Ultrasmall cationic superparamagnetic iron oxide nanoparticles as nontoxic and efficient MRI contrast agent and magnetic-targeting tool.

Fully dispersible, cationic ultrasmall (7 nm diameter) superparamagnetic iron oxide nanoparticles, exhibiting high relaxivity (178 mM(-1)s(-1) in 0.47 T) and no acute or subchronic toxicity in Wistar rats, were studied and their suitability as contrast agents for magnetic resonance imaging and material for development of new diagnostic and treatment tools demonstrated. After intravenous injection (10 mg/kg body weight), they circulated throughout the vascular system causing no microhemorrhage or thrombus, neither inflammatory processes at the mesentery vascular bed and hepatic sinusoids (leukocyte rolling, adhesion, or migration as evaluated by intravital microscopy), but having been spontaneously concentrated in the liver, spleen, and kidneys, they caused strong negative contrast. The nanoparticles are cleared from kidneys and bladder in few days, whereas the complete elimination from liver and spleen occurred only after 4 weeks. Ex vivo studies demonstrated that cationic ultrasmall superparamagnetic iron oxide nanoparticles caused no effects on hepatic and renal enzymes dosage as well as on leukocyte count. In addition, they were readily concentrated in rat thigh by a magnet showing its potential as magnetically targeted carriers of therapeutic and diagnostic agents. Summarizing, cationic ultrasmall superparamagnetic iron oxide nanoparticles are nontoxic and efficient magnetic resonance imaging contrast agents useful as platform for the development of new materials for application in theranostics.

Evaluation of the mutagenic effect of the iodinated contrast medium Urografina® 292 using the micronucleus test in mouse bone marrow cells.

Contrast media (CM) are frequently used in diagnostic radiology and in radiotherapy as a diagnostic tool and in treatment planning. Previous studies have demonstrated that these compounds induce chromosomal aberrations. This study evaluates the mutagenic effects induced by the contrast medium Urografina® 292 (meglumine amidotrizoate and sodium-ionic dimmer) in bone marrow cells (BMC) of mice in vivo. Micronuclei assay was performed in BMC of CF-1 mice injected with CM 1.5 and 3.0 mL/kg intravenous doses and 1.0, 2.0, 3.0 mL/kg intraperitoneal doses. The animals were beheaded 24 h after treatment by cervical dislocation, and femur BMC from each animal were used in the micronucleus test. The group treated with the highest intravenous injection of Urografina® 292 (3.0 mL/kg) presented an increase in the frequency of micronucleated polychromatic erythrocytes (MNPCEs) in relation at the control group (P<0.05). The results obtained after intraperitoneal administration of CM showed that all doses (1.0 mL/kg, 2.0 mL/kg and 3.0 mL/kg) increased the frequency of MNPCEs, being significantly different from the negative control (P< 0.01). The present results suggest that iodinated contrast media Urografina® 292 may cause a significant increase of cytogenetic damage in bone marrow cells of mice.

Sodium butyrate decreases the activation of NF-κB reducing inflammation and oxidative damage in the kidney of rats subjected to contrast-induced nephropathy.

BACKGROUND: Contrast-induced nephropathy (CIN) is associated with a combination of hypoxic and toxic renal tubular damage, renal endothelial dysfunction and altered intra-renal microcirculation. Recently, sodium butyrate (SB) has been focused on since it possesses anti-inflammatory activities. Thus, based on the lack of information on the effects of SB in acute kidney injury (AKI), we investigated the possible effects of SB after CIN in rats. METHODS: Wistar rats were divided into three groups: (1 sham) control, (2 MI) AKI treated with contrast medium and (3 MI + SB) AKI plus SB. Six days after contrast administration, blood and kidney were removed for the determination of creatinine, interleukin (IL)-6 levels, oxidative damage parameters and histologic analyses. Nuclear factor kappa B (NF-κB), pIκBα and vasodilator-stimulated phosphoprotein (VASP) protein content were determined by immunoblotting. RESULTS: After 6 days, the levels of creatinine increased significantly in the MI group, and this was attenuated using SB. SB treatment was associated with a decrease on the levels of lipid peroxidation, but not the protein oxidation, and IL-6 levels, as well as tubular damage. These effects are probably mediated, in part, by a decrease on the activation of NF-κB in the kidney, but not alteration in pVASP content. CONCLUSIONS: The current experiment suggests that NF-κB induced an inflammatory response after CIN and SB could inhibit NF-κB expression protecting against CIN in rats.

Cytotoxicity of Portland cement with different radiopacifying agents: a cell death study.

INTRODUCTION: The aim of this study was to investigate the cytotoxicity of white Portland cement (PC) alone or associated with bismuth oxide (PCBi), zirconium oxide (PCZir), and calcium tungstate (PCCa) in 2 cell lineages. METHODS: Murine periodontal ligament cells (mPDL) and rat osteosarcoma cells (ROS 17/2.8) were exposed for 24 hours to specific concentrations of fresh PC and PC associations with radiopacifiers. Zinc oxide-eugenol cement and hydrogen peroxide treatment were applied as cytotoxic positive controls. Cell viability after incubation with the cements was assessed by mitochondrial dehydrogenase enzymatic assay. Cell morphology was microscopically analyzed by cresyl violet staining, and the mechanism of cell death was determined by acridine orange/ethidium bromide methodology. All data were analyzed statistically by analysis of variance and Tukey post hoc test (P < .05). The correlation among cell death by apoptosis or necrosis and pH values was established by Pearson linear coefficient. RESULTS: The mitochondrial dehydrogenase enzymatic assay only revealed significant cell death rate at high concentrations of cement elutes. PC alone was not cytotoxic, even at 100 mg/mL. Microscopic images showed that none of the PC formulations caused damage to any cell lines. Statistical analysis of apoptosis/necrosis data demonstrated that PC and PC plus radiopacifying agents promoted significant necrosis cell death only at 100 mg/mL. CONCLUSIONS: The mPDL cells were more sensitive than ROS17/2.8. The results showed that PC associated with bismuth oxide, zirconium oxide, or calcium tungstate is not cytotoxic to mPDL or ROS17/2.8. Zirconium oxide and calcium tungstate might be good alternatives as radiopacifying agents.

Radiopacifiers do not induce genetic damage in murine fibroblasts: an in vitro study.

AIM: To evaluate whether several radiopacifiers are able to induce genetic damage in a laboratory cell culture study. METHODOLOGY: Murine fibroblasts were exposed to barium sulphate, bismuth oxide or zirconium oxide, at final concentrations ranging from 10 to 1000 microg mL(-1) for 1 h at 37 degrees C. The negative control group was treated with a vehicle control [phosphate buffered solution (PBS)] for 1 h at 37 degrees C and the positive control group was treated with hydrogen peroxide (at 10 microM) for 5 min on ice. Genotoxicity data were assessed by the single-cell gel (comet) assay. RESULTS: All the tested compounds did not induce DNA breakage as depicted by the mean tail moment in all the concentrations analysed. CONCLUSION: Exposure to the tested radiopacifiers may not be a factor that increases the level of DNA lesions in mammalian cells as detected by a single-cell gel (comet) assay.

Micronucleus induction in mouse polychromatic erythrocytes by an X-ray contrast agent containing iodine.

In this article, the authors report the results of in vivo studies on bone marrow polychromatic erythrocytes (PCE) from mice treated with Urografina®292 (a mixture of sodium amidotrizoate and meglumine amidotrizoate) and with purified sodium amidotrizoate and meglumine amidotrizoate separately or in combination at the same ratio and concentration as that of the highest dose of Urografina®292 used in the experiment. The results showed that Urografina®292 significantly increased the frequencies of micronucleated polychromatic erythrocytes (MNPCEs) in both male (p=0.0082 and p=0.0062) and female (p=0.0350 and p=0.0101) mice treated with doses of 14.3 and 20.0 ml/kg body weight, respectively. When lower doses were used (5.7 and 8.6 ml/kg body weight), the treated mice did not show any significant increase in the frequencies of MNPCEs compared with the negative control group. The same result was observed for both male and female animals treated with purified sodium amidotrizoate and meglumine amidotrizoate separately or in combination. In addition, there was a significant positive correlation between the Urografina®292 doses used and the frequency of micronuclei. These results supported the hypothesis that small amounts of aryl amines present in all X-ray contrast agents containing diatrizoate and closely related triiodobenzoates were responsible for genotoxicity. The frequencies of PCEs in treated animals were determined to estimate the toxicity of Urografina®292, sodium amidotrizoate, and meglumine amidotrizoate to bone marrow, and the results indicated that they did not show any significant difference compared with the negative control group. The fact that mutagenic agents are also generally carcinogenic contributes to the concern with regard to the possible long-term risks of these agents in case of patients who are exposed to iodine-containing X-ray contrast agents during radiodiagnostic procedures.

Nefropatía por medios de contraste / Contrast induced nephropathy

La Nefropatía por contraste (NC) constituye un importante problema en nuestros días debido a la alta frecuencia de estudios realizados, como angiografías o tomografías computadas.Esta situación se define como una elevación fija (0,5 mg/dl) o proporcional (25) de la creatininemia luego de la exposición al medio de contraste. Generalmente, más que la única causa, representa un factor contribuyente en el desarrollo de la insuficiencia renal aguda. Los principales factores de riesgo son : la diabetes mellitus, el clearance de creatinina bajo y una edad mayor a los 75 años.La principal estrategia para prevenir la NC consiste en la administración de fluidos.Los profesionales involucrados en la atención de los pacientes con esta enfermedad deben conformar guías institucionales con el objetivo de prevenir este problema. (AU)

Nefropatía por medios de contraste / Contrast induced nephropathy

La Nefropatía por contraste (NC) constituye un importante problema en nuestros días debido a la alta frecuencia de estudios realizados, como angiografías o tomografías computadas.Esta situación se define como una elevación fija (0,5 mg/dl) o proporcional (25) de la creatininemia luego de la exposición al medio de contraste. Generalmente, más que la única causa, representa un factor contribuyente en el desarrollo de la insuficiencia renal aguda. Los principales factores de riesgo son : la diabetes mellitus, el clearance de creatinina bajo y una edad mayor a los 75 años.La principal estrategia para prevenir la NC consiste en la administración de fluidos.Los profesionales involucrados en la atención de los pacientes con esta enfermedad deben conformar guías institucionales con el objetivo de prevenir este problema.

Complicações do uso intravenoso de agentes de contraste à base de gadolínio para ressonância magnética / Complications from the use of intravenous gadolinium-based contrast agents for magnetic resonance imaging: [review]

Os agentes de contraste à base de gadolínio são muito mais seguros que o contraste iodado, no entanto, existem complicações que devem ser reconhecidas, para orientação e tratamento adequados. A incidência total de reações adversas aos meios de contraste em ressonância magnética varia entre 2 por cento e 4 por cento. Casos de reações adversas agudas maiores ao gadolínio, como laringoespasmo e choque anafilático, são raros. As complicações crônicas com o uso do gadolínio também existem e, recentemente, foi descrita associação entre seu uso e uma doença dermatológica rara que ocorre em pacientes com insuficiência renal. A fibrose nefrogênica sistêmica foi tema de anúncio público oficial pela agência americana de regulação de drogas, a Food and Drug Administration. Esta doença progressiva caracteriza-se pelo espessamento e endurecimento da pele e fibrose, que podem acometer outras partes do corpo. Os pacientes que desenvolveram esta complicação apresentavam insuficiência renal crônica, estavam em acidose metabólica e foram submetidos a angiografia por ressonância magnética, provavelmente com injeção de grande volume de contraste paramagnético. Esta revisão tem o objetivo de apresentar uma descrição sucinta dos tipos de meios de contraste à base de gadolínio, possíveis complicações e medidas para prevenção e tratamento destas.

Gadolinium-based contrast agents are much safer than the iodinated ones; however complications may occur and should be recognized for appropriate orientation and management. The total incidence of adverse reactions to contrast agents in magnetic resonance imaging ranges between 2 percent and 4 percent. Cases of severe acute reactions to gadolinium, such as laryngospasm and anaphylactic shock, are rare. Chronic complications secondary to the use of gadolinium also can occur and, recently an association between its use and a rare dermatologic disease occurring in patients with renal failure has been reported. Nephrogenic systemic fibrosis was the subject of an official health notification issued by the American Food and Drug Administration. This progressive disease is characterized by hardened skin with fibrotic nodules and plaques which may involve other parts of the body. Patients who have been affected by this disorder presented chronic renal failure, with metabolic acidosis and had been submitted to magnetic resonance angiography, probably involving exposure to large amounts of intravenous paramagnetic contrast. This review is aimed at presenting a succinct description of the gadolinium-based contrast agent types, possible secondary complications, their preventive measures and management.

Nefropatía inducida por medios de contraste radiológico yodados / Contrast-induced nephropathy

La nefropatía inducida por medios de contraste radiológico yodados (NIACR) es una causa relativamente común de insuficiencia renal aguda en el medio hospitalario, asociada a un aumento considerable en la morbilidad y la mortalidad secundarias. La comprensión de su fisiopatología multifactorial, es aún incipiente, por lo que se carece de agentes profilácticos específicos y efectivos. La única medida preventiva aceptada mundialmente es la hidratación con solución salina pero se están estudiando para ese propósito otros compuestos. En este artículo se revisan la epidemiología y patogénesis de la NIACR, así como los factores de riesgo y las estrategias de prevención.

Contrast-induced nephropathy (CIN) is a relatively common cause of acute renal insufficiency in the hospital milieu. It has been associated with a considerable increase in morbidity andmortality, as well as in the length of hospital stay. Clearly, many factors are involved in the pathophisiology of this complication, whose understanding is far from complete; therefore, there is still a lack of specific and effective prophylactic agents. In this article we review the epidemiology and pathogenesis of CIN, as well as the risk factors and preventive strategies.

Avaliação do conhecimento de médicos não-radiologistas sobre reações adversas aos contrastes iodados / Evaluation of nonradiologist physicians' knowledge about adverse reactions to iodinated contrast media

OBJETIVO: Avaliar o conhecimento dos médicos não-radiologistas sobre reações adversas ao meio de contraste iodado, sua prevenção e as condições clínicas que aumentam seu risco. MATERIAIS E MÉTODOS: Estudo transversal com 203 médicos não-radiologistas (assistentes, residentes e estagiários) de várias especialidades, utilizando um questionário com dez questões de múltipla escolha abordando profilaxia, fatores de risco e condutas relacionadas ao desenvolvimento de reações adversas aos meios de contraste iodados. Os resultados foram analisados com o programa Statistic Package for Social Sciences, Windows®, versão 12.0. RESULTADOS: Asma, alergia alimentar, ansiedade e doença isquêmica do coração foram considerados fatores de risco por 80,9 por cento, 78,9 por cento, 5,9 por cento e 4,1 por cento dos participantes, respectivamente. Para 23,4 por cento dos médicos, não há contra-indicações absolutas ao uso do meio de contraste iodado. As condutas profiláticas em pacientes com reação prévia ao meio de contraste iodado e em diabéticos em uso de metformina foram corretamente indicadas por 84,5 por cento e 53,7 por cento dos participantes, respectivamente. As questões abordando nefropatia induzida por meio de contraste iodado, uso de anti-sépticos tópicos iodados em pacientes com história de reação adversa ao meio de contraste iodado e ansiedade foram acertadas por 86,1 por cento, 45,5 por cento, e 5,9 por cento dos participantes, respectivamente. CONCLUSÃO: Os médicos não-radiologistas demonstraram conhecimento razoável sobre reações adversas aos meios de contraste iodados. É necessária melhor integração e comunicação entre radiologistas e médicos das demais especialidades.

OBJECTIVE: To evaluate the nonradiologist physicians' knowledge about adverse reactions to iodinated contrast media, as well as prevention and associated risk factors. MATERIALS AND METHODS: A transversal study was developed with 203 nonradiologist physicians (assistants, residents and trainees) of different specialties, who completed a questionnaire including ten multiple choice questions regarding prophylaxis, risk factors and conduct related to the development of adverse reactions to iodinated contrast media. The Statistic Package for Social Science version 12.0 for Windows® was utilized for statistical analysis. RESULTS: Asthma, food allergy, anxiety and ischemic heart disease were considered as risk factors by, respectively, 80.9 percent, 78.9 percent, 5.9 percent and 4.1 percent of the participants. According to 23.4 percent of the physicians, there is no absolute contraindication to the use of iodinated contrast media. Correct prophylactic measures for patients with previous adverse reaction to iodinated contrast media and in diabetic patients using metformin were indicated, respectively, by 84.5 percent and 53.7 percent of the respondents. Questions about contrast-induced nephropathy, use of iodinated topical antiseptics in patients with previous adverse reaction to iodinated contrast media, and anxiety were correctly answered by, respectively, 86.1 percent, 45.5 percent and 5.9 percent of the participants. CONCLUSION: Nonradiologist physicians have shown a reasonable knowledge about adverse reactions to iodinated contrast media. A better integration and communication among radiologists and physicians of other specialties is warranted.

Evaluation of tissue response to MTA and Portland cement with iodoform.

OBJECTIVE: The aim of this study was to evaluate the biocompatibility of Portland cement with the addition of iodoform, compared to MTA (ProRoot). STUDY DESIGN: Eighteen Wistar albino rats were divided into 3 groups of 6 animals each. Polyethylene tubes were filled either with freshly mixed MTA or Portland cement mixed with iodoform (20% wt/wt) and implanted subcutaneously. An empty tube served as control. After 7, 30, or 60 days, the implants together with the surrounding tissues were removed in blocks. Sections were evaluated for the presence and thickness of a fibrous capsule, presence of granulation tissue, and the severity of inflammatory response. Data were submitted to nonparametric statistical analysis with individual comparisons between groups at a significance level of P < 0.05. RESULTS: There were no differences between inflammatory responses at 7 and 30 days. After 60 days from surgical removal, there was significantly more tissue reaction to the MTA and Portland cement compared to the control group. CONCLUSION: There were no significant differences regarding inflammatory responses between MTA and Portland cement with iodoform after 7, 30, or 60 days. After 60 days, the fibrous capsule around the Portland cement appeared more organized than tissue surrounding MTA implants. After 60 days, there was still a significantly increased tissue reaction to the 2 cements compared to the empty polyethylene tubes.

Espécies reativas de oxigênio na exposição a radiocontrastes e hipóxia em células epiteliais do túbulo renal / Reactive oxygen species in renal tubular epithelial cells exposed to radiocontrasts and hypoxia

Radiocontrastes a base de iodo são utilizados para angiografia, urografia ou tomografia computadorizada. Esses compostos absorvem radiação em escala proporcional à concentração de iodo na solução e, em tese, não deveriam interagir com o organismo. Porém, na prática clínica, tem sido constatado que os RC não são totalmente inertes e mostram um certo grau de interação. Os efeitos colaterais mais comuns incluem reações de hipersensibilidade sistêmica, reações adversas cardíacas, efeitos vasculares e efeitos adversos renais, sendo que o agente de contraste já é considerado o segundo s maior agente nefrotóxico usado na prática clínica.O perfil dos pacientes submetidos a procedimentos com RC tem se modificado: são cada vez mais velhos e apresentam mais fatores de risco associados como diabetes. problemas cardíacos. desidratação e insuficiência renal pré-existente. A incidência de nefropatia causada pelo radiocontraste (CIN), que ocorre em 1 por cento a 6 por cento dos pacientes hospitaiizados pode aumentar para mais de 50 por cento quando os paciente, apresentam fatores de risco. 0 único procedimento atualmente usado na prática clínica para amenizar os danos renais é a hidratação do paciente antes da administração do agente de contraste, de modo que se faz urgente o conhecimento de novas formas de prevenção da CIN. O uso de RC desencadeia uma resposta hemodinâmica renal bifásica, onde um período de vasodilatação inicial, que dura alguns segundos, é seguido de um período de vasoconstrição, que diminui o fluxo sangüíneo renal, a taxa de filtração glomerular e a tensão de oxigênio principalmente na medula renal. A diminuição do fluxo sangüínea e da tensão de oxigênio causam necrose nos ramos espessos ascendentes medulares e aumentam a creatinina sérica nos dias subsequentes à administração dos RC. Ainda o RC apresenta unta nefrotoxicidade celular direta. São apontados vários mecanismos para a citotoxicidade direta provocada pelo RC: prejuízo das ligações intercelulares, distúrbios de polaridade de células renais, vacuolização citoplasmática com alteração lisossomal e a geração de espécies reativas de oxigênio(ROS). Uma das formas de prevenção da CIN seria a administração de antioxidantes que bloqueiam a ação das ROS. No presente trabalho, a N-acetil-L-cisteína (NAC), vitamina E, cimetidina, ácido ascórbico dentre outros compostod, foram testados como antioxidantes...

Nefropatía por contraste, un problema común en cardiología intervencionista / Radiocontrast nephropathy

La incidencia de deterioro de la función renal inducida por agentes de contraste (nefropatía por contraste) ha aumentado significativamente en los últimos años a consecuencia del creciente número de procedimientos intervencionistas diagnósticos y terapéuticos realizados en pacientes con patologías cardíacas ó extracardíacas. La nefropatía por contraste, si bien suele ser reversible, dista de ser una complicación benigna, ya que supone una prolongación de la estadía hospitalaria y en algunos casos, en particular en pacientes de alto riesgo, conlleva el riesgo de deterioro irreversible de la función renal. A partir de un conocimiento más acabado de su fisiopatología se han ensayado diversas estrategias para reducir la incidencia de la nefropatía por contraste. De ellas, las más eficaces resultaron ser la hidratación correcta y la utilización de medios de contraste de baja osmolaridad. Resulta entonces sumamente importante alertar, no sólo a cardiólogos intervencionistas, sino también a todos los médicos que deciden derivar a sus pacientes a este tipo de procedimientos con agentes de radiocontraste acerca de la fisiopatología, la presentación clínica y la identificación de grupos de riesgo, a fin de implementar simples medidas preventivas o terapéuticas. (AU)

Meio de contraste ioversol em neuroradiologia canina / Ioversol contrast medium in canine neuroradiology

O ioversol, contraste iodado hidrossolúvel näo iônico, na concentraçäo de 320mg 1/ml foi utilizado para a realizaçäo de 26 estudos neuroradiográficos contrastados (mielografias, epidurografias, e ventriculografia cerebral) em 23 cäes. Devido à rápida absorçäo do contraste, as melhores radiografias foram obtidas nos primeiros 30 minutos. O produto ofereceu apropriadas radiopacidade, tempo de permanência, difusäo e miscibilidade no líqüor, facilitando os diagnósticos, assim como mínima ocorrência de reaçöes indesejáveis durante e após o procedimento radiológico. Apesar de terem sido utilizados para a anestesia, as associaçöes zolazepam-tiletamina e levomepromazina; xilazina ou diazepam-tiopental sódico, nenhum paciente desenvolveu convulsöes. A apresentaçäo do ioversol em frasco ampola foi também outra vantagem, por diminuir o desperdício e facilitar a reesterilizaçäo do excedente na altoclave.

Los medios de contraste radiológico en pediatría / The contrast mediums use in pediatric radiology

Los medios de contraste empleados en radiología pediátrica no difieren de los que se utilizan en adultos. Los agentes de uso intravascular son agentes triyodados y a pesar de que son consideradas de entre las substancias menos tóxicas por unidad de peso de todas las drogas empleadas en medicina, su uso lleva implícito el riesgo de provocar algún tipo de reacción de intoleracia. En el presente artículo se hace un análisis breve de los medios de constraste que existen en el mercado en la actualidad así como de los tipos de reacciones que desencadenan. Se hace hincapié en que muchas de las reacciones están relacionadas con alta osmolaridad de los compuestos y que pueden reducirse sustancialmente con nuevas substancias pero que tienen un costo muy elevado.