INTRODUÇÃO: A avaliação do mediastino quanto à presença de metástases linfonodais é importante na escolha do tratamento dos pacientes com câncer de pulmão de não pequenas células. Apesar da tomografia computadorizada ser o exame de imagem de escolha no estadiamento do câncer de pulmão, tem limitações conhecidas quanto à avaliação dos linfonodos regionais. O objetivo deste trabalho é avaliar a acurácia do SPECT/TC utilizando o radiofármaco 99mTc-sestamibi no estadiamento linfonodal do mediastino em pacientes com diagnóstico de carcinoma de pulmão de não pequenas células e candidatos a tratamento cirúrgico. MÉTODOS: Foi realizada coleta prospectiva de dados de 41 pacientes entre dezembro de 2006 a fevereiro de 2009. Os pacientes foram submetidos à tomografia computadorizada de tórax e ao SPECT/TC com 99mTc-sestamibi no prazo máximo de 30 dias antes da cirurgia. O SPECT/TC foi considerado positivo quando havia captação no mediastino e a tomografia de tórax, quando havia linfonodos maiores do que 10 mm no menor eixo. Os resultados da interpretação do SPECT/TC com sestamibi e da TC de tórax foram comparados aos encontrados na patologia, definido como método padrão ouro. RESULTADOS: O SPECT/TC identificou de maneira correta seis dos 19 casos com envolvimento dos linfonodos hilares e um dos sete casos com metástases ganglionares no mediastino pela patologia. Os valores de sensibilidade, especificidade, valores de predição positivo e negativo para o 99mTc-sestamibi SPECT/TC na avaliação do hilo foram respectivamente de: 31,6%, 95,5%, 85,7% e 61,8% e para o mediastino de 14,3%, 97,1%, 50% e 84,6%. A tomografia de tórax encontrou sensibilidade para a análise dos linfonodos hilares e mediastinais de 47,4% e 57,1%, especificidade de 95,5%, e 91,2%, valores de predição positivo de 90% e 57,1% e negativo de 67,7% e 91,2%, respectivamente. CONCLUSÃO: Nos pacientes com câncer de pulmão de não pequenas células com doença inicial e ressecável o SPECT/TC com 99mTc-sestamibi no estadiamento linfonodal do mediastino apresentou baixa sensibilidade e acurácia, apesar da alta especificidade. O SPECT/TC não adicionou informações relevantes à TC de tórax, que poderiam justificar o seu emprego no estadiamento pré-operatório do carcinoma de pulmão de não pequenas células / INTRODUCTION: The proper nodal staging of non-small cell lung cancer is important to choose the best treatment modality. Although CT is the first-line imaging test for primary staging of lung cancer, it is well known its limitations on mediastinum nodal staging. The aim was to evaluate the accuracy of SPECT/CT using 99mTc-sestamibi in the nodal staging of patients with non-small cell lung cancer and potential candidates towards surgical treatment. METHODS: A prospective data collection of 41 patients was conducted from December 2006 to February 2009. The patients underwent chest CT and SPECT/CT with 99mTc-sestamibi within 30 days interval before surgery. SPECT/CT was considered positive when there was focal uptake of sestamibi in the mediastinum and CT scan when there was lymph nodes larger than 10 mm in short axis. The results of SPECT/CT and CT were correlated with pathology findings after surgery. RESULTS: SPECT/CT correctly identified six of 19 cases with involvement of hilar lymph nodes and one of seven cases with nodal metastases in the mediastinum. The sensitivity, specificity, positive and negative predictive value for 99mTc-sestamibi SPECT/CT in the assessment of the hilum were respectively: 31.6%, 95.5%, 85.7% and 61.8% and for the mediastinum 14.3%, 97.1%, 50% and 84.6%. Chest tomography showed a sensitivity of hilar and mediastinal lymph nodes of 47.4% and 57.1%, specificity of 95.5% and 91.2%, positive predictive value of 90% and 57.1% and negative predictive value of 67.7% and 91.2%, respectively. CONCLUSION: SPECT/CT with 99mTc-sestamibi showed very low sensitivity and accuracy for nodal staging of patients with non-small cell cancer despite its high specificity. Moreover, the performance of SPECT/CT added no relevant information compared to CT that could justify its use in the routine preoperative staging of non-small cell lung carcinoma

Radionuclide molecular imaging is an emerging multidisciplinary technique that is used in modern medicine to visualise diseases at cellular and molecular levels. This thesis is based on five papers (I-V) and focuses on the development of site-specific radiolabelled recombinant anti-HER2 Affibody molecules and preclinical evaluations in vitro and in vivo of the labelled conjugates. This work is part of a preclinical development of an Affibody molecule-based tracer for molecular imaging of HER2 expressing tumours. Papers I and II report the evaluation of the Affibody molecule ZHER2:2395-C, site-specifically labelled with the radiometals 111In (for SPECT) and 57Co (as a surrogate for 55Co, suitable for PET applications) using a thiol reactive DOTA derivative as a chelator. Both conjugates demonstrated very suitable biodistribution properties, enabling high contrast imaging just a few hours after injection. Papers III and IV report the development and optimization of a technique for site-specific labelling of ZHER2:2395-C with 99mTc using an N3S chelating peptide sequence. 99mTc-ZHER2:2395-C demonstrated high and specific tumour uptake and rapid clearance of non-bound tracer from the blood, resulting in high tumour-to-non-tumour ratios shortly after injection, enabling high contrast imaging. In addition, in the study described in paper IV, freeze-dried kits previously developed for 99mTc-labelling were optimised, resulting in the development of a kit in which all the reagents and protein needed for labelling of ZHER2:2395-C with 99mTc were contained in a single vial. Paper V reports the evaluation of an anti-HER2 Affibody molecule, ABY-025, with a fundamentally re-engineered scaffold. Despite the profound re-engineering, the biodistribution pattern of 111In-ABY-025 was very similar to that of two variants of the parental molecule. It seems reasonable to believe that these results will also be applicable to Affibody molecules towards other targets. Hopefully, this work will also be helpful in the development of other small proteinaceous tracers.

Investigations in the 99mTc chemistry are stimulated by the search for new radiopharmaceuticals for nuclear medical applications. To understand the coordination mode of Tc with various complexing agents, macroscopic studies of technetium coordination chemistry are often performed using the low energy ß-emitting radionuclide 99Tc, which has a much longer half life (t1/2 = 2.12 x 105 years) than 99mTc, in the mg level. Investigations of Re coordination chemistry are done in conjunction with Tc studies because Re possesses chemical properties similar to those of Tc. For some chemical tasks, Re provides a non-radioactive alternative to work with Tc radioisotopes. In addition, 186Re and 188Re are of great interest to nuclear medicine as they possess nuclear properties favorable for use in therapeutic radiopharmaceuticals. Our investigations of Tc and Re coordination chemistry are toward this goal. A large series of technetium and rhenium complexes resulted from this studies have been characterized by X-ray crystal structure determinations. This survey covers the structural investigations performed by P.Leibnitz and G.Reck (BAM) from 1992 till now. It summarizes results obtained in the Rossendorf technetium group and is not intended to compete with the well-written reviews published so far.

Αντικείμενο της παρούσας διατριβής αποτελεί η μελέτη της απεικόνισης και ποσοτικοποίησής της με χρήση τεχνικών μοριακής απεικόνισης. Ένα νέο κυκλικό πεπτιδικό παράγωγο RGDfK (Arg-Gly-Asp-D‐Phe–Lys), το cRGDfK-Orn3-CGG, αξιολογήθηκε ως νέο μοριακό μέσο στόχευσης του καρκίνου μέσω της ειδικής στόχευσης των υποδοχέων ιντεγκρίνης ανβ3 που υπερεκφράζονται κατά την αγγειογένεση. Το νέο πεπτιδικό παράγωγο φέρει τον περιφερειακό υποκαταστάτη CGG (Cys-Gly-Gly), κατάλληλο για την επισήμανση με σύμπλοκα του πεντασθενούς 99mTc(V) καθώς και για την σύζευξη με νανοσωματίδια. Συγκεκριμένα, αναπτύχθηκαν σιδηρομαγνητικά νανοσωματίδια (10±2 nm) συζευγμένα με το νέο παράγωγο RGD, κατάλληλα τόσο για SPECT/MRI απεικόνιση όσο και για υπερθερμία. Ειδικότερα, αξιολογήθηκαν ως νέα μοριακά μέσα απεικόνισης: 99mΤc-RGD (cRGDfK-Orn3-CGG), 99mΤc-NPs και 99mΤc-NPs-RGD, αναφορικά με τα ραδιοχημικά, ραδιοβιολιγικά και in vivo απεικονιστικά χαρακτηριστικά τους. Τα επισημασμένα παράγωγα λήφθηκαν σε υψηλές αποδόσεις και παρουσίασαν ικανοποιητική σταθερότητα in vitro: α) με την πάροδο του χρόνου, β) σε παρουσία περίσσειας ανταγωνιστών για το 99mTc, γ) σε παρουσία ανθρωπίνου πλάσματος ή ορού. Η μελέτη της in vivo συμπεριφοράς, αλλά και η βιοκατανομή των νέων παραγώγων πραγματοποιήθηκε σε φυσιολογικούς μύες και σε παθολογικά πρότυπα καρκίνου τύπου γλοιοβλαστώματος U87MG. Η αξιολόγηση της χωροχρονικής κατανομής της αγγειογένεσης κατέδειξε μέγιστη στόχευση στις ιντεγκρίνες ανβ3 σε ποσοστό 11,60±3,05 % ID/g για το παράγωγο 99mTc-RGD και 9,01±0,19 ID/g για τα στοχευμένα νανοσωματίδια 99mTc-NPs-RGD. Το 99mTc-RGD σχεδιάστηκε κατάλληλα ώστε να αποβάλλεται από τον οργανισμό μέσω του ουροποιητικού συστήματος, με την προσθήκη του υδρόφιλου μορίου ορνιθίνης (Orn3) στη δομή του. Ενώ, τα 99mTc-NPs αποβάλλονται κυρίως μέσω του ηπατοχολικού συστήματος, τα στοχευμένα 99mTc-NPs-RGD παρουσιάζουν χαμηλότερη πρόσληψη στο ήπαρ και υψηλότερη πρόσληψη στους νεφρούς, η οποία μπορεί να αποδοθεί στην πρόσδεση του RGD παραγώγου στην επιφάνεια των NPs. Ικανοποιητικές απεικονίσεις των όγκων ελήφθησαν και με τα επισημασμένα παράγωγα 99mTc-RGD και 99mΤc-NPs. Τέλος, η in vivo αξιολόγηση της θερμικής απόκρισης των NPs ανέδειξε ικανοποιητικά αποτελέσματα, με αντικαρκινική δράση σε πειραματόζωο που φέρει U87MG όγκο. Τα παραπάνω αρχικά αποτελέσματα οδηγούν στο συμπέρασμα ότι τα στοχευμένα νανοσωματίδια είναι πολλά υποσχόμενα στο πεδίο της μοριακής απεικόνισης για τον ποσοτικό προσδιορισμό της χωροχρονικής κατανομής της αγγειογένεσης με στόχο τη διάγνωση αλλά και τη θεραπευτική προσέγγιση. / The aim of the present project is the in vivo evaluation of quantitative monitoring of angiogenesis making use of the molecular imaging methodology. A new cyclic RGDfK (Arg-Gly-Asp-D‐Phe–Lys) derivative, namely the cRGDfK-Orn3-CGG, was evaluated as eventually promising in early tumor detection through specifically targeting integrin ανβ3 receptors, overexpressed in angiogenesis. This new peptide, availing the 99mTc-chelating moiety CGG (Cys-Gly-Gly), is appropriately designed for 99mTc-labeling, as well as consequent conjugation onto nanoparticles. Specifically, RGD-conjugated iron oxide nanoparticles (10±2 nm) have been developed appropriately for SPECT/MRI imaging and hyperthermia treatment. Particularly, they were evaluated as tumor imaging agents: 99mΤc-RGD (cRGDfK-Orn3-CGG), 99mΤc-NPs and 99mΤc-NPs-RGD. The new derivatives were examined with regard to their radiochemical, radiobiological and imaging characteristics. It has been demonstrated that they were obtained in high radiochemical yield and presented high in vitro stability being examined: a) at different time-points, b) in the presence of an excess of antagonist moites for 99mTc, c) in human plasma or serum. The in vivo study and the biodistribution evaluation of radiolabeled products were assessed in normal mice and in pathological models (scid mice) bearing experimental U87MG glioblastoma tumors. Τhe quantitative evaluation of angiogenesis spatial distribution confirmed high specific binding of the 99mTc-RGD peptides to ανβ3 integrins, with significantly high tumor uptake 11.60±3.06 % ID/g, while targeting with 99mTc-NPs-RGD demonstrates high tumor uptake 9.01±0.19 ID/g. The 99mTc-RGD was appropriately designed to have urine excretion due to the ornithine (Orn3) linker, while the 99mTc-NPs exhibits hepatobiliary excretion, compared to 99mTc-NPs-RGD, which exhibit lower values of liver uptake with a significantly higher kidney uptake, which can be attributed to the attachment of the RGD derivative on the surface of NPs. Satisfactory tumor images were obtained with the radiolabeled derivatives 99mTc-RGD and 99mΤc-NPs. Finally, the in vivo heating efficiency experiment showed that hyperthermia induction with the aid of iron oxide NPs was feasible, resulting to anti-tumor effect in a U87MG tumor-bearing mouse. The above preliminary results indicate that targeted iron oxide NPs are promising candidates for the quantitative monitoring of angiogenesis for molecular imaging and potential cancer therapy.

Made available in DSpace on 2015-07-22T20:50:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-01-28. Added 1 bitstream(s) on 2015-08-11T03:25:36Z : No. of bitstreams: 1 Publico-031a.pdf: 1380064 bytes, checksum: a39cd3315496717421b8559fdaf9abc1 (MD5). Added 1 bitstream(s) on 2015-08-11T03:25:36Z : No. of bitstreams: 2 Publico-031a.pdf: 1380064 bytes, checksum: a39cd3315496717421b8559fdaf9abc1 (MD5) Publico-031b.pdf: 482011 bytes, checksum: 260e81c2a0b890366702213b55e9c097 (MD5). Added 1 bitstream(s) on 2015-08-11T03:25:36Z : No. of bitstreams: 3 Publico-031a.pdf: 1380064 bytes, checksum: a39cd3315496717421b8559fdaf9abc1 (MD5) Publico-031b.pdf: 482011 bytes, checksum: 260e81c2a0b890366702213b55e9c097 (MD5) Publico-031c.pdf: 2097879 bytes, checksum: 4bc50a710c97b4814bc74f0720170504 (MD5) / Fundamentos: isquemia miocárdica pode ocorrer durante uma sessão de atividade física em programa de reabilitação cardiovascular. Não está descrito, no entanto, se ela pode ser desenvolvida quando da prescrição de exercício com base na freqüência cardíaca correspondente ao Iimiar anaeróbico ventilatório obtido pelo teste cardiopulmonar. Objetivos: verificar a ocorrência de isquemia miocárdica na prescrição de exercício com base no limiar anaeróbico ventilatório em programa de reabilitação cardiovascular, utilizando a cintilografia miocárdica. Métodos: foram avaliados 39 coronariopatas (35 homens e 4 mulheres) com idade entre 45 e 75 anos (media=59,76) com diagn6stico de doença comprovada por cinecoronariografia e cintilografia miocárdica de esforço com MIBI_99mTc pela técnica Gated-Spect associada a um primeiro teste cardiopulmonar. Um segundo teste foi realizado para estabelecer a intensidade de treinamento no limiar. Nova cintilografia foi obtida durante um terceiro teste, com dura<;ao de 20 minutos, na carga e freqüência cardíaca prescrita, correspondendo a fase aer6bica continua de uma sessão de reabilita<;ao cardiovascular. Resultados: as cintilografias de perfusão miocárdica analisadas por escores revelaram valores de repouso de 6,4; do pica do esforço 13,9 e de 10,7 durante 0 exercício prescrito, com diferenças estatisticamente significativas entre eles (p<0,05). A presença de isquemia miocárdica durante 0 exercício foi definida pela diferença ≥2 entre 0 escore de esforço e 0 escore de repouso. Dessa maneira, 25 (64%) pacientes foram classificados como isquêmicos e 14 (36%) em não isquêmicos. Somente 7 (18%) pacientes apresentaram alterações eletrocardiográficas isquêmicas e 2 (5,12%) angina do peito durante 0 exercício prescrito. Conclusão: a cintilografia miocárdica com MIBI_99mTc evidenciou que a aplicação de exercícios, com base no limiar anaeróbico ventilatório, pode produzir isquemia miocárdica em pacientes com coronariopatia. A ocorrência de angina do peito e as alterações eletrocardiográficas isquêmicas foram indicadores pouco sensíveis de isquemia durante sessão de exercícios em programa de reabilitação cardiovascular nesta população. A prevalência de 64% de isquemia observada no estudo não deve ser interpretada como uma representatividade da população de pacientes que são submetidos a programa de exercício. As alterações no cuidado do paciente e no programa de exercício foram implementadas como resultado dos nossos achados (isquemia durante exercício prescrito). / Background: Myocardial ischemia may occur during an exercise session in cardiac rehabilitation programs. However, it has not been established whether it is elicited when exercise prescription is based on heart rate corresponding to the anaerobic threshold as measured by cardiopulmonary exercise testing. Objectives: To assess the incidence of myocardial ischemia in cardiac rehabilitation programs according to myocardial perfusion SPECT in exercise programs based on the anaerobic threshold. Methods: Thirty-nine patients (35 men and 4 women) diagnosed with coronary artery disease by coronary angiography and stress technetium-99msestamibi gated SPECT associated with a baseline cardiopulmonary exercise test were assessed. Ages ranged from 45 to 75 years. A second cardiopulmonary exercise testing determined training intensity at the anaerobic threshold. Repeat gated-SPECT was obtained after a third cardiopulmonary exercise testing at the prescribed workload and heart rate. Results: Myocardial perfusion images, analyzed using a score system: 6.4 at rest, 13.9 at peak stress, and 10.7 during the prescribed exercise (p<0.05). The presence of myocardial ischemia during exercise was defined as a difference ³ 2 between the summed stress score and summed rest score. Accordingly, 25 (64%) patients were classified as ischemic and 14 (36%) as nonischemic. Conclusion: MIBI-SPECT has shown myocardial ischemia during exercise within the anaerobic threshold. The 64% prevalence of ischemia observed in the study should not be looked on as representative of the whole population of patients undergoing exercise program. The changes in patient care and exercise program were implemented as a result of our findings (ischemia during the prescribed exercise). / TEDE / BV UNIFESP: Teses e dissertações

Made available in DSpace on 2014-10-09T12:32:29Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:10:15Z (GMT). No. of bitstreams: 1 03182.pdf: 1972055 bytes, checksum: 9981ae33d320ed8dd71a0aaa2f020331 (MD5) / Tese(Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Made available in DSpace on 2014-12-17T14:13:33Z (GMT). No. of bitstreams: 1 MonicaOB.pdf: 219560 bytes, checksum: 3e717232b47facd68d9fede60401e898 (MD5) Previous issue date: 2007-12-05 / Radiobiocomplexes are used to obtain images in nuclear medicine and employed in basic research. Blood constituents labeled with technetium-99m (99mTc) have also been employed as radiobiocomplexes and used also experimental model for evaluation of the biological effects of natural or synthetic drugs. The analysis of the morphology and the morphometrics parameters (perimeter/?rea ratio) can be used to evaluate the effects of drugs upon the structure of the membrane of red blood cells. Cinnamomum zeylanicum (cinnamon) is a spice used as herbal medicine to treat diseases. The aim of this study was to evaluate the effect of in vitro and in vivo treatment with an aqueous cinnamon extract on the labeling of blood constituents with 99mTc and on the morphology of red blood cells from Wistar rats. In the in vitro treatment, isolated blood sample from animals were incubated with cinnamon extract. In the in vivo treatment, blood samples were also withdrawn from animals treated with cinnamon extract. In both cases, the radiolabeling of blood constituents was done. The morphological analysis of red blood cells was also done. As control, blood or animals treated with NaCl 0.9%. The data obtained on the labeling of blood constituents with 99mTc experiments indicated that the in vitro treatment with cinnamon extract was capable to decrease signiicantly (p<0.05) the percentage of radioactivity in cellular compartments and on the fixation of cellular and plasma proteins. These effects were not observed on the in vivo treatment. The results obtained for the morphology of red blood cells suggest that the in vitro and in vivo treatments did not alter the morphology and the perimeter/area ratio. The in vitro treatment with aqueous cinnamon extract could affect the membrane structures related with the oxidation status of the stannous ion pertechnetate ion, altering the labeling of blood constituentes with 99mTc. This study was a multidisciplinary experimental research. It was developed with the contribution of the different Departments and Services of the Hospital Universit?rio Pedro Ernesto of the Universidade do Estado do Rio de Janeiro / Radiobiocomplexos s?o utilizados para obten??o de imagens em medicina nuclear e empregados na pesquisa b?sica. Constituintes sang??neos marcados com tecn?cio-99m t?m sido empregados como radiobiocomplexos e utilizados como modelo experimental para avalia??o de efeitos biol?gicos de drogas naturais ou sint?ticas. A an?lise da forma e de par?metros morfom?tricos (rela??o per?metro/?rea) pode ser usada para avaliar os efeitos de drogas sobre a estrutura da membrana de hem?cias. Cinnamomum zeylanicum (canela) ? uma especiaria usada como planta medicinal para tratar doen?as. O objetivo desse estudo foi avaliar efeitos de um extrato aquoso de Cinnamomum zeylanicum na marca??o de constituintes sangu?neos com tecn?cio-99m e na morfologia de hem?cias de ratos Wistar. No tratamento in vitro, amostras de sangue de animais foram isoladas e incubadas com um extrato de canela. No tratamento in vivo, animais foram tratados com um extrato de canela e amostras de sangue foram isoladas. Em ambas as situa??es foram realizadas a radiomarca??o de constituintes sangu?neos e a an?lise morfol?gica. Como controle, o sangue ou os animais foram tratados com cloreto de s?dio 0,9%. Os dados obtidos nos experimentos de marca??o de constituintes sang??neos com tecn?cio-99m indicaram que o tratamento in vitro com extrato de canela foi capaz de diminuir significativamente (p<0,05) a porcentagem de radioatividade nos compartimentos celulares e na fixa??o das prote?nas celulares e plasm?ticas. Esses efeitos n?o foram observados no tratamento in vivo. Os resultados obtidos na morfologia de hem?cias sugerem que os tratamentos in vitro e in vivo n?o alteram a forma nem a raz?o per?metro/?rea. O tratamento in vitro com o extrato aquoso de canela poderia afetar estruturas da membrana celular relacionadas ao transporte de ?ons ou ao estado de oxida??o do ?on estanoso ou do ?on pertecnetato, alterando a marca??o de constituintes sang??neos com tecn?cio-99m. Esse estudo ? uma pesquisa experimental com car?ter multidisciplinar. Foi desenvolvido em colabora??o com diferentes Departamentos e Servi?os da ?rea biom?dica do Hospital Universit?rio Pedro Ernesto, UERJ, atestando o car?ter multidisciplinar da pesquisa

Made available in DSpace on 2014-12-17T14:13:34Z (GMT). No. of bitstreams: 1 AdalgisaIM.pdf: 212398 bytes, checksum: 91a56cbfe357d683d0b60cf3fa34bf87 (MD5) Previous issue date: 2007-08-14 / Medicinal plants have been studied and used in the world. Lantana camara has medicinal properties and it has been used in folk medicine. The aim was to verify the effect of a lantana extract on the labeling of blood constituents with 99mTc, and to evaluate the effect of an aqueous extract of Lantana camara on the morphology of RBC withdrawn from Wistar rats. The results showed that lantana extract has decreased the fixation of radioactivity on the IF-P. This effect was not observed in the BC compartment and in IF-BC. The BC-%ATI was decreased in all concentrations tested when the BC was washed. The osmotic fragility assay and morphological analysis were carried out. In presence of the extract, the data obtained indicated that (i) an increase of the hemolysis and (ii) modifications on the morphology of RBC. These effects of the Lantana camara could be associated with some pharmacological properties of the chemical compounds of this studied extract / Extratos de plantas medicinais s?o utilizados amplamente em todo o mundo. Entretanto, efeitos biol?gicos associados aos mesmos n?o t?m sido investigados exaustivamente. Atrav?s do uso de suas folhas e flores a Lantana camara (Cambar? de espinho) tem sido usado para tratamento de v?rias doen?as na medicina popular. O presente estudo teve como objetivo verificar o efeito do extrato desta planta na marca??o de constituintes sang??neo com tecn?cio 99m, bem como a morfologia de hem?cias de ratos Wistar. Os resultados mostraram que o extrato de Lantana camara acarretou uma diminui??o de fixa??o de radioatividade na fra??o insol?vel do plasma. Este efeito n?o foi observado na c?lula e nem na fra??o insol?vel da c?lula. O percentual de atividade teve diminui??o em todas as concentra??es quando as c?lulas foram lavadas, o que n?o foi observado com o controle. O extrato estudado aumentou a fragilidade osm?tica das hem?cias e modificou a morfologia dessas c?lulas. Os efeitos do extrato de Lantana camara podem estar associados a algumas propriedades farmacol?gicas de componentes qu?micos do extrato estudado. O estudo teve car?ter multidisciplinar com a participa??o das seguintes ?reas do conhecimento: Radiobiologia, Bot?nica, Fitoterapia e Hematologia

Made available in DSpace on 2014-12-17T14:13:49Z (GMT). No. of bitstreams: 1 MarciaOP_DISSERT.pdf: 660946 bytes, checksum: 587d1049df3f129a5c11e9b6394de8fc (MD5) Previous issue date: 2010-08-31 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Derivatives of propionic acid NSAIDs are irreversible inhibitors of cyclooxygenase enzyme widely used. The aim of this study was to evaluate, through different experimental models, biological effects of derivatives of propionic acid (fenoprofen, naproxen, ibuprofen and ketoprofen) in cellular and molecular level. The labeling of blood constituents with technetium-99m (99mTc) and morphological analysis of erythrocytes of blood of rats, as well as growth, survival of cultures of Escherichia coli (E. coli) and the assessment of bacterial plasmid electrophoretic profiles were models used for experimental evaluation of possible biological effects of antiinflammatory drugs. The results show that, in general, anti-inflammatory drugs evaluated were not able to alter the labeling of blood constituents with 99mTc, the morphology of red blood cells from blood of rats, as well as the growth of cultures of E. coli and the electrophoretic profile of plasmid DNA. However, naproxen appears to cytotoxic effect on bacterial cultures, plasmids and genotoxic effects in reducing the action of stannous chloride in cultures of E. coli. The use of experimental fast performance and low cost was important for assessment of biological effects, contributing to a better understanding of the properties of propionic acid derivatives studied. anti-inflammatory, blood constituents, technetium-99m, stannous chloride, Escherichia coli; DNA / Os derivados do acido propi?nico s?o antiinflamat?rios n?o esteroidais inibidores irrevers?veis da enzima cicloxigenase amplamente utilizados. O objetivo deste trabalho foi avaliar, atrav?s de diferentes modelos experimentais, efeitos biol?gicos de derivados do ?cido propi?nico (fenoprofeno, naproxeno, ibuprofeno e cetoprofeno) em n?vel celular e molecular. A marca??o de constituintes sangu?neos com tecn?cio 99m (99mTc) e a an?lise morfol?gica de hem?cias de sangue de ratos Wistar, bem como, o crescimento, sobreviv?ncia de culturas de Escherichia coli (E. coli) e a avalia??o do perfil eletrofor?tico plasm?dios bacterianos, foram modelos experimentais utilizados para avalia??o de poss?veis efeitos biol?gicos dos antiinflamat?rios. Os resultados obtidos demonstram que, de modo geral, os antiinflamat?rios avaliados n?o foram capazes de alterar a marca??o de constituintes sangu?neos com 99mTc, a morfologia de hem?cias de sangue de ratos Wistar, assim como, o crescimento de culturas de E. coli e o perfil eletrofor?tico de plasm?dios. Entretanto, o naproxeno parece apresentar efeito citot?xico em culturas bacterianas, efeito genot?xico em plasm?dios e diminui??o da a??o do cloreto estanoso em culturas de E. coli. A utiliza??o de modelos experimentais de r?pida realiza??o e baixo custo se mostrou importante para avalia??o de efeitos biol?gicos, contribuindo para uma melhor compreens?o das propriedades dos derivados do ?cido propi?nico estudados. Esse trabalho teve car?ter multidisciplinar e na vig?ncia dos aux?lios concedidos pela CAPES, FAPERJ e CNPq

Made available in DSpace on 2014-10-09T12:32:29Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:10:15Z (GMT). No. of bitstreams: 1 03182.pdf: 1972055 bytes, checksum: 9981ae33d320ed8dd71a0aaa2f020331 (MD5) / Tese(Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP