Dissertations / Theses on the topic 'Long-term side effects'

Background Long-term side effects associated with the treatment of Hodgkin’s lymphoma (HL) have frequently been reported during the last decades. Studies have shown increased mortality in HL survivors. Following Hodgkin’s lymphoma, second malignancies (SM) and cardiovascular disease (CVD) are the most common causes of death in individuals treated for HL. This study investigates the incidence of side effects such as SM, CVD and infections in a cohort diagnosed with HL in Sweden between 1965 and 1995. In addition, this study identifies covariate risk factors for late side effects in order to develop strategies that prevent morbidity and mortality in HL survivors. Methods Using the Swedish Cancer Registry (SCR) at the National Board of Health and Welfare and the Multi-Generation Registry at Statistics (MGR) Sweden, we identified 6946 individuals diagnosed with HL between the years 1965 and 1995, and their first degree relatives (FDR) (n=17 858). In addition we identified the malignancies and inpatient care for CVD and infections for the HL cohort and their FDR. The standard incidence ratio (SIR) was calculated for the risk of SM, CVD and infections. For SM and CVD the risk also was stratified and calculated for family history of disease. The Swedish Hodgkin Intervention and Prevention study (SHIP), a prospective study, invited 702 individuals treated for HL at the age of 45 years or younger and who were treated in the region of Skåne, Uppsala or Umeå. The participants completed a questionnaire and were invited to an out-patient visit to an oncologist with clinical examination and blood tests. Any pathological findings were referred for further investigation. Results An increased risk for SM in HL long-term survivors was observed and seems to increase with the number of FDRs with cancer. There was also an increased risk for inpatient care due to congestive heart failure (CHF) and coronary artery disease (CAD). A family history of CHF and CAD further increased the risk for these diseases. The risk for inpatient care due to infections was increased and remained increased after 20 years or longer. The risk for infections was associated with splenectomy and hypothyroidism. Radiotherapy was an independent risk factor for cardiovascular disease in the cohort of the prospective study. ConclusionLong-term survivors from HL have an increased risk for developing late side effects such as SM, CVD and infections. Since many HL patients are young and the cure rate from the disease is high, it is of great importance to offer focused surveillance programs to selected individuals who are at high risk, e.g. individuals who received radiotherapy as part of their treatment and who have other known risk factors for cardiovascular disease such as hypertension, hypercholesterolemia, family history and smoking.

Magister Scientiae - MSc
Despite recent advances in radiotherapy, some tumours have shown to be resistant to treatment and patients still experience long term side effects. Gold nanoparticles (AuNPs) have been identified as effective radiosensitizers when employed concurrently with kilovoltage X-rays, which could selectively increase the dose delivered to a patient's tumour. The clinical application of proton radiation has gained renewed attention due to the lower integral body dose of protons compared to traditional X-ray based therapy. While extensive research has been formed on the behaviour of AuNPs in photon beams, limited information is available on the combination of AuNPs and proton radiation. Several questions remain regarding the interaction of protons with the AuNPs and possible dose enhancement effects at different depths along the Spread Out Bragg Peak (SOBP).

Attention Deficit/Hyperactivity Disorder (ADHD) was originally thought to occur only in children, but is increasingly recognised as causing functional impairment also in adulthood. The overall aim of this thesis was to achieve a comprehensive understanding of ADHD in adulthood. A questionnaire based on the DSM-IV criteria of ADHD, reported childhood symptoms, reading and spelling problems, difficulties and suffering and general assessment of functioning (GAF) was distributed to three samples: the general population (GP), outpatient psychiatry (OPP) and female prison inmates. Symptoms consistent with ADHD were more than three times higher in the OPP sample than in the GP sample (6.6 versus 2.1%). ADHD symptoms and related problems occurred in 50% of the prison inmates. A cohort of 168 patients diagnosed with ADHD in adulthood was interviewed about current ADHD symptoms and psychiatric comorbidity on axis I and II. The lifetime prevalence of psychiatric comorbidity on axis I was 92% and current comorbidity, including autism spectrum disorders and Tourette’s syndrome, was 47%. The sex-specific pattern of the comorbid disor-ders was similar to that in the general population. Forty-six per cent of the patients endorsed the specific criteria for at least one personality disorder. After a mean follow-up of six years, there was remission of adult ADHD in about 30% of the patients, regardless of whether there was ongoing medication or not. There were no differences in function and quality of life, except for global general improvement, which was better in patients currently on medication. The most prevalent long-term side effects of pharmacological treatment with mainly stimulants were decreased appetite, dry mouth, anxiousness/restlessness and an increase in pulse frequency. The discontinuation rate was about 50%: 29% discontinued because of a perceived lack of effect, followed by elevated mood or hypomania (11%). No detectable evidence of tolerance and increased need for dosage over time was observed. To conclude, Symptoms of ADHD is highly overrepresented in OPP and in female inmates compared with the GP. Furthermore, adults diagnosed with ADHD have a high lifetime prevalence of psychiatric comorbidity. Long-term pharmacological treatment with stimulants is safe with relatively mild and tolerable adverse effects. Continued medication, however, is not related to remission.

Lors de la liaison d’un glucocorticoïde (GC) naturel ou synthétique (par exemple, la Dexaméthasone) au récepteur des glucocorticoïdes (GR), les GCs régulent l’expression de gènes cibles soit par (i) transactivation par liaison ‘’directe’’ à un élément de liaison à l’ADN de type ‘’(+)GRE’’, (ii) transrépression ‘’directe’’ par liaison à un élément de type ‘’nGRE’’ ou (iii) transrépression ‘’indirecte’’ par interaction physique directe avec des facteurs de transcription pro-inflammatoires tels que AP-1 et NF-κB. Les effets anti-inflammatoires bénéfiques des GCs sont généralement attribués à la transrépression indirecte, alors que nombre de leurs effets secondaires pathologiques indésirables paraissent liés à la transactivation et/ou à la transrépression directe. Notre laboratoire a récemment découvert qu’un composé non-stéroïdien dénommé CpdX ainsi que ses dérivés deutérés, ne présentent ni la fonction de transactivation, ni celle de transrépression directe du GR, tout en stimulant son activité bénéfique de transrépression indirecte. Notre projet a consisté à caractériser un composé non-stéroïdien dit CpdX, ainsi que ses dérivés, quant à leurs activités thérapeutiques et à démontrer qu’elles sont semblables à celles des glucocorticoïdes anti-inflammatoires, couramment utilisés, tout en étant débarrassés de leurs effets pathologiques secondaires, tels que l’ostéoporose, l’atrophie cutanée et le syndrome métabolique. Pour atteindre nos objectifs, nous avons utilisés des modèles de souris présentant soit les affections cutanées (dermatites de contact ou atopique, psoriasis), l'asthme, l’arthrite rhumatismale, la colite ulcérative ou la conjonctivite allergique, associés à des études d’immunologie et de biologie moléculaire et cellulaire. Mon travail de thèse a démontré que CpdX, et certains de ses dérivés deutérés, présentent une activité anti-inflammatoire dans le traitement de ces modèles ‘’souris’’ (Partie I). Nous avons aussi montré que le traitement par CpdX et ses dérivés n’induit pas les effets secondaires pathologiques des glucocorticoïdes (Partie II), ouvrait ainsi la vue à une nouvelle ère dans le traitement à long-terme de maladies inflammatoires, sans provoquer les effets pathologiques indésirables des traitements actuels aux glucocorticoïdes
Upon binding of natural or synthetic glucocorticoids (GCs) (e.g. Dexamethasone) to their glucocorticoid receptor (GR), GCs regulate the expression of target genes either by (i) direct transactivation through direct binding to “(+)GRE” DNA binding sites (DBS), (ii) direct transrepression through binding to “IR nGRE” DBSs or (iii) tethered indirect transrepression mediated through interaction with transactivators, such as NFkB, AP1, or STAT3 bound to their cognate DBSs. The beneficial anti-inflammatory effects of GCs have been generally ascribed to tethered transrepression, whereas many of their long-term undesirable side-effects could be due to transactivation and/or direct transrepression. Our laboratory recently reported that a non-steroidal compound, named CpdX, selectively lacks both direct transactivation and direct transrepression functions, while still exerting an indirect transrepression activity. The goal of our project was to characterize CpdX and some of its derivatives as effective anti-inflammatory drugs similar to glucocorticoids, but lacking their main deleterious side-effects, e.g. osteoporosis, skin atrophy and metabolic disorders. To this end, we have used experimental mouse model for skin disorders (atopic dermatitis, contact dermatitis, and psoriasis), asthma, rheumatoid arthritis, ulcerative colitis and allergic conjunctivitis, combined with immunology, molecular and cellular biology. My thesis studies have demonstrated that in mouse models, CpdX and its derivatives exhibit anti-inflammatory activities, which are similar to those of glucocorticoids (Part I). Importantly, we further show that CpdX and its derivatives do not exhibit the long-term debilitating side-effects of glucocorticoids (Part II). Thereby paving the way to a new era in the long-term therapy of major inflammatory diseases

Short term studies have suggested that ground based timber harvesting on wet sites can alter soil properties and inhibit early survival and growth of seedlings. Persistence of such negative effects may translate to losses in forest productivity over a rotation. During the fall and winter of 1989, numerous salvage logging operations were conducted during high soil moisture conditions on wet pine flats in the lower coastal plain of South Carolina following Hurricane Hugo. A long-term experiment (split-plot within an unbalanced randomized complete block design) allowed assessment of long term effects of rutted and compacted primary skid trails and subsequent site preparation on soil properties and loblolly pine (Pinus taeda L.) productivity. The experiment had 12 blocks, four levels of site preparation as the whole plot factor (bedding, disking with bedding, disking, and no site preparation), and two levels of traffic as the subplot factor (primary skid trail, no obvious traffic). After 23 years, bedding and disking with bedding treatments effectively enhanced soil physical properties and stand productivity via promoting greater survival and stocking, but had little effect on the size of individual trees relative to disking and no site preparation treatments. Primary skid trails significantly reduced the size of individual trees, but had no appreciable long term effects on soil properties or stand productivity after 23 years. The study suggests that bedding is the most efficient practice to enhance soil properties, seedling survival, and stand productivity on wet sites. However, site preparation is not necessary for these soils and sites, if strictly intended to restore soil properties and stand productivity in primary skid trails. Reduction in individual tree sizes on primary skid trails emphasizes benefits in minimizing the spatial extent of disturbance.
Master of Science

The objective was to determine the effects of immunocastration (Improvest) on reproductive characteristics in boars. Seventy-two boars were used in a randomized design with three treatments: single injection (SI) or double injection (DI) of Improvest, and intact controls (no Improvest; CNT) (n = 24/group). At wk 10, 15, 20, 25, and 40, blood was collected and serum harvested to evaluate testosterone concentrations via RIA. At wk 25, 18 pigs (n = 6/ group) were sacrificed and testes were removed, weighed, and measured. Libido was assessed at 32, 36, 47, 60, and 63+ wk of age (1 to 5; 1 = no libido; 5 = high libido) and semen collected beyond 60 wk of age. Testosterone concentrations were less for DI boars compared to CNT boars and SI boars at 20 and 25 wk of age (P < 0.001), but not different at 40 wk of age. All testicular measurements and weight were less for DI boars compared to SI and CNT boars (P < 0.001). There was no treatment effect on libido between 32 to 63+ wk of age. Semen volume, gel weight and total number of sperm cells were not different among treatments. Sperm concentration was greater for DI than SI (P = 0.011), and tended to be greater for DI compared to CNT (P = 0.102). Sperm motility tended to be greater for DI boars compared to CNT boars (P = 0.066). The results show that there are no permanent effects of immunocastration on reproductive characteristics in boars.
Master of Science

Different scandals around the globe during the past, in specific during the last decade, have intrigued the stakeholders to question the roles of both auditors and management. But most of the fingers since then have been raised on the role of auditors, because it is the auditors who are entrusted with the responsibility to detect any errors or frauds in the financial reports of the client-firm. Apart from this, the long-term auditor client relationship has been the center of attention in most of the discussions and debates as well. Numerous studies have been conducted by the academic researchers, financial and professional analysts, regulatory authorities and governing bodies, and in some cases by the auditors and the firms as well regarding the effects of long-term auditor-client relationship on audit quality, equity risk premium, financial reports quality, audit pricing etc. These studies provide us with different results, both with the positive and negative associations and effects of long-term auditor-client relationship on the basis of different factors and contexts. For long, auditing has been discussed in different studies and research areas but mostly in association with publicly listed companies. Less attention has been paid to the relationship of auditors and clients as far as clients in SMEs are concerned. In any country around the globe, SMEs are of major contribution in terms of backing the economy, giving it both the boost and the stability, as they collectively form the major chunk of the economy. If we specify our study to the SMEs in Sweden, then 99% of the enterprises in Sweden represent the SME sector; in addition they employ around 60% of the manpower. Based on these facts, and due to less attention given to auditor-client relationship in terms of SMEs, instead of; we have directed our concerns towards the study of effects of auditor-client relationship on audit quality in SMEs in this particular research study. In this study, we have opted for qualitative research with semi-structured interviews to be used as the tool for data collection. Interviews were conducted with two different groups of interviewees, one group representing the auditors and the other group representing the client-firms (SMEs). A total of seven interviews were conducted in order to strengthen and validate the results for our research question. Due to the limitations of this study, mostly in terms of cost and time, samples were selected from Umeå, Sweden. The data interview structure, data analysis and discussion, and conclusions were all made based on existing theories summarized in the theoretical review of this study. The results of this study suggests that (1) long-term audit tenure is beneficial for the audit quality if certain risk factors like risk of auditor independence and risk of developing complacency are controlled; and (2) factors such as NAS, industry specialization, knowledge and experience of the auditor, internal control in the client-firm, professional ethics, proper audit plan, providence of unbiased information by the client, and appointment of the auditor by the client-firm itself enhances the audit quality.

博士
國立陽明大學
公共衛生研究所
94
Adverse metabolic effects have emerged as the most serious medical consequences of pharmacotherapy with some atypical antipsychotics. With the widespread use of atypical antipsychotics over the past several years, the associated side effect as weight gain, diabetes mellitus and dyslipidemia became apparent. The metabolic side effects were associated with increased relapse rate due to poor drug compliance, higher rates of morbidity and mortality due to an increased risk for cardiovascular and malignant disorders. Although numerous reports focused on the metabolic side effect with atypical antipsychotics, selection bias was associated with reports from side effect surveillance or claim data. Large- scaled longitudinal cohort study and reports about the prevalence of metabolic syndrome (MS) were sparse. Furthermore, although the non-Caucasians had been identified as the risk factor for developing DM, few reports of Chinese patients were published. The study was performed among the hospitalized patients in the Yu-Li Veterans Hospital, with the advantage of optimally control for possible confounding factors of diet, activity level and drug compliance. First part of the study is the long-term cohort study for weight change up to ten years among 876 patients on clozapine (n=349), olanzapine (n=188), and first generation antipsychotic (FGA,n=342). The second part is a survey of metabolic syndrome among 510 patients on clozapine (n=188), olanzpine (n=94), and risperidone (n=228). The related genetic polymorphism, adiponectin level, prolactin level and pharmacokinetic metabolites concentration were also evaluated to have an integrated analysis from long-term clinical data and related biomarkers. Cohort study for weight change (1) The first study sample was 96 patients on clozapine without exposure of other atypical antipsychotics. The multiple linear regression model showed two factors, significant initial clinical response and lower BBMI, were associated with more weight gain. The patients with significant initial clinical response had more 8-year weight gain than those without good initial clinical response (13.8±8.4 vs 4.5±12.0kg, respectively, p=0.03), and the significance showed since the third month. The genetic polymorphism data was further integrated into the GEE model for 8-year weight change showed alpha 2a-1291C>G and C825T polymorphism in the human G protein beta3 could predict 14-monthweight change, and TNF-α polymorphism could predict weight change up to 8 years. (2) Among 349 patients on clozapine (mixed subjects with and without exposure of other atypical antipsychotics), duration of clozapine treatment and baseline BMI were significant predictors for 8-year weight change. And the linear mixed model showed the weight gain reached a plateau until the 42th month, a consistent result with previous report. The clozapine metabolites concentration and CYP 1A2-t155g genetic polymorphism were not significant predictors for weight change. (3) Among total 876 cases, the GEE model showed four significant factors: antipsychotic classes, baseline BMI, treatment duration and age on initiation of atnispychtics, were to 12-month weight change. Olanzapine (p<0.0001) and clozapine (p<0.0007) had significantly more weight gain than FGA. The patients with baseline BMI less than 25 had more weight gain of 2.8 kg (p<0.0001). The younger to begin antipsychotic treatment, the more weight gain will be noted (p=0.0023) Prevalence of metabolic syndrome and predictive factors. According to the 2005 IDF criteria, the prevalence of central obesity, hypertriglycemia, low-HDL, hypertension, hyperglycemia and MS was 38.2%, 20.5%, 69.2%, 30.4%, 20.4%, and 23.5%, respectively; or 23.1% by NECP ATP III criteria, twice higher than that of Taiwan general population (12.9%). Compared to olanzapine and risperidone, the patients on clozapine had higher prevalence of central obesity, hypertryglycemia and metabolic syndrome. Weight gain is the significant predictors for metabolic syndrome and all metabolic components among patients on clozapine.The prevalence of diabetes mellitus was 14.5%, although no difference of prevalence was noted between different antipsychotics, the patients with DM in the clozapine group were significantly younger than that of patients on olanzapine and risperidone (p=0.001), and the GEE model showed treatment duration of clozapine and TNF-α were predictors for DM. Conclusion: The study was the largest Chinese cohort for weight gain and metabolic syndrome mong patients with mental disorders. The result showed atypical antipsychotics, clozapien and olanzapine, had significant higher risk of weight gain than FGA; and the earlier age at initiation of antipschotics, treatment duration, normal baseline BMI were risk factors for subsequent weight gain. The initial clinical response and TNF-α polymorphism can predict the weight gain associated with clozapie up to 8 years. The prevalence of MS among patients on atypical antipsychotics is 23.5%, which is higher than that of general population. The patients treated with clozapine had significantly higher prevalence of metabolic syndrome and hypertriglycemia than patients treated with olanzapine and risperidone. The patients with DM in the clozapine group were significantly younger than that of patients on olanzapine and risperidone; treatment duration and TNF-α were predictors for patients on clozapine developed DM. Limitation of the study was the nature of observation study, that the risk metabolic syndrome with olanzapine may have been underestimated due to high rate of disconinuation. In conclusion, the result showed metabolic syndrome was important issue for long-term care of patients with mental disorder, close monitoring and early intervention may be required for patients with risk factors.

博士
臺灣大學
預防醫學研究所
98
Background: FGAs had treatment-resistant, short-term EPS and long-term TD problems in schizophrenia treatment. SGAs were the choices for these problems. But which one of the SGA is the better choice does not have definitive conclusions. There were no related randomized controlled shifting studies. We compare the efficacy of two SGAs, risperidone and olanzapine, in schizophrenic patients with above three clinical problems. Materials and Methods: Patients were recruited as the inclusion and exclusion criteria of these three studies. These three studies are all flexible-dose, rater-blind, randomized controlled trial. In treatment-resistant to only one line of FGA study, subjects were randomly assigned to another FGA, risperidone or olanzapine group and study duration was 8 weeks. The primary endpoint of this study is the change of PANSS total score. In dystonia and parkinsonism study, subjects were randomly assigned to risperidone or olanzapine group and study duration was 8 weeks. The primary endpoint of this study is the proportion of subjects that need anticholinergic medications to treat clinical significant dystonia or parkinsonism. In TD study, subjects were randomly assigned to risperidone or olanzapine group and study duration was 24 weeks. The primary endpoint of this study is the change of AIMS total score. The statistical methods included chi-square or Fisher’s exact test for binominal data, Kaplan-Meier method or Cox regression model for survival analysis, independent, paired t-test and ANOVA for continuous variables, linear mixed model for repeated measurements. If continuous variables did not fit normal distribution and equal variance assumption, Mann-Whitney U test, Wilcoxon signed ranks test or Kruskal-Wallis test would be used. Results: In treatment-resistant to only one line of FGA study, there were no significant differences among the three groups in PANSS total score changes (FGA: -14.9±16.6, risperidone: -12.7±14.3, olanzapine: -14.8±13.7; p=0.890). Worsened EPS and higher proportion of subjects needed to use anti-EPS drugs in the FGA group. SGA group was associated with significant body weight gain. In dystonia and parkinsonism study, patients taking risperidone had significantly higher incidence of using anticholinergic drugs to manage dystonia or parkinsonism during the study (14/35 vs. 4/35, OR=5.17, 95% CI=1.49-17.88, p=0.013). If we used survival analysis to deal with the event time of anticholinergic drug use and censored cases, risperidone still had a higher hazard ratio (Log-rank test: p=0.0023; hazard ratio: 4.60, 95% CI: 1.70-11.52). In TD study, there were no significant differences among risperidone and olanzapine groups in AIMS total score changes (-7.4 ± 6.9, -6.2 ± 8.0; p=0.548). Discussion: In treatment-resistant to only one line of FGA study, FGA demonstrated similar efficacy of psychotic symptom reductions as risperidone or olanzapine. The findings suggest that side effect profiles might be taken into considerations for choosing the next antipsychotic drug. In dystonia and parkinsonism study, the results of this study favor olanzapine as a better choice in schizophrenic patients with intolerant EPS. This result is compatible with Maudsley prescription guideline suggests olanzapine as the first line medication and risperidone as second line medication. In TD study, the results of this study do not favor olanzapine as a better choice in schizophrenic patients with TD. This result is not compatible with Maudsley prescription guideline which suggests olanzapine as the first line medication and risperidone does not take into consideration in schizophrenic patients with TD.

Thesis (Ph.D.)--State University of New York at Buffalo, 2008.
Title from PDF title page (viewed on Jan. 15, 2009) Available through UMI ProQuest Digital Dissertations. Thesis adviser: Meier, Scott T. Includes bibliographical references.

Thesis (Ph.D.)--State University of New York at Buffalo, 2008.
Title from PDF title page (viewed on Jan. 23, 2009) Available through UMI ProQuest Digital Dissertations. Thesis adviser: Roe-Clark, Marcia Includes bibliographical references.

Anthropogenic pollutants are continuously released into the environment, which can result in long term exposure to soil organisms. Currently, standard guidelines focus on the assessment of effects to only one life stage, mostly juveniles, during a fixed exposure time. Additionally, these methods evaluate harmful effects of compounds to e.g. organism’s survival, reproduction and avoidance. Results obtained when testing these endpoints, even when combined, can under-/over-estimate potential damage to soil fauna. Therefore, the main aim of this thesis was to develop and explore different methodologies to assess the effects of pollutants, namely using different life stages of the soil ecotoxicological model species Folsomia candida and multigenerational exposure. Moreover, it was aimed to integrate a multi-endpoint approach, by comparing the sensitivity of the endpoints proposed in the standard methods, with additional tested ones. The assessment of the effects of a well-known and studied metal, cadmium, to different life stages of F. candida provided new and valuable information to understand how these organisms are affected. Cadmium decreased reproduction after exposure of adults, while no effect on hatching, survival and reproduction was observed when organisms were exposed from eggs. Therefore, effects of contaminants can cause different impact depending on the organism’s age. Also, an assessment of different endpoints may result in more detailed conclusions. After evaluation the concentration addition (CA) model to predict the toxicity of a mixture (biocidal product), both to assess reproduction and avoidance behaviour, two distinct results were obtained. While the model was able to predict effects on reproduction, it strongly underestimated the impact on avoidance. The evaluation of the impact of pollutants after multigenerational exposure showed to have an unpredictable impact over the generations. While the impact of ivermectin (veterinary product) to survival and reproduction of F. candida was similar in all three tested generations, the size of the organisms decreased. Effects on size were also observed after exposure to an insect growth regulator – teflubenzuron, in addition to a decrease in survival and reproduction with increasing time of exposure, i.e. along generations. Since size has a crucial role to reproduction, the continuity of the population may be at risk if exposed during long periods of time. Also, different results from cellular and biochemical markers were obtained across generations, which contributed to the understanding of the effects and mechanisms involved after long term exposure. This thesis shows that the present guidelines can be improved by the incorporation of new parameters in addition to the currently required or standard endpoints. The multi-endpoint approach used in this work, which incorporated measurement of size and evaluation of cellular and biochemical markers, in combination with standard endpoints such as survival, reproduction and avoidance, showed the added value of the inclusion of a more integrative approach to the current risk assessment framework.
Os poluentes antropogénicos são continuamente libertados para o meio ambiente, o que pode resultar numa exposição de longa duração para os organismos do solo. Atualmente, as normas padrão visam a avaliação de efeitos em apenas um estádio de vida, geralmente juvenis, durante um determinado período de tempo. Além disso, estes métodos avaliam os efeitos nocivos destes compostos p.e. na sobrevivência, reprodução e comportamento de evitamento dos organismos. Os resultados obtidos com estes parâmetros, mesmo quando combinados, podem potencialmente sub/sobrestimar as consequências para a fauna do solo. Assim, o principal objetivo desta tese foi desenvolver e explorar diferentes metodologias para avaliar os efeitos de poluentes, especificamente usando diferentes estádios de vida do organismo modelo ecotoxicológico Folsomia candida e a exposição multigeracional. Além disso, objetivou-se integrar uma abordagem multiparamétrica, comparando a sensibilidade dos parâmetros propostos pelos métodos padrão, com outros já testados. A avaliação dos efeitos de um conhecido e bastante estudado metal, o cádmio, em diferentes estágios de vida da Folsomia candida, forneceu novas e valiosas informações para perceber como estes organismos são afetados. O cádmio diminuiu a reprodução após a exposição de adultos, contudo não foram observados efeitos ao nível da eclosão, sobrevivência e reprodução quando os organismos foram expostos a partir de ovos. Assim, os efeitos dos contaminantes podem causar impactos diferentes dependendo da idade dos organismos. Além disso, uma avaliação de diferentes parâmetros permite conclusões mais detalhadas. Após a avaliação do modelo de concentraçãoadição (CA) para prever a toxicidade de uma mistura (produto biocida) na reprodução e evitamento, dois resultados distintos foram obtidos. Enquanto que o modelo foi capaz de prever os efeitos na reprodução, subestimou fortemente o impacto no evitamento. A avaliação do impacto dos poluentes após exposição multigeracional mostrou ter consequências imprevisíveis ao longo das gerações. Enquanto que o impacto do fármaco antiparasitário ivermectina na sobrevivência e reprodução de F. candida foi similar nas três gerações testadas, o tamanho dos organismos diminuiu. Efeitos no tamanho foram também observados após exposição ao inseticida teflubenzuron, além de uma diminuição na sobrevivência e reprodução com o aumento do tempo de exposição, isto é, ao longo das gerações. Dado que o tamanho é essencial para a capacidade reprodutiva, a continuidade das populações pode estar em risco se estiverem expostas durante longos períodos de tempo. Além disso, foram obtidos diferentes resultados de marcadores celulares e bioquímicos entre gerações, o que contribuiu para a compreensão dos efeitos e mecanismos envolvidos após uma longa exposição. Esta tese demonstra que as normas atuais podem ser melhoradas com a inclusão de novos parâmetros aos que são requeridos atualmente ou considerados padrão. A abordagem multiparamétrica usada neste trabalho, que incorporou a medição do tamanho e avaliação de biomarcadores, em combinação com os parâmetros padrão, tais como a sobrevivência, reprodução e evitamento, mostrou a importância da inclusão de uma abordagem mais integrativa no quadro atual de avaliação de risco.
Programa Doutoral em Biologia