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1.
ACS Appl Mater Interfaces ; 13(38): 45325-45334, 2021 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-34533945

RESUMEN

Sonosensitizers play crucial roles in the controlled production of reactive oxygen species (ROS) under ultrasound (US) irradiation with high tissue-penetration depth for noninvasive solid tumor therapy. It is desirable to fabricate structurally simple yet multifunctional sonosensitizers from ultrafine nanoparticles for ROS-based multimode therapy to overcome monomode limitations such as low ROS production yields and endogenous reductive glutathione (GSH) to ROS-based treatment resistance. We report the facile high-temperature solution synthesis of ultrafine W-doped TiO2 (W-TiO2) nanorods for exploration of their sonodynamic, chemodynamic, and GSH-depleting activities in sonodynamic-chemodynamic combination tumor therapy. We found that W5+ and W6+ ions doped in W-TiO2 nanorods play multiple roles in enhancing their ROS production. First, W doping narrows the band gap from 3.2 to 2.3 eV and introduces oxygen and Ti vacancies for enhancing their sonodynamic performance. Second, W5+ doping endows W-TiO2 nanorods with Fenton-like reaction activity to produce •OH from endogenous H2O2 in the tumor. Third, W6+ ions reduce endogenous GSH to glutathione disulfide (GSSG) and, in turn, form W5+ ions that further enhance their chemodynamic activity, which greatly modifies thae oxidation-reduction tumor microenvironment in the tumor. In vivo experiments display the excellent ability of W-TiO2 nanorods for enhanced tumor eradication in human osteosarcoma models under single US irradiation. Importantly, the ultrafine nanorod morphology facilitates rapid excretion from the body, displaying no significant systemic toxicity. Our work suggests that multivalent metal doping in ultrafine nanomaterials is an effective and simple strategy for the introduction of new functions for ROS-based multimode therapy.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Nanotubos/química , Osteosarcoma/tratamiento farmacológico , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Animales , Antineoplásicos/química , Antineoplásicos/efectos de la radiación , Línea Celular Tumoral , Femenino , Glutatión/metabolismo , Humanos , Radical Hidroxilo/metabolismo , Ratones Endogámicos BALB C , Nanotubos/efectos de la radiación , Fármacos Sensibilizantes a Radiaciones/química , Fármacos Sensibilizantes a Radiaciones/efectos de la radiación , Oxígeno Singlete/metabolismo , Titanio/química , Titanio/efectos de la radiación , Titanio/uso terapéutico , Microambiente Tumoral/efectos de los fármacos , Tungsteno/química , Tungsteno/efectos de la radiación , Tungsteno/uso terapéutico , Terapia por Ultrasonido , Ondas Ultrasónicas
2.
PLoS One ; 14(6): e0217757, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31216296

RESUMEN

PURPOSE: Electron radiotherapy is a labor-intensive treatment option that is complicated by the need for field shaping blocks. These blocks are typically made from casting Cerrobend alloys containing lead and cadmium. This is a highly toxic process with limited precision. This work aims to provide streamlined and more precise electron radiotherapy by 3D using printing techniques. METHODS: The 3D printed electron cutout consists of plastic shells filled with 2 mm diameter tungsten ball bearings. Five clinical Cerrobend defined field were compared to the planned fields by measuring the light field edge when mounted in the electron applicator on a linear accelerator. The dose transmitted through the 3D printed and Cerrobend cutouts was measured using an IC profiler ion chamber array with 6 MeV and 16 MeV beams. Dose profiles from the treatment planning system were also compared to the measured dose profiles. Centering and full width half maximum (FWHM) metrics were taken directly from the profiler software. RESULTS: The transmission of a 16MeV beam through a 12 mm thick layer of tungsten ball bearings agreed within 1% of a 15 mm thick Cerrobend block (measured with an ion chamber array). The radiation fields shaped by ball bearing filled 3D printed cutout were centered within 0.4 mm of the planned outline, whereas the Cerrobend cutout fields had shift errors of 1-3 mm, and shape errors of 0.5-2 mm. The average shift of Cerrobend cutouts was 2.3 mm compared to the planned fields (n = 5). Beam penumbra of the 3D printed cutouts was found to be equivalent to the 15 mm thick Cerrobend cutout. The beam profiles agreed within 1.2% across the whole 30 cm profile widths. CONCLUSIONS: This study demonstrates that with a proper quality assurance procedure, 3D-printed cutouts can provide more accurate electron radiotherapy with reduced toxicity compared to traditional Cerrobend methods.


Asunto(s)
Neoplasias/radioterapia , Impresión Tridimensional , Tungsteno/uso terapéutico , Electrones , Sustancias Peligrosas/efectos adversos , Sustancias Peligrosas/uso terapéutico , Humanos , Plomo/efectos adversos , Plomo/uso terapéutico , Método de Montecarlo , Neoplasias/patología , Aceleradores de Partículas , Cintigrafía , Radioterapia , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos
3.
Biomater Sci ; 6(6): 1379-1389, 2018 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-29652059

RESUMEN

Tumor-associated macrophages are highly versatile effector cells that have been used to kill tumor cells. Herein, the macrophages as cell-based biocarriers are used for the targeted delivery of photothermal reagents for promoting the efficiency of killing tumor cells by activating the anti-tumor immune response and photothermal therapy (PTT). In this design, macrophages cause the phagocytosis of tumor cells and activate the anti-tumor immune response by secreting plenty of cytokines. Meanwhile, to improve the tumor-killing effect and track the collaborative therapy system in vivo, a novel nanoplatform based on tungsten oxide (W18O49, WO) nanoparticles and fluorescent dyes loaded in polylactic-co-glycolic acid (PLGA) for PTT has been successfully constructed. Subsequently, the nanoparticles are swallowed by macrophages acting as cell-based biocarriers to target the tumor and promote solid tumor ablation in vivo in animal experiments. This system is expected to bring a huge application potential in the visually guided dual-modal therapeutic platform for tumor targeting therapy in vivo.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Colorantes Fluorescentes/administración & dosificación , Verde de Indocianina/administración & dosificación , Macrófagos/citología , Nanopartículas/administración & dosificación , Neoplasias/terapia , Óxidos/administración & dosificación , Tungsteno/administración & dosificación , Animales , Femenino , Colorantes Fluorescentes/uso terapéutico , Hipertermia Inducida/métodos , Verde de Indocianina/uso terapéutico , Ratones , Ratones Endogámicos C57BL , Nanopartículas/uso terapéutico , Neoplasias/diagnóstico por imagen , Neoplasias/patología , Imagen Óptica , Óxidos/uso terapéutico , Fagocitosis , Fototerapia/métodos , Nanomedicina Teranóstica , Tungsteno/uso terapéutico
4.
ACS Nano ; 11(9): 9103-9111, 2017 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-28853861

RESUMEN

Developing tumor-homing nanoparticles with integrated diagnostic and therapeutic functions, and meanwhile could be rapidly excreted from the body, would be of great interest to realize imaging-guided precision treatment of cancer. In this study, an ultrasmall coordination polymer nanodot (CPN) based on the coordination between tungsten ions (WVI) and gallic acid (W-GA) was developed via a simple method. After polyethylene glycol (PEG) modification, PEGylated W-GA (W-GA-PEG) CPNs with an ultrasmall hydrodynamic diameter of 5 nm were rather stable in various physiological solutions. Without the need of chelator molecules, W-GA-PEG CPNs could be efficiently labeled with radioisotope 64Cu2+, enabling positron emission tomography (PET) imaging, which reveals efficient tumor accumulation and rapid renal clearance of W-GA-PEG CPNs upon intravenous injection. Utilizing the radio-sensitizing function of tungsten with strong X-ray absorption, such W-GA-PEG CPNs were able to greatly enhance the efficacy of cancer radiotherapy in inhibiting the tumor growth. With fast clearance and little long-term body retention, those W-GA-PEG CPNs exhibited no appreciable in vivo toxicity. This study presents a type of CPNs with excellent imaging and therapeutic abilities as well as rapid renal clearance behavior, promising for further clinic translation.


Asunto(s)
Neoplasias de la Mama/radioterapia , Complejos de Coordinación/química , Radioisótopos de Cobre/química , Ácido Gálico/análogos & derivados , Nanopartículas/química , Polietilenglicoles/química , Tungsteno/química , Animales , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Complejos de Coordinación/farmacocinética , Complejos de Coordinación/uso terapéutico , Radioisótopos de Cobre/farmacocinética , Radioisótopos de Cobre/uso terapéutico , Femenino , Ácido Gálico/farmacocinética , Ácido Gálico/uso terapéutico , Riñón/metabolismo , Ratones , Nanopartículas/uso terapéutico , Polietilenglicoles/farmacocinética , Polietilenglicoles/uso terapéutico , Tomografía de Emisión de Positrones/métodos , Distribución Tisular , Tungsteno/farmacocinética , Tungsteno/uso terapéutico
5.
J Photochem Photobiol B ; 174: 10-17, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28750318

RESUMEN

The simultaneous imaging and photothermal therapy of tumors have attracted much attention, and a prerequisite is to obtain multifunctional nanomaterials. Ideally, one kind of nanoparticles with single component can be used as both imaging agent and photothermal agent. Herein, we have developed the PEGylated (NH4)xWO3 (denoted as (NH4)xWO3-PEG) nanorods as multifunctional nanoparticles with single semiconductor component. (NH4)xWO3-PEG nanorods with about 30nm diameter and length of several hundred nanometers have been obtained through a solvothermal synthesis-PEGylation two-step route. Under the irradiation of 980-nm laser with intensity of 0.72Wcm-2, aqueous dispersion of (NH4)xWO3-PEG nanorods (0.67-5.44mmol/L) displays high elevation (17.6-34.5°C) of temperature in 400s, accompanied by an excellent long-term photothermal stability. Furthermore, (NH4)xWO3-PEG nanorods exhibit as high as 6 times X-ray attenuation ability compared to that of the clinically used iodine-based X-ray computed tomography (CT) contrast agent (Iopromide). More importantly, after PBS solution of (NH4)xWO3-PEG nanorods is injected into the tumor of mice, the tumor can be effectively detected by CT imaging. Moreover, cancer cells in vivo can be further destroyed by the photothermal effects of (NH4)xWO3-PEG nanorods, under the irradiation of 980-nm laser with the safe intensity of 0.72Wcm-2 for 10min. Therefore, (NH4)xWO3-PEG nanorods can be used as a new kind of stable and efficient multifunctional nanoagent with single component for simultaneous CT imaging and photothermal therapy of tumor.


Asunto(s)
Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/terapia , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/terapia , Nanotubos , Óxidos/uso terapéutico , Fototerapia/métodos , Polietilenglicoles/química , Tomografía Computarizada por Rayos X/métodos , Tungsteno/uso terapéutico , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Animales , Transformación Celular Neoplásica , Estabilidad de Medicamentos , Células HeLa , Humanos , Neoplasias Pulmonares/patología , Ratones , Ratones Desnudos , Óxidos/química , Nanomedicina Teranóstica , Tungsteno/química
7.
Bauru; s.n; 2016. 94 p. ilus, tab.
Tesis en Portugués | LILACS, BBO - Odontología | ID: biblio-881415

RESUMEN

A atresia maxilar é um quadro de desarranjo de desenvolvimento do arco dentário presente em diversos tipos de má oclusão, desde as alterações transversais mais simples e puras até as formas mais graves, contemplando as divergências verticais e sagitais. O diagnóstico desta atresia, muitas vezes, é simplificado na presença ou não de mordida cruzada posterior, sendo ela unilateral ou bilateral. No entanto, faz-se necessário uma avaliação mais criteriosa que compreenda não só a própria alteração de forma do arco dentário, mas também as modificações oclusais subsequentes, como relação sagital de classe II ou III de Angle ou as discrepâncias verticais. Uma das possíveis formas de tratamento ortodôntico está ligada as expansões rápidas da maxila, método de incrementos ósseos por meio de forças ortopédicas, quando o indivíduo ainda apresenta potencial de crescimento craniofacial, ou seja, crianças e adolescentes. Já na vida adulta, esta possibilidade de ganhos ortopédicos não mais está presente e a opção não cirúrgica é o tratamento ortodôntico compensatório, por meio de expansão dentoalveolar do arco maxilar. O objetivo deste trabalho foi descrever os resultados de expansão dentoalveolar, obtidos utilizando-se o arco auxiliar de expansão em TMA (tungstênio, molibdênio e alloy), a partir de medidas lineares e angulares obtidas, bem como a integridade da cortical óssea vestibular desta área. Foi realizado um estudo retrospectivo de análise de tomografias computadorizadas, contidas na documentação ortodôntica de 13 pacientes tratados em uma clínica particular, realizadas antes e após a realização desta mecânica de expansão dentoalveolar. Para esta expansão, estes pacientes foram submetidos à instalação de um sobre-arco utilizado por vestibular como um arco auxiliar, sendo justaposto e unido ao fio de nivelamento principal (0,017x0,025 Termoativado) em cinco pontos, sendo 2 pontos nas entradas do tubo dos primeiros molares, 2 pontos entre os pré-molares e 1 ponto entre os incisivos centrais, por meio de fio de amarrilho 0,010 aço. Os resultados apresentaram ganhos estatisticamente significantes para aumento da distância das cúspides ao plano vertical mediano de todos os dentes medidos, bem como aumento da inclinação vestibular destes. A cortical óssea demonstrou adaptação, tendo deslocamento na mesma direção do movimento dentário, porém em menor quantidade. O aumento transversal das distâncias inter-dentárias também apresentou aumentos significativos e condizentes com a literatura. Desta forma, o arco auxiliar de expansão demonstrou-se eficiente para expansão dentoalveolar no paciente adulto, por meio de aumento da inclinação vestibular, com deslocamento dentário maior que o movimento de crista óssea, apresentado ganhos transversais significantes.(AU)


The Maxillary constriction is a developmental disorder present in various types of malocclusion, from the most simple and pure transverse changes to the most severe forms, causing vertical and sagittal problems. This malocclusion diagnosis is often simplified in the presence or not of posterior crossbite, which can be uni or bilateral. However, a complete evaluation must include not only the dental arch form changes, but also the subsequent occlusal modifications, such as sagittal relationships of Class II or III malocclusions and vertical discrepancies. Maxillary constriction treatment can be performed by rapid maxillary expansion, using orthopedic forces when there is still craniofacial growth. In adults, the possibility of orthopedic changes is no longer present and the non-surgical option is compensatory orthodontic treatment with dentoalveolar expansion, when the disorder magnitude allows. The objective of this study was to evaluate the effects of dentoalveolar expansion, obtained with a TMA (tungsten and molybdenum alloy) auxiliary expansion archwire, by means of linear and angular measurements, and the integrity of the buccal cortical bone in the posterior area. A retrospective analysis of CT scans, of orthodontic records of 13 patients treated at a private clinic, performed immediately before and after the auxiliary expansion archwire, was used. For the expansion, the patients underwent installation of a secondary arch combined with the primary archwire (0.017x0.025-inch heatactivated Ni-Ti), ligated in five points. Two points in the first molar tube entries, 2 points between the premolars and 1 point between the central incisors, with a 0.010- inch steel ligature wire. The results showed statistically significant transverse increase and buccal inclination for all teeth. The cortical bone showed adaptability and displacement in the same direction of tooth movement, but in smaller amounts. Thus, the auxiliary expansion arch wire proved to be effective to correct dentoalveolar constriction in adult patients, by increasing the buccal dental inclination with larger displacements than the bone crest adaptation and with significant transverse gains.(AU)


Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Proceso Alveolar/anatomía & histología , Maloclusión/terapia , Aparatos Ortodóncicos , Técnica de Expansión Palatina/instrumentación , Aleaciones/uso terapéutico , Molibdeno/uso terapéutico , Odontometría , Diseño de Aparato Ortodóncico , Valores de Referencia , Estudios Retrospectivos , Estadísticas no Paramétricas , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Tungsteno/uso terapéutico
8.
J Control Release ; 217: 211-20, 2015 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-26381897

RESUMEN

We report on dopamine-conjugated hyaluronic acid (HA-D), a mussel-inspired facile capping material that can modify tungsten oxide (WO3) nanoparticles to be both biocompatible and targetable, allowing precise delivery (WO3-HA) to a tumor site. Near-infrared (NIR) irradiated WO3-HA showed a rapid and substantial rise in photothermal heat to complete in vitro thermolysis of malignant MDAMB and A549 cancer cellsbut was found to be relatively less sensitive to normal MDCK cells. A long-term in vivo investigation of ~10 nm HA thickness on WO3 (WO3-HA) nanoparticles demonstrated efficient photo-thermal conversion with time-dependent tumor target accumulation. This long-termin vivo survival study ofWO3-HA showed promising biocompatibility, with a complete recovery from malignant tumor. Due to the importance of keeping simplicity in the design of therapeutic nanoparticles, we therefore expect that this facile scheme (HA-D) would contribute to the biocompatible development of versatile metallic nanoparticles for photothermal applications.


Asunto(s)
Dopamina/administración & dosificación , Ácido Hialurónico/administración & dosificación , Nanopartículas del Metal/administración & dosificación , Neoplasias/terapia , Óxidos/administración & dosificación , Fototerapia , Tungsteno/administración & dosificación , Animales , Línea Celular Tumoral , Supervivencia Celular , Perros , Dopamina/química , Dopamina/uso terapéutico , Humanos , Ácido Hialurónico/química , Ácido Hialurónico/uso terapéutico , Luz , Células de Riñón Canino Madin Darby , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Ratones Endogámicos BALB C , Óxidos/química , Óxidos/uso terapéutico , Tungsteno/química , Tungsteno/uso terapéutico
9.
Bol Asoc Med P R ; 106(1): 17-24, 2014.
Artículo en Español | MEDLINE | ID: mdl-24791359

RESUMEN

OBJECTIVE: Describe the outcomes of patients diagnosed with indirect carotid-cavernous fistula treated by endovascular methods. DESIGN: A retrospective case series. PARTICIPANTS: Twelve patients with dural cavernous sinus fistula with important ophthalmologic involvement admitted and treated at the National Institute of Neurology and Neurosurgery between February 1990 and January 2005. INTERVENTION: Patients were managed by endovascular embolization for all fistulas. OUTCOME MEASURES: Angiographic controls to 24 hours and at 6 and 12 months were performed. RESULTS: 67 % were female and 33 % male. The mean age was 44 years. 67 % were spontaneous and 33% of traumatic origin. All patients had eye involvement with proptosis (92%) and involvement of the oculomotor nerve (67%). Headache and pulsatile tinnitus were not frequent ophthalmologic data. All were diagnosed by cerebral angiography, 33 % were type C, type D 67 %, and none of the type B classification Barrow. In 17 % of cases the distal arterial robbery showed severe. Predominance of anterior and superior venous drainage in 83 % and 42 % of cases occurred respectively. The surgical approach was arterial in 84% of cases, while in 17 % venous through the superior ophthalmic vein. Cyanoacrylate embolization material was used in 58 % of the cases, as it was associated with the use of removable ball with polyvinyl alcohol particles in 16 % in of venous approach cases. 17% detachable coils were utilized. There were no complications. After angiographic controls at 24 hours 100% occlusion was seen in patients treated with cyanoacrylate (58%) (p = 0.03). The remaining 42% were prescribed maneuver of manual compression. At 12-months angiography all patients had 100% occlusion of the carotid-cavernous fistula. CONCLSUIONS: This is the world's second largest series with indirect carotid-cavernous fistulas treated after trauma. 100 % of cases were cured with the use of a transarterial-controlled approach and N-butyl-cyanoacrylate after long-term observation.


Asunto(s)
Arteria Carótida Interna , Seno Cavernoso , Malformaciones Vasculares del Sistema Nervioso Central/terapia , Embolización Terapéutica/métodos , Procedimientos Endovasculares/métodos , Adulto , Angioplastia de Balón/métodos , Arteria Carótida Externa , Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico por imagen , Malformaciones Vasculares del Sistema Nervioso Central/etiología , Angiografía Cerebral , Traumatismos Craneocerebrales/complicaciones , Enbucrilato/administración & dosificación , Enbucrilato/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Alcohol Polivinílico/administración & dosificación , Alcohol Polivinílico/uso terapéutico , Estudios Retrospectivos , Evaluación de Síntomas , Adhesivos Tisulares/administración & dosificación , Adhesivos Tisulares/uso terapéutico , Resultado del Tratamiento , Tungsteno/administración & dosificación , Tungsteno/uso terapéutico
10.
Dalton Trans ; 43(16): 6244-50, 2014 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-24598863

RESUMEN

Photothermal therapy (PTT) is limited by unsuitable photothermal agents and near-infrared (NIR) light. Herein, self-assembled PEGylated WO3-x hierarchical nanostructures, which could serve as excellent laser-cavity mirrors, were successfully prepared via a simple one-pot solvothermal route. The as-prepared WO3-x hierarchical nanostructures displayed strong near-infrared absorption. The absorption of pure water at 980 nm is 30 times higher than that at 915 nm, and the temperature of water only increased by 3.4 °C under the irradiation of a 915 nm laser with a power density of 1.0 W cm(-2) for 10 min, while the temperature of water increased as much as 15.1 °C for the 980 nm laser. With continuous excitation by 915 nm light, the photothermal conversion efficiency of these WO3-x hierarchical nanostructures was evaluated to be 28.1%. Thus, the WO3-x hierarchical nanostructures could serve as excellent laser-cavity mirrors of a 915 nm laser. The PTT study on cancer cells in vivo demonstrated that the WO3-x hierarchical nanostructures can generate enough heat for efficient photothermal therapy of cancer cells under the irradiation of a 915 nm laser with a power density of 1.2 W cm(-2) over a short period (5-10 min).


Asunto(s)
Nanoestructuras/uso terapéutico , Neoplasias/terapia , Óxidos/uso terapéutico , Fototerapia , Tungsteno/uso terapéutico , Animales , Línea Celular Tumoral , Humanos , Rayos Láser , Ratones , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Nanoestructuras/química , Nanoestructuras/ultraestructura , Neoplasias/patología , Óxidos/química , Polietilenglicoles/química , Temperatura , Tungsteno/química , Zinc/química
11.
AJNR Am J Neuroradiol ; 31(8): 1454-6, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20053805

RESUMEN

This study investigates the efficacy of chemonucleolysis using RGE in the treatment of cervical disk hernias in a small sample of patients who had cervical diskogenic or radicular pain secondary to disk herniations. Results were satisfactory in 89.5% patients, with no adverse events recorded during the procedure or after. The use of RGE shows promising results and might be a feasible and safe alternative in the treatment of cervical disk hernias.


Asunto(s)
Vértebras Cervicales , Etanol/uso terapéutico , Quimiólisis del Disco Intervertebral/métodos , Desplazamiento del Disco Intervertebral/terapia , Solventes/uso terapéutico , Medios de Contraste , Fluoroscopía , Geles/uso terapéutico , Humanos , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/patología , Imagen por Resonancia Magnética , Tungsteno/uso terapéutico
12.
Rofo ; 179(11): 1159-65, 2007 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-17926254

RESUMEN

PURPOSE: Primary and secondary hypervascularized liver tumors may be treated with transarterial chemoembolization (TACE). The purpose of this study was to experimentally quantify the effect of different chemoembolization materials on the PET activity concentration in PET/CT. MATERIALS AND METHODS: Different concentrations of lipiodol, tungsten, tantalum, and a different number of platinum coils embedded in a carrier substance were placed in a liver phantom. An insert filled with only the carrier substance served as the negative control. The liver phantom was placed in a body phantom. The liver phantom was filled with 63.3 KBq [18-F]-Fluor-2-deoxy-D-glucose (FDG)/ml water, the body phantom was filled with 19.7 KBq FDG/ml water. PET/CT was performed and PET attenuation correction was performed based on the CT data. We defined: Activity concentration over embolization material (kBq/ml) approximately measured activity concentration; activity concentration over negative control (kBq/ml) approximately real activity concentration. An overestimation of the activity concentration was quantified by the following ratio: Activity concentration overestimation = activity concentration over embolization material (kBq/ml)/activity concentration over negative control (kBq/ml). RESULTS: All chemoembolization materials led to an overestimation of the PET activity concentration when using CT information for PET attenuation correction. The extent of overestimation is dependent on the concentration and the density of the chemoembolizing agent. PET activity overestimation was 11-151% with lipiodol, 34-1827% with tungsten, 16-1205% with tantalum, and 4-29% with platinum coils. CONCLUSION: Conventional chemoembolization materials cause an overestimation of the PET activity concentration in CT-based attenuation-corrected PET/CT images. This is of importance for the clinical routine since activity concentration quantification may not be used in the presence of chemoembolizing agents for imaging follow-up. If an increased FDG uptake is detected after transarterial chemoembolization, non-attenuation-corrected PET images must be assessed in addition to the attenuation-corrected images in order to differentiate artificially increased tracer uptake from a true increase in activity concentration of the tracer. The use of non-attenuating chemoembolizing materials (e.g. drug-eluting beads) for TACE may serve as an alternative to avoid embolization-associated PET artifacts.


Asunto(s)
Quimioembolización Terapéutica/instrumentación , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Fluorodesoxiglucosa F18/farmacocinética , Humanos , Aceite Yodado/administración & dosificación , Aceite Yodado/uso terapéutico , Neoplasias Hepáticas/irrigación sanguínea , Fantasmas de Imagen , Estudios Retrospectivos , Tantalio/administración & dosificación , Tantalio/uso terapéutico , Tungsteno/administración & dosificación , Tungsteno/uso terapéutico
13.
Free Radic Biol Med ; 41(9): 1353-60, 2006 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-17023262

RESUMEN

Hyperlipidemia enhances xanthine oxidase (XO) activity. XO is an important source of reactive oxygen species (ROS). Since ROS are thought to promote atherosclerosis, we hypothesized that XO is involved in the development of atherosclerosis. ApoE(-/-) mice were fed a Western-type (WD) or control diet. In subgroups, tungsten (700 mg/L) was administered to inhibit XO. XO is a secreted enzyme which is formed in the liver as xanthine dehydrogenase (XDH) and binds to the vascular endothelium. High expression of XDH was found in the liver and WD increased liver XDH mRNA and XDH protein expression. WD induced the conversion of XDH to the radical-forming XO. Moreover, WD increased the hepatic expression of CD40, demonstrating activation of hepatic cells. Aortic tissue of ApoE(-/-) mice fed a WD for 6 months exhibited marked atherosclerosis, attenuated endothelium-dependent relaxation to acetylcholine, increased vascular oxidative stress, and mRNA expression of the chemokine KC. Tungsten treatment had no effect on plasma lipids but lowered the plasma XO activity. In animals fed a control diet, tungsten had no effect on radical formation, endothelial function, or atherosclerosis development. In mice fed a WD, however tungsten attenuated the vascular superoxide anion formation, prevented endothelial dysfunction, and attenuated KC mRNA expression. Most importantly, tungsten treatment largely prevented the development of atherosclerosis in the aorta of ApoE(-/-) mice on WD. Therefore, tungsten, potentially via the inhibition of XO, prevents the development of endothelial dysfunction and atherosclerosis in ApoE(-/-) mice on WD.


Asunto(s)
Apolipoproteínas E/fisiología , Aterosclerosis/prevención & control , Dieta , Inhibidores Enzimáticos/uso terapéutico , Tungsteno/uso terapéutico , Xantina Oxidasa/antagonistas & inhibidores , Animales , Apolipoproteínas E/genética , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/enzimología , Western Blotting , Ratones , Ratones Noqueados , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Superóxidos/metabolismo , Xantina Oxidasa/genética , Xantina Oxidasa/metabolismo
14.
Cardiovasc Revasc Med ; 6(2): 52-7, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16263359

RESUMEN

BACKGROUND: Intracoronary beta-radiation therapy reduces in-stent restenosis (ISR). We aimed to determine the safety and feasibility of intracoronary radiation therapy (IRT) utilizing tungsten (188W), a beta emitter. METHODS: A total of 30 patients with angiographic evidence of ISR in a previously treated native coronary artery underwent percutaneous coronary intervention (PCI; balloon angioplasty, ablation by atherectomy, or laser angioplasty). After the intervention, a noncentered delivery catheter with a side guide 0.014-in. wire carrying a tungsten (188W) coil, with an active length of 33 mm, was inserted. Patients were randomized to a radiation dose of 18, 22, or 25 Gy at 2 mm from the center of the source. Aspirin and Plavix, at 300 mg loading dose, were administered prior to intervention. Plavix 75 mg/day was prescribed for 6 months after the procedure. RESULTS: At 6 months follow-up, the overall binary angiographic restenosis rate was 18.8%. Target vessel revascularization (TVR) was 23% and target lesion revascularization related major adverse cardiac events (TLR-MACE) was 13.3%, without any intergroup differences. A comparison with the original Washington Radiation for In-stent restenosis Trial (WRIST) radiation cohort utilizing an 192Iridium source (prescription dose 15 Gy at 2 mm from the source) showed similar TVR and TLR-MACE rates of 30% and 18%, respectively. The TVR and TLR-MACE rates in the WRIST placebo cohort were 70% and 66%, respectively. CONCLUSIONS: Vascular brachytherapy with tungsten (188W) is feasible and safe. The 6-month clinical outcomes are similar to the original WRIST radiation group.


Asunto(s)
Braquiterapia/métodos , Oclusión de Injerto Vascular/radioterapia , Radioisótopos/uso terapéutico , Stents , Tungsteno/uso terapéutico , Antiinflamatorios no Esteroideos/administración & dosificación , Aspirina/administración & dosificación , Partículas beta/efectos adversos , Partículas beta/uso terapéutico , Clopidogrel , Estudios de Cohortes , Angiografía Coronaria/métodos , Relación Dosis-Respuesta en la Radiación , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Revascularización Miocárdica/métodos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Radioisótopos/efectos adversos , Ticlopidina/administración & dosificación , Ticlopidina/análogos & derivados , Resultado del Tratamiento , Tungsteno/efectos adversos
15.
Clin Exp Rheumatol ; 23(3): 345-50, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15971422

RESUMEN

OBJECTIVE: Arthritis is associated with increased articular formation of nitrotyrosine, which may contribute to injury. Nitrotyrosine is formed by nitration of tyrosine by reactive nitrogen species such as peroxynitrite, the formation of which may be enhanced by xanthine oxidoreductase (XOR), since it can generate nitric oxide from nitrite/nitrate, and superoxide during xanthine metabolism. We hypothesized that inactivation of XOR would protect against antigen-induced arthritis (AIA) and decrease nitrotyrosine formation. METHODS: AIA was induced with methylated bovine serum albumin (mBSA) in three groups of Wistar rats: animals fed on (1) tungsten-enriched chow (0.7 g/kg) (TG), which inactivates XOR, (2) standard chow (SG), and (3) rats treated with allopurinol (50 mg/kg/day; p.o.) (AG). Nitrotyrosine in patella-synovium was quantified by mass spectrometry three weeks after intra-articular (i.a.) antigen injection. RESULTS: Treatment with tungsten, but not allopurinol, suppressed plasma and articular XOR activity at < or = 0.9% of normal levels. XOR inactivation was associated with increased knee swelling 24-48 hrs post i.a. mBSA, compared with controls (mean increase +/- SEM of knee diameter from baseline of 3.3 +/- 0.5, 2.0 +/- 0.3 and 1.9 +/- 0.2 mm in TG, SG and AG (n = 14 each group), respectively; p < 0.05, TG vs SG, ANOVA). Mean ratio of articular nitrotyrosine-tyrosine (+/- SEM) was increased in the XOR-inactivated group, compared with controls: 12.3 +/- 0.7, 9.6 +/- 0.8 and 10.4 +/- 0.5 pg/microg in TG, SG and AG, respectively; p < 0.05, TG vs SG. CONCLUSION: Contrary to expectation, XOR inactivation was associated with increased joint swelling and articular tyrosine nitration in acute AIA, suggesting a novel, protective role for XOR in inflammatory arthritis.


Asunto(s)
Artritis Experimental/enzimología , Articulaciones/enzimología , Tirosina/análogos & derivados , Tirosina/metabolismo , Xantina Deshidrogenasa/antagonistas & inhibidores , Alopurinol/uso terapéutico , Animales , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Bovinos , Inhibidores Enzimáticos/uso terapéutico , Articulaciones/patología , Masculino , Radiografía , Ratas , Ratas Wistar , Albúmina Sérica Bovina/administración & dosificación , Rodilla de Cuadrúpedos/diagnóstico por imagen , Rodilla de Cuadrúpedos/efectos de los fármacos , Rodilla de Cuadrúpedos/patología , Membrana Sinovial/efectos de los fármacos , Membrana Sinovial/enzimología , Membrana Sinovial/patología , Tungsteno/uso terapéutico , Xantina Deshidrogenasa/metabolismo
16.
Phys Med Biol ; 47(20): 3605-27, 2002 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-12433123

RESUMEN

The radial depth-dose distribution of a prototype 188W/188Re beta particle line source of known activity has been measured in a PMMA phantom, using a novel, ultra-thin type of LiF:Mg,Cu,P thermoluminescent detector (TLD). The measured radial dose function of this intravascular brachytherapy source agrees well with MCNP4C Monte Carlo simulations, which indicate that 188Re accounts for > or = 99% of the dose between 1 mm and 5 mm radial distance from the source axis. The TLDs were calibrated using a 90Sr/90Y beta secondary standard. Several correction factors are calculated using analytical and Monte Carlo methods. An analysis of the measurement uncertainty is made. Since it is partly determined by components of uncertainty arising from random effects, repeated measurements yield a lower uncertainty. The expanded uncertainty in the absolute dose at 2 mm radial distance equals 11%, 10%, 9% and 8% for 1, 2, 3 and 5 measurements, respectively. After a correction for source non-uniformity, the measured dose rate per unit source activity at 2 mm radial distance equals (1.53 +/- 0.16) Gy min(-1) GBq(-1) (2sigma), in agreement with the value of (1.45 +/- 0.01) Gy min(-1) GBq(-1) (2sigma) predicted by the MCNP4C simulations.


Asunto(s)
Braquiterapia/instrumentación , Método de Montecarlo , Radioisótopos/uso terapéutico , Planificación de la Radioterapia Asistida por Computador/instrumentación , Dosimetría Termoluminiscente/instrumentación , Partículas beta/uso terapéutico , Braquiterapia/métodos , Simulación por Computador , Diseño de Equipo , Análisis de Falla de Equipo/métodos , Níquel , Fantasmas de Imagen , Proyectos Piloto , Polimetil Metacrilato , Dosis de Radiación , Planificación de la Radioterapia Asistida por Computador/métodos , Reproducibilidad de los Resultados , Renio/uso terapéutico , Sensibilidad y Especificidad , Dosimetría Termoluminiscente/métodos , Titanio , Tungsteno/uso terapéutico
17.
Phys Med Biol ; 45(5): 1319-34, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-10843107

RESUMEN

In this paper, we present results from three different simulation models that are used to determine the dose distribution around a 188W/188Re coronary brachytherapy source with EGS4 Monte Carlo simulations. The three models are found to give similar results within 10%. Agreement was found with experimental data from measurements in a PMMA phantom. It has been shown that in the therapeutically relevant region the beta line source can be characterized by the radial depth-dose distribution in water.


Asunto(s)
Braquiterapia/métodos , Angioplastia Coronaria con Balón , Fenómenos Biofísicos , Biofisica , Braquiterapia/estadística & datos numéricos , Vasos Coronarios/efectos de la radiación , Humanos , Modelos Teóricos , Método de Montecarlo , Fantasmas de Imagen , Polimetil Metacrilato , Radioisótopos/uso terapéutico , Renio/uso terapéutico , Tungsteno/uso terapéutico
18.
Med Phys ; 27(4): 668-75, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10798688

RESUMEN

PURPOSE: The objective was to determine the dosimetry of a potential endovascular brachytherapy source consisting of a coiled tungsten wire mounted on the distal end of a drive wire and neutron-activated to contain the parent-daughter nuclides tungsten-188 (188W) and rhenium-188 (188Re). METHODS: A coiled tungsten wire 40 mm in length was neutron-activated by double-neutron capture for 78 hours at 1.9 x 10(15) h/cm2/s to contain 925 MBq (25 mCi) of 188W/188Re in equilibrium. The dose-fall off from this source was determined using three independent methods: (a) Thermoluminescence dosimetry with small LiF-100 rods, (b) Gafchromic film dosimetry, and (c) Bang gel dosimetry. In addition, a Monte Carlo simulation was performed to compute the beta-dose. RESULTS: Each of the three measurement methods recorded similar values for the dose fall-off within the distances useful for endovascular brachytherapy. The Monte Carlo calculations closely approximated the measured results in the treatment range between 1 and 3 mm and may thus be useful for evaluating changing geometries in the development of catheters and source setups. A 2 min restenosis treatment delivering 20 Gy at a radius of 2 mm would require a source of 1384.8 MBq/cm (37.4 mCi/cm). CONCLUSIONS: The dose distribution from a 188W/188Re source is similar to that of a 90Y-source. An added advantage of the 188W/188Re source is that it can be used for at least two months and still provides fast treatment times because of the parent isotope's half-life of 69 days. The additional gamma emission from the source is too small to impose a serious radiological hazard. The high atomic number and density of the source material allows direct fluoroscopic imaging without additional markers.


Asunto(s)
Braquiterapia/métodos , Endotelio Vascular/efectos de la radiación , Radioisótopos/uso terapéutico , Radiometría/métodos , Renio/uso terapéutico , Dosimetría Termoluminiscente/métodos , Tungsteno/uso terapéutico , Partículas beta , Braquiterapia/instrumentación , Electrones , Dosimetría por Película/instrumentación , Dosimetría por Película/métodos , Fluoruros/química , Geles , Compuestos de Litio/química , Método de Montecarlo , Polímeros , Dosimetría Termoluminiscente/instrumentación
20.
Inflammation ; 16(1): 13-9, 1992 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-1544679

RESUMEN

Exposure to recombinant human tumor necrosis factor-alpha (TNF-alpha) or calcium ionophore (A23187) for 4 h increased (P less than 0.05) lactate dehydrogenase (LDH) release from cultured bovine brain endothelial cells (EC). In contrast, treatment with endotoxin or interleukin-1 did not increase (P greater than 0.05). LDH release from brain EC. Pretreatment with tungsten decreased (P less than 0.05) xanthine oxidase activity in brain EC and decreased (P less than 0.05) LDH release from brain EC following exposure to TNF. Our results suggest that TNF-alpha injures brain microvascular EC and that this effect may be mediated by xanthine oxidase.


Asunto(s)
Encéfalo/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Tungsteno/uso terapéutico , Animales , Encéfalo/metabolismo , Bovinos , Células Cultivadas , L-Lactato Deshidrogenasa/metabolismo , Xantina Deshidrogenasa/metabolismo , Xantina Oxidasa/metabolismo
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