RESUMO
Human undifferentiated thyroid carcinoma (UTC) is a very aggressive tumor which lacks an adequate treatment. The UTC human cell line ARO has a selective uptake of BPA in vitro and after transplanting into nude mice. Applications of boron neutron capture therapy (BNCT) to mice showed a 100% control of growth and a 50% histological cure of tumors with an initial volume of 50 mm(3) or less. As a further step towards the potential application in humans we have performed the present studies. Four dogs with diagnosis of spontaneous UTC were studied. A BPA-fructose solution was infused during 60 min and dogs were submitted to thyroidectomy. Samples of blood and from different areas of the tumors (and in one dog from normal thyroid) were obtained and the boron was determined by ICP-OES. Selective BPA uptake by the tumor was found in all animals, the tumor/blood ratios ranged between 2.02 and 3.76, while the tumor/normal thyroid ratio was 6.78. Individual samples had tumor/blood ratios between 8.36 and 0.33. These ratios were related to the two histological patterns observed: homogeneous and heterogeneous tumors. We confirm the selective uptake of BPA by spontaneous UTC in dogs and plan to apply BNCT in the future.
Assuntos
Compostos de Boro/farmacocinética , Compostos de Boro/uso terapêutico , Terapia por Captura de Nêutron de Boro/veterinária , Doenças do Cão/metabolismo , Doenças do Cão/radioterapia , Fenilalanina/análogos & derivados , Fenilalanina/farmacocinética , Fenilalanina/uso terapêutico , Neoplasias da Glândula Tireoide/veterinária , Animais , Doenças do Cão/patologia , Cães , Feminino , Humanos , Masculino , Camundongos , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia , Distribuição TecidualRESUMO
A study of the (10)B-enriched p-boronophenylalanine-fructose complex ((10)BPA-F) infusion procedure in potential BNCT patients, including four melanoma of extremities and two high-grade gliomas (glioblastoma and ganglioglioma) was performed. T/B and S/B ratios for (10)B concentrations in tumor (T), blood (B) and skin (S) were determined. The T/B ratio for the glioblastoma was in the 1.8-3.4 range. The ganglioglioma did not show any significant boron uptake. For the nodular metastasic melanoma T/B values were between 1.5 and 2.6 (average 2.1+/-0.4), corresponding to the lower limit of the mean values reported for different melanoma categories. This result might suggest a lower boron uptake for nodular metastasic melanomas. S/B was 1.5+/-0.4. An open two-compartment pharmacokinetic model was applied to predict the boron concentration during the course and at the end of a BNCT irradiation.
Assuntos
Compostos de Boro/farmacocinética , Compostos de Boro/uso terapêutico , Terapia por Captura de Nêutron de Boro , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/radioterapia , Frutose/análogos & derivados , Frutose/farmacocinética , Frutose/uso terapêutico , Melanoma/metabolismo , Melanoma/radioterapia , Adulto , Idoso , Argentina , Boro/sangue , Boro/farmacocinética , Feminino , Ganglioglioma/metabolismo , Ganglioglioma/radioterapia , Glioblastoma/metabolismo , Glioblastoma/radioterapia , Humanos , Masculino , Melanoma/secundário , Pessoa de Meia-IdadeRESUMO
A Phase I/II protocol for treating cutaneuos melanomas with BNCT was designed in Argentina by the Comisión Nacional de Energía Atómica and the medical center Instituto Roffo. The first of a cohort of thirty planned patients was treated on October 9, 2003. This article depicts the protocol-based procedure and describes the first clinical case, treatment regime and planning, patient irradiation, retrospective dosimetric analysis and clinical outcome. Considering the low acute skin toxicity and the complete response in 21 of the 25 subcutaneous melanoma nodules treated, a second irradiation was performed in a different location of the extremity of the same patient. The corresponding clinical outcome is still under evaluation.
Assuntos
Terapia por Captura de Nêutron de Boro , Frutose/análogos & derivados , Melanoma/radioterapia , Neoplasias Cutâneas/radioterapia , Argentina , Boro/sangue , Boro/farmacocinética , Compostos de Boro/farmacocinética , Compostos de Boro/uso terapêutico , Terapia por Captura de Nêutron de Boro/métodos , Protocolos Clínicos , Feminino , Frutose/farmacocinética , Frutose/uso terapêutico , Humanos , Melanoma/metabolismo , Melanoma/secundário , Pessoa de Meia-Idade , Planejamento da Radioterapia Assistida por Computador , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/secundário , Resultado do TratamentoRESUMO
Herein we propose and validate the hamster cheek pouch model of oral cancer for boron neutron capture therapy (BNCT) studies. This model serves to explore new applications of the technique, study the biology and radiobiology of BNCT, and assess the uptake of boron compounds and response of tumor, precancerous tissue, and clinically relevant normal tissues. These issues are central to evaluating and improving the therapeutic gain of BNCT. The success of BNCT is dependent on the absolute amount of boron in the tumor, and the tumor:blood and tumor:normal tissue boron concentration ratios. Within this context, biodistribution studies are pivotal. Tumors were induced in the hamsters with a carcinogenesis protocol that uses dimethyl-1,2-benzanthracene and mimics spontaneous tumor development in human oral mucosa. The animals were then used for biodistribution and pharmacokinetic studies of boronophenylalanine (BPA). Blood, tumor, precancerous pouch tissue surrounding tumor, normal pouch tissue, tongue, skin, cheek mucosa, palate mucosa, liver, and spleen, were sampled at 0-12 h after administration of 300 mg BPA/kg. The data reveal selective uptake of BPA by tumor tissue and, to a lesser degree, by precancerous tissue. Mean tumor boron concentration was 36.9 +/- 17.5 ppm at 3.5 h and the mean boron ratios were 2.4:1 for tumor:normal pouch tissue and 3.2:1 for tumor:blood. Higher doses of BPA (600 and 1200 mg BPA/kg) increased tumor uptake. Potentially therapeutic absolute boron concentrations, and tumor:normal tissue and tumor:blood ratios can be achieved in the hamster oral cancer model using BPA as the delivery agent.
Assuntos
Compostos de Boro/administração & dosagem , Terapia por Captura de Nêutron de Boro/métodos , Neoplasias Bucais/metabolismo , Neoplasias Bucais/radioterapia , Fenilalanina/análogos & derivados , Fenilalanina/administração & dosagem , Radiossensibilizantes/administração & dosagem , 9,10-Dimetil-1,2-benzantraceno , Animais , Boro/sangue , Boro/farmacocinética , Compostos de Boro/farmacocinética , Carcinógenos , Bochecha , Cricetinae , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Injeções Intraperitoneais , Injeções Intravenosas , Injeções Subcutâneas , Mesocricetus , Neoplasias Bucais/sangue , Neoplasias Bucais/induzido quimicamente , Fenilalanina/farmacocinética , Radiossensibilizantes/farmacocinética , Distribuição TecidualRESUMO
Two existing sequential chemical extraction schemes, involving respectively five and six leaching steps with solutions of increasing dissolving power, were compared. The methods have been applied to surface sediment samples collected in a marine estuary zone potentially exposed to contamination arising from nearby industrial activities. A certified reference material (MURST-ISS-A1) consisting of an Antarctic bottom sediment for which no information regarding phase dependent concentration is available, was also analyzed. In order to evaluate the partition of metals among different geochemical forms, the concentrations of cadmium, chromium, lead and zinc were measured in the liquid extracts by Zeeman-corrected flame atomic absorption and by inductively coupled plasma-atomic emission spectrometry. The total metal concentrations were determined after strong acid attack, and the adequacy of this total digestion/dissolution technique was verified by its application to the reference material. Comparison of total metal concentrations with the sum of concentrations associated with the individual phases was employed to assess possible analyte losses or contaminations. Precisions for both sequential procedures were comparable, but some inconsistencies in mass balances were found in one of the samples for the distribution of Zn in the soluble/exchangeable fractions and for Cd in the bound to carbonates form. In addition, the six steps procedure produced lower concentration values in the case of elements associated to the residual fraction. For the five steps method mass balances showed acceptable agreement, with average recoveries in the 87 to 106% range. On the whole, differences in metal distributions were observed, being more marked for the bottom sediment. Significant proportions of the studied elements, with the exception of Cr, were found as easily extractable forms. X-ray diffraction and petrographic observation of the surface sediments allowed qualitative correlation between the leaching results obtained and the presence of defined geochemical phases.
Assuntos
Sedimentos Geológicos/análise , Metais Pesados/análise , Poluentes Químicos da Água/análise , Argentina , Cádmio/análise , Cromo/análise , Chumbo/análise , Água do Mar/análise , Espectrofotometria Atômica , Difração de Raios X , Zinco/análiseRESUMO
The development of an analytical methodology for the specific determination of arsenite, arsenate and the organic species monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), is described. The method is based on an ion chromatographic separation, coupled on-line to post-column generation of the gaseous hydrides by reaction with sodium tetrahydroborate in acidic medium. Detection and measurement were performed by inductively coupled plasma spectrometry operated in the atomic emission mode. Arsenic emission was monitored at 193.7 nm. Different types and sizes of anion-exchange columns, silica and polymeric, were tested using EDTA as eluent. Composition, acidity and flow-rate of the mobile phase were optimized in order to obtain the required resolution. Complete elution and resolution of the four species was achieved in about 6 min. Linear calibration curves were obtained in the 0.05-2 microg ml(-1) range for As(III), As(V) and MMA, and between 0.1 and 2.0 microg ml(-1) for DMA. The absolute limits of detection for 200-microl sample injections were in the ng range, with DMA the compound measured with less sensitivity. Results of the analyses of natural samples, such as river and ground waters spiked with the studied species, suggested that analyte recoveries might be dependent on the sample composition.
Assuntos
Arsenicais/análise , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Água/química , Artefatos , Hidrogênio/química , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The simultaneous injection of volatile hydride species and hydrogen gas, originating in reagent decomposition, was monitored during the operation of a continuous hydride generation manifold employed for the determination of trace arsenic by HG-ICP-AES. Line and background intensities as well as the FWHM of the hydrogen Hgamma and Hdelta lines were measured, and electron number densities (ne) estimated from Stark broadening of the line profiles. Results were compared with those obtained by conventional pneumatic injection of aqueous solutions. Overlapping with atomic nitrogen lines at 410 nm and 411 nm tends to distort the Hdelta line profile for the hydrogen-seeded plasma, rendering unreliable results. The N I lines seem to be quenched by the presence of water aerosol. More consistent results were obtained with the Hgamma line. When no solutions are pumped through the hydride generation manifold ("dry" plasma), the measured ne value was (1.57 +/- 0.22) x 10(15)cm(-3). Conversely, when the reducing reagent flow was replaced by pure water (corresponding to the injection of water vapor in equilibrium that is swept by the argon carrier gas passing through the phase separator), the electron concentration is 25% higher. In that case the ne value agrees between the experimental error with that obtained for a plasma in which a water aerosol is introduced at a flow rate of 1 mL/min. An enhancement of 52% relative is observed in ne when the system is operated under optimized conditions for arsine generation, employing sodium tetrahydroborate in acidic medium as reducing agent (i.e. hydrogen seeded plasma). It was also observed that the continuum emission near 410 nm for the hydrogen containing plasma correlates with the measured electron number density, suggesting that the background enhancement under hydride generation conditions may respond to the ion-electron recombination mechanism.
RESUMO
The use of Eriochrome Black T in an alkaline, 40% methanol solution was found to be appropriate as post-column reagent for the determination of rare earths by ion chromatography. Detection of individual lanthanides and lanthanum was carried out at 512 nm and 650 nm after separation by dynamic cation exchange chromatography with gradient elution on C18 column and employing a solution containing alpha-hydroxyisobutiric acid/sodium octanesulfonate at pH 3.8 as eluent. The effect of the presence of micelles in the post-column reagent was studied. Sensitivities obtained by the addition of the cationic surfactants cetylpyridinium chloride (CPC) and hexadecyltrimethylammonium bromide (CTAB) were lower than those measured without surfactant addition. In some cases, the signal was totally suppressed. No change in sensitivity was observed with non-ionic (Triton X-100) or anionic (sodium dodecylsulphate, SDS) surfactants but a slight improvement in the baseline noise was observed with the SDS. An evaluation of the influence of chemical and operational variables on the post column reaction (PCR) reagent was carried out either by spectrophotometric tests or by chromatographic experiments. A comparison was performed between three PCR reagents: Eriochrome Black T and xylenol orange in the presence of a cationic surfactant and arsenazo III. Calibration response was linear up to an analyte concentration of 5.0 micrograms ml-1. Absolute detection limits lower than 7 and 17 ng were obtained at the detection wavelengths of 650 nm and 512 nm respectively, for all the natural lanthanides and lanthanum.
Assuntos
Compostos Azo/química , Cromatografia Líquida/métodos , Indicadores e Reagentes/química , Metais Terras Raras/análise , Íons , Sensibilidade e Especificidade , Análise EspectralRESUMO
Se midió magnesio (Mg++) sérico y musuclar en monos Cebus apella infectados con diferentes cepas de T. cruzi (CA1, Colombiana y Tulahuén). Los animales se dividieron en cuatro grupos: 1) control (n = 6); 2) CAI (n = 7); 3) Colombiana (n = 2), y 4) Tulahuén (n = 3), según el diseño experimental que se observa en la Tabla 1. En todos los grupos se realizó una biopsia del tensor faciae latae para determinar el Mg++ muscular mediante espectrofotometría de absorción atómica y simultáneamente se tomaron muestras de sangre de la vena femoral para medir magnesemia por complejación, durante la etapa crónica d ela enfermedad. No se observaron diferencias estadísticas, por análisis de varianza, entre los diferentes grupos (Tabla 2). Por lo tanto, podemos inferir que la enfermedad de Chagas no modifica per se los valores de Mg++ sérico y muscular