov (United States)

    Weiss, Karl Heinz; Stremmel, Wolfgang

    2014-05-01

    Wilson's disease is an autosomal recessively inherited copper overload disorder that leads to hepatic and/or neurologic symptoms. More than a century after the first description of Wilson's disease, the available medical treatment options have not been standardized. The efficacy of the commonly used drugs is satisfactory for hepatic disease, but disappointing in the neurologic patients, including the risk of neurologic deterioration after the initiation of chelation therapy. An approach to overcome this problem is the careful and systematic assessment of biochemical response patterns and the quantitative monitoring of symptoms using validated rating scales. Standardized dosage strategies that address changes in copper pools might improve adherence and reduce side effects. Such an approach may reduce long-term morbidity. In this paper, we discuss considerations for an effective medical treatment and requirements for future studies in Wilson's disease.

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

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

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

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

    Science.gov (United States)

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

    2014-10-13

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

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

    Science.gov (United States)

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

    2015-09-01

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

  7. Risk assessment by myocardial perfusion imaging for coronary revascularization, medical therapy, and noncardiac surgery.

    Science.gov (United States)

    Papaioannou, Georgios I; Heller, Gary V

    2003-01-01

    Stress myocardial perfusion imaging (MPI) has become an important tool in risk stratification of patients with known coronary artery disease. A normal myocardial perfusion scan has a high negative predictive value and is associated with low annual mortality rate ( 20% of the left ventricle), defects in more than 1 coronary vascular territory, transient or persistent left ventricular cavity dilation, and ejection fraction less than 45% have a high annual mortality rate (> 3%). Those patients should undergo coronary revascularization whenever feasible, as the cardiac event rate increases in proportion to the magnitude of the jeopardized myocardium. Stress MPI can be used to demonstrate ischemia in patients with symptoms early after coronary artery bypass surgery (/= 5 years) after coronary artery bypass surgery. With respect to patients who underwent percutaneous interventions, stress MPI can help detect in-stent restenosis early after the intervention (3-6 months) or assess the progression of native coronary disease afterward. Since preliminary data suggest that a reduction in the perfusion defect size may translate to a reduction of coronary events, stress MPI can help assess the efficacy of medical management of coronary disease. Finally, stress MPI is indicated for perioperative cardiac risk stratification for noncardiac surgery in patients with intermediate risk predictors (mild angina, prior myocardial infarction or heart failure symptoms, diabetes mellitus, renal insufficiency) and poor functional capacity or in those who undergo high-risk surgery with significant implications in further preoperative management.

  8. Can Biomarker Assessment on Circulating Tumor Cells Help Direct Therapy in Metastatic Breast Cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Turner, Natalie [Sandro Pitigliani Medical Oncology Department, Prato Hospital, Istituto Toscano Tumori, Via Ugo Foscolo, Prato, PO 59100 (Italy); Pestrin, Marta [Sandro Pitigliani Medical Oncology Department, Prato Hospital, Istituto Toscano Tumori, Via Ugo Foscolo, Prato, PO 59100 (Italy); Translational Research Laboratory, Prato Hospital, Via Ugo Foscolo, Prato, PO 59100 (Italy); Galardi, Francesca; De Luca, Francesca [Translational Research Laboratory, Prato Hospital, Via Ugo Foscolo, Prato, PO 59100 (Italy); Malorni, Luca [Sandro Pitigliani Medical Oncology Department, Prato Hospital, Istituto Toscano Tumori, Via Ugo Foscolo, Prato, PO 59100 (Italy); Translational Research Laboratory, Prato Hospital, Via Ugo Foscolo, Prato, PO 59100 (Italy); Di Leo, Angelo, E-mail: adileo@usl4.toscana.it [Sandro Pitigliani Medical Oncology Department, Prato Hospital, Istituto Toscano Tumori, Via Ugo Foscolo, Prato, PO 59100 (Italy)

    2014-03-25

    Circulating tumor cell (CTC) count has prognostic significance in metastatic breast cancer, but the predictive utility of CTCs is uncertain. Molecular studies on CTCs have often been limited by a low number of CTCs isolated from a high background of leukocytes. Improved enrichment techniques are now allowing molecular characterisation of single CTCs, whereby molecular markers on single CTCs may provide a real-time assessment of tumor biomarker status from a blood test or “liquid biopsy”, potentially negating the need for a more invasive tissue biopsy. The predictive ability of CTC biomarker analysis has predominantly been assessed in relation to HER2, with variable and inconclusive results. Limited data exist for other biomarkers, such as the estrogen receptor. In addition to the need to define and validate the most accurate and reproducible method for CTC molecular analysis, the clinical relevance of biomarkers, including gain of HER2 on CTC after HER2 negative primary breast cancer, remains uncertain. This review summarises the currently available data relating to biomarker evaluation on CTCs and its role in directing management in metastatic breast cancer, discusses limitations, and outlines measures that may enable future development of this approach.

  9. Can Biomarker Assessment on Circulating Tumor Cells Help Direct Therapy in Metastatic Breast Cancer?

    Directory of Open Access Journals (Sweden)

    Natalie Turner

    2014-03-01

    Full Text Available Circulating tumor cell (CTC count has prognostic significance in metastatic breast cancer, but the predictive utility of CTCs is uncertain. Molecular studies on CTCs have often been limited by a low number of CTCs isolated from a high background of leukocytes. Improved enrichment techniques are now allowing molecular characterisation of single CTCs, whereby molecular markers on single CTCs may provide a real-time assessment of tumor biomarker status from a blood test or “liquid biopsy”, potentially negating the need for a more invasive tissue biopsy. The predictive ability of CTC biomarker analysis has predominantly been assessed in relation to HER2, with variable and inconclusive results. Limited data exist for other biomarkers, such as the estrogen receptor. In addition to the need to define and validate the most accurate and reproducible method for CTC molecular analysis, the clinical relevance of biomarkers, including gain of HER2 on CTC after HER2 negative primary breast cancer, remains uncertain. This review summarises the currently available data relating to biomarker evaluation on CTCs and its role in directing management in metastatic breast cancer, discusses limitations, and outlines measures that may enable future development of this approach.

  10. Multi-observation PET image analysis for patient follow-up quantitation and therapy assessment

    Energy Technology Data Exchange (ETDEWEB)

    David, S; Visvikis, D; Roux, C; Hatt, M, E-mail: simon.david@etudiant.univ-brest.fr [INSERM U650, LaTIM, Brest, F-29200 (France)

    2011-09-21

    In positron emission tomography (PET) imaging, an early therapeutic response is usually characterized by variations of semi-quantitative parameters restricted to maximum SUV measured in PET scans during the treatment. Such measurements do not reflect overall tumor volume and radiotracer uptake variations. The proposed approach is based on multi-observation image analysis for merging several PET acquisitions to assess tumor metabolic volume and uptake variations. The fusion algorithm is based on iterative estimation using a stochastic expectation maximization (SEM) algorithm. The proposed method was applied to simulated and clinical follow-up PET images. We compared the multi-observation fusion performance to threshold-based methods, proposed for the assessment of the therapeutic response based on functional volumes. On simulated datasets the adaptive threshold applied independently on both images led to higher errors than the ASEM fusion and on clinical datasets it failed to provide coherent measurements for four patients out of seven due to aberrant delineations. The ASEM method demonstrated improved and more robust estimation of the evaluation leading to more pertinent measurements. Future work will consist in extending the methodology and applying it to clinical multi-tracer datasets in order to evaluate its potential impact on the biological tumor volume definition for radiotherapy applications.

  11. Assessment of the Effects of Zoledronic Acid Therapy on Bone Metabolic Indicators in Hormone-Resistant Prostate Cancer Patients with Bone Metastatasis

    Science.gov (United States)

    Demirtas, Abdullah; Sahin, Nurettin; Caniklioglu, Mehmet; Kula, Mustafa; Ekmekcioglu, Oguz; Tatlisen, Atila

    2011-01-01

    Purpose. Assessment of effects of zoledronic acid therapy on bone metabolic indicators in hormone-resistant prostate cancer patients with bone metastasis. Material and Methods. Hormone-resistant prostate cancer patients who were identified to have metastases in their bone scintigraphy were taken to trial group. Before administration of zoledronic acid, routine tests for serum calcium, total alkalen phosphates were studied. Sample sera for bone metabolic indicators BALP, PINP, and ICTP were collected. Bone pain was assessed via visual analogue scale and performance via Karnofsky performance scale. Four mg zoledronic acid was administered intravenously once a month. Results. When serum levels of bone forming indicators PINP; BALP were compared before and after therapy, there were insignificant decreases (P = .33, P = .21, resp.). Serum levels of bone destruction indicator ICTP was compared, and there was a significant decrease after zoledronic acid therapy (P = .04). When performances of the patients were compared during therapy period, performances decreased significantly due to progress of illness (P = .01). All patients had ostalgia caused by bone metastases at various degrees. Significant decrease in pain scores was observed (P < .01). Conclusion. Zoledronic acid therapy decreased bone destruction and was effective in palliation of pain in patient with bone metastasis. Using bone metabolic indicators during followup of zoledronic acid therapy might be useful. PMID:22084798

  12. p-Isothiocyanatobenzyl-desferrioxamine: a new bifunctional chelate for facile radiolabeling of monoclonal antibodies with zirconium-89 for immuno-PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Perk, Lars R.; Vosjan, Maria J.W.D.; Budde, Marianne [VU University Medical Center, Department of Otolaryngology/Head and Neck Surgery, De Boelelaan 1117, PO Box 7057, MB, Amsterdam (Netherlands); Visser, Gerard W.M. [VU University Medical Center, Nuclear Medicine and PET Research, Amsterdam (Netherlands); Jurek, Paul; Kiefer, Garry E. [Macrocyclics Inc., Dallas, TX (United States); Dongen, Guus A.M.S. van [VU University Medical Center, Department of Otolaryngology/Head and Neck Surgery, De Boelelaan 1117, PO Box 7057, MB, Amsterdam (Netherlands); VU University Medical Center, Nuclear Medicine and PET Research, Amsterdam (Netherlands)

    2010-02-15

    Immuno-PET is an emerging imaging tool for the selection of high potential antibodies (mAbs) for imaging and therapy. The positron emitter zirconium-89 ({sup 89}Zr) has attractive characteristics for immuno-PET with intact mAbs. Previously, we have described a multi-step procedure for stable coupling of {sup 89}Zr to mAbs via the bifunctional chelate (BFC) tetrafluorophenol-N-succinyldesferal (TFP-N-sucDf). To enable widespread use of {sup 89}Zr-immuno-PET, we now introduce the novel BFC p-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) and compare its performance in {sup 89}Zr-immuno-PET with the reference BFC TFP-N-sucDf. Three mAbs were premodified with Df-Bz-NCS and labeled with {sup 89}Zr at different pHs to assess the reaction kinetics and robustness of the radiolabeling. Stability of both {sup 89}Zr-Df-Bz-NCS- and {sup 89}Zr-N-sucDf-conjugates was evaluated in different buffers and human serum. Comparative biodistribution and PET studies in tumor-bearing mice were undertaken. The selected conjugation conditions resulted in a chelate:mAb substitution ratio of about 1.5:1. Under optimal radiolabeling conditions (pH between 6.8-7.2), the radiochemical yield was >85% after 60 min incubation at room temperature, resulting in radioimmunoconjugates with preserved integrity and immunoreactivity. The new radioimmunoconjugate was very stable in serum for up to 7 days at 37 C, with <5% {sup 89}Zr release, and was equally stable compared to the reference conjugate when stored in the appropriate buffer at 4 C. In biodistribution and imaging experiments, the novel and the reference radioimmunoconjugates showed high and similar accumulation in tumors in nude mice. The novel Df-Bz-NCS BFC allows efficient and easy preparation of optimally performing {sup 89}Zr-labeled mAbs, facilitating further exploration of {sup 89}Zr-immuno-PET as an imaging tool. (orig.)

  13. Rating scales for cervical dystonia: a critical evaluation of tools for outcome assessment of botulinum toxin therapy.

    Science.gov (United States)

    Jost, Wolfgang H; Hefter, Harald; Stenner, Andrea; Reichel, Gerhard

    2013-03-01

    Botulinum neurotoxin is the therapy of choice for all forms of cervical dystonia (CD), but treatment regimens still vary considerably. The interpretation of treatment outcome is mainly based on the clinical experience and on the scientific value of the rating scales applied. The aim of this review is to describe the historical development of rating scales for the assessment of CD and to provide an appraisal of their advantages and drawbacks. The Tsui score and the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) have been widely employed in numerous clinical studies as specific instruments for CD. The obvious advantage of the Tsui score is its simplicity so that it can be easily implemented in clinical routine. The TWSTRS allows a more sophisticated assessment of functional features of CD, but only the Tsui score includes a rating for tremor. Other benefits of the TWSTRS are the disability and pain subscales, but despite its value in clinical trials, it might be too complex for routine clinical practice. None of the rating scales used at present has been rigorously tested for responsiveness to detect significant changes in clinical status after therapeutic interventions. Moreover, clinical data support a new classification of CD leading to a differentiation between head and neck subtypes. As the current rating scales are not able to cover all these aspects of the disorder, further research is needed to develop a valid and reliable instrument which considers the most current classification of CD.

  14. Utility of comprehensive assessment of strain dyssynchrony index by speckle tracking imaging for predicting response to cardiac resynchronization therapy.

    Science.gov (United States)

    Tatsumi, Kazuhiro; Tanaka, Hidekazu; Yamawaki, Kouhei; Ryo, Keiko; Omar, Alaa Mabrouk Salem; Fukuda, Yuko; Norisada, Kazuko; Matsumoto, Kensuke; Onishi, Tetsuari; Gorcsan, John; Yoshida, Akihiro; Kawai, Hiroya; Hirata, Ken-ichi

    2011-02-01

    The strain delay index is reportedly a marker of dyssynchrony and residual myocardial contractility. The aim of this study was to test the hypothesis that a relatively simple version of the strain dyssynchrony index (SDI) can predict response to cardiac resynchronization therapy (CRT) and that combining assessment of radial, circumferential, and longitudinal SDI can further improve the prediction of responders. A total of 52 patients who underwent CRT were studied. The SDI was calculated as the average difference between peak and end-systolic strain from 6 segments for radial and circumferential SDI and 18 segments for longitudinal SDI. Conventional dyssynchrony measures were assessed by interventricular mechanical delay, the Yu index, and radial dyssynchrony by speckle tracking strain. Response was defined as a ≥15% decrease in end-systolic volume after 3 months. Of the individual parameters, radial SDI ≥6.5% was the best predictor of response to CRT, with sensitivity of 81%, specificity of 81%, and an area under the curve of 0.87 (p SDIs was 100%. In contrast, rates in patients with either 1 or no positive SDIs were 42% and 22%, respectively (p SDIs). In conclusion, the SDI can successfully predict response to CRT, and the combined approach leads to more accurate prediction than using individual parameters.

  15. Assessment of the efficacy of laser hyperthermia and nanoparticle-enhanced therapies by heat shock protein analysis

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Fei [Department of Precision Instrument, Tsinghua University, Beijing, 100084 (China); Zhang, Ye; Zhang, Juan; Liu, Ran, E-mail: liuran@tsinghua.edu.cn [Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, 100084 (China); Guo, Junwei [Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, 100084 (China)

    2014-03-15

    Tumor thermotherapy is a method of cancer treatment wherein cancer cells are killed by exposing the body tissues to high temperatures. Successful clinical implementation of this method requires a clear understanding and assessment of the changes of the tumor area after the therapy. In this study, we evaluated the effect of near-infrared laser tumor thermotherapy at the molecular, cellular, and physical levels. We used single-walled carbon nanotubes (SWNTs) in combination with this thermotherapy. We established a mouse model for breast cancer and randomly divided the mice into four groups: mice with SWNT-assisted thermotherapy; mice heat treated without SWNT; mice injected with SWNTs without thermotherapy; and a control group. Tumors were irradiated using a near-infrared laser with their surface temperature remaining at approximately 45 °C. We monitored the tumor body growth trend closely by daily physical measurements, immunohistochemical staining, and H and E (hematoxylin-eosin) staining by stage. Our results showed that infrared laser hyperthermia had a significant inhibitory effect on the transplanted breast tumor, with an inhibition rate of 53.09%, and also significantly reduced the expression of the heat shock protein Hsp70. Furthermore, we have found that protein analysis and histological analysis can be used to assess therapeutic effects effectively, presenting broad application prospects for determining the effect of different treatments on tumors. Finally, we discuss the effects of SWNT-assisted near-infrared laser tumor thermotherapy on tumor growth at the molecular, cellular, and physical levels.

  16. 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.

  17. The Role of Diffusion-Weighted Imaging (DWI in Locoregional Therapy Outcome Prediction and Response Assessment for Hepatocellular Carcinoma (HCC: The New Era of Functional Imaging Biomarkers

    Directory of Open Access Journals (Sweden)

    Johannes M. Ludwig

    2015-11-01

    Full Text Available Reliable response criteria are critical for the evaluation of therapeutic response in hepatocellular carcinoma (HCC. Current response assessment is mainly based on: (1 changes in size, which is at times unreliable and lag behind the result of therapy; and (2 contrast enhancement, which can be difficult to quantify in the presence of benign post-procedural changes and in tumors presenting with a heterogeneous pattern of enhancement. Given these challenges, functional magnetic resonance imaging (MRI techniques, such as diffusion-weighted imaging (DWI have been recently investigated, aiding specificity to locoregional therapy response assessment and outcome prediction. Briefly, DWI quantifies diffusion of water occurring naturally at a cellular level (Brownian movement, which is restricted in multiple neoplasms because of high cellularity. Disruption of cellular integrity secondary to therapy results in increased water diffusion across the injured membranes. This review will provide an overview of the current literature on DWI therapy response assessment and outcome prediction in HCC following treatment with locoregional therapies.

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

    Science.gov (United States)

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

    2013-10-02

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

  19. Boron neutron capture therapy for newly diagnosed glioblastoma multiforme: An assessment of clinical potential

    Energy Technology Data Exchange (ETDEWEB)

    Hopewell, J.W., E-mail: john.hopewell@gtc.ox.ac.uk [Green Templeton College and Particle Therapy Cancer Research Institute, University of Oxford, Oxford (United Kingdom); Gorlia, T. [Data Center, EORTC, Brussels (Belgium); Pellettieri, L. [Hammercap Medical AB, Stockholm (Sweden)] [Department of Neurosurgery, Goeteborg University, Goeteborg (Sweden); Giusti, V. [Hammercap Medical AB, Stockholm (Sweden)] [Department of Mechanical, Nuclear and Production Engineering, University of Pisa, Pisa (Italy); H-Stenstam, B. [Nykoeping Hospital, County of Sormland (Sweden); Skoeld, K. [Hammercap Medical AB, Stockholm (Sweden)

    2011-12-15

    The purpose of this analysis was to assess the potential of BNCT, with L-boronophenylalanine (L-BPA), as first line radiotherapy for glioblastoma multiforme (GBM). The survival of patients with newly diagnosed GBM from a phase II BNCT study was compared with those from the two arms of a phase III study with conventional radiotherapy (RT) vs. RT plus concomitant and adjuvant medication with temozolomide (TMZ). A small subgroup, for which the methylation status of the O{sup 6}-methylguanine-DNA methyltransferase (MGMT) DNA-repair gene was known, was also considered. The results indicated that the use of BNCT with BPA should be explored in a stratified randomized phase II trial in which patients with the unmethylated MGMT DNA-repair gene are offered BNCT vs. RT plus TMZ.

  20. Feasibility of the Music Therapy Assessment Tool for Awareness in Disorders Of Consciousness (MATADOC for use with Pediatric Populations

    Directory of Open Access Journals (Sweden)

    Wendy L Magee

    2015-05-01

    Full Text Available Measuring responsiveness to gain accurate diagnosis in populations with disorders of consciousness (DOC is of central concern because these patients have such complex clinical presentations. Due to the uncertainty of accuracy for both behavioral and neurophysiological measures in DOC, combined assessment approaches are recommended. A number of standardized behavioral measures can be used with adults with DOC with minor to moderate reservations relating to the measures’ psychometric properties and clinical applicability. However, no measures have been standardized for use with pediatric DOC populations. When adapting adult measures for children, confounding factors include developmental considerations for language-based items included in all DOC measures. Given the lack of pediatric DOC measures, there is a pressing need for measures that are sensitive to the complex clinical presentations typical of DOC and that can accommodate the developmental levels of pediatric populations. The Music Therapy Assessment Tool for Awareness in Disorders of Consciousness (MATADOC is a music-based measure that has been standardized for adults with DOC. Given its emphasis on non-language based sensory stimuli, it is well-suited to pediatric populations spanning developmental stages. In a pre-pilot exploratory study, we examined the clinical utility of this measure and explored trends for test-retest and inter-rater agreement as well as its performance against external reference standards. In several cases, MATADOC items in the visual and auditory domains produced outcomes suggestive of higher level functioning when compared to outcomes provided by other DOC measures. Preliminary findings suggest that the MATADOC provides a useful protocol and measure for behavioral assessment and clinical treatment planning with pediatric DOC. Further research with a larger sample is warranted to test a version of the MATADOC that is refined to meet developmental needs of

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

    Science.gov (United States)

    You, Changjiang; Piehler, Jacob

    2014-05-01

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

  2. Selective separation of indium by iminodiacetic acid chelating resin

    Directory of Open Access Journals (Sweden)

    M. C. B. Fortes

    2007-06-01

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

  3. Magnetic memory effect in chelated zero valent iron nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-11-15

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

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

    Science.gov (United States)

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

    2014-05-01

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

  5. Selective separation of indium by iminodiacetic acid chelating resin

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-04-15

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

  6. Comparative assessment of two Artemisinin based combination Therapies in the treatment of Uncomplicated Malaria among University students in Nigeria

    Directory of Open Access Journals (Sweden)

    Okonta Matthew J

    2013-06-01

    Full Text Available Background: In line with the recommendation of artemisininbased combination therapy (ACT by WHO in the effective treatment of uncomplicated malaria, African nations including Nigeria changed their malaria treatment policy to combination therapies. To date, about 15 African nations adopted artesunate /amodiaquine (AA as their first line agent while Nigeria adopted artemether /lumefantrine (AL. Objective: The objective of this study is to compare the treatment outcome among patients treated with AA to those treated with AL for acute uncomplicated malaria. Method: The study was conducted at Nnamdi Azikiwe University campuses using quantitative methods. Two hundered and ninety six patients were randomly allocated to one of two treatment group- AA and AL with 148 patients per group. All the patients were educated about the drugs and adherence. Adherence and treatment outcomes including parasite clearance and the drugs’ effects on biochemical parameters among others were assessed by follow up visits on third, seventh, fourteenth and twenty eighth-day post treatment. Data were analysed using Cox Regression model on SPSS 17.0. Result: Both drugs were well adhered to and tolerated. One case of Steven Johnson-like reaction was observed with AL. Fever resolution and parasite clearance was similar in both groups with adequate clinical and parasitological response (ACPR by day 28 for AL and AA being 70.3% and 85.1% respectively. Conclusion: Our findings is in favour of higher efficacy of AA with respect to their ACPR. More controlled studies will be needed to ascertain the adoption of AL as first line drug in malaria treatment in Nigeria.

  7. Changes in Vaginal Bacterial Concentrations with Intravaginal Metronidazole Therapy for Bacterial Vaginosis as Assessed by Quantitative PCR▿

    Science.gov (United States)

    Fredricks, David N.; Fiedler, Tina L.; Thomas, Katherine K.; Mitchell, Caroline M.; Marrazzo, Jeanne M.

    2009-01-01

    Several fastidious bacteria have been associated with bacterial vaginosis (BV) using broad-range bacterial PCR methods such as consensus sequence 16S rRNA gene PCR, but their role in BV remains poorly defined. We describe changes in vaginal bacterial concentrations following metronidazole therapy for BV. Vaginal swabs were collected from women with BV diagnosed using Amsel clinical criteria, and vaginal fluid was assessed by Gram stain to generate Nugent scores. Follow-up swabs were collected 1 month after a 5-day course of vaginal 0.75% metronidazole gel and analyzed for 24 subjects with cured BV and 24 subjects with persistent BV. Changes in bacterial concentrations were measured using eight bacterium-specific 16S rRNA gene quantitative PCR assays. DNA from several fastidious BV-associated bacteria (BVAB) were present at high concentrations in the vagina prior to treatment. Successful antibiotic therapy resulted in 3- to 4-log reductions in median bacterial loads of BVAB1 (P = 0.02), BVAB2 (P = 0.0004), BVAB3 (P = 0.03), a Megasphaera-like bacterium (P < 0.0001), Atopobium species (P < 0.0001), Leptotrichia/Sneathia species (P = 0.0002), and Gardnerella vaginalis (P < 0.0001). Median posttreatment bacterial levels did not change significantly in subjects with persistent BV except for a decline in levels of BVAB3. The presence or absence of BV is reflected by vaginal concentrations of BV-associated bacteria such as BVAB1, BVAB2, Leptotrichia/Sneathia species, Atopobium species, Gardnerella vaginalis, and a Megasphaera-like bacterium, suggesting that these bacteria play an important role in BV pathogenesis and may be suitable markers of disease and treatment response. PMID:19144794

  8. Multimodality imaging assessments of response to metformin therapy for breast cancer in nude mice

    Institute of Scientific and Technical Information of China (English)

    MAO Yi; XIA Rui; WANG Lei; WANG Yu-qing; GAO Fa-bao

    2013-01-01

    Background Metformin is the most widely used anti-diabetic drug in the world.An increasing body of evidence shows metformin also blocks cell cycle progression and selectively induces apoptosis via caspase activation in some breast tumor cells.Diffusion-weighted imaging (DWl) and bioluminescence imaging (BLI) have great potential in the evaluation of the early response to cancer therapies.We used DWl and BLI in evaluating the response of breast cancer to metformin.Methods The luciferase-engineered human breast cancer cell line MDA-MB-231 was inoculated into the mammary fat pad of nude mice.Twelve female nude mice bearing tumors were divided into two groups.The mice in the treatment group received metformin (2 mg/ml in drinking water daily) after tumor inoculation,and the mice in the control group were offered drinking water without any drug added.We performed 7T magnetic resonance imaging and optical imaging every week.Imaging included T1-and T2-weighted imaging,DWl,and BLI.After imaging.The tumors were collected and subjected to histological analysis.Results The mean photons/second of tumors in the treatment group was (3.00±0.43)×106 at day one,(1.01±0.14)×107 at 2 weeks,(5.79±1.42)×107 at 4 weeks,and (2.33±0.70)×107 at 8 weeks.The mean photons/second of tumors in the control group was (3.29±0.59)×106 at day one,(3.59±0.63)×107 at 2 weeks,(3.87±0.56)×108 at 4 weeks,and (4.12±1.72)x108 at 8 weeks.Compared to the control group,the treatment group showed an obvious decrease in the mean bioluminescence (photons/s) of the tumors and fewer metastases.Histological examination confirmed the presence of fewer metastases.DWI showed the apparent diffusion coefficient (ADC) value of the tumors; the mean ADC value was (0.9287±0.04346)x10-3 mm2/s in the treated tumors and (0.7553±0.01804)x103 mm2/s in the untreated tumors.The ADC value of tumors in the treatment group was significantly higher than the control tumors (P=0.0013).Conclusions The growth and

  9. Psychometric Properties of the Malay Version of the Loewenstein Occupational Therapy Cognitive Assessment for Geriatrics (M-LOTCA-G) among the Malaysian Elderly Population

    Science.gov (United States)

    Mohd Natar, Ahmad Kamal; Nagappan, Rajendran; Ainuddin, Husna Ahmad; Masuri, Ghazali; Thanapalan, Chandra Kannan K.

    2015-01-01

    Current cognitive screening tests are difficult to use due to their deficit in cultural and conceptual significance and translation into other languages. The purpose of this study was to translate the Loewenstein Occupational Therapy Cognitive Assessment for Geriatrics (LOTCA-G) into Malay language and test its reliability and validity for…

  10. Can virtual reality exposure therapy gains be generalized to real-life? : A meta-analysis of studies applying behavioral assessments

    NARCIS (Netherlands)

    Morina, Nexhmedin; Ijntema, Hiske; Meyerbröker, Katharina; Emmelkamp, Paul M G

    2015-01-01

    In virtual reality exposure therapy (VRET), patients are exposed to virtual environments that resemble feared real-life situations. The aim of the current study was to assess the extent to which VRET gains can be observed in real-life situations. We conducted a meta-analysis of clinical trials apply

  11. Development and implementation of an anthropomorphic pediatric spine phantom for the assessment of craniospinal irradiation procedures in proton therapy

    Directory of Open Access Journals (Sweden)

    Dana J Lewis

    2014-03-01

    analysis criterion for the film planes.--------------------------------------Cite this article as: Lewis DJ, Summers PA, Followill DS, Sahoo N, Mahajan A, Stingo FC, Kry SF. Development and implementation of an anthropomorphic pediatric spine phantom for the assessment of craniospinal irradiation procedures in proton therapy. Int J Cancer Ther Oncol 2014; 2(2:020227. DOI: 10.14319/ijcto.0202.27

  12. Antiretroviral therapy in HIV-infected patients: a proposal to assess the economic value of the single-tablet regimen

    Directory of Open Access Journals (Sweden)

    Colombo GL

    2013-02-01

    Full Text Available Giorgio L Colombo,1,2 Sergio Di Matteo,2 Franco Maggiolo31University of Pavia, Department of Drug Sciences, School of Pharmacy, Pavia, Italy, 2Studi Analisi Valutazioni Economiche, Milan, Italy, 3Division of Infectious Diseases, Ospedali Riuniti, Bergamo, ItalyBackground: The aim of this study was to assess the economic value of a reduced number of pills in patients infected with the immunodeficiency virus (HIV and on highly active antiretroviral therapy by a cost-effectiveness model.Methods: An incremental cost-effectiveness analysis of efavirenz, tenofovir, and emtricitabine (TDF-FTC-EFV as a single-tablet regimen versus a multipill regimen, with reference to untreated HIV-infected patients, was carried out from the perspective of the Italian National Health Service. The comparisons were performed with the help of a Markov decision model over a 10-year time horizon. Based on the ADONE (ADherence to ONE pill study, it was then possible to identify the utility score increment in patients switching from a multipill regimen of TDF-FTC + EFV therapy to a single-tablet regimen.Results: The single-tablet regimen (0.755 quality-adjusted life-years [QALYs]/year resulted in better patient quality of life, with a higher number of QALYs than for the TDF-FTC + EFV multipill regimen (0.716 QALYs/year. The single-tablet regimen was the most cost-effective treatment strategy, with an incremental cost-effectiveness ratio of €22,017.00 versus €26,558.00 for the multipill regimen. A 24% decrease in cost of the multipill regimen determined equivalence with the single-tablet regimen in terms of the incremental cost-effectiveness ratio. Univariate sensitivity and probabilistic analysis carried out on the main variables did not highlight significant variations with respect to the base case scenario.Conclusion: The single-tablet regimen resulted in better adherence, and therefore better quality of life as perceived by patients, corresponding to a €4541.00 lower

  13. 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

  14. Additional dose assessment from the activation of high-energy linear accelerators used in radiation therapy

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    Ateia Embarka

    2008-01-01

    Full Text Available It is well known that medical linear accelerators generate activation products when operated above certain electron (photon energies. The aim of the present work is to assess the activation behavior of a medium-energy radiotherapy linear accelerator by applying in situ gamma-ray spectrometry and dose measurements, and to estimate the additional dose to radiotherapy staff on the basis of these results. Spectral analysis was performed parallel to dose rate measurements in the isocenter of the linear accelerator, immediately after the termination of irradiation. The following radioisotopes were detected by spectral analysis: 28Al, 62Cu, 56Mn, 64Cu, 187W, and 57Ni. The short-lived isotopes such as 28Al and 62Cu are the most important factors of the clinical routine, while the contribution to the radiation dose of medium-lived isotopes such as 56Mn, 57Ni, 64Cu, and 187W increases during the working day. Measured dose rates at the isocenter ranged from 2.2 µSv/h to 10 µSv/h in various measuring points of interest for the members of the radiotherapy staff. Within the period of 10 minutes, the dose rate decreased to values of 0.8 µSv/h. According to actual workloads in radiotherapy departments, a realistic exposure scenario was set, resulting in a maximal additional annual whole body dose to the radiotherapy staff of about 3.5 mSv.

  15. Implementing in vasion neutron capture therapy (INCT) using capillary neutron optical systems (CNOS) assessment

    Science.gov (United States)

    Borisov, G. I.; Kumakhov, M. A.; Kondratenko, R. I.; Spryshkova, R. A.

    2005-07-01

    During LNCT the exposed object represents a practically ideal trap for neutrons In this instance, the number of neutrons that entered the object through the inlet hole is equal to the number of nuclear reactions of their absorption. Using this model and nuclear data about all considered nuclides for a biological tissue, the following INCT characteristics were theoretically calculated with regard to introduction of dosage-forming preparations based on different concentrations of lOB, l57Gd and 235U nuclides: - effective masses irradiated by thermal neutrons, - energies absorbed in the object for one thermal neutron entered, - partial content of basic dosage-forming reactions, - partial content of absorbed dosage of thermal neutrons from basic dosage-forming reactions, - quantity of thermal neutrons needed to create a total absorbed dosage of 5 Gr within the focal spot area of 0,28 cm2, - number of nuclear reactions with dosage-forming nuclides of preparations per one cell based on the cell volume of 7x7x7 m. It follows from the data obtained that dosage-forming nuclide 10B is not only the optimal but also the only one suitable for INCT. Using the obtained outcome, one can assess parameters of capillary neutron optical systems (CNOS) that are pre-requisite to implement INCT at particular experimental channels (EC) of research nuclear reactors.

  16. Assessing appropriateness of antimicrobial therapy: in the eye of the interpreter.

    Science.gov (United States)

    DePestel, Daryl D; Eiland, Edward H; Lusardi, Katherine; Destache, Christopher J; Mercier, Renée-Claude; McDaneld, Patrick M; Lamp, Kenneth C; Chung, Thomas J; Hermsen, Elizabeth D

    2014-10-15

    To address the increase of drug-resistant bacteria and widespread inappropriate use of antimicrobials, many healthcare institutions have implemented antimicrobial stewardship programs to promote appropriate use of antimicrobials and optimize patient outcomes. However, a consensus definition of appropriate use is lacking. We conducted a multicenter observational study to compare 4 definitions of appropriateness--a study site-specific definition, use supported by susceptibility data, use supported by electronic drug information resources (Clinical Pharmacology/Micromedex), or study site principal investigator (PI) opinion-among patients receiving 1 or more of 13 identified antimicrobials. Data were collected for 262 patients. Overall, appropriateness with the 4 definitions ranged from 79% based on PI opinion to 94% based on susceptibility data. No single definition resulted in consistently high appropriate use for all target antimicrobials. For individual antimicrobials, the definitions with the highest rate of appropriate use were Clinical Pharmacology/Micromedex support (6 of 7 antimicrobials) and susceptibility data (5 of 7 antimicrobials). For specific indications, support from susceptibility data resulted in the highest rate of appropriate use (4 of 7 indications). Overall comparisons showed that appropriateness assessed by PI opinion differed significantly compared with other definitions when stratified by either target antimicrobial or indication. The significant variability in the rate of appropriate use highlights the difficulty in developing a standardized definition that can be used to benchmark judicious antimicrobial use.

  17. Assessment of colour vision in epileptic patients exposed to single-drug therapy.

    Science.gov (United States)

    López, L; Thomson, A; Rabinowicz, A L

    1999-01-01

    Diplopia, blurred vision and colour disturbances are well-known side effects associated with anti-epileptic drugs (AEDs). Farnsworth-Munsell 100-hue colour test (F-100) is an accepted and sensitive tool to detect changes in colour perception. To determine the impact of AEDs upon colour vision, we evaluated 37 consecutive patients with complex partial seizures exposed to monotherapy with phenytoin (PHT, carbamazepine (CBZ) or valproic acid (VPA). All had normal IQ and no congenital disturbances in colour vision or ocular diseases. Twenty normal controls were used for statistical analysis. Thirteen patients were exposed to PHT, 12 to CBZ and 12 to VPA. Visual colour perception was impaired in 30/37 (82%) of the study group. The most significant abnormality was detected in the blue-yellow axis in 10/13 patients exposed to PHT (p < 0.02) and in 8/12 treated with CBZ (p < 0.009). In 8/12 patients taking VPA, no significant abnormality was observed (p < 0.06). None of the studied patients complained of colour vision disturbances. Our findings strongly support the negative effect of AEDs upon colour vision discrimination, most likely due to changes at the retinal processing level. F-100 proved to be very useful to assess early toxicity due to AEDs.

  18. The Role of Speech and Language Therapy in Assessing and Managing Pharyngo-esophageal Diverticula.

    Science.gov (United States)

    Holmes, E; Kenny, C; Samuel, M; Regan, J; O'Rourke, J; McCoubrey, C

    2015-01-01

    This study explores the contribution of Speech and Language Therapists (SLTs) to the assessment and management of patients presenting on videofluoroscopic swallow studies (VFSS) with a suspected pharyngo-oesophageal diverticulum. Records for all patients who attended for VFSS in an acute hospital over an eleven-year period were examined (N = 1820). Twenty patients were identified on VFSS as having a suspected diverticulum. Symptoms suggestive of a diverticulum were found during both bedside clinical examination and radiographic examination e.g. respiratory difficulties (n = 15; 75%), voice changes (n = 14; 70/0). VFSS confirmed a reduced risk of aspiration for 14 patients (70%) using a combination of fluid modification (n = 9; 45%), food modification (n = 13; 65%) and swallow strategies (n = 14; 70%). VFSS confirmed aspiration directly related to the diverticulum in 11 patients (55%). Findings indicate that SLTs have the opportunity to identify potential diverticula and implement behavioural management to reduce associated health risks. This is of particular importance to patients who are awaiting, or cannot undergo, surgical repair of their diverticulum.

  19. Natural iron chelators: Protective role in A549 cells of flavonoids-rich extracts of Citrus juices in Fe(3+)-induced oxidative stress.

    Science.gov (United States)

    Ferlazzo, Nadia; Visalli, Giuseppa; Cirmi, Santa; Lombardo, Giovanni Enrico; Laganà, Pasqualina; Di Pietro, Angela; Navarra, Michele

    2016-04-01

    Exogenous iron in particulate matter and imbalanced iron homeostasis cause deleterious effects on health. Natural and synthetic iron chelators may be of therapeutic benefit, therefore we evaluated the protective effect of Citrus flavonoids-rich extracts from bergamot and orange juices in iron overloaded human lung epithelial cells. Cytofluorimetric, biochemical and genotoxic analyses were performed in Fe2(SO4)3 exposed A549, pretreated with each extract whose chemical composition was previously detected. Chelating activity was assessed in cells by a calcein ester. Both extracts reduced the generation of reactive oxygen species and membrane lipid peroxidation, improved mitochondrial functionality, and prevented DNA-oxidative damage in iron-exposed cells. Antioxidant effects were attributed to the chelating property, blocking upstream the redox activity of iron. Flavonoid-rich extracts also induced antioxidant catalase. The bergamot and orange juice extracts had a broad-spectrum protective effect. Their use prevents iron oxidative injury and these natural iron chelators could be used as therapeutic agents.

  20. {sup 177}Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment

    Energy Technology Data Exchange (ETDEWEB)

    Yadav, Madhav Prasad; Ballal, Sanjana; Tripathi, Madhavi; Damle, Nishikant Avinash; Bal, Chandrasekhar [All India Institute of Medical Sciences, Department of Nuclear Medicine, Ansari Nagar, New Delhi (India); Sahoo, Ranjit Kumar [All India Institute of Medical Sciences, Department of Medical Oncology, BR Ambedkar Rotary Cancer Hospital, New Delhi (India); Seth, Amlesh [All India Institute of Medical Sciences, Department of Urology, New Delhi (India)

    2017-01-15

    The purpose of this study was to evaluate the efficacy and safety of a novel theranostic agent, {sup 177}Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer (mCRPC). Thirty-one mCRPC patients with progressive disease despite second-line hormonal therapy and/or docetaxel chemotherapy were recruited for the study. All patients underwent diagnostic{sup 68}Ga-PSMA-HBED-CCPET/CT, prior to inclusion for therapy. Included patients then underwent quarterly {sup 177}Lu-DKFZ-PSMA-617 therapy. Hematological, kidney function, liver function tests, and serum PSA levels were recorded before and after therapy at 2 weeks, 4 weeks, and 3 month intervals. Biochemical response was assessed with trend in serum PSA levels. Metabolic response was assessed by PERCIST 1 criteria. Clinical response was assessed by visual analogue score (VASmax) analgesic score (AS), Karanofsky performance status (KPS), and toxicity and response criteria of the Eastern Cooperative Oncology Group (ECOG) criteria. The mean age of patients was 65.93 ± 9.77 years (range: 38-81 years). The mean activity administered in the 31 patients was 5069 ± 1845 MBq ranging from one to four cycles. There was a decline in the mean serum PSA levels from the baseline (baseline: 275 ng/mL, post 1st cycle therapy: 141.75 ng/mL). Based on biochemical response criteria 2/31, 20/31, 3/31, and 6/31 had complete response (CR), partial response(PR), stable disease (SD), and progressive disease (PD), respectively. Metabolic response revealed 2/6 patients with CR, and the remaining 3/6 patients with PR and 1/6 patients with SD. The mean VASmax score decreased from 7.5 to 3. The mean analgesic score decreased from 2.5 to 1.8 after therapy. The mean KPS score improved from 50.32 to 65.42 after therapies. The mean ECOG performance status improved from 2.54 to 1.78 after therapy. Two patients experienced grade I and grade II hemoglobin toxicity each. None of the patients experienced nephrotoxicity or hepatotoxicity

  1. Micro-computed tomography (CT) based assessment of dental regenerative therapy in the canine mandible model

    Science.gov (United States)

    Khobragade, P.; Jain, A.; Setlur Nagesh, S. V.; Andreana, S.; Dziak, R.; Sunkara, S. K.; Sunkara, S.; Bednarek, D. R.; Rudin, S.; Ionita, C. N.

    2015-03-01

    High-resolution 3D bone-tissue structure measurements may provide information critical to the understanding of the bone regeneration processes and to the bone strength assessment. Tissue engineering studies rely on such nondestructive measurements to monitor bone graft regeneration area. In this study, we measured bone yield, fractal dimension and trabecular thickness through micro-CT slices for different grafts and controls. Eight canines underwent surgery to remove a bone volume (defect) in the canine's jaw at a total of 44 different locations. We kept 11 defects empty for control and filled the remaining ones with three regenerative materials; NanoGen (NG), a FDA-approved material (n=11), a novel NanoCalcium Sulfate (NCS) material (n=11) and NCS alginate (NCS+alg) material (n=11). After a minimum of four and eight weeks, the canines were sacrificed and the jaw samples were extracted. We used a custombuilt micro-CT system to acquire the data volume and developed software to measure the bone yield, fractal dimension and trabecular thickness. The software used a segmentation algorithm based on histograms derived from volumes of interest indicated by the operator. Using bone yield and fractal dimension as indices we are able to differentiate between the control and regenerative material (pprocess and quality of bone were dependent upon the position of defect and time period of healing. This study presents one of the first quantitative comparisons using non-destructive Micro-CT analysis for bone regenerative material in a large animal with a critical defect model. Our results indicate that Micro-CT measurement could be used to monitor invivo bone regeneration studies for greater regenerative process understanding.

  2. Comparison between CT volume measurement and histopathological assessment of response to neoadjuvant therapy in rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pomerri, Fabio, E-mail: fabio.pomerri@unipd.it [Veneto Institute of Oncology IOV-IRCCS, via Gattamelata 64, 35128 Padua (Italy); Department of Medicine, University of Padua, via Giustiniani 2, 35128 Padua (Italy); Pucciarelli, Salvatore, E-mail: puc@unipd.it [Department of Oncological and Surgical Sciences, University of Padua, via Giustiniani 2, 35128 Padua (Italy); Gennaro, Gisella, E-mail: gisella.gennaro@pd.infn.it [Veneto Institute of Oncology IOV-IRCCS, via Gattamelata 64, 35128 Padua (Italy); Maretto, Isacco, E-mail: isac77@gmail.com [Veneto Institute of Oncology IOV-IRCCS, via Gattamelata 64, 35128 Padua (Italy); Nitti, Donato, E-mail: donato.nitti@unipd.it [Department of Oncological and Surgical Sciences, University of Padua, via Giustiniani 2, 35128 Padua (Italy); Muzzio, Pier Carlo, E-mail: pcmuzzio@unipd.it [Veneto Institute of Oncology IOV-IRCCS, via Gattamelata 64, 35128 Padua (Italy)

    2012-12-15

    Objectives: The aim of this study was to compare volume measurements on computed tomography (CT) images with histopathological assessments of chemoradiotherapy (CRT)-induced tumor regression in locally advanced rectal cancer (RC). Methods: In 25 patients (13 males, 12 females; median age, 63 years; age range, 44–79 years) with locally advanced RC treated with preoperative CRT and surgery, two radiologists measured tumor volume on CT images before and after CRT. CT-based tumor volumetry and the modified response evaluation criteria in solid tumors (mRECISTs) were compared with T and N downstaging after CRT, and with the tumor regression grade (TRG). Results: Tumor volumes were significantly smaller on CT images after CRT. The tumors regressed in 52% (13/25), 36% (9/25) and 40% (10/25) of patients, based on T downstaging, TRG and mRECIST findings, respectively. In terms of T downstaging, the pre- and post-CRT tumor volumes of responders and non-responders to the treatment differed statistically, while their tumor volume reduction rates and volume reductions according to the 65% mRECIST threshold did not. In terms of N downstaging and TRG, the differences between the responders’ and the non-responders’ pre- and post-CRT tumor volumes, tumor volume reduction rates, and mRECIST thresholds were never statistically significant. Conclusion: Measuring tumor size on CT images is of limited value in predicting the histopathological response to preoperative CRT in RC patients, so it may be unwise to select surgical treatment strategies based on CT volumetry.

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

    Science.gov (United States)

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

    2015-03-07

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

  4. Assessment of the effect of bariatric surgery on severe obstructive sleep apnea patients not tolerating CPAP therapy

    Directory of Open Access Journals (Sweden)

    H. Shaarawy

    2016-07-01

    Full Text Available Obstructive sleep apnea (OSA is increasingly prevalent worldwide and is associated with morbidity and mortality, the main line of treatment is CPAP but the compliance is doubtful, as obesity is highly linked to OSA weight loss can help in treatment. The aim of the present study: was to assess the effect of bariatric surgery on severe obstructive sleep apnea patients not tolerating CPAP therapy. Patients and methods: the study was done on 22 patients documented to have morbid obesity (BMI > 40 and severe OSA with Apnea Hypopnea Index (AHI >30/h and not tolerating CPAP therapy, patients were offered sleeve gastrectomy then were followed up for 12 months before another polysomnography was done to assess the presence of OSA and need for CPAP. Results: 22 patients completed the study. The mean age of the patients was 37.2 ± 17.3 years, 13 males and 9 females. After sleeve gastrectomy and follow up for 12 months the body weight decreased from 135.6 ± 17.8 to 101.3 ± 7.6 kg m (p = 0.001, BMI dropped from 48.2 ± 7.3 to 35.9 ± 4.8 kg m/m2 (p = 0.001, mean AHI decreased from 55.8 ± 8.3 to 12.8 ± 11.3 attacks/hour of sleep (p = 0.001 and CPAP pressure needed to control OSA was decreased from 13.2 ± 2.3 to 8.2 ± 3.9 cm H2O (p = 0.001. Conclusion: sleeve gastrectomy can be an alternate option of treatment for severe OSA patients who are not tolerating CPAP and surgery may cure the disease or at least improve compliance to CPAP by decreasing the needed pressure to control OSA.

  5. The meaningful assessment of therapy outcomes: Incorporating a qualitative study into a randomized controlled trial evaluating the treatment of adolescent depression.

    Science.gov (United States)

    Midgley, Nick; Ansaldo, Flavia; Target, Mary

    2014-03-01

    For many years, there have been heated debates about the best way to evaluate the efficacy and effectiveness of psychological therapies. On the one hand, there are those who argue that the randomized controlled trial (RCT) is the only reliable and scientifically credible way to assess psychological interventions. On the other hand, there are those who have argued that psychological therapies cannot be meaningfully assessed using a methodology developed to evaluate the impact of drug treatments, and that the findings of RCTs lack "external validity" and are difficult to translate into routine clinical practice. In this article, we advocate the use of mixed-method research designs for RCTs, combining the rigor of quantitative data about patterns of change with the phenomenological contextualized insights that can be derived from qualitative data. We argue that such an approach is especially important if we wish to understand more fully the impact of therapeutic interventions within complex clinical settings. To illustrate the value of a mixed-method approach, we describe a study currently underway in the United Kingdom, in which a qualitative study (IMPACT-My Experience [IMPACT-ME]) has been "nested" within an RCT (the Improving Mood With Psychoanalytic and Cognitive Behavioral Therapy [IMPACT] study) designed to evaluate the effectiveness of psychological therapies in the treatment of adolescent depression. We argue that such a mixed-methods approach can help us to evaluate the effectiveness of psychological therapies and support the real-world implementation of our findings within increasingly complex and multidisciplinary clinical contexts.

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

    Science.gov (United States)

    El-Gamel, Nadia E. A.

    2007-11-01

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

  7. Cognitive assessment of the elderly patients with type 2 diabetes:application of the Loewenstein Occupational Therapy Cognitive Assessment(LOTCA in a community sample

    Directory of Open Access Journals (Sweden)

    Yue-chang YANG

    2011-05-01

    Full Text Available Objective To assess the clinical application of Loewenstein Occupational Therapy Cognitive Assessment(LOTCA in evaluating the impairment of cognition in elderly patients with type 2 diabetes(DM2.Methods Community based 58 elderly patients with DM2 in a community in Shanghai(60 years and older,having received education for 9 years or longer were enrolled and screened by Mini-Mental State Examination(MMSE.According to the MMSE scores,21 subjects were assigned to case group(MMSE score < 24,implying cognition impairment,and 37 to control group(MMSE score ≥ 24,implying normal cognition.Meanwhile,a group of community-based 40 elderly subjects without DM2(60 years or older,having received education for 9 years or longer,and MMSE score ≥ 24 were enrolled as the blank control.Difference among the baseline data(age,sex ratio and incidence of hypertension among the 3 groups mentioned above was negligible.The cognition function was assessed with the LOTCA,and the scores acquired were then compared among the 3 groups.Results The total LOTCA scores showed significant difference among the 3 groups.Each LOTCA score,except the score of perception subtest(object identification,was lower in case group than in control and blank group.In control group,the scores were lower than in blank group of the subtest of perception(object constancy,visual-motor organization test and the subtests thereof(reproduction of two-dimensional models,colored and plain block design construction,and reproduction of a puzzle,thinking operation test and the subtests thereof(ROC unstructured,pictorial sequence B,and geometrical sequence,and of concentration test.Conclusions Cognitive impairment may occur in the early stage of elderly patients with DM2.In comparison with MMSE scale,LOTCA is superior in measuring the cognitive impairment during the early stage of elderly DM2 patients and stratifying the severity of the impairment.

  8. Reliability and validity of the Functional Assessment of Chronic Illness Therapy-Palliative care (FACIT-Pal) scale.

    Science.gov (United States)

    Lyons, Kathleen Doyle; Bakitas, Marie; Hegel, Mark T; Hanscom, Brett; Hull, Jay; Ahles, Tim A

    2009-01-01

    The Functional Assessment of Chronic Illness Therapy (FACIT) system provides a general, multidimensional measure of health-related quality of life (FACT-G) that can be augmented with disease or symptom-specific subscales. The 19-item palliative care subscale of the FACIT system has undergone little psychometric evaluation to date. The aim of this paper is to report the internal consistency, factor structure, and construct validity of the instrument using the palliative care subscale (FACIT-Pal). Two hundred fifty-six persons with advanced cancer in a randomized trial testing a palliative care psychoeducational intervention completed the 46-item FACIT-Pal at baseline. Internal consistency was greater than 0.74 for all subscales and the total score. Seventeen of the 19 palliative care subscale items loaded onto the four-factor solution of the established core measure (FACT-G). As hypothesized, total scores were correlated with measures of symptom intensity (r=-0.73, P<0.001) and depression (r=-0.75, P<0.001). The FACIT-Pal was able to discriminate between participants who died within three months of completing the baseline and participants who lived for at least one year after completing the baseline assessment (t=-4.05, P<0.001). The functional well-being subscale discriminated between participants who had a Karnofsky performance score of 70 and below and participants with a Karnofsky performance score of 80 and above (t=3.40, P<0.001). The findings support the internal consistency reliability and validity of the FACIT-Pal as a measure of health-related quality of life for persons with advanced cancer.

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

    Institute of Scientific and Technical Information of China (English)

    HU Binghuan; CHEN Wending; LIN Jinhuo

    1993-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Suwakon Wongjaikam

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

  12. Scale invariant feature transform in adaptive radiation therapy: a tool for deformable image registration assessment and re-planning indication

    Science.gov (United States)

    Paganelli, Chiara; Peroni, Marta; Riboldi, Marco; Sharp, Gregory C.; Ciardo, Delia; Alterio, Daniela; Orecchia, Roberto; Baroni, Guido

    2013-01-01

    Adaptive radiation therapy (ART) aims at compensating for anatomic and pathological changes to improve delivery along a treatment fraction sequence. Current ART protocols require time-consuming manual updating of all volumes of interest on the images acquired during treatment. Deformable image registration (DIR) and contour propagation stand as a state of the ART method to automate the process, but the lack of DIR quality control methods hinder an introduction into clinical practice. We investigated the scale invariant feature transform (SIFT) method as a quantitative automated tool (1) for DIR evaluation and (2) for re-planning decision-making in the framework of ART treatments. As a preliminary test, SIFT invariance properties at shape-preserving and deformable transformations were studied on a computational phantom, granting residual matching errors below the voxel dimension. Then a clinical dataset composed of 19 head and neck ART patients was used to quantify the performance in ART treatments. For the goal (1) results demonstrated SIFT potential as an operator-independent DIR quality assessment metric. We measured DIR group systematic residual errors up to 0.66 mm against 1.35 mm provided by rigid registration. The group systematic errors of both bony and all other structures were also analyzed, attesting the presence of anatomical deformations. The correct automated identification of 18 patients who might benefit from ART out of the total 22 cases using SIFT demonstrated its capabilities toward goal (2) achievement.

  13. Ambulatory ECG-based T-wave alternans monitoring for risk assessment and guiding medical therapy: mechanisms and clinical applications.

    Science.gov (United States)

    Verrier, Richard L; Ikeda, Takanori

    2013-01-01

    Identification of individuals at risk for sudden cardiac death (SCD), the main cause of adult mortality in developed countries, remains a major challenge. The main contemporary noninvasive marker, left ventricular ejection fraction (LVEF), has not proved adequately reliable, as the majority of individuals who die suddenly have relatively preserved cardiac mechanical function. Monitoring of T-wave alternans (TWA), a beat-to-beat fluctuation in ST-segment or T-wave morphology, on ambulatory electrocardiogram (AECG) is an attractive approach on both scientific and clinical grounds. Specifically, TWA's capacity to assess risk for malignant arrhythmias has been shown to rest on sound electrophysiologic principles and AECG-based TWA monitoring can be performed in the flow of routine clinical evaluation. This review addresses: (1) electrophysiologic and ionic mechanisms underlying TWA's predictivity, (2) principles and practical aspects of AECG-based TWA monitoring, (3) clinical evidence supporting this approach to SCD risk stratification, and (4) current and potential applications in guiding medical therapy.

  14. ASSESSMENT OF RELATED ANAMNESTIC AND CLINICAL FACTORS ON EFFICACY AND SAFETY OF ANTI-HELICOBACTER PYLORI THERAPY

    Directory of Open Access Journals (Sweden)

    D. N. Andreev

    2016-01-01

    Full Text Available The article presents the results of a prospective clinical study in which 100 patients with H. pylori-associated peptic ulcer disease of stomach/duodenum were examined. The aim of the study was to assess the effect of concomitant anamnestic and clinical factors on the efficacy and safety of eradication therapy (ET. Type 2 diabetes mellitus is a factor that significantly reduces the efficiency of ET with OR 0.21 (95% CI 0,06-0,69, p = 0,0102. Using a macrolide antibiotics prior to ET during the previous 12 months is associated with a reduction in the effectiveness of H. pylori eradication with OR 0.27 (95% CI 0,08-0,90, p = 0,0342. Despite the lack of statistical significance observed negative effect on the efficiency of ET factors such as smoking and increased BMI. Smoking, female gender, age over 50 years and the presence of type 2 diabetes mellitus had no significant impact on the safety profile of ET. 

  15. PainVision® Apparatus for Assessment of Efficacy of Pulsed Radiofrequency Combined with Pharmacological Therapy in the Treatment of Postherpetic Neuralgia and Correlations with Measurements

    Directory of Open Access Journals (Sweden)

    Dong Wang

    2017-01-01

    Full Text Available Objective. PainVision device was a developed application for the evaluation of pain intensity. The objective was to assess the efficacy and safety of pulsed radiofrequency (PRF combined with pharmacological therapy in the treatment of postherpetic neuralgia (PHN. We also discussed the correlation of the measurements. Method. Forty patients with PHN were randomized for treatment with PRF combined with pharmacological therapy (PRF group, n=20 or pharmacological therapy (control group, n=20 at postoperative 48 hours. The efficacy measure was pain degree (PD that was assessed by PainVision and visual analog scale (VAS, short form Mcgill pain questionnaire (SF-Mcgill, and numeric rate scale sleep interference score (NRSSIS. Correlations between PD, VAS, SF-Mcgill, and NRSSIS were determined. Results. The PD for persistent pain (PP and breakthrough pain (BTP at postoperative 48 hours assessed by PainVision were significantly lower in PRF group than in control group (PD-PP, P<0.01; PD-BTP, P<0.01. PD and VAS were highly correlated for both persistent pain (r=0.453, ρ=0.008 and breakthrough pain (r=0.64, ρ=0.001. Conclusion. PRF was well tolerated and superior to isolated pharmacological therapy in the treatment of PHN. PainVision device showed great value in the evaluation of pain intensity and PD had an excellent correlation with VAS and SF-Mcgill.

  16. A NOVEL METAL CHELATE AFFINITY ADSORBENT FOR PROTEIN UPTAKE

    Institute of Scientific and Technical Information of China (English)

    WANGYongjian; BAIShu; 等

    2001-01-01

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

  17. 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.

  18. 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.

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

    Science.gov (United States)

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

    2005-01-26

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

  20. Beryllium Chelation by Dicarboxylic Acids in Aqueous Solution.

    Science.gov (United States)

    Schmidt, Michael; Bauer, Andreas; Schmidbaur, Hubert

    1997-05-07

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

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

    Science.gov (United States)

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

    2012-11-01

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

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

    Science.gov (United States)

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

    2014-06-12

    The 18-kDa translocator protein (TSPO) is overexpressed in many types of cancers and is also abundant in activated microglial cells occurring in inflammatory neurodegenerative diseases