Hiperkalemia crónica, diagnóstico y manejo. Consenso colombiano / Chronic hyperkalemia, diagnosis and management. Colombian consensus

Resumen Objetivo: Generar recomendaciones para el diagnóstico, el manejo y el seguimiento de la hiperkalemia crónica. Método: Este consenso fue realizado por nefrólogos y cardiólogos siguiendo la metodología GRADE. Resultados: La hiperkalemia crónica puede definirse como una condición bioquímica, con o sin manifestaciones clínicas, caracterizada por una elevación recurrente de las concentraciones séricas de potasio que puede requerir una intervención farmacológica, no farmacológica o ambas. Puede clasificarse en leve (K+ 5,0 a < 5,5 mEq/l), moderada (K+ 5,5 a 6,0 mEq/l) o grave (K+ > 6,0 mEq/l). Su incidencia y prevalencia no han sido claramente determinadas. Se consideran factores de riesgo la enfermedad renal crónica, la insuficiencia cardiaca crónica, la diabetes mellitus, la edad ≥ 65 años, la hipertensión arterial y el tratamiento con inhibidores del sistema renina-angiotensina-aldosterona (iSRAA), entre otros. No hay consenso sobre el manejo de la hiperkalemia crónica. Se sugiere identificar y eliminar o controlar los factores de riesgo, brindar asesoramiento sobre la ingesta de potasio y, para quien esté indicado, optimizar la terapia con iSRAA, administrar aglutinantes orales del potasio y corregir la acidosis metabólica. Conclusiones: Se recomienda prestar atención al diagnóstico, el manejo y el seguimiento de la hiperkalemia crónica, en especial en los pacientes con factores de riesgo.

Abstract Objective: Generate recommendations for the diagnosis, management, and follow-up of chronic hyperkalemia. Method: This consensus was made by nephrologists and cardiologists following the GRADE methodology. Results: Chronic hyperkalemia can be defined as a biochemical condition with or without clinical manifestations characterized by a recurrent elevation of serum potassium levels that may require pharmacological and or non-pharmacological intervention. It can be classified as mild (K+ 5.0 to < 5.5 mEq/L), moderate (K+ 5.5 to 6.0 mEq/L) or severe (K+ > 6.0 mEq/L). Its incidence and prevalence have yet to be determined. Risk factors: chronic kidney disease, chronic heart failure, diabetes mellitus, age ≥ 65 years, hypertension, and drugs that inhibit the renin angiotensin aldosterone system (RAASi), among others. There is no consensus for the management of chronic hyperkalemia. The suggested pattern for patients is to identify and eliminate or control risk factors, provide advice on potassium intake and, for whom it is indicated, optimize RAASi therapy, administer oral potassium binders and correct metabolic acidosis. Conclusions: The recommendation is to pay attention to the diagnosis, management, and follow-up of chronic hyperkalemia, especially in patients with risk factors.

Potential of natural products containing 3-acyl tetramic acid as antibacterial precursors / 药学学报

The natural products containing 3-acyl tetramic acid units have a large number of complex and diverse structures, showing a variety of biological activities such as antibacterial, antiviral, anti-tumor and so on, especially antibacterial activity which are regarded as a potential reservoir of new antibiotics. In this paper, the antibacterial activities of various natural products containing 3-acyl tetramic acids and the new research hotspots and directions are reviewed.

Comparative evaluation of chelating efficacy of nano-chitosan, pomegranate extract, and ethylenediaminetetraacetic acid on primary radicular dentin An in vitro study

Background: Irrigation is a crucial aspect of root canal treatment, and it is imperative to employ chelating agents to eliminate the smear layer during biomechanical preparation. They in turn react with mineral content of dentin, leading to decreased strength and increased susceptibility to fracture. Aims: This study aimed to assess and compare mineral loss and microhardness from primary root canal dentin following the usage of different irrigating solutions and determine the least detrimental irrigant among the tested solutions. Materials and Methods: Sixty-six primary anterior teeth were divided into three groups with 22 in each– Group I: 17% ethylenediaminetetraacetic acid (EDTA) Group II: 0.2% Nano chitosan Group III: Pomegranate extract. The decoronated teeth were split longitudinally. Half of it was directly subjected to Vickers test, and the other half was immersed in a magnetic stirrer bath containing test solution to record the mineral loss from solution. Postmicrohardness values were recorded on the specimen and compared with initial values. Statistical Analysis Used: Statistical analysis was done using SPSS software (Version 20, SPSS, IBM, Armonk, NY, U. S. A). Results: Descriptive statistics were calculated, and the groups were compared using analysis of variance test and post hoc Tukey test. Pomegranate extract showed least effect on mineral content and microhardness compared to 17% EDTA and 0.2% nano chitosan. P ≤ 0.05 was considered statistically significant. Conclusion: Pomegranate aril extract showed better results with selected parameters.

Study of anti-diabetic, beta-carotene-bleaching inhibiting and iron chelating properties of Carissa opaca root extracts

Abstract Degenerative diseases diabetes and oxidative stress constitute a major health concern worldwide. Medicinal plants are expected to provide effective and affordable remedies. The present research explored antidiabetic and antioxidant potential of extracts of Carissa opaca roots. Methanolic extract (ME) was prepared through maceration. Its fractions were obtained, sequentially, in hexane, chloroform, ethyl acetate and n-butanol. An aqueous decoction (AD) of the finely ground roots was obtained by boiling in distilled water. The leftover biomass with methanol was boiled in water to obtain biomass aqueous decoction (BAD). The extracts and fractions showed considerable porcine pancreatic α-amylase inhibitory activity with IC50 in the range of 5.38-7.12 mg/mL while acarbose had 0.31 mg/mL. The iron chelating activity in terms of EC50 was 0.2939, 0.3429, 0.1876, and 0.1099 mg/mL for AD, BAD, ME, and EDTA, respectively. The EC50 of beta-carotene bleaching activity for AD, BAD, ME, and standard BHA were 4.10, 4.71, 3.48, and 2.79 mg/mL, respectively. The total phenolic content (TPC) and total flavonoid content (TFC) of AD and BAD were also considerable. In general, ethyl acetate fraction proved to be the most potent. Thus, the C. opaca roots had excellent antioxidant activity while having moderate α-amylase inhibitory potentia

Effect of Chelating Agents on Push-Out Bond Strength of NeoMTA Plus to Root Canal Dentin

ABSTRACT Objective To evaluate and compare the effect of 17% Ethylenediaminetetraacetic Acid (EDTA), 9% Etidronic acid (HEDP), and 7% Maleic acid (MA) on the push-out bond strength of NeoMTA Plus sealer to the coronal, middle, and apical thirds of root canal dentin. Material and Methods Forty single-rooted human maxillary central incisors were selected and decoronated to 12 mm long root fragments. Working length was established and root canals were then enlarged up to rotary Protaper F3. After each instrumentation, the root canal was irrigated with 2.5% NaOCl. For the final irrigation regimen, the specimens were divided into 4 groups (n=10) and treated with EDTA, HEDP, MA or Saline. Root canals were coated with NeoMTA Plus sealer, and obturation was done with single cone obturation technique. Subsequently, three horizontal sections were taken from the coronal, middle and apical thirds of each specimen, and POBS was measured using a universal testing machine. The type of bond failures was assessed under a stereomicroscope. Statistical analysis was done with One-way ANOVA with Tukey's Post hoc analysis. Results MA and EDTA showed the highest POBS. There was no significant difference in bond strength between MA and EDTA (p>0.05). HEDP and Saline showed lower POBS. Among all the four groups, the coronal third showed the highest values, followed by middle and apical thirds. Conclusion The type of chelating agent used during the root canal treatment significantly affects the bond strength of NeoMTA Plus to the root canal dentin.

Recent advances in research on chelators as metallo-β-lactamase inhibitors / 中国药科大学学报

@#The major reason for the resistance of Gram-negative bacteria to β-lactam antibiotics is the expression of β-lactamases.Metallo-β-lactamases (MBL) hydrolyze almost all types of β-lactam antibiotics including carbapenems, posing a challenge to global public health. Developing MBL inhibitors is an important method to treat the infections caused by resistant bacteria. As an important type of MBL inhibitors, chelating agents can inhibit MBL by chelating, stripping, and binding Zn2+ in the active center of MBL.This review summarizes recent publications on chelators as MBL inhibitors, discussing their chemical structures, inhibitory potency, synergistic effects with antibiotics, selectivity and mechanism of action, including EDTA and related compounds, aspergillomarasmine A (AMA) and its derivatives, NOTA and related compounds, pyridine carboxylic acid and pyridine methylamine compounds, aiming to provide reference for future development of potent, selective and safe clinical MBL inhibitors.

The strategy change of targeting iron homeostasis for leukemia therapy: from iron chelation to iron overload as a therapeutic strategy to induce ferroptosis / 白血病·淋巴瘤

Iron, an indispensable element for life, is involved in all kinds of vital physiological activities. Due to its potential toxicity, the body has a strict regulation mechanism of iron metabolism to maintain the "iron homeostasis". Dysregulation of iron metabolism and subsequent accumulation of excess iron are closely associated with the development and progression of leukemia. Specifically, due to the pro-oxidative nature of iron and its damaging effects on DNA, excess iron promotes the progression of leukemia; on the other hand, leukemia cells need to obtain more iron than normal cells to maintain rapid growth and proliferation, which is known as "iron addiction". Iron chelators can remove iron in leukemia cells and induce differentiation and apoptosis of leukemia cells. However, "iron addiction" makes leukemia cells more susceptible to iron overload, and is more sensitive to a new form of iron-catalyzed cell death which was named ferroptosis. According to the different needs of leukemia cells and normal cells for iron, the method of selectively killing leukemia cells through iron overload may become a new strategy for leukemia treatment. This paper reviews the strategy of targeting iron homeostasis for leukemia therapy.

Molhabilidade de um cimento endodôntico à base de resina epóxi na dentina tratada com diferentes protocolos de quelação / Wettability of an epoxy resin-based root canal sealer on dentin treated with different chelating protocols

Objetivo: Avaliar a molhabilidade do cimento AH Plus em contato com a dentina radicular após diferentes protocolos quelantes envolvendo ácido etidrônico (HEBP) e o EDTA. Métodos: Cinquenta e seis fatias de dentina radicular foram utilizadas e irrigadas com 5.25% de hipoclorito de sódio (NaOCl) ou com uma mistura de 5.25%NaOCl/18%HEBP para simular a irrigação durante o preparo químico-mecânico. As amostras irrigadas com NaOCl foram divididas em 5 grupos, de acordo com o agente quelante: G1- água destilada (AD); G2-17%EDTA; G3-17%EDTA+2.5%NaOCl; G4-18%HEBP; e G5-18%HEBP+2.5%NaOCl. As amostras irrigadas com a mistura de NaOCl/HEBP foram dividias em 2 grupos: G6-AD; G7-NaOCl/HEBP+2.5%- NaOCl. Todos os protocolos receberam irrigação de AD entre as substâncias irrigadoras e como lavagem final. O goniômetro Rame-Hart foi utilizado para mesurar o ângulo de contato entre a superfície da dentina radicular e o cimento. O teste estatístico Kruskal-Wallis e Dunn foram aplicados (p<0.05). Resultados: Os grupos onde a smear layer foi removida apresentaram menor ângulo de contato (p<0.05), com exceção do G7. O G6 apresentou o menor ângulo de contato do AH Plus, entretanto, a irrigação final com NaOCl (G7) aumentou significativamente o ângulo de contato. G2 e G4 apresentaram comportamento similar e a irrigação final com NaOCL (G3 e G4) não modificou a molhabilidade da dentina. Conclusão: O tratamento da dentina radicular com a mistura NaOCl/HEBP, quando usada como irrigante, conferiu boa molhabilidade desta superfície ao cimento AH Plus(AU).

Evaluate the wettability of AH Plus in contact with root dentin after different chelating protocols involving etidronic acid (HEBP) and EDTA. Material and Methods: Fifty six human polished root dentin slices were used. They were irrigated with 5.25% sodium hypochlorite (NaOCl) or a mixture of 5.25%NaOCl/18%HEBP to simulate irrigation during chemomechanical preparation. The specimens irrigated with NaOCl were divided into 5 groups regarding chelating agents: G1-destiled water (DW); G2- 17%EDTA; G3-17%EDTA+2.5%NaOCl; G4-18%HEBP; and G5-18%HEBP+2.5%NaOCl. The specimens irrigated with the mixture NaOCl/HEBP were divided into 2 groups: G6-DW; G7-NaOCl/HEBP+2.5%NaOCl. All protocols received irrigation with DW between irrigants and as final rinse. Rame-Hart goniometer was used to measure the contact angle between the dentin surfaces and the sealer. Kruskal-Wallis and Dunn tests were applied (p<0.05). Results: Groups in which the smear layer was removed showed a lower contact angle (p<0.05), except for G7. The G6 showed the lowest contact angle of AH Plus, but the NaOCl final irrigation (G7) increased the angle. G2 and G4 have similar behaviour and final irrigation with NaOCl (G3 and G5) did not change wettability when these chelators were used. Conclusions: The mixture NaOCl/HEBP showed good effect on the wettability of sealer on to the root canal dentine, when used as main irrigant (AU).

Elevated Iron Chelating Activity of Ilex paraguariensis Leaf Infusion: in vitro and in vivo Pilot Studies

Abstract This study presents an Ilex paraguariensis leaf infusion with important potential as natural iron-chelating. The impact of infusion time and the water volume to obtain an Ilex paraguariensis leaf infusion with high phenolic content and iron chelating activity, such as the stability of these proprieties in the storage time and temperature (immediately and after 24 h at 8 and 25 (C) were assessed. The acute consumption effect of this infusion to reduce iron absorption in vivo was also evaluated. A preliminary crossover trial with volunteers that ingested a meal containing non-haem iron (11.4 mg) with the treatments: Ilex paraguariensis leaf infusion with the highest phenolic content and iron chelating activity (200 mL) or control (200 mL water). Blood samples were withdrawn before and 1, 2, 3 and 4 h after the meal for serum iron measurement. The highest phenolic content (18.1 mg/mL) and iron chelating activity ((100%) were observed for 10 min infusion time using 30 g leaves/300 mL water. Storage at 8 or 25 (C for 24 h decreased total phenolics and di-caffeoylquinic acids by 23.5% and 25.5%, respectively (p< 0.05), without affecting the iron-chelating activity due to a saturating chelating effect at 3.34 mg/mL phenolic content. Inhibition of the iron absorption in vivo by infusion was 78% considering the iron recovery at peak maximum. The in vitro and preliminary in vivo results showed a functional property of the Ilex paraguariensis leaf infusion that may be useful for adjuvant management of iron overload diseases.

Application progress of time-resolved fluorescence in immunoassay / 公共卫生与预防医学

Time resolved fluoroimmunoassay (TRFIA) is an immunoassay technology developed on the basis of the unique fluorescence properties of rare earth elements. TRFIA combines the advantages of radioimmunoassay, enzyme-linked immunoassay and common fluorescence immunoassay. It has high sensitivity, strong specificity, good stability, wider measurement range, long fluorescence life, simple operation and non-radiation, and shows a good prospect in the field of immunoassay. In this paper, several common TRFIA materials are discussed based on the latest research progress of time-resolved fluorescence in immunoassay. The application of TRFIA in immunodiagnosis, food detection, environmental monitoring and so on is elaborated, and its development direction and application are prospected.

Influence of EDTA and its Association with Benzalkonium Chloride on Enterococcus faecalis Adhesion to Dentin / Influencia del EDTA y su Asociación con Cloruro de Benzalconio en la Adhesión de Enterococcus faecalis a la Dentina

ABSTRACT: The aim of this in vitro study was to investigate the influence of ethylenediaminetetraacetic acid (EDTA) associated with the benzalkonium chloride (BAK) on the adhesion and formation of Enterococcus faecalis biofilms attached to coated dentin. Discs standard bovine dentin blocks were treated with the coating materials evaluated: Saline solution (control), 17 % EDTA, 17 % EDTA associated with 1 % BAK for 5 minutes and subsequently washed with saline solution. Afterwards, biofilms of E. faecalis (ATCC 29212) were grown on the surface of coated dentin blocks for time intervals of 1 hour and 7 days (n = 20) and were subsequently washed with phosphate-buffered saline (PBS). Bacterial viability and total biovolume were analyzed by confocal laser scanning microscopy (CLSM) using the Live/Dead technique. Nonparametric Kruskal-Wallis followed by Dunn tests were used to determine statistical differences (a = 5 %). The 17 % EDTA + 1 % BAK group showed significantly lower biovolume and bacterial viability values at the end of 1 hour (p < 0.05). After 7 days of contamination, the 17 % EDTA and 17 % EDTA + 1 % BAK groups showed similar results that differed statistically from those of the control group (p < 0.05). The saline solution group showed higher values. The use of BAK associated with EDTA on dentin blocks surfaces before exposure to contamination was able to interfere in the adhesion of E. faecalis to dentin. Also, dentin treatment by BAK associated with a chelating agent influences the secondary biofilm formation, which could have important effects on the long-term success of root canal treatment.

RESUMEN: El objetivo del estudio consistió en investigar in vitro, la influencia del ácido etilendiamino-tetraacético (EDTA) con cloruro de benzalconio (BAK) en la adhesión y formación de biopelículas de Enterococcus faecalis a la dentina. Discos de dentina bovina fueron tratadas con solución salina (control), 17 % de EDTA, 17% de EDTA asociado con 1 % de BAK durante 5 minutos y lavadas con solución salina. Las biopelículas de E. faecalis (ATCC 29212) se cultivaron sobre los discos de dentina durante intervalos de tiempo de 1 hora y 7 días (n = 20), lavados con solución salina tamponada con fosfato (PBS). La viabilidad bacteriana y el biovolumen total se analizaron mediante microscopía de barrido por láser (CLSM) utilizando la técnica Live / Dead. Se realizó prueba no paramétrica de Kruskal-Wallis, seguida por Dunn con una diferencia estadística (a = 5 %). El grupo de 17 % EDTA + 1 % BAK mostró valores significativamente menores de biovolumen y viabilidad bacteriana al final de 1 hora (p < 0,05). Después de 7 días de contaminación, los grupos de 17 % EDTA y 17 % EDTA + 1 % BAK mostraron resultados similares que diferían estadísticamente del grupo control (p < 0,05). La solución salina mostró valores más altos. La asociación de BAK con EDTA antes de la contaminación interfirió en la adhesión de E. faecalis. Además, el tratamiento de la dentina por BAK asociado con EDTA influye en la formación de biopelículas secundarias, lo que podría tener efectos importantes sobre el éxito a largo plazo del tratamiento del conducto radicular.

Cytotoxicity of chelating agents used in endodontics and their influence on mmps of cell membranes

Abstract This study evaluated the cytotoxic effect and the ability to inhibit matrix metalloproteinases (MMP-2 and MMP-9) of 0.2% chitosan (CH) and 1% acetic acid (AA) compared with 17% ethylenediaminetetraacetic acid (EDTA). Cell viability assay was performed according to ISO 10993-5 with mouse fibroblasts (L929). The culture was exposed to 0.2% CH, 1% AA, and 17% EDTA. The chelating agents were evaluated immediately after contact with the cells and after 6 h, 12 h, and 24 h of incubation. Cell viability was analyzed using the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Inhibition of the gelatinolytic activity of MMP-2 and MMP-9 was evaluated by gelatin zymography. Different concentrations of CH were evaluated: 50 mM, 5 mM, 0.5 mM, and 0.05 mM. EDTA (0.5 mM) was used as a positive control. The results demonstrated that CH and AA had an initial cytotoxic effect, which decreased after 6 h, 12 h, and 24 h, being statistically similar to EDTA (P > 0.05). Additionally, CH at concentrations of 50 mM, 5 mM, and 0.5 mM had an inhibitory effect on MMP-2 and MMP-9, similar to that of the control with EDTA. The chelating agents had no cytotoxic effects after 24 h. MMP-2 and MMP-9 were inhibited by the experimental solutions.

Resumo Este estudo avaliou o efeito citotóxico e a capacidade de inibição das metaloproteinases da matriz extracelular (MMP-2 e MMP-9) pela quitosana 0,2%(CH) e o ácido acético 1% (AA) em comparação com o ácido etilenodiaminotetracético 17% (EDTA). O ensaio de viabilidade celular foi realizado de acordo com a ISO 10993-5 com fibroblastos de camundongo (L929). A cultura foi exposta a CH 0,2%, AA 1% e EDTA 17%. Os agentes quelantes foram avaliados imediatamente após o contato com as células e após 6 h, 12 h e 24 h de incubação. A viabilidade celular foi analisada utilizando o ensaio de brometo de 3- (4,5-dimetitiazol-2-il) -2,5-difeniltetrazólio (MTT). A inibição da atividade gelatinolítica de MMP-2 e MMP-9 foi avaliada por zimografia de gelatina. Diferentes concentrações de CH foram avaliadas: 50 mM, 5 mM, 0,5 mM e 0,05 mM. EDTA (0,5 mM) foi usado como controlo positivo. Os resultados demonstraram que CH e AA apresentaram um efeito citotóxico inicial, que diminuiu após 6 h, 12 h e 24 h, sendo estatisticamente similar ao EDTA (P> 0,05). Adicionalmente, CH a concentrações de 50 mM, 5 mM e 0,5 mM tiveram um efeito inibidor sobre MMP-2 e MMP-9, semelhante ao controlo com EDTA. Os agentes quelantes apresentaram efeitos não citotóxicos após 24 h. MMP-2 e MMP-9 foram inibidas pelas soluções experimentais.

Establishment of an in vitro screening model for uranium decorporation chelators based on the competitive ELISA method / 药学学报

Uranium [U(Ⅵ)] in the blood is known to form stable complexes with apotransferrin (apo-Tf), which plays an important role in mediating the cytotoxicity induced by U(Ⅵ) transported to cells. The present study aimed to establish an new in vitro screening model of U(Ⅵ) decorporation agents through exploring the capability of chelating agents competing with U(Ⅵ) binding to apo-transferrin based on enzyme-linked immunosorbent assay (ELISA). The optimal concentrations of apo-Tf coated antigen, Tf antibody, secondary antibody and U(Ⅵ) treatment were achieved and the stability and reproducibility of this method were validated by methodology study. Using this model, the ability of four chelating agents to mobilize the U(Ⅵ) binding to apo-Tf was evaluated, and the rank of competitiveness was catechol-3,6-bis(methyleiminodiacetic acid） (CBMIDA) ≈ Tiron > apo-Tf > DTPA-CaNa3 ≈ DTPA-ZnNa3. The efficacy of these chelating agents in removal of U(Ⅵ) was tested by animal experiments. The results showed that immediate administration of CBMIDA or Tiron after injection of U(Ⅵ) in mice significantly promoted urinary U(Ⅵ) excretion and reduced U(Ⅵ) accumulation in kidneys and femurs, while DTPA-CaNa3 and DTPA-ZnNa3 have no obvious effects as compared to U(Ⅵ)-exposed mice alone, which was consistent with the results of competitive ELISA method. The animal experiments conform to the rules of the Animal Research Ethics Committee of School of Pharmacy of Fudan University. These results show that the new proposed method is rapid, simple and convenient with good reproducibility and has the potential to be used for in vitro screening of U(Ⅵ) decorporation agents.

Treatment of iron overload syndrome: a general review

SUMMARY INTRODUCTION Iron overload is a broad syndrome with a large spectrum of causative etiologies that lead to iron deposition. When iron exceeds defenses, it causes oxidative damage and tissular disfunction. Treatment may prevent organ dysfunction, leading to greater life expectancy. METHODS Literature from the last five years was reviewed through the use of the PubMed database in search of treatment strategies. DISCUSSION Different pharmacological and non-pharmacological strategies are available for the treatment of iron overload and must be used according to etiology and patient compliance. Therapeutic phlebotomy is the basis for the treatment of hereditary hemochromatosis. Transfusional overload patients and those who cannot tolerate phlebotomy need iron chelators. CONCLUSION Advances in the understanding of iron overload have lead to great advances in therapies and new pharmacological targets. Research has lead to better compliance with the use of oral chelators and less toxic drugs.

RESUMO INTRODUÇÃO A síndrome de sobrecarga de ferro engloba um grande espectro de etiologias que levam a um aumento da quantidade de ferro nos tecidos. Esse ferro excede a capacidade de proteção dos tecidos, levando a dano oxidativo e lesão tissular. Tratamento pode prevenir esse dano, levando à melhor sobrevida. METODOLOGIA A literatura dos últimos cinco anos foi revisada por meio de pesquisa na base de dados PubMed buscando identificar estratégias de tratamento. DISCUSSÃO Medidas farmacológicas e não farmacológicas estão disponíveis para o tratamento da síndrome de sobrecarga de ferro e devem ser utilizadas de acordo com a etiologia e a aceitação do paciente. A flebotomia terapêutica é base do tratamento dos pacientes com hemocromatose hereditária. Pacientes com sobrecarga transfusional ou aqueles que não toleram flebotomias devem utilizar quelantes de ferro. CONSIDERAÇÕES FINAIS Avanços no entendimento da síndrome de sobrecarga de ferro têm levado a grandes progressos na terapêutica, com promessas de abordagem de novos alvos farmacológicos. A evolução da pesquisa tem possibilitado melhor aderência com o uso de quelantes orais e com possibilidade de drogas menos tóxicas.

Mesilato de desferroxamina como candidato a adjuvante farmacêutico e cosmético / Desferroxamine mesylate as a candidate for pharmaceutical and cosmetic adjuvant

Este trabalho propôs o uso do fármaco quelante mesilato de desferroxamina (DFO) como agente adjuvante para estabilização química e microbiológica de formulações. Soluções de ácido ascórbico (AA) 5,0% (p/v) foram preparadas com sistemas antioxidantes constituídos por diferentes combinações de DFO, ácido etilenodiamino tetra-acético (EDTA) e metabissulfito de sódio, cada adjuvante na concentração máxima de 0,1% (p/v). Os sistemas foram testados previamente quanto à atividade antioxidante, mediante adição de um complexo de ferro (III) redox-ativo e ensaio baseado em fluorescência. Os sistemas também foram associados ao metilparabeno e avaliados quanto à atividade antimicrobiana pelo método turbidimétrico, utilizando-se a técnica de microdiluição em meios líquidos e cepas padrão de bactérias e fungos, incluindo S. aureus (ATCC 6538), E. coli (ATCC 8739), P. aeruginosa (ATCC 9027), C. albicans (ATCC 10231) e A. brasiliensis (ATCC 16404). As soluções de AA foram expostas a condições de teste de estabilidade acelerada e avaliadas quanto à estabilidade química, empregando-se método volumétrico validado para quantificar AA. Verificou-se que o EDTA foi o agente quelante que melhor contribuiu na estabilidade química da solução de AA, entretanto, o DFO apresentou desempenho muito superior ao EDTA para bloquear a atividade pró-oxidante do ferro. Além disso, o DFO foi fator relevante na inibição do crescimento microbiano e demonstrou sinergia com o metilparabeno. A otimização estatística dos resultados indicou que o uso do DFO nos sistemas antioxidante e conservante pode reduzir consideravelmente a concentração dos adjuvantes convencionais, EDTA, metabissulfito e metilparabeno, os quais são muitas vezes associados a reações de hipersensibilidade ou a danos ao meio ambiente

In this work it was proposed the use of the chelating drug desferroxamine mesylate (DFO) as adjuvant for chemical and microbiological stabilization of formulations. Ascorbic acid (AA) solutions 5.0% (w/v) were prepared with antioxidant systems containing different combinations of DFO, ethylenediaminetetraacetic acid (EDTA) and sodium metabisulphite, using a maximum concentration of 0.1% (w/v) for each adjuvant. Previously, the systems were spiked with a redox-active iron (III) complex and tested for antioxidant activity by fluorescence-based assay. The systems also were associated with methylparaben and evaluated for antimicrobial activity by turbidimetric method, using the microdilution technique and standard strains of bacteria and fungi, including S. aureus (ATCC 6538), E. coli (ATCC 8739), P. aeruginosa (ATCC 9027), C. albicans (ATCC 10231) and A. brasiliensis (ATCC 16404). The AA solutions were exposed to accelerated stability test conditions and evaluated for chemical stability, using a volumetric method that was validated to quantify AA. It was found that EDTA was the chelating agent that most contributed to the chemical stability of AA solution, however, DFO demonstrated a much higher performance to EDTA to block the pro-oxidant activity of iron. In addition, DFO was a relevant factor in the inhibition of microbial growth and showed synergy with methylparaben. The statistical optimization of the results indicated that the use of DFO in the antioxidant and preservative systems might considerably reduce the concentration of the conventional adjuvants, EDTA, metabisulphite and methylparaben, which are often associated with hypersensitivity reactions or environmental damage

Phenolic Profile, Essential Oil Composition and Bioactivity of Lasia spinosa (L) Thwaites

Abstract Lasia spinosa (L.) Thwaites is a widely used ethnomedicinal plant in Bangladesh. In this study, we investigated phenolic contents, volatile compounds and fatty acids, and essential oil components of extracts prepared from aerial parts of the plant. The main volatile compounds were methyl ester of oleic acid, palmitic acid and stearic acid as determined by GC/MS. Phenolic contents of the extracts were determined qualitatively and quantitatively by HPLC/TOF-MS. Six phenolic compounds (syringic acid, morin, gentistic acid, 4-hydroxybenzoic acid, cinnamic acid, and apigenin) were found in the extracts. GC/MS analysis of steam distilled essential oil showed camphor, α-pinene and δ-3-carene as the main constituents. In DPPH radical scavenging assay, the highest free radical scavenging activity was observed for the methanol extract with an IC50 value of 0.48 ± 0.04 mg/mL, whereas, in metal chelating activity on ferrous ions (Fe2+) assay, the highest chelating activity was observed for hexane extract (IC50 = 0.55 ± 0.08 mg/mL). The extracts and essential oil were tested against five severe human pathogenic bacteria using disc diffusion assay and subsequent MIC values were also determined. All the extracts (except methanol extract) and the essential oil were found to possess potential antimicrobial activity with corresponding inhibition zone and minimum inhibitory concentration (MIC) ranging from 9-23 mm and 62.5-500 µg/mL. This study has been explored the plant Lasia spinosa can be seen as a potential source of biologically active compounds.

Fruiting increases total content of flavonoids and antiproliferative effects of Cereus jamacaru D.C. cladodes in sarcoma 180 cells in vitro

Objective: To evaluate the influence of fruiting phenological stage on total flavonoid content, antioxidant activity, and antiproliferative effects of Cereus jamacaru (C. jamacaru) (mandacaru) cladodes and fruit. Methods: Fruit and cladodes at vegetative and fruiting stage of C. jamacaru were collected. The fruit was dissected and bark, pulp, and seeds were separated. Vegetative and fruiting cladodes, together with bark, pulp, and seeds were used to obtain five hydroalcoholic extracts. The extracts were investigated for total flavonoid content, using AlCl3 colorimetric method, antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical scavenging capacity and Fe2+ ion chelating activity, and in vitro antiproliferative effects (sarcoma 180 cells) by 3-(4,5- dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Results: The extract of C. jamacaru cladodes at the fruiting stage showed higher flavonoid content compared to the other extracts. Seed extracts showed the highest antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) assays, and the extract of cladodes at vegetative stage showed better antioxidant activity in Fe2+ ion chelating activity. The extract of fruiting cladodes promoted higher antiproliferative effects compared to the other extracts. Conclusions: These findings suggest that fruiting increases the content of flavonoids and antiproliferative effects of C. jamacaru cladodes. Data reinforce the potential use of C. jamacaru cladodes and fruits as natural antioxidants and potent anticancer agent.

Gadolinium Deposition in the Brain: Current Updates

Gadolinium-based contrast agents (GBCAs) are commonly used for enhancement in MR imaging and have long been considered safe when administered at recommended doses. However, since the report that nephrogenic systemic fibrosis is linked to the use of GBCAs in subjects with severe renal diseases, accumulating evidence has suggested that GBCAs are not cleared entirely from our bodies; some GBCAs are deposited in our tissues, including the brain. GBCA deposition in the brain is mostly linked to the specific chelate structure of the GBCA: linear GBCAs were responsible for brain deposition in almost all reported studies. This review aimed to summarize the current knowledge about GBCA brain deposition and discuss its clinical implications.

Activators and Inhibitors of α-glucosidase from Penicillium chrysogenum

α-glucosidase (EC: 3.2.1.20) from Penicillium chrysogenum Thom ATCC 10106 was induced by GSH at the lower concentrations. H2O2 was inhibitor at all tested concentrations and the IC50 was 92.2%v/v. AMP, ADP and ATP enhanced the activity revealing that α-glucosidase is endothermic enzyme. The chelating agents are ethylenediaminetetraacetate (EDTA), α-α-dipyridyl and o-phenanthroline inhibited the enzyme. IC50 for these three compounds were 7.1, 10.2 and 10.9 mM, respectively. The highest activity of α-glucosidase was recorded at 150 mM phosphate buffer. Mannitol as polyol protected the enzyme against heat inactivation. The five sugars trehalose, lactose, raffinose, glucose and sucrose protected α-glucosidase against thermo-inactivation at 60ºC. Also, sarcosine as a product of glycine provided α-glucosidase with appreciable thermostability at 60ºC.

The toxicological mechanisms and detoxification of depleted uranium exposure

Depleted uranium (DU) has been widely applied in industrial and military activities, and is often obtained from producing fuel for nuclear reactors. DU may be released into the environment, polluting air, soil, and water, and is considered to exert both radiological and chemical toxicity. In humans and animals, DU can induce multiple health effects, such as renal tubular necrosis and bone malignancies. This review summarizes the known information on DU's routes of entry, mechanisms of toxicity, and health effects. In addition, we survey the chelating agents used in ameliorating DU toxicity.