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.

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.

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.

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.

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).

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.

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.

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.

Dolor abdominal como presentación por intoxicación por plomo: Caso clínico / Abdominal pain as a presentation by lead poisoning: Case report

La intoxicación aguda por plomo no es una patología que con frecuencia vemos en el consultorio de pediatría. Los síntomas por intoxicación por plomo pueden ser digestivos o neurológicos, y, muchas veces, se puede confundir con otras patologías. De ahí, la importancia de tener presente y pensar en esta patología y, ante la alta sospecha, pedir estudios complementarios que confirmen la intoxicación por plomo. Este es el caso de un niño de 9 años, que consulta por dolor abdominal agudo acompañado de vómitos. Luego de realizar un minucioso examen físico y una detallada anamnesis, se tiene una alta sospecha diagnóstica de intoxicación "aguda" por plomo, motivo por el cual se interna. Después de tomar una muestra venosa para confirmar el nivel de plomo, se realiza un tratamiento con quelante, bajo la supervisión de un especialista en toxicología.

Acute lead poisoning is not a common pathology seen in the pediatrician's office. Lead poisoning symptoms can be digestive or neurological, and they can be confused with other pathologies. That is the reason why it should be considered and, in case of doubt, complementary studies to confirm lead poisoning should be requested. This is the case of a nine-year-old child that comes to the office with a strong abdominal pain and vomiting, and after a close physical examination and a detailed anamnesis, a suspicious diagnosis of "acute" lead poisoning is obtained. Therefore, the infant is hospitalized, and after taking a venous sampling to confirm the lead level, a chelation therapy is performed under the toxicology expert's supervision.

Antimicrobial Effect and Surface Tension of Some Chelating Solutions with Added Surfactants

Abstract This study assessed the antimicrobial efficacy and surface tension of established irrigating solutions with a new experimental chelating solution in infected dentin tubes. Twenty-five specimens were randomly assigned to each of the irrigating solutions. Twenty specimens were used as negative and positive controls. After 21 days of contamination with E. faecalis, the irrigating solutions MTAD, QMiX and Tetraclean NA were delivered into each infected root canal. The solutions were removed and dentin samples were withdrawn from the root canals with sterile low-speed round burs with increasing ISO diameters. The dentin powder samples obtained with each bur were immediately collected in separate test tubes containing 3 mL of BHI broth. After that, 100 μL from each test tube was cultured on blood agar. The grown colonies were counted and recorded as colony-forming units (CFU). The surface tension of the irrigants was measured using a Cahn DCA-322 Dynamic Contact Angle Analyzer. A Kruskal Wallis nonparametric ANOVA and a Friedman test were used (p<0.05). Tetraclean NA showed lower surface tension and CFU values than MTAD and QMiX. Better antibacterial action and low surface tension were observed for Tetraclean NA, probably due to the improved penetration into the root canal and dentinal tubes

Resumo Este estudo avaliou a eficácia antimicrobiana e tensão superficial de soluções irrigadoras e uma nova solução quelante em tubos de dentina infectada. Vinte e cinco espécimes foram aleatoriamente distribuídos conforme as soluções irrigantes. Decorrifdos 21 dias de contaminação com E. faecalis, a soluções de irrigação MTAD, QMiX e Tetraclean NA foram distribuídas em cada canal radicular infectado. As soluções foram removidas e as amostras de dentina foram retiradas dos canais radiculares com brocas esféricas de baixa velocidade com diâmetros ISO sucessivamente maiores. As amostras do pó de dentina obtidas com cada broca foram imediatamente colocadas em tubos de ensaio separados contendo 3 mL de caldo BHI. A seguir, 100 μL de cada amostra do tubo de teste foi cultivada em agar de sangue. As colônias crescidas foram contadas e registadas como unidades formadoras de colônias (UFC). A tensão superficial das soluções irrigantes foi medida utilizando o método de Wilhelmy. A análise não paramétrica de Kruskal-Wallis e o teste de Friedman foram utilizados (p<0,05). Tetraclean NA apresentou menor tensão de superfície e menores valores de UFC do que MTAD e QMiX. A melhor ação antibacteriana e baixa tensão superficial foram observadas para Tetraclean NA, provavelmente devido à melhor penetração no canal radicular e túbulos dentinários.

The effect of combination treatment using iron chelator deferasirox and cisplatin on proliferation and apoptosis in non-small cell lung cancer / 天津医药

Objective To investigate the combination effect using iron chelators deferasirox and cisplatin on A549 cell proliferation and apoptosis and to provide evidences to explore an effective way to treat lung cancer. Methods Lung adeno?carcinoma cells were cultured by conventional way, with administration of different concentrations of deferasirox and cisplat?in. Cell growth inhibition was observed under an inverted microscope. Proliferation inhibition was evaluated by MTT assay. Morphological changes of cell apoptosis was detected using DAPI,AO/EB straning and flow cytometry. Results After a cer?tain time of incubation with different concentrations of the combined drugs,the cell number reduce significantly, which was counted under invert microscope. Cells were dispersed with each other and adherent cells appear shrunken and poor in re?fractivity. MTT assay showed that inhibition of cell proliferation was in a concentration-time-dependent manner. Chromatin condensation, nuclear condensation and other typical apoptotic morphology were detected after DAPI and AO/EB straning. Flow cytometry showed that apoptosis increased with rising drug concentration. So combination therapy was significantly pro-apoptotic. Conclusion Deferasirox has the ability to inhibit proliferation of A549 cells and can promote tumor cell apoptosis and enhances cancer cell tolerance when combined with cisplatin. It can also reduce the amount and toxicity of cis?platin. It provides a basis for finding an effective way to treat lung cancer.

Progress in evaluation and treatment of hepatic iron overload / 临床肝胆病杂志

Iron overload is a metabolic disorder characterized by excessive iron deposition in the liver,pancreas,heart,endocrine organs, etc.,resulting in structural damage and dysfunction.The liver is the primary organ for iron storage,and excessive iron deposition induces liver inflammation and fibrosis,which may progress to cirrhosis and even liver cancer,with a poor prognosis.Accurate evaluation and effec-tive treatment can reduce liver injury caused by iron overload and improve patients′survival.

A drug will not function unless it is bound to a receptor: a longstanding confusion in basic pharmacology.

The disparity between the general definition of a ‘drug’ and the wide-spread mechanism of actions of receptor-dependent drugs may often mislead to believe that a drug-receptor interaction is always indispensable for a drug to exert its action. This short review is intended to rectify this basic misconception in pharmacology with the aid of a list of examples of several receptor-independent drugs in context to their mode of actions.

Etidronate from Medicine to Endodontics: effects of different irrigation regimes on root dentin roughness

An increase in dentin roughness, associated with surface composition, contributes to bacterial adherence in recontaminations. Surface roughness is also important for micromechanical interlocking of dental materials to dentin, and understanding the characteristics of the surface is essential to obtain the adhesion of root canal sealers that have different physico-chemical characteristics. OBJECTIVES: To evaluate the effects of sodium hypochlorite (NaOCl), ethylenediaminetetraacetic (EDTA), etidronic (HEBP), and citric acid (CA) associated with different irrigation regimens on root dentin roughness. MATERIAL AND METHODS: Forty-five root halves of anterior teeth were used. The root parts were sectioned in thirds, embedded in acrylic resin and polished to a standard surface roughness. Initially, the samples of each third were randomly assigned into 3 groups and treated as follows: G1 - saline solution (control); G2 - 5% NaOCl+18% HEBP mixed in equal parts; and G3 - 2.5% NaOCl. After initial measuments, the G3 samples were distributed into subgroups G4, G5 and G6, which were subjected to 17% EDTA, 10% CA and 9% HEBP, respectively. Following the new measuments, these groups received a final flush with 2.5% NaOCl, producing G7, G8 and G9. The dentin surface roughness (Ra) was determined before and after treatments using a profilometer. The Wilcoxon test (α<0.05) was used to compare the values before and after treatments, and the Friedman test (α<0.05) to detect any differences among root thirds. RESULTS: (i) NaOCl did not affect the surface roughness; (ii) there was a significant increase in roughness after the use of chelating agents (P<0.01); and (iii) only the G3 group showed a difference in surface roughness between apical third and other thirds of the teeth (P<0.0043). CONCLUSION: Only the irrigation regimens that used chelating agents altered the roughness of root dentin. .

Ecocardiografia de pacientes talassêmicos sem insuficiência cardíaca em tratamento com transfusões sanguíneas e quelação / Echocardiography in thalassemic patients on blood transfusions and chelation without heart failure

FUNDAMENTO: Pacientes com talassemia major (TM) apresentam hemólise crônica e necessitam de transfusões sanguíneas egularmente que podem causar cardiomiopatia por sobrecarga de ferro e insuficiência cardíaca crônica. A hemocromatose é caracterizada por acúmulo excessivo de ferro nos tecidos; acometimento do coração é a principal causa de óbito em pacientes com talassemia. OBJETIVO: Avaliar as estruturas e a função cardíaca por meio de ecocardiografia com Doppler convencional e Doppler tecidual em pacientes com TM, sem evidência clínica de insuficiência cardíaca. MÉTODOS: Trata-se de estudo observacional prospectivo de 18 pacientes com TM que recebem transfusão sanguínea regularmente. Para avaliar, separadamente, os efeitos da anemia e da transfusão sanguínea, dois grupos controles pareados por gênero, idade, peso e altura foram incluídos: um com indivíduos saudáveis (Saudável, n = 18) e outro com pacientes com anemia por deficiência de ferro (Anemia, n = 18). Análise estatística foi realizada utilizando ANOVA seguida pelo teste de Tukey ou Kruskal-Wallis e teste de Dunn. RESULTADOS: As seguintes variáveis ecocardiográficas apresentaram valores significativamente mais elevados no grupo TM do que nos grupos Anemia e Saudável: índice de volume do átrio esquerdo (Saudável: 16,4 ± 6,08; Anemia: 17,9 ± 7,02; TM: 24,1 ± 8,30 cm/m); razão E/Em septal mitral (Saudável: 6,55 ± 1,60; Anemia: 6,74 ± 0,74; TM: 8,10 ± 1,31) e duração do fluxo reverso em veias pulmonares [Saudável: 74,0 (59,0-74,0); Anemia: 70,5 (67,0-74,0); TM: 111 (87,0-120) ms]. Arazão E/A mitral foi maior no grupo TM do que no grupo Anemia (Saudável: 1,80 ± 0,40; Anemia: 1,80 ± 0,24; TM: 2,03 ± 0,34). Não foram encontradas diferenças entre os grupos em variáveis estruturais do ventrículo esquerdo e em índices de função sistólica. CONCLUSÃO: A ecocardiografia com Doppler convencional e o Doppler tecidual permite que alterações na função diastólica do ventrículo esquerdo sejam identificadas em pacientes assintomáticos com talassemia major.

BACKGROUND: Patients with thalassemia major present chronic hemolysis and require regular blood transfusions which may cause iron overload cardiomyopathy and chronic heart failure. Hemochromatosis is characterized by excessive iron accumulation in tissues, and heart involvement is the main cause of death in patients with thalassemia. OBJECTIVE: The aim of this study was to evaluate cardiac structure and function by conventional Doppler echocardiography and tissue Doppler imaging in patients with TM and no clinical evidence of heart failure. METHODS: This is a prospective observational study including 18 patients with thalassemia major (TM) receiving regular blood transfusion. To separately evaluate anemia and blood transfusion effects, two gender, age, weight, and height-matched control groups were included: one with healthy individuals (Healthy, n=18) and one with iron deficient anemia patients (Anemia, n=18). Statistical analysis was performed using ANOVA followed by Tukey's test or Kruskal-Wallis's and Dunn's test. RESULTS: The following echocardiographic variables presented significantly higher values in TM than the Anemia and Healthy groups: left atrium volume index (Healthy: 16.4±6.08; Anemia: 17.9±7.02; TM: 24.1±8.30 cm³/m²); mitral septal E/Em ratio (Healthy: 6.55±1.60; Anemia: 6.74±0.74; TM: 8.10±1.31); and duration of reverse pulmonary vein flow [Healthy: 74.0 (59.0-74.0); Anemia: 70.5 (67.0-74.0); TM: 111 (87.0-120) ms]. The mitral E/A ratio was higher in TM than Anemia (Healthy: 1.80±0.40; Anemia: 1.80±0.24; TM: 2.03±0.34). No differences were found in left ventricular structures and systolic function indexes. CONCLUSION: Conventional Doppler echocardiography and tissue Doppler allow changes in left ventricular diastolic function to be identified in asymptomatic patients with thalassemia major.

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

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.

Comparación del efecto citotóxico de tres agentes quelantes sobre fibroblasto del ligamento periodontal humano. Estudio in vitro / Comparison of the cytotoxic effect of three chelating agents on human periodontal ligament fibroblast. In vitro study

Objetivo: Comparar in vitro el efecto citotóxico de tres agentes quelantes sobre fibroblastos del ligamento periodontal humano. Materiales y métodos: Se utilizaron cultivos de fibroblastos de ligamento periodontal humano, los cuales fueron colocados en contacto con los agentes quelantes a evaluar (RC-Prep, Glyde, EDTA al 17%) a intervalos de 15, 30 y 60 minutos. Se midió la absorbancia para cada uno de los grupos, para determinar el grado de actividad enzimática, que es indicador de muerte celular. Previo a la cuantificación de la absorbancia se corroboró microscópicamente la formación de los cristales de formazán, los cuales se forman alrededor de los fibroblastos, y su presencia es indicador de integridad de la membrana y de la actividad metabólica. Por microscopia se verificó la formación de cristales de formazan, después de agregar azul de tripán. Resultados: El Glyde mostró mayor grado de citotoxicidad, con una diferencia estadísticamente significativa, al compararlo con EDTA 17% y el RC-PREP. El EDTA presentó mayor citotoxicidad que el RC-PREP a los 15minutos, evento que cambió a los 30 y 60 minutos. Conclusiones: Los agentes quelantes RC-Prep, Glyde y EDTA tienen un efecto citotóxico a nivel de los fibroblastos del ligamento periodontal, siendo el EDTA el de menor efecto citotóxico a los 30 y 60 minutos comparado con RC-Prep y Glyde.

Objectives: To compare in vitro, the cytotoxic effect of three chelating agents on human periodontal ligament fibroblasts, RC-Prep, Glyde and EDTA. Methods: Fibroblast cultures of human periodontal ligament were used, which are placed in contact with chelating agents to evaluate (RC-Prep, Glyde, 17% EDTA) at time intervals of 15,30 and 60 minutes. Absorbance was measured for each group to determine the degree of enzyme activity, which is an indicator of cell death. Prior to the measurement of absorbance was confirmed microscopically, the formation of formazan crystals, which are formed around fibroblasts, and its presence is an indicator of membrane integrity and metabolic activity. Microscopy verified the formation of formazan crystals, after adding trypan blue. Results: Glyde showed greater cytotoxicity with a statistically significant difference when compared with 17% EDTA and RC-PREPchelants. The EDTA showed higher cytotoxicity than the RC-PREP to 15min, and that event changed at 30 and 60 minutes. Conclusion: It was shown experimentally that the chelating agents RC-Prep, EDTA and Glyde have a cytotoxic effect at the periodontal ligament fibroblasts. EDTA has a lowest cytotoxic effect at 30 and 60 minutes compared to RC-Prep and Glyde.

A importância do atendimento pré-hospitalar nas queimaduras químicas no Brasil / The importance of pre hospital care in chemical burns in Brazil

O autor apresenta dois relatos de casos que demonstram o aumento da eficáciae eficiência envolvendo os serviços de atendimentos pré-hospitalares de urgências relacionados às queimaduras químicas. A relação tempo x qualidade de prognóstico decorre de uma otimização dos recursos tecnológicosexistentes e disponíveis, agregando valores e resultados. A utilização de um descontaminante químico do tipo quelante, como o Diphoterine, pode modificar a história evolutiva de uma agressão por produtos químicos, minimizando ou eliminando as sequelas advindas dos mesmos.

The author presents two case reports that demonstrate the increased effectiveness and efficiency, involving the pre hospital care services emergency related to chemical burns. The relationship time x quality of prognosis stems from an optimization of existing technological resources and available, aggregating values and results. The use of a chemical decontaminant to the remnants of chelation type, such as Diphoterine can modify the evolutionary history of an aggression by chemical products, minimizing or eliminating the consequences arising thereof.