The X-band EPR spectrometry system was modified to allow for the in situ monitoring of free radical changes in attached, intact plant leaves, which were caused by stress factors such as exposure to excessive photon flux density, ozone or sulphur dioxide. This was done through use of the dewar insert of the variable temperature accessory as a guide, the construction of 'T' shaped cellulose acetate holders to which leaves could be attached with adhesive tape, and modification of the gas flow system used for controlled temperature studies. Kinetic studies of free radical formation were possible with leaves which had minimal underlying Fe⁺⁺ and Mn⁺⁺ signals. In leaves with large underlying signals a Varian software program was used to subtract overlapping signals from each other, thereby revealing the free-radical signal changes which occurred under different light regimes and stress conditions. Preliminary investigation disclosed the formation of a new signal upon prolonged exposure to far-red light and the effect of oxygen depletion upon photosynthetic Signals I and II. Leaves subject to high photon flux density reveal an unreported free-radical signal, which decays upon exposure to microwave radiation; and concomitant damage to Photosystems I and II. Upon elimination of this signal leaves return to the undamaged state or reveal permanent damage to either photo-system, depending upon the degree of damage. Kentucky bluegrass and perennial ryegrass leaves subject to low levels of ozone (up to 80ppb) for periods of 8 hours show no changes in free-radical signal formation. At intermediate levels of ozone (80-250ppb) a new free-radical signal was formed within 3 hours of fumigation, Signal II was decreased and Signal I decayed. These changes were reversible if fumigation was terminated. At fumigation levels exceeding 250ppb a different new irreversible free-radical signal was formed in darkness within 1.5 hours of fumigation. Radish, Kentucky bluegrass and perennial ryegrass leaves subject to high levels of sulphur dioxide (10-500ppm) reveal the formation of Signal I upon irradiation with broad-band white or 650nm light, thereby indicating an interruption of normal electron flow from PSII to PSI. Damage to the oxygen-evolving complex and reaction centre of PSII is also revealed through changes in Signal II and the Mn⁺⁺ signal. These changes in the normal EPR signals are dose-dependent. Leaves subject to low levels of sulphur dioxide (600-2000ppb) reveal the disappearance of Signal I after 3 hours of fumigation and the formation of a new free-radical signal with parameters similar to the sulphur trioxide free-radical signal. These latter changes are partially reversible upon termination of fumigation. After prolonged exposure to either ozone or sulphur dioxid a free-radical signal with parameters similar to the superoxid anion free-radical signal is formed in plant leaves. / Land and Food Systems, Faculty of / Graduate

Recent evidence strongly suggests that aluminum toxicity is important in determining the structural and functional characteristics of freshwater communities affected by acid precipitation. To determine the effect dissolved aluminum has on lotic invertebrates previously unexposed to anthropogenic acidification, experiments were carried out in a second-order headwater stream 50 km east of Vancouver, British Columbia during August 1982. In three separate experiments, HC1 and/or A1C1₃ were added to Mayfly Creek during daylight hours, increasing acidity from pH 6.9 - 7.0 to pH 5.8 - 6.0 and total aluminum from < 0.1 mg/L to > 1.0 mg/L. Biological response was monitored by sampling invertebrate drift with 86 Mm nets. Relative to an unmanipulated, upstream control site, drift density doubled in response to added H⁺ alone (pH 5.9). When Al₃⁺ was added (pH 5.9) drift density increased fourfold. Following 48 h continuous dosing with HC1 (pH 5.9) there was an even greater response to added Al₃⁺. Ephemeroptera were able to detect dissolved aluminum and responded almost immediately (within 45 min). Similarly, Trichoptera and Chironomidae detected increased H⁺ concentrations and responded immediately. Response to augmented Al₃⁺ by Trichoptera, Hydracarina, and Chironomidae was delayed 6 h. However, pre-exposing animals to 48 h HC1 resulted in enhanced aluminum sensitivity for Chironomidae and for Simulium and Plecoptera, which had not responded within 10 h to H⁺ or Al₃⁺ alone. It is proposed that rapid increases in drift density are due to behavioral escape responses, while delayed responses are probably associated with physiological impairment. Evidence was also obtained suggesting that during early stages of morphological development Ephemeroptera and Chironomidae are more sensitive to increased Al₃⁺ and H⁺ concentrations than during later developmental stages. In laboratory experiments using artificial stream channels, Chironomidae larvae and Ephemeroptera nymphs were exposed to CI⁻ and H⁺ concentrations, equal to those during field experiments. Results showed that drift behavior in these animals is not stimulated by mildly elevated chloride concentrations. These studies demonstrate that increased dissolved aluminum concentrations intensify biological response to acidification, and confirm acid sensitivity patterns for Ephemeroptera and Chironomidae reported by others. The observed acid insensitivity of Plecoptera, simuliids, and Trichoptera also conforms to previously described patterns. Experimentally manipulating this community produced results closely resembling those obtained in similar studies for areas currently affected by acid precipitation. The major difference in results between studies is that invertebrate communities previously unexposed to acidification contain more species sensitive to mild acidification. These latter animals are particularly sensitive to the presence of elevated dissolved aluminum concentrations. / Science, Faculty of / Zoology, Department of / Graduate

In this research, beta-lactoglobulin was chemically modified by attaching different levels of stearic acid to the protein. The effect of this modification on hydrophobic!ty, emulsifying and foam properties, digestibility and allergenicity of the protein was investigated. It was found that the effect of fatty acid attachment or lipophilization depended on the amount of fatty acids attached to the protein. Incorporation of the hydrophobic ligands led to increased hydrophobic interactions, resulting in a decreasing solubility with extent of incorporation. Furthermore, the surface hydrophobicity measurements showed that the two fluorescence probes 8-anilinonaphthalene-l-sulfonate (ANS) and cis-parinaric acid (CPA) used for the surface hydrophobicity measurements were not equivalent This may support the. observation by earlier workers that ANS measures aromatic hydrophobicity and CPA aliphatic hydrophobicity. The studies on surface functional properties i.e. emulsifying and foaming properties, indicated that there was some improvement in these functional properties at low and medium levels of incorporation which decreased as the extent of fatty acid attachment further increased. The improvement, of these functional properties could be attributed to improved amphiphilicity of the proteins at these levels of incorporation. This research also showed that both high solubility and high ANS surface hydrophobicity is needed for the best emulsifying properties. In vitro digestibility studies showed a decrease in digestibility of the modified proteins with increased lipophilization. From the passive cutaneous anaphylaxis experiments, it was found that the level of fatty acid attachment to the protein had a significant effect on its ability to elicit IgE antibodies. Increased ability to elicit IgE antibodies was observed at a low level of fatty acid. When a medium level of fatty acid was attached the ability to elicit antibodies was reduced and almost completely destroyed when a higher level of fatty acid was incorporated. The above observations could be explained by the fact that the low level incorporation of fatty acid led to changes in the protein structure which exposed more allergenic sites. The almost complete destruction of the allergenicity could be attributed to denaturation of the protein which reduced or destroyed available allergenic sites. The antigenicity or binding of the modified proteins to the IgG antibodies raised against the native protein was studied by both direct and competitive enzyme linked immunosorbent assay. It was found that at low and medium levels of incorporation, the proteins demonstrated increased binding ability compared to the native protein. This was attributed to the increased exposure of antigenic sites on the protein with fatty acid incorporation. However, the protein with high level of incorporated fatty acid showed decreased binding ability. / Land and Food Systems, Faculty of / Graduate

Chinese hamster V79-171B cells grown for about 24 hours in suspension culture display increased resistance to cell killing by ionizing radiation compared with cells grown as monolayers, an observation originally termed the "contact effect". More recently, development of that resistance was shown to be accompanied by changes in the conformation of the DNA which reduce its denaturation rate in high salt/weak alkali. These changes in DNA conformation, mediated by the cellular micro-environment, appear to be responsible for the contact effect. The conditions necessary for the development of the effect are not, however, completely understood. In particular, when cells grown as monolayers on petri plates are suspended in spinner culture flasks, their growth characteristics change in three distinct ways. First, cells in suspension no longer have a solid substrate, so they remain round. Second, after several hours, they begin to aggregate to form "spheroids", so that three-dimensional intercellular cell contact develops. Third, cells in the stirred suspension cultures are not subjected to high local concentrations of metabolic by-products or surrounded by a zone depleted of nutrients, as are cells in monolayer culture. The studies described here were designed to determine how each of these factors influence changes in DNA conformation, as assayed using the alkali unwinding technique. Our results indicated that a round shape may not be an essential requirement, since cells spread out on the surface of cytodex beads in suspension culture, and sparsely-seeded cells in monolayer culture demonstrated at least a partial contact effect. Three-dimensional intercellular contact does not always seem necessary for the development of the contact effect. Cells grown in a methyl cellulose matrix developed radioresistance, even though the cells formed only small clusters of less than five cells. Similarly, suspension culture cells which were prevented from aggregating by frequent exposure to trypsin, also developed the contact effect. There was no evidence that nutrient depletion plays a role in the failure of cells grown as monolayers to develop a contact effect. However, cells grown as spheroids in the presence of monolayer cells, or in monolayer cell-conditioned medium, did not display a full contact effect. This indicates a role for monolayer cell-produced factors (possibly extracellular matrix proteins) in preventing the development of the contact effect. We conclude that changes in DNA conformation and the increase in radiation resistance, seen in V79-171b cells grown as spheroids, are not the result of intercellular contact or round shape of the cells. This radioresistance appears to be the result of an absence of monolayer cell-produced factors which could control both cell shape and DNA conformation. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

The detrimental effect of ethanol on coordinated movement and the similarity of this effect to that of pathological damage to the cerebellum or the inferior olive (10) suggests that ethanol profoundly effects the olivocerebellar system. Each cerebellar Purkinje cell (PC) displays two distinct action potential responses: the simple spike (SS), evoked intrinsicly and via the parallel fibres, and the complex spike (CS), evoked via a solitary climbing fibre (CF) which originates from the 10. Ethanol (1.5 g/kg, i.v.) was found to have no significant effect on the CS activity evoked by direct electrical activation of CFs, while it significantly reduced, in parallel, that evoked by cerebral cortex stimulation and that occurring spontaneously. In addition, ethanol, applied both systemically and locally by micropressure, reduced the spontaneous activity of inferior olive (10) neurones. These results strongly suggest an action of ethanol local to the 10 nucleus, perhaps by a direct action on the 10 neurones themselves. Elimination of spontaneous CS activity by the electrolytic lesioning of the contralateral 10 did not significantly alter spontaneous SS firing rate. However, subsequent administration of ethanol i.v. did produce a significant increase of SS rate, indicating that only part of ethanol-evoked SS rate increase is dependant upon the reduction of CS activity. Simple spike regularity was not significantly altered by either 10 lesioning or i.v. ethanol. Ethanol applied locally to PC's by micropressure was found to reduce the period of inhibition evoked by local stimulation of the cerebellar cortex in the majority of the cells tested. This result is in agreement with the previously reported effects of intravenous ethanol on this inhibition, thought to be mediated by gamma-aminobutyric acid (GABA). Both intravenously and locally applied ethanol antagonized the inhibition of PC's evoked by locally applied GABA. These results, while in agreement, are contrary to the reported effects of ethanol in other systems. Intravenously administered ethanol did not significantly alter Golgi cell spontaneous firing, while it did significantly reduce the period of inhibition of Golgi cell firing evoked by 10 stimulation. / Pharmaceutical Sciences, Faculty of / Graduate

Orientador: Simone dos Santos Aguiar / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T11:47:25Z (GMT). No. of bitstreams: 1 Nobrega_VirginiaTafas_M.pdf: 3339539 bytes, checksum: c286b90582a441ee1bb2f4b87b025ed0 (MD5) Previous issue date: 2014 / Resumo: Introdução: As taxas de sobrevida para leucemia linfoblástica aguda (LLA) na infância vêm apresentando aumento significativo nos últimos anos. Em decorrência disso, o número de adultos jovens sobreviventes se eleva a cada ano, tendo muitos deles uma série de complicações decorrentes do tratamento. O objetivo deste estudo é investigar a incidência e prevalência dos efeitos adversos tardios do tratamento antineoplásico, em sobreviventes de leucemia linfocítica aguda. Pacientes e Métodos: Desenho do estudo de coorte retrospectivo. Foram selecionados sobreviventes de LLA, que foram diagnosticados com menos de 18 anos, e estejam fora de tratamento há, pelo menos, dois anos. Os dados deste estudo foram coletados dos prontuários dos pacientes que foram submetidos a avaliação médica e exames complementares. Os efeitos adversos apresentados foram avaliados através desta revisão. Resultados obtidos: Dos 38 sobreviventes analisados, 55% (n=21) apresentaram algum tipo de comorbidade e 13,5% foram afetados por mais de uma alteração. A dislipidemia acometeu 18,4% (n=7) da população estudada, sendo a comorbidade mais prevalente com 35%. A baixa densidade óssea também apareceu com bastante frequência, acometendo 15% dos casos estudados. O tempo fora de terapia teve uma média de 7,92 anos (variação 2-16 anos). Conclusão: A necessidade de realizar o acompanhamento desses pacientes, não só através do exame físico, mas também de exames de imagem e laboratoriais foi evidente no nosso estudo. É possível que o acompanhamento regular, desde o término da terapia, até 20 ou 30 anos depois, leve à redução da intensidade e prevalência de comorbidades nessa população / Abstract: Background: Survival rates for acute lymphocytic leukemia in childhood have shown significant increase in recent years. Consequently, the number of young adult survivors rises each year, and some of those has a set of complications resulting from therapy. The aim of this study is to investigate the incidence and prevalence of late adverse effects of antineoplastic treatment in survivors of acute lymphoblastic leukemia. Patients and Methods: Retrospective cohort study. Survivors of acute lymphoblastic leukemia, younger than 18 years old at diagnosis, and off treatment for at least two years, have been selected. These were following-up at outpatient¿s clinic, where the information was collected and examinations performed. Adverse effects presented were evaluated by reviewing medical records. Results: Of the 38 survivors studied, 55,2% (n = 21) had some type of comorbidity and 13.5% were affected by more than one change. Dyslipidemia struck 18.4% (n = 7) of the population studied, and the most prevalent comorbidity with 35%. Low bone mineral density also appeared quite frequently, affecting approximately 16% of the group. The time off therapy had an average of 7.92 years (range 2-16 years). Conclusion: The necessity of follow-up of these patients, but only by physical examination, but imaging and laboratory was evident in our study. It is possible that with regular monitoring, since the completion of therapy, up to 20 or 30 years, leading to the reduction of the intensity and prevalence of comorbidities in this population / Mestrado / Saude da Criança e do Adolescente / Mestra em Ciências

Este estudo teve como objetivos analisar a ocorrência de neutropenia induzida pelas drogas utilizadas nos protocolos de quimioterapia neoadjuvante ou adjuvante entre mulheres com câncer de mama seguidas no Ambulatório de Mastologia do HCFMRPUSP e identificar os domínios de qualidade de vida (QV) mais afetados entre as mulheres durante o tratamento quimioterápico. Foi realizada avaliação das toxicidades hematológicas a cada ciclo de tratamento quimioterápico de mulheres com câncer de mama, seguidas no referido ambulatório. A avaliação da QV se deu em três momentos do tratamento com a aplicação do questionário EORTC QLQ-C30 e do módulo específico para câncer de mama o QLQ-BR23. Foram incluídas 79 mulheres, sendo que 34,2% apresentavam-se na faixa etária de 51 a 60 anos. De acordo com a terapêutica utilizada, 50,6% receberam tratamento quimioterápico neoadjuvante; 63,3% apresentaram neutropenia em algum momento e 20,2% apresentaram dois episódios de neutropenia Observou-se um total de 116 episódios neutropênicos ao longo do estudo; destes, 46,5% grau II. A análise da QV mostrou que nas três medidas avaliadas, antes do início do tratamento, no meio e ao final, as diferenças entre os escores de sintomas foram estatisticamente significantes (p<0,05). Quando comparadas as três aplicações, observou-se uma piora dos sintomas incluindo fadiga, dispnéia, náusea e vômito. Os resultados encontrados sugerem o desenvolvimento de novos estudos com maiores amostragens, aumento na peridiocidade das avaliações de QV entre os ciclos de quimioterapia concomitante a utilização de instrumentos específicos para avaliar o real impacto da neutropenia na QV. A partir de tais informações, torna-se possível determinar quais indivíduos possuem maior risco em desenvolver neutropenia, possibilitando os enfermeiros oncológicos a desempenhar um papel chave na melhoria da QV destes pacientes. / The aim of this work is to analyze the occurrence of neutropenia induced by drugs used on the protocol of neo-adjuvant and adjuvant chemotherapy among women with breast cancer watched at Ambulatório de Mastologia do HCFMRP-USP and to identify the most affected domain of quality of life (QL) among women during chemotherapy treatment. A test of the hematologic toxicity was carried out in each cycle of chemotherapeutic treatment of women with breast cancer watched at the referred ambulatory. The QL test happened in three moments during the treatment with the application of the EORTC QLQ-C30 questionnaire and the specific module for breast cancer, the QLQ-BR23. A number of seventy-nine women were included, of which 34,2% presented ages between 51 to 60 years old. According to the used therapy, 50,6% of the patients received neo-adjuvant chemotherapy treatment; 63,3% presented neutropenia at some point and 20,2% presented episodes of neutropenia. It was observed a total number of 116 neutropenic episodes along the study; among them, 46,5% with grade II. The QL analysis showed that in the three measures tested, before the beginning of the treatment, in the middle and at the end, the differences among the scores of symptoms were statistically significant (p<0,05). When the administration of the medicine was compared, it was observed an aggravation of symptoms such as fatigue, dyspnea, nausea and vomiting. The findings suggest the development of new studies with larger samples, increase of periodicity in the QL tests application ensuring the use of specific instruments in each chemotherapy cycle to test the real impact of neutropenia in the QL. Having this information, it is possible to determine which people are more in risk of developing neutropenia, making possible for the oncologic nurses to perform an important role in the improvement of the QL in these patients.

De nos jours, les femmes sont confrontées à deux tendances épidémiologiques fortes : une constante augmentation de l’incidence de l’obésité, et l’augmentation de l’incidence du cancer du sein. Les Françaises de plus de 50 ans doivent faire face à ces deux problèmes majeurs de santé publique, l’obésité pouvant augmenter le risque de cancer du sein de 30 à 50% en post-ménopause. Néanmoins, grâce aux progrès du dépistage et des thérapies, la mortalité diminue, et le nombre de femmes ayant reçues un traitement contre le cancer du sein augmente. Les traitements par chimiothérapie présentent de nombreux effets secondaires, parmi lesquels une variation de poids significative au cours du traitement (gain ou perte) qui semble perdurer dans le temps. Que ce soit une perte ou un gain de poids, une telle variation a été associée à un mauvais pronostic pour ces patientes. S’agissant de données principalement issues de cohortes américaines présentant un IMC plus élevé qu’une population européenne, le centre Jean Perrin a mené une étude rétrospective afin de vérifier ces résultats sur une population française (Thivat et al. 2010). Cette étude a tout d’abord confirmé qu’un IMC élevé au moment du diagnostic était associé un mauvais pronostic. De plus, la variation de poids observé au cours du traitement par chimiothérapie (gain et perte ≥5% du poids initial) était associée à une augmentation significative du risque de rechute et de décès. Néanmoins, les causes de cette variation de poids et les mécanismes impliqués dans ce mauvais pronostic restent encore mal connus. L’objectif de ce travail est de caractériser la variation de poids en termes de composition corporelle et d’étudier les facteurs de la balance énergétique responsables de ces variations. Les facteurs biologiques associés à la variation de la composition corporelle, potentiellement impliqués dans le mauvais pronostic, sont également étudiés. Le premier chapitre consiste en une étude bibliographique permettant de décrire la pathologie du cancer du sein (partie I), les modifications du métabolisme énergétique suite à un traitement par chimiothérapie (partie II), le rôle du tissu adipeux brun dans la régulation du métabolisme énergétique (partie III) et pour finir, l’impact des modifications du métabolisme énergétique sur la santé des patientes (partie IV). Dans le deuxième chapitre sont présentés les résultats des études réalisées. La première étude, toujours en cours, est exposée sous forme de rapport, tandis que les deux suivantes sont sous forme d’article. Une discussion générale de l’ensemble des résultats dégage les perspectives de recherche à envisager pour donner suite à ce travail. / Today, women face two strong epidemiological trends: a steady increase in the incidence of obesity, and an increase in the incidence of breast cancer. French women over the age of 50 face these two major public health problems, with postmenopausal obesity increasing the risk of breast cancer by 30 to 50%. Nevertheless, thanks to advances in screening and therapies, mortality is decreasing, and the number of women who have received treatment for breast cancer is increasing.Chemotherapy treatments have many side effects, including a significant change in weight during treatment (gain or loss) that seems to persist over time. Whether it is gain or loss, such weight variation has been associated with poor prognosis for these patients. Since data come mainly from American cohorts with a higher BMI than a European population, the Jean Perrin Center conducted a retrospective study to verify these results in a French population (Thivat et al., 2010). This study first confirmed that a high BMI at the time of diagnosis was associated with a poor prognosis. In addition, the weight change observed during chemotherapy treatment (gain and loss ≥5% of initial weight) was associated with a significant increase in the risk of relapse and death. Nevertheless, the causes of this weight variation and the mechanisms involved in this poor prognosis are still insufficiently understood. The objective of this work is to characterize the variation of weight in terms of body composition and to study the factors of the energy balance responsible for these variations. Biological factors associated with the change in body composition, potentially implicated in the poor prognosis, are also studied. The first chapter consists in a bibliographic review describing the pathology of breast cancer (Part I), the changes in energy metabolism following chemotherapy treatment (Part II), the role of brown adipose tissue in the regulation of energy metabolism (Part III) and finally, the impact of changes in energy metabolism on patient health (Part IV). In the second chapter the results of the studies carried out are presented. The first study, still in progress, is presented as a report, while the next two are in article form. A general discussion of all the results identifies the research perspectives to be considered in order to follow up on this work.

No description available.

An evidence-based systematic review of elderberry and elderflower (Sambucus nigra) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.