BEHAVIORAL AND NEUROCHEMICAL CHANGES DURING INTRANASAL ADMINISTRATION OF ALPHA-GLUTAMYL-TRYPTOPHAN AND CHELATE COMPLEX OF ZINC ARGINYL-GLYCINATE ON MONOAMINE SYSTEMS DYSFUNCTIONS KNOCK-OUT MODELS.

Monoamine neurotransmitter system dysfunctions lead to behavioral disorders, cognitive metabolic, and other pathological conditions. In this case, different amino acids are precursors of monoamines, while the parenteral path of monoamine administration has pharmacological restrictions. Therefore, intranasal administration one of the most promising methods of delivering an active substance is. The purpose of the work is to study the effect of intranasal administration of a chelate complex of zinc arginyl-glycinate and alpha-glutamyl-tryptophan dipeptide on behavioral and neurochemical changes in acute and chronic experiments. MATERIAL AND METHODS: The studies used outbred Wistar and DAT-KO rats, and inbred C57Bl6 and TAAR1-KO mice. Using intranasal administration of a chelate complex of zinc arginyl-glycinate and alpha-glutamyl-tryptophan dipeptide we tested methods for evaluating different behavioral indicators and the level of cerebral monoamines and their metabolites. RESULTS: An anxiolytic effect of zinc arginyl-glycinate and its combination with alpha-glutamyl-tryptophan was revealed. Both drugs have a physiological effect on the autonomic nervous system, but the determination of their operating mechanisms requires further research. CONCLUSION: Thus, these data indicate that intranasal delivery of the dipeptides is effective during acute and chronic intranasal administration in rodents, the latter showed a change in the anxiety indicator. Acute AG intranasal administration demonstrated signs of lower anxiety and depressive-like behavior in C57Bl6 mice. The acute intranasal administration of a chelate complex zinc arginyl-glycinate and combination with alpha-glutamyl-tryptophan in doses of 50-100 mg/kg of body weight may be used for pre-clinical studies as a new anxiolytic/antidepressant.

Relapse following withdrawal of D-penicillamine from combination (D-penicillamine + zinc) therapy in hepatic Wilson disease.

OBJECTIVES: Long-term D-penicillamine (D-pen) therapy in Wilson disease (WD) has numerous adverse effects which advocates its withdrawal, but with an inherent risk of relapse. This prospective observational study was conducted with the objective of evaluating incidence of relapse following withdrawal of D-pen from combination (D-pen + zinc) therapy in maintenance phase of previously symptomatic hepatic WD. METHODS: Hepatic WD patients <18 years of age and on combination therapy for >2 years with 6 months of biochemical remission were included. Biochemical remission was defined as achievement of (i) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.5 times upper limit of normal (ULN), (ii) serum albumin >3.5 g/dL, international normalized ratio (INR) <1.5 and (iii) 24-h urinary copper excretion (UCE) <500 mcg/day, nonceruloplasmin-bound-copper (NCC) <15 mcg/dL. After D-pen withdrawal, monthly liver function test (LFT) and INR and 3 monthly UCE and NCC were done till 1 year or relapse (elevation of AST/ALT/both >2 times ULN or total bilirubin >2 mg/dL), whichever occurred earlier. RESULTS: Forty-five patients enrolled with median combination therapy duration of 36 months. Sixty percent of them had their index presentation as decompensated cirrhosis. Fourteen patients (31.8%) relapsed (cumulative incidence: 4 at 3 months, 11 at 6 months, and 14 at 12 months after D-pen discontinuation). All relapsers had index presentation as decompensated cirrhosis. On Cox-regression, ALT at D-pen withdrawal was an independent predictor of relapse (hazard ratio [HR]: 1.077, 95% confidence interval [CI]: 1.014-1.145, p = 0.017) with area under the receiver operating characteristic (AUROC) of 0.860. ALT ≥40 U/L predicted risk of relapse with 85.7% sensitivity, 70.9% specificity. CONCLUSION: Incidence of relapse after withdrawal of D-pen from combination therapy is 31.8% in hepatic WD. ALT ≥40 U/L, at the time of D-pen stoppage, predicts future relapse.

Sodium thiosulfate and pamidronate for treatment of calciphylaxis: case report / Tiosulfato de sodio y pamidronato para el tratamiento de calcifilaxis: reporte de caso

Abstract Introduction: Calciphylaxis is an infrequent disease that almost exclusively affects patients with chronic kidney disease, although cases have been observed in patients without renal function impairment. The diagnosis is mainly made by clinical manifestations and subsequently confirmed by radiological and histological study. The optimal treatment is not known, although there is a consensus that a multifactorial approach is required. Clinical Case: A 68-year-old woman on hemodialysis for 2 years, who presented a painful nodular lesion in the left thigh, a skin biopsy was performed resulting in a diagnosis of calciphylaxis. Treatment and Outcome: Treatment was started with intravenous sodium thiosulfate. Pamidronate is added intravenously, three months later, due to an unfavorable evolution. After 6 months of treatment, improvement in nodular lesions and healing of the ulcerated lesion was observed to be generally well tolerated treatment. Conclusion: The combined treatment of sodium thiosulfate, pamidronate and calcitomimetics has been effectiveand safe for the treatment of calciphylaxis, inducing complete remission.

Resumen: Introducción: La calcifilaxis es una enfermedad infrecuente que afecta casi exclusivamente a pacientes con insuficiencia renal, aunque se han observado casos en pacientes sin deterioro de la función renal. El diagnóstico es clínico confirmándose con estudio radiológico e histológico. No se conoce con exactitud el tratamiento óptimo, aunque hay consenso en que se requiere un abordaje multifactorial. Caso Clínico: Mujer de 68 años en hemodiálisis desde hace 2 años, que presenta una lesión nodular dolorosa en muslo izquierdo, resultando un diagnostico compatible con calcifilaxis, tras biopsia cutánea. Tratamiento y resultado: Inicia tratamiento con tiosulfato de sodio vía venosa. Tres meses más tarde y ante la evolución desfavorable, se añade al tratamiento pamidronato vía intravenosa. Tras 6 meses de tratamiento se observa mejoría de las lesiones nodulares y cicatrización de la lesión ulcerada, habiéndose experimentado buena tolerancia. Conclusión: El tratamiento combinado de tiosulfato de sodio, pamidronato y calcimiméticos ha resultado efectivo y seguro para el tratamiento de la calcifilaxis, induciendo su remisión completa.

Protocolos de irrigação final em Endodontia: revisão sistemática / Final irrigation protocols in Endodontics: systematic review

Introdução: a ação mecânica dos instrumentos no sistema de canais limita-se ao canal principal, o que valoriza a necessidade de um irrigante com propriedades ótimas para melhorar a limpeza e desinfecção. Objetivos: revisar os diferentes protocolos de irrigação final adotados em Endodontia. Métodos: foram selecionados estudos in vitro e in vivo, para apontar as soluções químicas empregadas, suas possíveis associações e os métodos de agitação. Resultados: ficou evidente a necessidade de mais de uma substância durante a preparação e, também, a associação com um agente quelante, sob agitação, como forma de potenciar a desinfecção dos canais. Conclusão: observou-se que o uso de NaOCl 2,5% associado a EDTA 17%, MTAD ou CHX 2%, sob agitação, parece ser a combinação considerada mais efetiva na literatura, podendo, portanto, ser indicada como irrigantes finais em Endodontia. (AU)

Intoxicación familiar por mercurio elemental: caso clínico / Family poisoned by elemental mercury: a case report

Introduction: mercury is a heavy metal widely dispersed in nature, occurring in three chemical forms. Exposure to mercury at work sites and even at home may be clinically significant. Objective: to update the knowledge about the risks of this toxic element. Case report: the case of a teenager and his family poisoned by elemental mercury is reported. The diagnostic process was difficult, mainly due to an initial presumption of probable infectious etiology, unavailability of key anamnestic data and unusual clinical behavior, with signs and symptoms of multisystem compromise (neurological, hepatic, renal and dermatological compromise). Discussion: the study was based on literature review of various clinical presentations regarding this poisoning and its management, emphasizing the need for dimercaptosuccinic acid chelator. As a major public health problem, the importance of education and implementation of public policies to have a mercury-free environment is discussed.

Introducción: el mercurio es un metal pesado ampliamente distribuido en el medio ambiente, en sus tres formas químicas. La exposición a dicho metal en recintos laborales e incluso en el hogar, puede llegar a ser clínicamente significativa. Objetivo: actualizar el conocimiento acerca de los riesgos de este tóxico. Caso clínico: se presenta el caso clínico de un adolescente y su familia intoxicados por mercurio elemental, cuyo proceso diagnóstico fue difícil, principalmente por la presunción inicial de una probable etiología infecciosa, falta de disponibilidad de datos anamnésticos claves y el inusual comportamiento clínico, con signos y síntomas de compromiso multisistémico (neurológico, hepático, renal y dermatológico). Discusión: se revisa la literatura en relación a las diversas formas de presentación clínica de esta intoxicación y su manejo, destacando la utilidad del quelante ácido dimercaptosuccínico. Por ser un importante problema de salud pública, se destaca la trascendencia de la educación e implementación de políticas públicas por un ambiente libre de mercurio.

Influence of concentration, time and method of application of citric acid and sodium citrate in root conditioning

OBJECTIVES: The aim of this study was to establish the parameters of concentration, time and mode of application of citric acid and sodium citrate in relation to root conditioning. MATERIAL AND METHODS: A total of 495 samples were obtained and equally distributed among 11 groups (5 for testing different concentrations of citric acid, 5 for testing different concentrations of sodium citrate and 1 control group). After laboratorial processing, the samples were analyzed under scanning electron microscopy. A previously calibrated and blind examiner evaluated micrographs of the samples. Non-parametric statistical analysis was performed to analyze the data obtained. RESULTS: Brushing 25% citric acid for 3 min, promoted greater exposure of collagen fibers in comparison with the brushing of 1% citric acid for 1 minute and its topical application at 1% for 3 min. Sodium citrate exposed collagen fibers in a few number of samples. CONCLUSION: Despite the lack of statistical significance, better results for collagen exposure were obtained with brushing application of 25% citric acid for 3 min than with other application parameter. Sodium citrate produced a few number of samples with collagen exposure, so it is not indicated for root conditioning.

Time-dependent effects of chitosan on dentin structures

Complete debridement with smear layer removal are essential measures for achieving a successful outcome of root canal treatment. The aim of this study was to evaluate the effects of chitosan at different concentrations on the removal of the smear layer and on dentin structure after 3 and 5 min of application. Twelve recently extracted maxillary canine teeth were instrumented using the crown-down technique and irrigated with 1% sodium hypochlorite. The specimens were distributed according to the time and concentration of the final irrigating solution: G1: 0.1% chitosan for 3 min; G2: 0.2% chitosan for 3 min; G3: 0.37% chitosan for 3 min; G4: 0.1% chitosan for 5 min; G5: 0.2% chitosan for 5 min; G6: 0.37% chitosan for 5 min. All samples were prepared for SEM analysis. G1 exhibited removal of the smear layer, but not the smear plugs. G2 showed visible and open tubules with slight erosion of the peritubular dentin. Cleaning in G3 was similar to that in G2, however, the erosive effect was greater. There was expansion of the diameter of the tubules in G4; and in G5 and G6, there was severe erosion with deterioration of dentin surface. In conclusion, 0.2% chitosan for 3 min appeared to be efficient for removing the smear layer, causing little erosion of dentin.

Completo debridamento dos canais radiculares com a remoção da smear layer são medidas essenciais no sucesso do tratamento endodôntico. O objetivo deste estudo foi avaliar os efeitos da quitosana, em diferentes concentrações, na remoção da smear layer e na estrutura da dentina, após 3 e 5 min de aplicação. Doze dentes caninos superiores, recém extraídos, foram instrumentados pela técnica crown-down e irrigados com hipoclorito de sódio 1%. Os espécimes foram distribuídos em seis grupos conforme o tempo e a concentração da solução irrigante final: G1: quitosana 0,1% por 3 min; G2: quitosana 0,2% por 3 min; G3: quitosana 0,37% por 3 min; G4: quitosana 0,1% por 5 min; G5: quitosana 0,2% por 5 min; G6: quitosana 0,37% por 5 min. Todas as amostras foram preparadas para avaliação em MEV. Os resultados mostraram que o G1 apresentou remoção da smear layer, mas não da smear plug. O G2 mostrou túbulos visíveis e abertos com ligeira erosão da dentina peritubular. A limpeza no G3 foi semelhante à do G2, no entanto, o efeito erosivo foi maior. No G4 houve ampliação do diâmetro dos túbulos e no G5 e G6, severa erosão com deterioração da superfície dentinária. Concluiu-se que a quitosana 0,2% por 3 min foi eficiente na remoção da smear layer, ocasionando pequena erosão.

Efeito da 1, 10-fenantrolina e seus derivados complexados em metal na atividade proteolítica de Leishmania braziliensis / Effect of 1, 10-phenanthroline and its complexed metal derivatives in proteolytic activity of Leishmania braziliensis

Leishmanioses são um grupo de doenças com um largo espectro de manifestações clínicas, as quais variam desde lesões cutâneas até o envolvimento visceral severo, podendo levar ao ótibo. A leishmaniose é, ainda hoje, uma doença negligenciada, estando entre os agravos prioritários do programa de pesquisa sobre doenças da pobreza da Organização Mundial da Saúde (OMS). Além de não haver vacinas disponíveis, a terapia é baseada em medicamentos injetáveis que causam sérios efeitos colaterais, tornando o tratamento inviável para muitos países endêmicos. Drogas derivadas de metal representam um novo arsenal terapêutico antimicrobiano e anti-câncer. Os inibidores de peptidase/agentes quelantes tais como 1,10-fenantrolina e seus derivados, no estado livre de metal ou como ligantes com metais de transição, interferem com a função de vários sistemas biológicos. Em trabalhos anteriores, nosso grupo descreveu que o parasito L. braziliensis produziu moléculas gp63 sensíveis a 1,10-fenantrolina. No presente trabalho, demonstramos a distribuição celular da molécula gp63 em uma cepa virulenta de L. braziliensis por meio de análises bioquímicas e imuno-histoquímica. Depois disso, relatamos os efeitos inibitórios de três compostos derivados da 1,10-fenantrolina, 1,10-fenantrolina-5,6-dioma (phendio), [Cu(phendio)2] e [Ag(phendio)2], nas atividades metalopeptidases celulares e extracelulares produzidas por promastigotas de L. braziliensis, bem como as suas ações sobre a viabilidade do parasita e na interação com as células de macrófagos murinos. As moléculas gp63 foram detectadas em compartimentos de parasitos, incluindo membrana citoplasmatica e bolsa flagelar. O tratamento de promastigotas de L. braziliensis durante 1 hora com 1,10-fenantrolina e seus derivados resultou numa inibição significativa da viabilidade celular e mostrou um mecanismo de ação irreversível. Estes inibidores de metalopeptidases induziram apoptose em promastigotas de L. braziliensis, demonstrada através ...

Leishmaniasis is a group of diseases with a wide spectrum of clinical manifestations, which range from self-limited skin lesions to severe visceral involvement that can lead to death. Leishmaniasis is still a neglected disease, and it is among the priorities of the research program on diseases of poverty of World Health Organization (TDR/WHO). There is no available vaccine and the treatment is based on drugs that cause serious side effects, and are unaffordable in several endemic countries. Metal-based drugs represent a novel antimicrobial and anti-cancer therapeutics arsenal. Peptidase inhibitors/chelating agents such as 1,10-phenanthroline and its substituted derivatives, either the metal-free state or as ligands coordinated to transition metals, interfere with crucial functions of several biological systems. In previous works, our group described that L. braziliensis produced gp63 molecules sensible to 1,10-phenanthroline. Herein, we initially studied the cellular distribution of gp63 in a virulent strain of L. braziliensis by biochemical and immunocytochemical analyses. After that, we reported the inhibitory effects of three 1,10-phenanthroline derivative compounds, 1,10-phenanthroloine-5,6-dione (phendio), [Cu(phendio)2] and [Ag(phendio)2], on both cellular and extracellular metallopeptidase activities produced by L. braziliensis promastigotes as well as their actions on the parasite viability and on the interaction with murine macrophage cells. The gp63 molecules were detected in several parasite compartments, including cytoplasm, membrane lining the cell body and flagellum, and flagellar pocket. The treatment of L. braziliensis promastigotes for 1 hour with 1,10-phenanthroline and its derivatives resulted in a significant inhibition of cell viability and showed an irreversible mechanism of action. These metallopeptidase inhibitors induced apoptosis in L. braziliensis promastigotes as judged by annexin/propidium iodide staining and TUNEL assays ...

Alteraciones electrolíticas y del equilibrio ácido-base en la enfermedad renal crónica avanzada / No disponible

1. Los riñones representan los órganos clave para mantener el balance de los diferentes electrolitos corporales y del equilibrio ácido-base. La pérdida progresiva de función renal se traduce en una serie de modificaciones adaptativas y compensatorias renales y extrarrenales que permiten mantener la homeostasis con filtrados glomerulares hasta cifras en torno a 10-25ml/min. Con filtrados glomerulares inferiores a 10ml/min, casi siempre existirán anomalías del medio interno con repercusiones clínicas.2. Alteraciones del balance de Agua. En la Enfermedad Renal Crónica (ERC) avanzada, el rango de osmolalidad urinaria se aproxima progresivamente a la plasmática, haciéndose isostenúrica. La traducción clínica son los síntomas de nicturia y poliuria, especialmente en nefropatías tubulointersticiales. La sobrecarga de agua se (..)(AU)

1. The kidneys are the key organs to maintain the balance of the different electrolytes in the body and the acid-base balance. Progressive loss of kidney function results in a number of adaptive and compensatory renal and extrarenal changes that allow homeostasis to be maintained with glomerular filtration rates in the range of 10-25 ml/min. With glomerular filtration rates below 10 ml/min, there are almost always abnormalites in the body’s internal environment with clinical repercussions.2. Water Balance Disorders: In advanced chronic kidney disease(CKD), the range of urine osmolality progressively approaches plasma osmolality and becomes isostenuric. This manifests clinically as symptoms of nocturia and polyuria, especially intubulointerstitial kidney diseases. Water overload will result in (..) (AU)

Quelantes del fósforo (P) en diálisis: eficacia y coste. Soluciones de diálisis peritoneal / No disponible

La prevalencia del consumo de sevelamer es alta, la mitad de los pacientes son tratados con este quelante sin calcio. Durante 2007 han aparecido dos trabajos randomizados que analizan la eficacia del sevelamer sobre las sales de cal-cio. El estudio más potente estadísticamente hablando no encuentra diferencias respecto a la mortalidad entre ambos grupos, sevelamer y sales de calcio, excepto en mayores de 65 años que es favorable al sevelamer. En el otro estudio con menos potencia estadística se observa una menor mor-talidad en el grupo tratado con sevelamer. Ambos estudios tienen varias deficiencias y oportunamente ese mismo año aparece el meta-análisis al respecto, concluyendo que no hay una evidencia significativa que demuestre una eficacia superior del sevelamer sobre las sales de calcio, por lo que no es recomendable la extensión generalizada de su uso, como quelante de primera línea. En determinadas situaciones clínicas se valorará su utilización. Respecto al coste/beneficio, al no tener evidencia de obtener mayores beneficios clínicos con el sevelamer que con las sales de calcio, la prudencia y moderación en su uso será necesaria por el alto coste/beneficio demostrado. Delo contrario contribuiremos a aumentar el gasto en estos pacientes ya de por sí muy elevado, con un coste de vida ganada por año de los más elevados en medicina. El coste/beneficio del sevelamer sigue siendo poco atractivo desde el punto de vista económico, aunque se excluya la diálisis y trasplante en estos enfermos (AU)

Sevelamer use has a high prevalence, and half of patients are treated with this non calcium binder. Two randomized studies appeared in 2007 that compared the efficacy of sevelamer over calcium salts. In the more statistically potent of the two studies, no differences were found in mortality between the sevelamer and calcium groups, except for a benefit in favor of sevelamer in patients older than 65 years. In the other less statistically potent study, lower mortality was observed in the sevelamer group. Both studies have various deficiencies and a timely meta-analysis of the two studies appearing that same year concluded that there was no significant evidence demonstrating a superior efficacy of sevelamer over calcium salts. Therefore, generalized extension of its use as a first-line binder is not recommended. However, its use can be assessed in specific clinical situations .With regard to the cost-benefit ratio, as there is no evidence that greater clinical benefits are obtained with sevelamer than with calcium salts, prudence and moderation in its use are needed because of the high cost/benefit ratio demonstrated. Otherwise, we will contribute to increasing the already very high treatment cost in these patients, with one of the highest costs per life year gained in medicine. The cost/benefit ratio of sevelamer remains unattractive from an economic point of view, even if dialysis and transplant are excluded in these patients (AU)

Intoxicación aguda por arsénico con inusual evolución favorable / Acute accidental arsenic intoxication with unusual favourable course

Describimos un caso de ingesta accidental de arsenito sódico en un joven agricultor. Desarrolló como únicas manifestaciones un cuadro autolimitado de vómitos, dolor abdominal, cólico y alteraciones electrocardiográficas en la repolarización. Pudo darse el alta con recuperación completa. Se detectaron niveles tóxicos de arsénico en sangre y orina (AU)

We report a case of acute accidental sodium arsenite intake in a young farmer, with the only manifestations of a self-limited clinical picture of vomiting, colicky abdominal pain and electrocardiographic repolarisation disturbances. The patient was eventually discharged after complete recovery. Toxic arsenic levels were detected in plasma and urine (AU)

Effect of the sodium hypochlorite and citric acid association on smear layer removal of primary molars

O objetivo deste estudo foi avaliar a capacidade da associação entre hipoclorito de sódio e ácido cítrico em diferentes concentrações para remover "smear layer" (SL) coronária de dentes decíduos. Para isso, foram utilizados 28 molares decíduos, nos quais se realizou a remoção do teto e do assoalho da câmara pulpar, obtendo-se discos de esmalte e dentina. Produziu-se SL nas paredes internas dos discos utilizando-se brocas em alta rotação e eles foram irrigados com hipoclorito de sódio a 1%, ácido cítrico em diferentes concentrações (AC- 4%, AC- 6%, AC-8% e AC-10%) e cloreto de sódio a 0,9%. As amostras foram esplitadas e observadas no MEV. Foram atribuídos escores às fotomicrografias obtidas, de acordo com a quantidade de SL presente. Observou-se que todas as concentrações de ácido cítrico empregadas após o hipoclorito de sódio foram capazes de remover SL. Os resultados foram analisados pelo teste de Kruskal-Wallis, não havendo diferença estatística significativa entre os escores dos grupos testados. Verificou-se, entretanto, que AC-8% AC-10% promoveram destruição de dentina peritubular e que AC-4% apresentou maior número de amostras com SL densa. A partir dos resultados obtidos sugere-se a utilização de ácido cítrico a 6,0% em associação ao hipoclorito de sódio a 1% como substâncias químicas auxiliares para irrigação de dentes decíduos.

Intoxicación por metales / Metal poisoning

Los metales están entre los tóxicos más antiguos conocidos por el hombre. En el industrializado mundo actual las fuentes de exposición a metales son ubicuas tanto en el campo laboral como a partir de agua, los alimentos o el ambiente contaminados. Su toxicidad está caracterizada por el elemento metálico en cuestión pero se ve modificada por el tipo de compuesto, orgánico o inorgánico y sus características de hidro o liposolubilidad, que determina su toxicocinética y por tanto sus posibilidad de alcanzar sus dianas. Las biomoléculas más afectadas por los metales son las proteínas con actividad enzimática por lo que su patología es multisistema. Los principales sistemas afectados son el gastrointestinal, neurológico central y periférico, hemático y renal. Algunos de los compuestos metálicos son carcinógenos. Los metales se benefician de un tratamiento condicionado por su reactividad química. Pueden ser inactivados y eliminados mediante la administración de substancias quelantes que producen con ellos moléculas complejas, atóxicas y excretables. Los principales agentes quelantes son: BAL (British Anti-Lewisite o dimercaprol), DMPS (ácido 2,3-dimercapto-1-propanosulfonico) y DMSA (ácido meso-2,3-dimercatosuccínico o Succimer), EDTA, Penicilamina (beta, beta-dimetilcisteína) y Desferoxamina. Se exponen a continuación las características toxicocinéticas, mecanismo de acción, clínica y tratamiento de alguno de los metales y metaloides más relevantes: plomo, mercurio y arsénico (AU)

Efecto de la desferrioxamina y de ladeferiprona sobre la secreción de osteocalcina en células tipo osteoblasto / Effect of desferrioxamine and deteriprone on the 1, 25 (OH)2D3- stimulated osteocalcin secretion in osteoblast-like cells

La desferrioxamina y la deferiprona son dos drogas quelantes de metales que se emplean en la sobrecarga alumínica de los pacientes en diálisis. Se ha descrito que la desferrioxamina mejora la mineralización ósea, sin descensos importantes de la concentración de aluminio en hueso. Esto sugiere un efecto directo de la desferrioxamina sobre las células óseas. El objetivo de este trabajo fue evaluar el efecto de desferrioxamina y deferiprona sobre células óseas de estirpe osteoblástica. El estudió se realizó en cultivos de células MG-63. Las células se sembraron a una densidad de 15.000 cel/cm2 y se llevaron a confluencia en un medio DMEM con 10% FCS. Tras 72 horas, se reemplazó el medio por el de ensayo: 1% BSA, 10-9M 1,25(OH)2D3 y desferrioxamina 5, 10, 20, 40, 60, 80 μM o deferiprona 15, 30, 60, 120, 180, 240 μM. Como control se utilizó Tris-HCl a pH 7,4. A las 48 horas se recogieron los sobrenadantes y se midió la osteocalcina secretada. La desferrioxamina y la deferiprona inhibieron la secreción de osteocalcina inducida por vitamina D a concentraciones elevadas (desferrioxamina: 60 μM, 80 μM; deferiprona: 180 μM, 240 μM) mientras que la estimularon a bajas concentraciones (desferrioxamina 5 μM; deferiprona 15 μM). Estos resultados sugieren que tanto la desferrioxamina como la deferiprona son capaces de ejercer un efecto directo sobre el metabolismo del hueso independientemente de su capacidad quelante de metales (AU)

Desferrioxamine and deferiprone are both metal-chelating drugs often used in aluminum-overloaded dialysis patients. In these patients, desferrioxamine produces an improvement on bone mineralisation without a relevant decrease in bone aluminum. Thus, desferrioxamine might have a direct effect on bone cells. The aim of this study was to assess the effect of desferrioxamine and deferiprone on 1,25(OH)2D3-stimulated osteocalcin secretion in osteoblast-like cells. The study was carried out in MG-63 cell cultures. Cells were seeded at a density of 15,000 cel/cm2 and grown to confluence for 72 hours in DMEM supplemented with 10% FCS. The medium was then replaced by another medium containing 1% BSA, 10-9M 1,25(OH)2D3 and desferrioxamine 5, 10, 20, 40, 60, 80 μM or deferiprone 15, 30, 60, 120, 180, 240 μM. Tris-HCl at pH 7.4 was used as control. After 48 hours, supernatants were collected for the measurement of secreted osteocalcin. Desferrioxamine and deferiprone, at high doses (desferrioxamine: 60 μM, 80 μM; deferiprone: 180 μM, 240 μM), inhibited the 1,25(OH)2D3-induced osteocalcin secretion. On the contrary, at lower doses (desferrioxamine 5 μM; deferiprone 15 μM) stimulated the secretion. In summary, these results suggest that desferrioxamine and deferiprone exert a direct effect on bone cell metabolism that might be independent from their metalchelating properties (AU)

Tratamiento de la insuficiencia arterial periférica con quelación / treatment of peripheral arterial insuficiency by means of chelation

A 100 pacientes con insuficiencia arterial periférica de los miembros inferiores por aterosclerosis comprobada mediante cirugía o angiografías fueron tratados con quelación con ácido etilendiaminotetracético. El estudio oscilográfico y el índice doppler tobillo-brazo realizados antes y después del tratamiento mostraron una diferencia estadística significativa con un aumento promedio del índice de 0.319 por lo que los autores lo proponen como una alternativa terapéutica en pacientes con ateroesclerosis severa