864 resultados para Antineoplastic Combined Chemotherapy Protocols -- therapeutic use


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BACKGROUND: Dextran-40 is effective in reducing postoperative Doppler-detectable embolization in patients undergoing carotid endarterectomy (CEA). Dextrans are thought to have antithrombotic and antiplatelet effects. The mode of action is unclear. In rats, dextran blocks uptake of tissue plasminogen activator (tPA) by mannose-binding receptors. Because this would have the effect of enhancing endogenous fibrinolysis, we explored this effect of dextran-40 on fibrinolysis in man. METHODS: Twenty patients undergoing endovascular stenting for abdominal aortic aneurysm were randomized to receive 100 mL of 10% dextran-40 or saline, over 1 hour, during their operation in addition to heparin. Blood samples were taken preoperatively, intraoperatively (immediately after operative procedure), and 24 hours postoperatively. Thrombi were formed in a Chandler loop and used to assess endogenous fibrinolysis over 24 hours, measured as the fall in thrombus weight, and the release of fluorescently labelled fibrinogen from the thrombus. Plasma samples were analyzed for markers of fibrinolysis; plasmin-antiplasmin (PAP), PAI-1, and t-PA, and for functional von Willebrand factor (vWF). Platelet response to thrombin and other agonists was measured by flow cytometry. RESULTS: Thrombi formed ex vivo from the intraoperative blood samples from the dextran-treated patients exhibited significantly greater fibrinolysis vs preoperative samples, seen both as a significantly greater percentage reduction in thrombus weight (from 34.7% to 70.6% reduction) and as an 175% increase in the release of fluorescence (P < .05). Fibrinolysis returned to baseline levels the next day. No change was seen in the saline-treated group. Plasma levels of PAP and PAI-1 increased significantly postoperatively in the dextran-treated group vs the saline group (P < .05). The postoperative level of functional VWF was significantly lower in the dextran-treated group vs controls. A specific reduction occurred in the platelet response to thrombin, but not to other agonists, in the intraoperative samples from the dextran-treated group (11.1% vs 37.1%; P = .022), which was not seen in the controls. CONCLUSIONS: These data are consistent with a rise in plasmin due to dextran blockade of tPA uptake in vivo, leading to enhanced fibrinolysis, cleavage of vWF and of the platelet protease-activated receptor-1 (PAR-1) thrombin receptor. This suggests that dextran exerts a combined therapeutic effect, enhancing endogenous fibrinolysis, whilst also reducing platelet adhesion to vWF and platelet activation by thrombin. The proven antithrombotic efficacy of low-dose dextran in carotid surgery may be applicable to wider therapeutic use.

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1. Species’ distributions are likely to be affected by a combination of environmental drivers. We used a data set of 11 million species occurrence records over the period 1970–2010 to assess changes in the frequency of occurrence of 673 macro-moth species in Great Britain. Groups of species with different predicted sensitivities showed divergent trends, which we interpret in the context of land-use and climatic changes. 2. A diversity of responses was revealed: 260 moth species declined significantly, whereas 160 increased significantly. Overall, frequencies of occurrence declined, mirroring trends in less species-rich, yet more intensively studied taxa. 3. Geographically widespread species, which were predicted to be more sensitive to land use than to climate change, declined significantly in southern Britain, where the cover of urban and arable land has increased. 4. Moths associated with low nitrogen and open environments (based on their larval host plant characteristics) declined most strongly, which is also consistent with a land-use change explanation. 5. Some moths that reach their northern (leading edge) range limit in southern Britain increased, whereas species restricted to northern Britain (trailing edge) declined significantly, consistent with a climate change explanation. 6. Not all species of a given type behaved similarly, suggesting that complex interactions between species’ attributes and different combinations of environmental drivers determine frequency of occurrence changes. 7. Synthesis and applications. Our findings are consistent with large-scale responses to climatic and land-use changes, with some species increasing and others decreasing. We suggest that land-use change (e.g. habitat loss, nitrogen deposition) and climate change are both major drivers of moth biodiversity change, acting independently and in combination. Importantly, the diverse responses revealed in this species-rich taxon show that multifaceted conservation strategies are needed to minimize negative biodiversity impacts of multiple environmental changes. We suggest that habitat protection, management and ecological restoration can mitigate combined impacts of land-use change and climate change by providing environments that are suitable for existing populations and also enable species to shift their ranges.

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Mesenchymal stem cells (MSC) are multipotent cells which can be obtained from several adult and fetal tissues including human umbilical cord units. We have recently shown that umbilical cord tissue (UC) is richer in MSC than umbilical cord blood (UCB) but their origin and characteristics in blood as compared to the cord remains unknown. Here we compared, for the first time, the exonic protein-coding and intronic noncoding RNA (ncRNA) expression profiles of MSC from match-paired UC and UCB samples, harvested from the same donors, processed simultaneously and under the same culture conditions. The patterns of intronic ncRNA expression in MSC from UC and UCB paired units were highly similar, indicative of their common donor origin. The respective exonic protein-coding transcript expression profiles, however, were significantly different. Hierarchical clustering based on protein-coding expression similarities grouped MSC according to their tissue location rather than original donor. Genes related to systems development, osteogenesis and immune system were expressed at higher levels in UCB, whereas genes related to cell adhesion, morphogenesis, secretion, angiogenesis and neurogenesis were more expressed in UC cells. These molecular differences verified in tissue-specific MSC gene expression may reflect functional activities influenced by distinct niches and should be considered when developing clinical protocols involving MSC from different sources. In addition, these findings reinforce our previous suggestion on the importance of banking the whole umbilical cord unit for research or future therapeutic use.

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Background and purpose: The present study reports on the preparation and testing of a sustained delivery system for the immunomodulatory peptide P10 aimed at reducing the in vivo degradation of the peptide and the amount required to elicit a protective immune response against paracoccidioidomycosis. Experimental approach: BALB/c mice were infected with the yeast Paracoccidioides brasiliensis to mimic the chronic form of paracoccidioidomycosis. The animals were treated daily with sulfamethoxazole/trimethoprim alone or combined with peptide P10, either emulsified in Freund`s adjuvant or entrapped in poly(lactic acid-glycolic acid) (PLGA) nanoparticles at different concentrations (1 mu g, 5 mu g, 10 mu g, 20 mu g or 40 mu g center dot 50 mu L-1). Therapeutic efficacy was assessed as fungal burden in tissues and the immune response by quantitative determination of cytokines. Key results: Animals given combined chemotherapy and P10 nanotherapy presented a marked reduction of fungal load in the lungs, compared with the non-treated animals. After 30 days of treatment, P10 entrapped within PLGA (1 mu g center dot 50 mu L-1) was more effective than `free` P10 emulsified in Freund`s adjuvant (20 mu g center dot 50 mu L-1), as an adjuvant to chemotherapy. After treatment for 90 days, the higher doses of P10 entrapped within PLGA (5 or 10 mu g center dot 50 mu L-1) were most effective. Treatment with P10 emulsified in Freund`s adjuvant (20 mu g center dot 50 mu L-1) or P10 entrapped within PLGA (1 mu g center dot 50 mu L-1) were accompanied by high levels of interferon-gamma in lung. Conclusions and implications: Combination of sulfamethoxazole/trimethoprim with the P10 peptide entrapped within PLGA demonstrated increased therapeutic efficacy against paracoccidioidomycosis. P10 incorporation into PLGA nanoparticles dramatically reduced the peptide amount necessary to elicit a protective effect.

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Ex-Changi prisoner of war, and psychiatrist, Dr John Cade, sought a pharmacological treatment for bipolar disorder in the 1940s ; and in so doing, marked the beginning of psychopharmacology.

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The linkage and association between inherent blood pressure and underlying genotype is potentially confounded by antihypertensive treatment. We estimated blood pressure variance components (genetic, shared environmental, individual-specific) in 767 adult volunteer families by using a variety of approaches to adjusting blood pressure of the 244 subjects (8.2%) receiving antihypertensive medications. The additive genetic component of variance for systolic pressure was 73.9 mm Hg(2) (SE, 8.8) when measured pressures (adjusted for age by gender within each generation) were used but fell to 61.4 mm Hg(2) (SE, 8.0) when treated subjects were excluded. When the relevant 95th percentile values were substituted for treated systolic pressures, the additive genetic component was 81.9 mm Hg(2) (SE, 9.5), but individual adjustments in systolic pressure ranged from -53.5 mm Hg to +64.5 mm Hg (mean, +17.2 mm Hg). Instead, when 10 mm Hg was added to treated systolic pressure, the additive genetic component rose to 86.6 mm Hg(2) (SE, 10.1). Similar changes were seen in the shared environment component of variance for systolic pressure and for the combined genetic and shared environmental (ie, familial) components of diastolic pressure. There was little change in the individual-specific variance component across any of the methods. Therefore, treated subjects contribute important information to the familial components of blood pressure variance. This information is lost if treated subjects are excluded and obscured by treatment effects if unadjusted measured pressures are used. Adding back an appropriate increment of pressure restores familial components, more closely reflects the pretreatment values, and should increase the power of genomic linkage and linkage disequilibrium analyses.

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Background/Objectives: This study evaluates the feasibility among preschoolers of the 224-h dietary recalls (24-HDRs) method combined with a food-recording booklet (FRB), using EPIC-Soft pc-program for the 24-HDR (the software developed to conduct 24-HDRs in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study).
Subjects/Methods: A total of 20 and 25 (4- to 5-year-old) children were recruited, as a convenience sample, through worksites or day or healthcare in Denmark and Spain, respectively. One parent (or both parents together) completed two face-to-face 24- HDR, combined with an optional use of a FRB. Feasibility was evaluated by evaluation questionnaires completed by parents and interviewers.
Results: The face-to-face interviews were primarily conducted with the mothers. The FRB was used by 90% of the participants, and proxy persons, other than the parent, were also involved; involvement of proxy persons seems necessary in a majority of the recalls in both the countries.
Conclusions: The results suggest that 224-HDR with one parent combined with a FRB is feasible for registering preschoolers’ diet. An FRB and/or information from proxy persons, other than the parent, is needed for a majority of the parents. In future studies, it may be beneficial to develop the FRB more like a structured food record (FR), which might, in principle, change the method to a one-day FR method from more than a 24-HDR method. It is recommended then to further investigate the use of EPIC-Soft as a data-entry tool.

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The use of copper radioisotopes in cancer diagnosis and radionuclide therapy is possible using chelators that are capable of binding Cu(II) with sufficient stability in vivo to provide high tumour-to-background contrast. Here we report the design and synthesis of a new bifunctional chelator, 5-(8-methyl-3,6,10,13,16,19-hexaaza-bicyclo[6.6.6]icosan-1-ylamino)-5-oxopentanoic acid (MeCOSar), that forms copper complexes of exceptional stability by virtue of a cage amine (sarcophagine) ligand and a new conjugate referred to as SarTATE, obtained by the conjugation of MeCOSar to the tumour-targeting peptide Tyr(3)-octreotate. Radiolabeling of SarTATE with (64)Cu(II), a radioisotope suitable for positron emission tomography (PET), was fast (~20 min), easily performed at room temperature and consistently resulted in high radiochemical purity (>99%). In vitro and in vivo evaluation of (64)CuSarTATE demonstrated its high selectivity for tumour cells expressing somatostatin receptor 2 (sstr2). Biodistribution and PET imaging comparisons were made between (64)CuSarTATE and (64)Cu-labeled DOTA-Tyr(3)-octreotate ((64)CuDOTATATE). Both radiopharmaceuticals showed excellent uptake in sstr2-positive tumours at 2 h post-injection. While tumour uptake of (64)CuDOTATATE decreased significantly at 24 h, (64)CuSarTATE activity was retained, improving contrast at later time points. (64)CuSarTATE accumulated less than (64)CuDOTATATE in the non-target organs, liver and lungs. The uptake of (64)CuSarTATE in the kidneys was high at 2 h but showed significant clearance by 24 h. The new chemistry and pre-clinical evaluation presented here demonstrates that MeCOSar is a promising bifunctional chelator for Tyr(3)-octreotate that could be applied to a combined imaging and therapeutic regimen using a combination of (64)Cu- and (67)CuSarTATE complexes, owing to improved tumour-to-non-target organ ratios compared to (64)CuDOTATATE at longer time points.

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JUSTIFICATIVA E OBJETIVOS: A utilização das drogas agonistas dos alfa2-adrenoceptores para controlar a pressão arterial e freqüência cardíaca, propiciar menores respostas hemodinâmicas à intubação e extubação traqueal e poupar anestésicos já está difundida na literatura desde a introdução da clonidina. O desenvolvimento de agentes providos de maior seletividade alfa2-adrenoceptora que, por isso, determinam menos efeitos adversos, como a dexmedetomidina, recentemente liberada para utilização clínica, possibilitou que ocorressem maior sedação e analgesia com o seu uso. Despertou-se, então, o interesse em sua utilização como substitutos dos opióides, conhecidos por determinarem potente analgesia e sedação. O objetivo deste trabalho foi comparar a analgesia promovida pela dexmedetomidina e pelo sufentanil, utilizados em infusões contínuas durante anestesias de procedimentos otorrinolaringológicos e de cabeça e pescoço. MÉTODO: Os 60 pacientes estudados foram divididos em dois grupos de 30: G1, recebendo sufentanil e G2, dexmedeto- midina, na indução e manutenção anestésicas. Para a manutenção da anestesia utilizaram-se, também, o óxido nitroso e o propofol, em infusão contínua alvo-controlada. Foram avaliados os parâmetros hemodinâmicos (pressões arteriais sistólica e diastólica e freqüência cardíaca), tempos de despertar e de extubação após interrupção do propofol, locais onde foram extubados os pacientes, sala de operação (SO) ou sala de recuperação pós-anestésica (SRPA), tempo de permanência na SRPA, índice de Aldrete e Kroulik e as complicações apresentadas na SO e SRPA. RESULTADOS: G1 apresentou menores valores de pressões arteriais sistólica, diastólica e freqüência cardíaca, tempos de despertar e extubação maiores, maior número de extubações na SRPA, maior tempo de permanência na SRPA, valores mais baixos para Aldrete e Kroulik na alta da SRPA e mais complicações per e pós-operatórias. CONCLUSÕES: A utilização de dexmedetomidina como analgésico per-operatório apresentou melhores resultados que a de sufentanil, nos procedimentos selecionados neste trabalho, com relação à estabilidade hemodinâmica e às condições de despertar e de recuperação anestésica.

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Background: the clinical benefits of minocycline in combination with thorough scaling and root planing (SRP) have been examined in multicenter studies. The aim of this longitudinal investigation was to evaluate the clinical response to scaling and root planing combined with the use of locally delivered minocycline microspheres for 720 days in individuals with advanced chronic periodontitis.Methods: A total of 26 individuals aged 26 to 69 years (mean: 46.8 +/- 12.1 years) were included in this double-blind randomized clinical trial. After randomization, 13 individuals were selected for the test group (TG) and treated with SRP plus subgingival minocycline at baseline and 90, 180, and 270 days, and 13 individuals were selected for the control group (CG) and received SRP plus vehicle at the same time-points. Two homologous sites with probing depth (PD) >= 6 mm were chosen in each subject. To evaluate the clinical response after treatment, PD, plaque index (PI), and gingival index (GI) were assessed at baseline and 90, 180, 270, 360, and 720 days.Results: No statistical differences were found between test and control groups in relation to PD at the different timepoints. The mean values of PD demonstrated a higher reduction in the test group at 270 and 360 days. No statistical differences were observed at 90, 180, and 720 days between TG and CG (P < 0.05; Wilcoxon test). There were no statistically significant differences between TG and CG concerning PI and GI (P < 0.05; analysis of variance and t test) at all evaluated timepoints.Conclusion: Our findings demonstrated that both therapies reduced mean PD from 90 to 360 days; however, SRP combined with the use of subgingival minocycline showed a higher reduction at 270 and 360 days following therapy.

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Shiitake (Lentinula edodes (Berkeley) Pegler) is one of the most consumed mushrooms, for both therapeutic purposes and as food, therefore, the study of its biological properties is of great interest for producers and consumers. Aqueous extracts of the shiitake mushroom (L. edodes (Berkeley) Pegler) were evaluated by the micronucleus test (MN) in HEp-2 cells in vitro, to analyze their possible mutagenic and antimutagenic activities. None of the three extract concentrations tested (0.5, 1.0 and 1.5 mg/mL) presented mutagenicity at any of the preparation temperatures (4 degrees C, 22 +/- 2 degrees C and 60 degrees C). In the antimutagenicity evaluation, all extract concentrations at all preparation temperatures presented a strong protective activity for the HEp-2 cells in response to the alkylating agent methyl methanesulfonate (MMS) in the different treatment protocols: pre-treatment, simultaneous treatment and post-treatment. The extracts prepared at 22 +/- 2 degrees C presented the lowest frequencies of MN in the evaluations of mutagenicity and antimutagenicity, indicating these as the best option for potential therapeutic use. (c) 2006 Elsevier Ltd. All rights reserved.

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O presente estudo descreve, registra e compara estratégias de pesca e manejo comunitário de quelônios aquáticos em três comunidades da várzea de Santarém. Avaliou-se também o consumo de quelônios, incluindo preferências, rejeições e tabus alimentares, e uso destes como recursos terapêuticos na medicina popular. As técnicas de pesca de quelônios empregadas foram descritas, compreendendo variações espacial e sazonal de uso e espécies capturadas e seletividade das técnicas fundamentadas nos saberes locais. Analisaram-se ainda o rendimento das pescarias e as relações entre investimento e retorno das mesmas. Os dados foram coletados entre junho de 2007 a julho de 2008. Realizaram-se conversas informais, acompanhamento das atividades pesqueiras e observação participante nas comunidades. Entrevistas semi-estruturadas também foram realizadas adotando-se o método recordatório alimentar, monitoramento do consumo anual de quelônios e recordações das últimas pescarias de quelônios. Os primeiros relatos de manejo de quelônios na Amazônia são datados da época do contato entre populações ameríndias e europeias. Na década de 70 ações do governo brasileiro foram implementadas fundamentadas no gerenciamento centralizado no poder do Estado. Hoje, práticas de comanejo de quelônios ocorrem em vários lugares na Amazônia, como nas comunidades Ilha de São Miguel, Costa do Aritapera e Água Preta. Mesmo pautados na demanda comunitária os manejos dessas três comunidades apresentam perspectivas diferenciadas em virtude do variado grau de experiência com sistemas de manejo comunitário. A Ilha de São Miguel já realiza o manejo de quelônios há cerca de 40 anos com certo grau de sucesso, enquanto na Água Preta o co-manejo vem sendo estabelecido há 22 anos de forma menos rigorosa e na Costa do Aritapera não se obteve êxito em sua recente implementação. De modo geral, a inclusão dos principais usuários dos recursos naturais em seu manejo ainda se constitui uma tarefa de difícil execução. O grande desafio para o manejo de quelônios e outros recursos da fauna cinegética na Amazônia é o reconhecimento legal de seu uso. O consumo de quelônios é uma tradição enraizada na cultura amazônica, entretanto é criminalizado, constrangendo a maior parte da população a assumir seu uso. Por ser considerada atividade ilegal não há estimativas da quantidade de animais explorados, tornando difícil a implantação de formas de manejo comunitário sustentáveis. Percebeu-se na dieta dos ribeirinhos desse estudo a participação de peixe como principal fonte de proteína animal, enquanto o consumo de quelônios registrado foi relativamente pequeno. Constataram-se diferenças quanto às espécies de quelônios consumidas. Em geral, tracajá (Podocnemis unifilis) (carne e ovos) configura-se como quelônio mais consumido nas três comunidades, sendo a pitiu (Podocnemis sextuberculata) (carne e ovos) consumida principalmente na Costa do Aritapera. As tartarugas (Podocnemis expansa) são pouco utilizadas, não houve registros de coleta de seus ovos, sendo sua carne consumida principalmente na Ilha de São Miguel. Tais variações podem estar relacionadas à combinação de fatores ecológicos e ao histórico do manejo presentes em cada comunidade. Não foram observadas diferenças culturais nas comunidades estudadas quanto ao uso de quelônios. Tartaruga é a espécie mais rejeitada, usada principalmente na medicina popular; tracajá e pitiu em geral são os quelônios preferidos, sendo os três considerados reimosos (animais sujeitos a tabus alimentares em algumas circunstâncias, como doenças, menstruação, gravidez e pós-parto). A espécie mais capturada foi o tracajá, seguindo-se a pitiu e em menor proporção a tartaruga. O tracajá é encontrado em vários ambientes, sendo coletado durante o ano todo nas três comunidades; pitius são capturadas principalmente na Costa do Aritapera no período da seca e da vazante, quando estão concentradas durante a migração ao saírem das áreas inundáveis em direção aos rios e às praias de desova, enquanto tartarugas são pescadas nos lagos protegidos da Ilha de São Miguel, na enchente e na cheia. As técnicas de pesca apresentam uso diferenciado em função do nível do rio. Os pescadores reconhecem tais variações sazonais, as quais aliadas a um conjunto de saberes locais são utilizadas na seleção das técnicas de pesca de quelônios. A pesca de quelônios é realizada em geral de modo oportuno, durante as pescarias de peixes. O rendimento das pescarias de quelônio foi maior quando estas não incluíram a captura de peixes e quando realizadas com uso da mão. O rendimento com base na CPUEN diferiu entre as comunidades estudadas e entre os períodos de pesca, porém não houve diferença significativa no rendimento das pescarias entre esses parâmetros quando a biomassa foi utilizada nos cálculos de CPUE. O pescador, em geral, não está preocupado em maximizar seu rendimento, já que a maior parte das pescarias não se destina a comercialização. O rendimento, desta forma, acaba refletindo mais o acerto de um bom local de pesca do que o esforço de deslocamento empregado na mesma.Quando a mancha era boa os pescadores gastavam pouco tempo, enquanto em manchas menos produtivas gastavam mais tempo. Alguns pontos a serem adotados com vistas à concretização e sucesso do manejo comunitário são sugeridos nesse estudo: (1) definição clara dos direitos de acesso aos recursos e das sanções em caso de infração dos acordos; (2) estabelecimento de programas de capacitação de lideranças comunitárias; (3) criação de um fundo comunitário para desenvolvimento de outras atividades econômicas e investimento na melhoria da qualidade de vida dos moradores e nas próprias ações envolvidas no manejo; (4) reconhecimento e uso do conhecimento ecológico local e do direito de se utilizar o recurso; (5) ampliação regional do modelo comunitário para outras áreas, considerando que algumas espécies realizam grandes migrações; (6) monitoramento das populações exploradas; (7) avaliação periódica da efetivação do manejo e seu papel para os moradores locais; (8) repartição dos benefícios entre os comunitários. No caso específico dos quelônios recomendam-se também a proteção de outros ambientes além das áreas de nidificação e a determinação de um sistema de cotas voltado ao aproveitamento de ovos que seriam perdidos com possibilidade de comercialização para criadores.

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The development of a dose-dependent cardiomyopathy is the main limitation for the use of doxorubicin in chemotherapy protocols in both humans and animals. In this setting, the global myocardial function may be compromised resulting in signs of congestive heart failure. In this study, we investigated the ability of the Tei index of myocardial performance to identify myocardial dysfunction in healthy dogs receiving doxorubicin to a cumulative dose of 210 mg/m(2) over 147 days, comparing it with other standard echocardiographic indicators of systolic and diastolic function. Our results indicated that the Tei index, the isovolumic relaxation time, pre-ejection period and the pre-ejection period-to-left ventricular ejection time ratio were able to identify the cardiotoxic effects of doxorubicin on cardiac function when only 60 mg/m(2) had been administered, while the standard systolic and diastolic parameters, including left ventricular diameter at systole, ejection fraction, and fractional shortening needed at least 120 mg/mg(2) to deteriorate. We concluded that prolonged anthracycline therapy compromises both systolic and diastolic functions, which may be documented earlier by including the Tel index evaluation to the standard echocardiographic assessment of animals receiving doxorubicin.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)