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1.
Sci Rep ; 5: 8585, 2015 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-25717019

RESUMO

Low-frequency magnetic fields (LF-MF) generated by power lines represent a potential environmental health risk and are classified as possibly carcinogenic by the World Health Organization. Epidemiological studies indicate that LF-MF might propagate neurodegenerative diseases like Alzheimer's disease (AD) or amyotrophic lateral sclerosis (ALS). We conducted a comprehensive analysis to determine whether long-term exposure to LF-MF (50 Hz, 1 mT) interferes with disease development in established mouse models for AD and ALS, namely APP23 mice and mice expressing mutant Cu/Zn-superoxide dismutase (SOD1), respectively. Exposure for 16 months did not aggravate learning deficit of APP23 mice. Likewise, disease onset and survival of SOD1(G85R) or SOD1(G93A) mice were not altered upon LF-MF exposure for ten or eight months, respectively. These results and an extended biochemical analysis of protein aggregation, glial activation and levels of toxic protein species suggests that LF-MF do not affect cellular processes involved in the pathogenesis of AD or ALS.


Assuntos
Doença de Alzheimer/patologia , Esclerose Lateral Amiotrófica/patologia , Campos Magnéticos/efeitos adversos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Precursor de Proteína beta-Amiloide/metabolismo , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/psicologia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Proteínas de Ligação ao Cálcio/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Feminino , Proteína Glial Fibrilar Ácida , Masculino , Camundongos Transgênicos , Proteínas dos Microfilamentos/metabolismo , Microglia/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Estresse Oxidativo , Agregação Patológica de Proteínas/metabolismo , Aprendizagem Espacial , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1
2.
Clin Nucl Med ; 37(10): e245-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22899194

RESUMO

AIM: In somatostatin receptor-targeted therapy, renal toxicity is an expected side effect, and therefore pretherapeutic dosimetry based on a measured kinetics is preferable. In contrast, a convenient one single-time-point scan might also reveal relevant information on expected dose to organs. However, very early time points might not reflect the true retention by the renal cortex and therefore be of limited value to predict dose for the long-lived 177Lu. PATIENTS AND METHODS: Dosimetry with 111In-octreotide was performed in 24 patients, and the number of disintegrations (ND) were calculated for 177Lu. Uptake values for each time point were correlated with ND. RESULTS: The fitting algorithm was best with biexponential equations in 18 patients. Mean biologic half-life of the alpha component was 6 hours (+/-12 hours) and for the beta component 82 hours (+/-38 hours). For the early time points, correlation with ND was generally poor. For later time points, correlation increased markedly after 4 hours (4 hours: r = 0.83, 72 hours: r = 0.93) and were also capable of predicting dosimetry to some extent. CONCLUSION: In conclusion, thorough quantification of the 4 hours single-time-point scans seems to be enough to predict the expected renal dose for radionuclide therapies to some degree.


Assuntos
Rim/diagnóstico por imagem , Rim/metabolismo , Lutécio/efeitos adversos , Lutécio/metabolismo , Radioisótopos/efeitos adversos , Radioisótopos/metabolismo , Transporte Biológico , Feminino , Meia-Vida , Humanos , Rim/patologia , Rim/efeitos da radiação , Cinética , Lutécio/uso terapêutico , Masculino , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Tamanho do Órgão/efeitos da radiação , Radioisótopos/uso terapêutico , Radiometria , Cintilografia
3.
Am J Hum Biol ; 16(6): 697-703, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15495228

RESUMO

This study compared two different tetrapolar bioimpedance (BIA) devices for estimating body cell mass (BCM), validated them against whole-body counting of (40)K (TBK method), and developed improved prediction equations for estimating BCM from BIA. In 50 healthy volunteers (age 23-65 years, BMI 18.6-27.7 kg/m(2)), BCM was estimated with the BIA devices Nutriguard-M (Data Input, Germany) and Soft-Tissue-Analyzer-STA (Akern, Italy) and by the TBK method. Methods were compared by the Bland-Altman procedure. New prediction equations for BCM were developed by multiple stepwise regression analysis based on a single BIA parallel model. The Akern device gives similar mean estimates of BCM compared to the Data Input device in males (33.5 vs. 33.3 kg, P = 0.789), but higher values in females (24.6 vs. 22.8 kg; P < 0.001). Both BIA devices overestimate mean BCM relative to the TBK method; in males by 5.0 kg (Data Input, P < 0.001) and 5.1 kg (Akern, P < 0.001); in females by 2.3 kg (Data Input, P < 0.001) and 4.1 kg (Akern, P < 0.001). Limits of agreement between BIA and TBK methods are for males +/-4.99 kg (Data Input) and +/-7.16 kg (Akern); for females, +/-4.69 kg (Data Input) and +/-4.12 kg (Akern). New equations were developed for estimating BCM for both BIA analyzers (Data Input, R(2) = 0.91, SEE = 1.46 kg; Akern, R(2) = 0.90, SEE = 1.48 kg). Since estimates of BCM by the present BIA devices do not differ in males, they might be interchangeable. This does not hold true for females. Because both BIA devices overestimate BCM, the newly developed device-specific equations which reduce bias and limits of agreement should be applied.


Assuntos
Composição Corporal/fisiologia , Adulto , Fatores Etários , Idoso , Análise de Variância , Contagem de Células/métodos , Impedância Elétrica , Equipamentos e Provisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fatores Sexuais
4.
Eur J Nucl Med Mol Imaging ; 31(10): 1386-92, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15175836

RESUMO

PURPOSE: For the internal radiotherapy of neuroendocrine tumours, the somatostatin analogue DOTATOC labelled with 90Y is frequently used [90Y-DOTA-Phe1-Tyr3)-octreotide (SMT487-OctreoTher)]. Radiation exposure to the kidneys is critical in this therapy as it may result in renal failure. The aim of this study was to compare cumulative organ and tumour doses based upon dosimetric data acquired with the chemically identical 86Y-DOTA-Phe1-Tyr3-octreotide (considered as the gold standard) and the commercially available 111In-pentetreotide. METHODS: The cumulative organ and tumour doses for the therapeutic administration of 13.32 GBq 90Y-DOTA-Phe1-Tyr3-octreotide (three cycles, each of 4.44 GBq) were estimated based on the MIRD concept (MIRDOSE 3.1 and IMEDOSE). Patients with a cumulative kidney dose exceeding 27 Gy had to be excluded from subsequent therapy with 90Y-DOTA-Phe1-Tyr3-octreotide, in accordance with the directives of the German radiation protection authorities. RESULTS: The range of doses (mGy/MBq 90Y-DOTA-Phe1-Tyr3-octreotide) for kidneys, spleen, liver and tumour masses was 0.6-2.8, 1.5-4.2, 0.3-1.3 and 2.1-29.5 (86Y-DOTA-Phe1-Tyr3-octreotide), respectively, versus 1.3-3.0, 1.8-4.4, 0.2-0.8 and 1.4-19.7 (111In-pentetreotide), with wide inter-subject variability. Despite renal protection with amino acid infusions, estimated cumulative kidney doses in two patients exceeded 27 Gy. CONCLUSION: Compared with 86Y-DOTA-Phe1-Tyr3-octreotide, dosimetry with 111In-pentetreotide overestimated doses to kidneys and spleen, whereas the radiation dose to the tumour-free liver was underestimated. However, both dosimetric approaches detected the two patients with an exceptionally high radiation burden to the kidneys that carried a potential risk of renal failure following radionuclide therapy.


Assuntos
Tumores Neuroendócrinos/metabolismo , Octreotida/análogos & derivados , Octreotida/farmacocinética , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Medição de Risco/métodos , Somatostatina/análogos & derivados , Somatostatina/farmacocinética , Radioisótopos de Ítrio/farmacocinética , Carga Corporal (Radioterapia) , Feminino , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/radioterapia , Octreotida/uso terapêutico , Especificidade de Órgãos , Lesões por Radiação/prevenção & controle , Proteção Radiológica/métodos , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/uso terapêutico , Dosagem Radioterapêutica , Eficiência Biológica Relativa , Fatores de Risco , Somatostatina/uso terapêutico , Distribuição Tecidual , Radioisótopos de Ítrio/uso terapêutico
5.
J Am Geriatr Soc ; 50(1): 104-10, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12028254

RESUMO

OBJECTIVES: To cross-validate existing anthropometric and bioimpedance equations to establish their validity and accuracy for estimating intracellular water (ICW) in healthy older Germans and to develop a new equation with improved accuracy and precision for predicting ICW from multifrequency bioimpedance analysis (MFBIA). DESIGN: Cross-validation study. SETTING: University of Mainz. PARTICIPANTS: One hundred fifty-five healthy volunteers aged 60 to 80 years (77 men, 78 women; mean ages +/- standard deviation 67.7 +/- 4.8 and 68.6 +/- 5.5 years, respectively). MEASUREMENTS: ICW was measured by whole-body counting of (40)potassium ((40)K) ((40)K method) as the reference method and compared by cross-validation techniques against five existing bioimpedance and three anthropometric prediction equations. A new equation for estimating ICW from MFBIA was developed using the (40)K method as criterion method. RESULTS: Compared with the (40)K method, the existing bioimpedance and anthropometric equations showed large prediction errors in ICW estimates for older men (-32.3% to +37.7%) and women (-34.2% to +26.6%), depending significantly and positively on ICW volume and inversely on weight. A new equation for estimating ICW from MFBIA was developed (R(2)=0.933, standard error of the estimate (SEE)=0.92 L) involving phase angle at 5 kHz, impedance, height, and gender, with data from 100 subjects chosen at random. Cross-validation on an independent group (n=55, R(2)=0.958, SEE=0.68 L) showed no significant bias (0.013 +/- 1.52 L). CONCLUSIONS: Published bioimpedance and anthropometric prediction equations are not applicable to older Germans because they might be population-specific. The bioimpedance equation of the manufacturer of the bioimpedance analyzer used in this study provides accurate estimates of ICW for normal weight, but not overweight, older men. The newly developed equation improves accuracy and precision of ICW estimates by MFBIA.


Assuntos
Impedância Elétrica , Líquido Intracelular , Idoso , Idoso de 80 Anos ou mais , Antropometria , Feminino , Alemanha , Humanos , Masculino , Matemática , Obesidade , Radioisótopos de Potássio
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