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1.
Ecotoxicol Environ Saf ; 203: 110983, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32678760

RESUMO

Chelating agents have been considered as an important phytoremediation strategy to enhance heavy metal extraction from contaminated soil. A pot experiment was conducted to explore the effects of low molecular weight organic acids (LMWOAs) on the phytoremediation efficiency of copper (Cu) by castor bean, and soil enzyme activities. Results indicated that the addition of all the three kinds of LMWOAs (citric, tartaric, oxalic acids) did not decrease the biomass of castor bean, despite the fact they reduced the concentration of chlorophyll-a in leaves compared to the control. The Cu concentrations in the roots and shoots significantly increased by 6-106% and 5-148%, respectively, in the LMWOAs treatments so that the total accumulation of Cu by whole plants in all the LMWOAs treatments increased by 21-189% in comparison with the control. The values of the translocation factor (TF) and bio-concentration factor (BCF) of Cu in castor bean also rose following the addition of LMWOAs, indicating that the LMWOAs enhanced the uptake and transportation of Cu. Moreover, the application of LMWOAs did not significantly change the soil pH but significantly increased the activity of soil enzymes (urease, catalase, and alkaline phosphatase). The addition of exogenous LMWOAs increased the available Cu significantly in the soil, thus promoted the phytoextraction efficiency of Cu by castor bean. These results will provide some new insights into the practical use of LMWOAs for the phytoremediation of heavy-metal-contaminated soil employing castor bean.


Assuntos
Bioacumulação , Semente de Rícino/metabolismo , Quelantes/química , Cobre/metabolismo , Compostos Orgânicos/química , Poluentes do Solo/metabolismo , Solo/química , Ácidos/administração & dosagem , Ácidos/química , Biodegradação Ambiental , Semente de Rícino/efeitos dos fármacos , Quelantes/administração & dosagem , Peso Molecular , Compostos Orgânicos/administração & dosagem
2.
BMC Neurol ; 20(1): 255, 2020 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-32593295

RESUMO

BACKGROUND: Even though recent research has achieved significant advancement in the development of therapeutic approaches for Wilson's diseases (WD), the current treatment options available for WD are still limited, especially for WD patients with neurological symptoms. This study is intended to compare the therapeutic approaches for WD patients with neurological symptoms receiving either combined sodium 2, 3-dimercapto-1-propane sulfonate (DMPS) and zinc treatment or D-penicillamine (DPA) monotherapy as first-line therapy, and identify the more effective therapeutic approach. METHODS: The case records of 158 patients diagnosed with neurological WD were retrospectively analyzed. These patients treated with intravenous DMPS + Zinc and in combination with oral zinc as a maintenance therapy (Group 1) or DPA alone (Group 2) for 1 year. During the period of treatment, the neurological symptoms of the patients were assessed using the Global Assessment Scale (GAS) and Barthel index. The key hematological and biochemical parameters of the patients (such as the levels of aminotransferase, serum ceruloplasmin, 24-h urine copper excretion), as well as adverse effects were recorded and analyzed. RESULTS: Ninety-three patients in Group 1, displayed decreased GAS scores and increased Barthel indexes consistently in comparison with the baseline (P < 0.01). Among them, 82 patients (88.2%) exhibited significant neurological improvement after 1 year, while 8 patients (8.6%) experienced neurological deterioration. Among the 65 patients in Group 2, 37 patients (58.5%) exhibited neurological improvements, while 17 patients (26.2%) experienced neurological deterioration after 1-year follow up. Six patients discontinued their treatment midway due to their exacerbating neurological symptoms. A comprehensive comparison of the effectiveness of the two courses of treatment revealed that patients in group 1 demonstrated a higher improvement ratio (P < 0.01) and lower worsening ratio of the neurological symptoms for the patients (P < 0.01) in comparison to the patients in group 2. Meanwhile, renal function, liver enzyme and blood cell counts remained stabilized in group1. CONCLUSIONS: This study indicates that the combined therapeutic approach of DPMS and zinc may be a preferred first-line therapy in treating the neurological symptoms of WD, in comparison to the treatment with DPA.


Assuntos
Quelantes/administração & dosagem , Degeneração Hepatolenticular/tratamento farmacológico , Penicilamina/uso terapêutico , Unitiol/administração & dosagem , Zinco/administração & dosagem , Adulto , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
3.
Chem Commun (Camb) ; 56(29): 4037-4046, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32236263

RESUMO

Over the last decade, much work has been dedicated to improving the performance of gadolinium-based magnetic resonance imaging (MRI) contrast agents by tethering them to biocompatible gold nanoparticles. The enhancement in performance (measured in terms of 'relaxivity') stems from the restriction in motion experienced by the gadolinium chelates on being attached to the gold nanoparticle surface. More recently, the unique properties of gold nanoparticles have been exploited to create very promising tools for multimodal imaging and MRI-guided therapies. This review addresses the progress made in the design of gadolinium-functionalised gold nanoparticles for use in MRI, multimodal imaging and theranostics. It also seeks to connect the chemical properties of these assemblies with potential application in the clinic.


Assuntos
Quelantes/administração & dosagem , Meios de Contraste/administração & dosagem , Gadolínio/administração & dosagem , Ouro/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Humanos , Imagem por Ressonância Magnética , Imagem Multimodal , Nanomedicina Teranóstica
5.
J Biochem Mol Toxicol ; 34(6): e22483, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32125074

RESUMO

INTRODUCTION: Lead (Pb) is a ubiquitous toxic heavy metal that inflicts numerous clinical consequences on humans. Curcumin is the principal component of turmeric, which is reported to have antioxidative properties. This study aimed at evaluating the ameliorative effects of curcumin on Pb-induced hepatorenal toxicity in a rat model. METHODS: Thirty-six male Sprague-Dawley rats were randomly assigned into five groups with 12 rats in the control (normal saline) and six rats each for the lead-treated group (LTG) (50 mg/kg lead acetate [Pb acetate] for 4 weeks), recovery group (50 mg/kg Pb acetate for 4 weeks and left with no treatment for another 4 weeks), treatment group 1 (Cur100) (50 mg/kg Pb acetate for 4 weeks, followed by 100 mg/kg curcumin for 4 weeks), and treatment group 2 (Cur200) (50 mg/kg Pb acetate for 4 weeks, followed by 200 mg/kg curcumin for 4 weeks). All the experimental groups received oral treatments via orogastric-tube on alternate days. Pb concentration in the liver and kidney of the rats were evaluated using inductive-coupled plasma mass spectrometry techniques. RESULTS: Pb-administered rats revealed significant alteration in oxidative status and increased Pb concentration in their liver and kidney with obvious reduction of hemogram and increased in leukogram as well as aberration in histological architecture of the liver and kidney. However, treatment with curcumin reduces the tissue Pb concentrations and ameliorates the above mention alterations. CONCLUSIONS: The results in this study suggested that curcumin attenuates Pb-induced hepatorenal toxicity via chelating activity and inhibition of oxidative stress.


Assuntos
Antioxidantes/administração & dosagem , Quelantes/administração & dosagem , Curcumina/administração & dosagem , Rim/efeitos dos fármacos , Intoxicação por Chumbo/terapia , Fígado/efeitos dos fármacos , Compostos Organometálicos/toxicidade , Fitoterapia/métodos , Extratos Vegetais/administração & dosagem , Animais , Curcuma , Modelos Animais de Doenças , Rim/metabolismo , Intoxicação por Chumbo/sangue , Fígado/metabolismo , Masculino , Compostos Organometálicos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento
6.
Curr Pharm Biotechnol ; 21(8): 681-701, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31820684

RESUMO

BACKGROUND: The role of Fe+2, Cu+2 and Zn+2 in facilitating aggregation of Amyloid ß (Aß) and consequently, the progression of Alzheimer's disease (AD) is well established. OBJECTIVE: Development of non-toxic metal chelators is an emerging era in the treatment of AD, in which complete success has not been fully achieved. The purpose of this study was to determine plant extracts with high metal chelator and to encapsulate them in nano-micellar systems with the ability to pass through the Blood Brain Barrier (BBB). METHODS: Extracts of 36 different Anatolian plants were prepared, total phenolic and flavonoid contents were determined, and the extracts with high content were examined for their Fe+2, Cu+2 and Zn+2 chelating activities. Apolipoprotein E4 (Apo E) decorated nano-formulations of active extracts were prepared using Poly (Lactide-co-Glycolide) (PLGA) (final product ApoEPLGA) to provide BBB penetrating property. RESULTS: Verbascum flavidum aqueous extract was found as the most active sample, incubation of which, with Aß before and after metal-induced aggregation, resulted in successful inhibition of aggregate formation, while re-solubilization of pre-formed aggregates was not effectively achieved. The same results were obtained using ApoEPLGA. CONCLUSION: An optimized metal chelator nano-formulation with BBB penetrating ability was prepared and presented for further in-vivo studies.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Quelantes/farmacologia , Portadores de Fármacos/química , Metais Pesados/metabolismo , Nanopartículas/química , Extratos Vegetais/farmacologia , Agregados Proteicos/efeitos dos fármacos , Apolipoproteína E4/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Quelantes/administração & dosagem , Quelantes/isolamento & purificação , Quelantes/toxicidade , Composição de Medicamentos , Fibroblastos/efeitos dos fármacos , Humanos , Metais Pesados/toxicidade , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Cultura Primária de Células , Verbascum/química
7.
Int J Clin Pharmacol Ther ; 58(3): 166-173, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31724531

RESUMO

OBJECTIVE: Non-calcium containing phosphate binders (non-CPBs) are useful for the treatment of hyperphosphatemia without a concern of hypercalcemia in patients undergoing dialysis. However, due to their relatively high cost, prescribing non-CPBs is restricted in South Korea. This study was conducted to investigate prescribing patterns, especially switching between CPBs and non-CPBs, in dialysis patients in a real-world setting. MATERIALS AND METHODS: This is an observational study using the National Health Insurance Service claim data. The study population included patients who initiated dialysis between July 2012 and June 2013 and were prescribed phosphate binders at least once during the observation period (2012 - 2016) (n = 10,073). Medication costs and prescribing patterns including switching of phosphate binders were investigated. RESULTS: Compared with the first year of dialysis, the costs of phosphate binders more than doubled during the 4th year of dialysis (from US$ 28.4 to US$ 60.1), largely due to an increase in the cost of non-CPBs (from US$ 117.5 to US$ 237.8). Many patients continued to change drugs between CPBs and non-CPBs. The continuous prescription period of CPBs was shortened each time a drug was changed. A total of 551 patients (13.4%) changed their medication three times between CPBs and non-CPBs. CONCLUSION: Over time on dialysis, use of non-CPB increased and medication costs increased accordingly. Many patients continued to change drugs between CPBs and non-CPBs due to the restricted criteria of the health insurance. Further outcome research is necessary to evaluate the appropriateness of the clinical practice in which CPBs and non-CPBs are alternately used.


Assuntos
Quelantes/administração & dosagem , Substituição de Medicamentos/economia , Hiperfosfatemia/tratamento farmacológico , Padrões de Prática Médica/tendências , Diálise Renal , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quelantes/economia , Criança , Pré-Escolar , Custos de Medicamentos , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fosfatos/antagonistas & inibidores , República da Coreia , Adulto Jovem
8.
Clin Rheumatol ; 39(2): 561-569, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31673978

RESUMO

BACKGROUND: Calcific tendinitis of the rotator cuff is one of the most common causes of shoulder pain. Ultrasound-guided percutaneous lavage of calcific tendinopathy is performed when conservative treatments have failed. Sodium thiosulfate (STS) has recently been used with success in the treatment of tumoral calcinosis. The goal of this phase II study was to assess the tolerance and the feasibility of STS lavage of calcific tendinopathy. METHODS: We included patient with type hard calcifications. Patients were treated with puncture and lavage followed by injection of STS in the calcification. VAS pain at rest and during activities, ultrasound, and X-ray were evaluated at 1 week and 1 and 3 months. RESULTS: Seventeen patients were included. Baseline VAS at rest and during daily activities was a mean 40.2 ± 25.9 and 65.5 ± 21.6 respectively. All patients underwent the entire procedure with no adverse event. Calcium backflow could be obtained in 15 patients (88.2%). Five patients (30%) had more than 50% decrease of their calcific deposit size at 1 month and 8 (47%) patients at 3 months. VAS pain during activities and at rest decreased significantly at 3 months (p = 0.0004; p = 0.001). Efficacy would be demonstrated if 60% of the patients had more than 50% decrease size of their calcification CONCLUSION: Overall, STS was well tolerated with no side effect occurring during the procedure and the follow-up. However, no significant effect on calcium disappearance could be demonstrated compared with what is expected without STS. New studies using larger volume and repeated injections of STS are now needed. CLINICAL TRIAL REGISTRATION NUMBER: NCT02538939Key Points• Lavage of calcific tendinopathy of the rotator cuff with sodium thiosulfate is feasible• No adverse events have been observed after or in the 3 months after the procedure• We could not demonstrate that sodium thiosulfate increases the chance of calcium disappearance• New studies using larger volume and repeated injections of STS are needed to further explore the interest of sodium thiosulfate in the treatment of calcific tendinopathy.


Assuntos
Calcinose/tratamento farmacológico , Quelantes/administração & dosagem , Lesões do Manguito Rotador/tratamento farmacológico , Tiossulfatos/administração & dosagem , Adulto , Calcinose/diagnóstico por imagem , Feminino , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Lesões do Manguito Rotador/diagnóstico por imagem , Ultrassonografia
9.
Nephrol Dial Transplant ; 34(Suppl 3): iii45-iii50, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31800078

RESUMO

Hyperkalemia represents a common and potentially life-threating electrolyte abnormality, a complication frequently observed in patients with heart failure, kidney disease, diabetes or in those receiving drug therapies influencing the renin-angiotensin-aldosterone system. Elevated serum potassium levels are often the result of impaired urinary potassium elimination, inadequate or reduced cellular potassium uptake, severe heart failure, use of medications influencing potassium levels in the circulation, or, more commonly, a combination of these factors. Strategies for the treatment of nonemergent hyperkalemia include the use of cation-exchange resins, polymers or other novel mechanisms of potassium trapping, including sodium polystyrene sulfonate, patiromer and sodium zirconium cyclosilicate. These agents differ in their pharmacology and mechanism of action, clinical efficacy, including onset and extent of potassium-lowering effect, dosage and administration, and potential safety and adverse effect profiles. In this review, an evaluation of these characteristics, including clinical evidence and safety concerns, in the management of nonemergent hyperkalemia will be explored.


Assuntos
Hiperpotassemia/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Poliestirenos/administração & dosagem , Potássio/sangue , Silicatos/administração & dosagem , Quelantes/administração & dosagem , Relação Dose-Resposta a Droga , Humanos , Hiperpotassemia/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia , Resultado do Tratamento
10.
Indian Pediatr ; 56(11): 972-974, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729331

RESUMO

Hypercalcemia of malignancy, usually reported in adults in advanced stages, is rare in children. A 4-year-old boy presented with intermittent episodes of severe hypercalcemia, which improved with intravenous hydration therapy, furosemide and bisphosphonates as the initial manifestation of occult acute lymphoblastic leukemia. Pediatricians should rule out hematological malignancy in patients with severe hypercalcemia.


Assuntos
Difosfonatos/administração & dosagem , Hidratação/métodos , Furosemida/administração & dosagem , Hipercalcemia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Exame de Medula Óssea/métodos , Osso e Ossos/diagnóstico por imagem , Quelantes/administração & dosagem , Pré-Escolar , Diagnóstico Diferencial , Diuréticos/administração & dosagem , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/etiologia , Hipercalcemia/terapia , Masculino , Tomografia por Emissão de Pósitrons/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Índice de Gravidade de Doença
11.
G Ital Nefrol ; 36(5)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31580546

RESUMO

Calcific uremic arteriolopathy (CUA) is a highly morbid condition usually found in ESRD patients that has rarely been reported after renal transplantation and renal function restoration. Furthermore, little is known about the optimal management of CUA in this setting. Herein, we report on the clinical case of AB, a 70-year-old woman who developed CUA after renal transplantation and renal function restoration. However, other risk factors for CUA such as diabetes and warfarin treatment, due to mechanical aortic valve implantation, were present. Thirty-eight months after renal transplantation she developed erythema and livedo reticularis in both legs and a gradually enlarging skin ulcer in the right leg. A skin biopsy of the ulcer showed features compatible with the CUA, such as sub-intimal calcification and luminal obstruction of the small dermal arterioles, tissue ischemia and signs of adipocytes degeneration. A multidisciplinary approach was adopted, including medical and non-medical treatments such as surgical debridement and vacuum-assisted closure therapy. Medical treatments included a five weeks course of once a week intravenous infusion of pamidronate and intravenous sodium thiosulfate (STS) at increasing doses. Four months after beginning the therapy with STS, a complete healing of the ulcer on the right leg and the disappearance of the livedo reticularis on the left leg was noted. In conclusion, although rare CUA may develop also in renal transplanted patients, a timely and combined therapeutic approach is essential for its resolutive treatment. Sodium thiosulfate therapy has proven to be effective and tolerated.


Assuntos
Calciofilaxia/terapia , Transplante de Rim/efeitos adversos , Úlcera da Perna/terapia , Doenças Raras/terapia , Idoso , Anticoagulantes/uso terapêutico , Conservadores da Densidade Óssea/administração & dosagem , Calciofilaxia/etiologia , Quelantes/administração & dosagem , Terapia Combinada/métodos , Diabetes Mellitus , Feminino , Humanos , Úlcera da Perna/etiologia , Livedo Reticular/etiologia , Livedo Reticular/terapia , Pamidronato/administração & dosagem , Doenças Raras/etiologia , Fatores de Risco , Tiossulfatos/administração & dosagem , Varfarina/uso terapêutico
12.
Wounds ; 31(8): E54-E57, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31483755

RESUMO

INTRODUCTION: Calciphylaxis is a very complicated disease that usually presents in patients with end-stage renal disease (ESRD). Treatment for calciphylaxis is not well standardized and typically involves a multidisciplinary approach. One of the common medications used in calciphylaxis treatment is sodium thiosulfate (STS). However, its intravenous injection is associated with multiple side effects. CASE REPORT: The authors present a case report of an intralesional injection of STS followed by a literature review of the common treatment modalities and possible further use of intralesional injections. A 51-year-old man with ESRD on peritoneal dialysis presented with a right calf biopsy-proven calciphylaxis lesion measuring 3.1 cm x 3.9 cm. About the same time, he had Pseudomonas-associated peritoneal catheter peritonitis. The calciphylaxis lesion was treated with bimonthly intralesional injections of STS. The lesion had a complete resolution by week 9. CONCLUSIONS: The authors believe a higher local concentration of STS leading to a faster resolution and requiring less frequent injections needs to be further evaluated. Following additional studies, they also propose a greater use of intralesional STS injections in a select set of patients in the future.


Assuntos
Antibacterianos/administração & dosagem , Calciofilaxia/tratamento farmacológico , Quelantes/administração & dosagem , Infecções por Pseudomonas/tratamento farmacológico , Tiossulfatos/administração & dosagem , Nefropatias Diabéticas/complicações , Humanos , Injeções Intralesionais , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Pseudomonas aeruginosa , Resultado do Tratamento
13.
Rinsho Shinkeigaku ; 59(9): 565-569, 2019 Sep 25.
Artigo em Japonês | MEDLINE | ID: mdl-31474637

RESUMO

Wilson disease is an autosomal recessive disorder based on inborn error of copper metabolism. The copper accumulates in the liver, brain, cornea, kidney, and other organs. This disease should be considered any individual with liver abnormality except infant, any patient older than teenage with neurological (especially for extra pyramidal signs) or neuropsychiatric disorder with or without liver disease and sibling of Wilson disease patient. Typically, a combination of low serum ceruloplasmine levels and high levels of urinary copper contents is sufficient to establish a diagnosis. As other diagnostic tests, measurement of hepatic copper content and ATP7B gene analysis are available. The key strategy of treatment is to reduce the amount of copper in the liver and other tissues by administering both copper-chelating agents, such as D-penicillamine or Trientine, and/or zinc acetate. The author recommend zinc acetate monotherapy for mild to moderate hepatic disorder, Trientine mono therapy for mild to moderate neurologic disorder and combination therapy of Trientine and zinc acetate for sever hepatic or neurologic disorder.


Assuntos
Quelantes/administração & dosagem , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/tratamento farmacológico , Penicilamina/administração & dosagem , Trientina/administração & dosagem , Acetato de Zinco/administração & dosagem , Adolescente , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Biomarcadores/urina , Ceruloplasmina , Criança , Pré-Escolar , Cobre/metabolismo , ATPases Transportadoras de Cobre/genética , Diagnóstico Diferencial , Quimioterapia Combinada , Degeneração Hepatolenticular/genética , Humanos , Japão , Fígado , Pessoa de Meia-Idade , Mutação , Índice de Gravidade de Doença , Adulto Jovem
14.
Radiat Res ; 192(6): 630-639, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31545678

RESUMO

Occupational contamination is a potential health risk associated with plutonium inhalation. DTPA remains the chelating drug of choice to decorporate plutonium. In this study, plutonium was found to be more effectively removed from lungs by a single inhalation of nebulized DTPA solution at only 1.1 µmol.kg-1 than by a single intravenous (i.v.) dose of DTPA at 15 µmol.kg-1. When DTPA was inhaled promptly after contamination, it removed the transportable fraction of plutonium prior blood absorption, thereby preventing both liver and bone depositions. Conversely, DTPA injection was better than inhalation at reducing the extrapulmonary burden, probably due to the much greater circulating dose, favoring the mobilization of plutonium already translocated. Thus, prompt inhalation, concomitantly supplemented with i.v. injection, of DTPA induced an important decrease in extrapulmonary deposits. Repeated DTPA inhalations over several weeks were more efficient than a single inhalation in limiting both pulmonary and extrapulmonary plutonium retention, due at least in part to the chelation of the transportable fraction of lung plutonium. Furthermore, repeated DTPA injections remained better at reducing liver and bone plutonium retentions. Taken together, our results suggest that multiple DTPA inhalations may be considered an effective treatment after inhalation of plutonium, particularly given the ease of this needle-free delivery, for the two following conditions: 1. A treatment combining i.v. injection and inhalation should be given in an emergency scenario to efficiently chelate the activity already absorbed; 2. Inhalations should be administered daily to effectively trap the early transferable fraction.


Assuntos
Quelantes/administração & dosagem , Pulmão/efeitos dos fármacos , Pulmão/efeitos da radiação , Ácido Pentético/administração & dosagem , Plutônio/química , Lesões por Radiação/tratamento farmacológico , Administração por Inalação , Aerossóis/química , Animais , Masculino , Ratos , Ratos Sprague-Dawley
15.
Nat Commun ; 10(1): 3780, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31439844

RESUMO

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorders, yet no major breakthroughs have been made in AD human trials and the disease remains a paramount challenge and a stigma in medicine. Here we eliminate the toxicity of amyloid beta (Aß) in a facile, high-throughput zebrafish (Danio rerio) model using casein coated-gold nanoparticles (ßCas AuNPs). ßCas AuNPs in systemic circulation translocate across the blood brain barrier of zebrafish larvae and sequester intracerebral Aß42 and its elicited toxicity in a nonspecific, chaperone-like manner. This is evidenced by behavioral pathology, reactive oxygen species and neuronal dysfunction biomarkers assays, complemented by brain histology and inductively coupled plasma-mass spectroscopy. We further demonstrate the capacity of ßCas AuNPs in recovering the mobility and cognitive function of adult zebrafish exposed to Aß. This potent, safe-to-use, and easy-to-apply nanomedicine may find broad use for eradicating toxic amyloid proteins implicated in a range of human diseases.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/antagonistas & inibidores , Quelantes/administração & dosagem , Portadores de Fármacos/química , Nanopartículas Metálicas/química , Fragmentos de Peptídeos/antagonistas & inibidores , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Caseínas/administração & dosagem , Caseínas/farmacocinética , Quelantes/farmacocinética , Cognição/efeitos dos fármacos , Modelos Animais de Doenças , Portadores de Fármacos/farmacocinética , Embrião não Mamífero , Feminino , Ouro/química , Ensaios de Triagem em Larga Escala , Humanos , Masculino , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/toxicidade , Permeabilidade , Resultado do Tratamento , Peixe-Zebra
16.
Ecotoxicol Environ Saf ; 183: 109441, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31404725

RESUMO

OBJECTIVE: To explore the impacts of Pb exposure and the dimercaptosuccinic acid (DMSA) chelation therapy on bone metabolisms in young rats of different ages, as well as the potential mechanisms. METHOD: Young rats were exposed to 0.05%-0.1% Pb acetate for 19 days, during infanthood (postnatal day, PND2-20), childhood (PND21-39) and adolescenthood (PND40-58) respectively. In each developmental stage, rats were further divided into three subgroups: lead-exposed, one-course and two-course DMSA chelation therapy subgroups. Blood/bone lead concentrations, serum calciotropic hormones concentrations, and mRNA and protein expressions of bone turnover markers in the serum and bones were measured. Bone microstructures were analyzed using Micro-CT. RESULTS: Compared with lead-exposed during childhood and adolescenthood, increases in blood/bone lead levels, and the changes of blood/bone lead and trabecular bone microstructures after one-course DMSA chelation were most significant in rats lead-exposed during infanthood (P < .05). The serum osteocalcin (OC) concentrations, mRNA/protein expressions of OC and runt-related transcription factor 2 (RUNX2) in bones all decreased after Pb exposure, along with significant increases in serum C-terminal telopeptide of type I collagen (CTX) concentrations (P < .05). These effects were accompanied by changes of serum parathormone (PTH) and 1,25-dihydroxyvitamin D3 (1,25-(OH2)-D3) concentrations. DMSA chelation partially reversed the changes of bone microarchitectures, bone formation and resorption markers, and calciotropic-hormones, and the efficiency was greatest when the therapy was provided during infanthood. CONCLUSION: Developmental Pb exposure impaired bone microstructures and interfered bone metabolism, and the exposure effect was more obvious during infanthood than during childhood and adolescenthood. Lead effects were partially reversed by chelation therapy, and the efficacy may be most significant when the therapy was provided at younger ages.


Assuntos
Desenvolvimento Ósseo/efeitos dos fármacos , Osso e Ossos/metabolismo , Quelantes/uso terapêutico , Intoxicação por Chumbo/tratamento farmacológico , Chumbo/sangue , Succímero/uso terapêutico , Animais , Osso e Ossos/efeitos dos fármacos , Quelantes/administração & dosagem , Terapia por Quelação/métodos , Chumbo/metabolismo , Intoxicação por Chumbo/metabolismo , Intoxicação por Chumbo/fisiopatologia , Masculino , Ratos , Succímero/administração & dosagem
17.
Dermatol Ther ; 32(5): e13028, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31344296

RESUMO

We evaluated in a randomized, assessor-blinded, study the efficacy of a hydroxypropyl chitosan-based nail lacquer (HPC-NL) alone or in combination with oral biotin (HPC-NL + B) in the treatment of brittle nail syndrome (BNS). Fifty subjects (21 men; mean age 64 years) with BNS were enrolled. Twenty-six were randomly assigned to HPC-NL and 24 to the HPC-NL and biotin, 10 mg/daily (+B). Topical and oral treatments lasted for 4 consecutive months. The primary outcome was the evolution of the Onychodystrophy Global Severity Score (OGSS) assessing nail dystrophy, lamellar and longitudinal splitting, dyschromia, and pitting. At baseline, the OGSS, mean (SD), was 8.4 (2.1) in the HPC-NL group and 11.8 (2.3) in the HPC-NL + B group. The OGSS was significantly reduced during treatments in both groups. At Month 4, OGSS was reduced by 57% (HPC-NL) and 62% (HPC-NL + B). At the end of study period, the percentage of subjects with an OGSS reduction of ≥50% in comparison with baseline was 53% in the HPC-NL group and 80% in the HPC-NL + B group (p = .05). Both treatments were well tolerated. In subjects with BNS, HPC-NL alone is associated with a clinically relevant improvement of nail appearance. The combination of HPC-NL and oral biotin is associated with further clinical improvement.


Assuntos
Biotina/administração & dosagem , Quitosana/administração & dosagem , Doenças da Unha/tratamento farmacológico , Administração Oral , Administração Tópica , Quelantes/administração & dosagem , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Laca , Masculino , Pessoa de Meia-Idade , Doenças da Unha/diagnóstico , Unhas/patologia , Estudos Retrospectivos , Método Simples-Cego , Resultado do Tratamento , Complexo Vitamínico B/administração & dosagem
18.
Nat Commun ; 10(1): 2570, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31239437

RESUMO

Searching for actinide decorporation agents with advantages of high decorporation efficiency, minimal biological toxicity, and high oral efficiency is crucial for nuclear safety and the sustainable development of nuclear energy. Removing actinides deposited in bones after intake is one of the most significant challenges remaining in this field because of the instantaneous formation of highly stable actinide phosphate complexes upon contact with hydroxyapatite. Here we report a hydroxypyridinone-based ligand (5LIO-1-Cm-3,2-HOPO) exhibiting stronger affinity for U(VI) compared with the reported tetradentate hydroxypyridinone ligands. This is further revealed by the first principles calculation analysis on bonding between the ligand and uranium. Both in vitro uranium removal assay and in vivo decorporation experiments with mice show that 5LIO-1-Cm-3,2-HOPO can remove uranium from kidneys and bones with high efficiencies, while the decorporation efficiency is nearly independent of the treatment time. Moreover, this ligand shows a high oral decorporation efficiency, making it attractive for practical applications.


Assuntos
Osso e Ossos/química , Quelantes/administração & dosagem , Piridonas/administração & dosagem , Lesões por Radiação/terapia , Urânio/toxicidade , Adsorção , Animais , Osso e Ossos/metabolismo , Quelantes/química , Feminino , Humanos , Rim/química , Rim/metabolismo , Ligantes , Camundongos , Piridonas/química , Lesões por Radiação/induzido quimicamente , Lesões por Radiação/metabolismo , Urânio/química , Urânio/metabolismo
19.
Toxins (Basel) ; 11(5)2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31109001

RESUMO

High serum levels of gut-derived uremic toxins, especially p-cresyl sulfate (pCS), indoxyl sulfate (IS) and indole acetic acid (IAA), have been linked to adverse outcomes in patients with chronic kidney disease (CKD). Sevelamer carbonate could represent an interesting option to limit the elevation of gut-derived uremic toxins. The aim of the present study was to evaluate the adsorptive effect of sevelamer carbonate on different gut-derived protein-bound uremic toxins or their precursors in vitro, and its impact on the serum levels of pCS, IS and IAA in patients with CKD stage 3b/4. For the in vitro experiments, IAA, p-cresol (precursor of pCS) and indole (precursor of IS), each at a final concentration of 1 or 10 µg/mL, were incubated in centrifugal 30 kDa filter devices with 3 or 15 mg/mL sevelamer carbonate in phosphate-buffered saline at a pH adjusted to 6 or 8. Then, samples were centrifuged and free uremic toxins in the filtrates were analyzed. As a control experiment, the adsorption of phosphate was also evaluated. Additionally, patients with stage 3b/4 CKD (defined as an eGFR between 15 and 45 mL/min per 1.73 m2) were included in a multicenter, double-blind, placebo-controlled, randomized clinical trial. The participants received either placebo or sevelamer carbonate (4.8 g) three times a day for 12 weeks. The concentrations of the toxins and their precursors were measured using a validated high-performance liquid chromatography method with a diode array detector. In vitro, regardless of the pH and concentration tested, sevelamer carbonate did not show adsorption of indole and p-cresol. Conversely, with 10 µg/mL IAA, use of a high concentration of sevelamer carbonate (15 mg/mL) resulted in a significant toxin adsorption both at pH 8 (mean reduction: 26.3 ± 3.4%) and pH 6 (mean reduction: 38.7 ± 1.7%). In patients with CKD stage 3b/4, a 12-week course of treatment with sevelamer carbonate was not associated with significant decreases in serum pCS, IS and IAA levels (median difference to baseline levels: -0.12, 0.26 and -0.06 µg/mL in the sevelamer group vs. 1.97, 0.38 and 0.05 µg/mL in the placebo group, respectively). Finally, in vitro, sevelamer carbonate was capable of chelating a gut-derived uremic toxin IAA but not p-cresol and indole, the precursors of pCS and IS in the gut. In a well-designed clinical study of patients with stage 3b/4 CKD, a 12-week course of treatment with sevelamer carbonate was not associated with significant changes in the serum concentrations of pCS, IS and IAA.


Assuntos
Quelantes/administração & dosagem , Cresóis/sangue , Indicã/sangue , Ácidos Indolacéticos/sangue , Insuficiência Renal Crônica/tratamento farmacológico , Sevelamer/administração & dosagem , Ésteres do Ácido Sulfúrico/sangue , Toxinas Biológicas/sangue , Adsorção , Idoso , Quelantes/química , Cresóis/química , Método Duplo-Cego , Feminino , Trato Gastrointestinal/química , Trato Gastrointestinal/metabolismo , Humanos , Indicã/química , Ácidos Indolacéticos/química , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Sevelamer/química , Ésteres do Ácido Sulfúrico/química , Uremia
20.
Environ Sci Pollut Res Int ; 26(18): 18032-18052, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31079302

RESUMO

The global burden of heavy metal especially mercury, arsenic, lead, and cadmium toxicities remains a significant public health challenge. Developing nations are particularly at high risk and carry the highest burden of this hazard. Chelation therapy has been the mainstay for treatment of heavy metal poisoning where the chelating agent binds metal ions to form complex ring-like structures called "chelates" to enhance their elimination from the body. Metal chelators have some drawbacks such as redistribution of some heavy metals from other tissues to the brain thereby increasing its neurotoxicity, causing loss of essential metals such as copper and zinc as well as some serious adverse effects, e.g., hepatotoxicity. The use of natural antidotes, which are easily available, affordable, and with little or no side effects compared to the classic metal chelators, is the focus of this review and suggested as cheaper options for developing nations in the treatment of heavy metal poisoning.


Assuntos
Antídotos/uso terapêutico , Produtos Biológicos/uso terapêutico , Quelantes/uso terapêutico , Terapia por Quelação/métodos , Intoxicação por Metais Pesados/prevenção & controle , Metais Pesados/toxicidade , Antídotos/administração & dosagem , Produtos Biológicos/administração & dosagem , Quelantes/administração & dosagem , Humanos , Inativação Metabólica , Metais Pesados/metabolismo
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