From 2011 to 2031, the Canadian population living with neurological conditions is expected to double, but the population able to give informal care is not keeping pace, leading to a greater care burden. One element of this increasing care burden is emotional care. However, the effects of giving emotional care on caregiver health outcomes have not been sufficiently explored in the caregiving literature, where the majority of studies focus on instrumental forms of care, or fail to differentiate between different aspects of caregiving. This problem is further complicated by findings from other contexts which indicate that emotional supporting and helping others actually benefits the supporter or helper. Informed by the stress process and other ancillary theories, I use data from the 2012 General Social Survey to test several hypotheses which may help us understand the mental health, functional health, and caregiver burden of caregivers of persons with neurological conditions who emotionally support their care receivers, and of caregivers who are the sole provider of emotional support. The results suggest that emotionally supporting a care receiver with a neurological condition is detrimental to caregiver mental health, and that being the sole emotional supporter is detrimental to caregiver mental health, functional health, and experience of burden. A significant interaction effect also exists between emotional supporting and caregiver gender for functional health. These findings have important implications for future research, for intervention planners, and for caregivers themselves. / Graduate / 2020-08-06

Cerca de 20 % dos casos familiares de esclerose lateral amiotrófica (ELAf) são causados por mutações na enzima Cu,Zn-superóxido dismutase (SOD1). Inicialmente se supôs que as enzimas mutantes teriam a atividade SOD comprometida, entretanto isto não foi comprovado. Atualmente, considera-se que as enzimas mutantes adquiram propriedades tóxicas. Quais seriam estas propriedades e como levariam à degeneração do neurônio motor são questões ainda não respondidas. Neste trabalho, comparamos neuroblastomas humanos transfectados com SOD1 G93A associada à ELAf (SH-SY5YG93A), e SOD1 selvagem (SH-SY5YWT) com células parentais (SH-SY5Y) em relação ao crescimento, viabilidade, produção basal de oxidantes, atividades SOD e peroxidásica e modificações estruturais da SOD. As células transfectadas apresentaram aumento na taxa de crescimento e na produção basal de oxidantes. As células SH-SY5YWT e SH-SY5YG93A mantiveram a expressão de SOD1 e atividade consistente com o aumento esperado de duas vezes, em estágios iniciais de cultura. A atividade peroxidásica do homogenato da célula SH-SY5YG93A foi maior. Após quatro semanas, a linhagem SH-SY5YG93A manteve a expressão de SOD1, mas as atividades dismutásica e peroxidásica diminuíram. A expressão de SOD1 aumentou a proporção de formas alteradas de SOD1, como enzima reduzida, multímeros formados por ponte dissulfeto e formas insolúveis em detergente, particularmente na linhagem SH-SY5YG93A. Entre estas formas insolúveis, identificamos um dímero covalente de SOD. Estas formas alteradas provavelmente são responsáveis pela ativação do proteassomo e estresse do retículo endoplasmático, verificados nas células transfectadas. Concluindo, a superexpressão da SOD1 foi suficiente para elevar as formas imaturas e oligomerizadas de SOD1 e a oxidação basal, e a mutação G93A ressaltou estes processos. / Some familial ALS (fALS) are caused by mutations in the Cu,Zn-superoxide dismutase enzyme (SOD1). It was thought that the mutated enzymes would have impaired SOD activity, but this has not been corroborated so far. Presently, it is more accepted that the mutated enzymes acquire a new toxic function. What this new toxic function is and how it relates to the degeneration of motor neurons remains debatable. Here, we compared human neuroblastoma cells transfected with fALS mutant G93A (SH-SY5YG93A) or wild-type SOD1 (SH-SY5YWT) with parent cells (SH-SY5Y) in regard to growth, viability, basal oxidant production, SOD and peroxidase activities, and SOD forms. Transfected cells presented increased growth rate and basal oxidant production. SH-SY5YWT and SH-SY5YG93A cells in early culture stage showed SOD expression and activity consistent with the expected two-fold increase; SH-SY5YWT homogenates showed increased peroxidase activity. After four weeks, SH-SY5YG93A maintained SOD1 expression levels but peroxidase and dismutase activities were lower. SOD1 expression increased the levels of altered SOD1 forms such as the reduced enzyme, disulfide multimers and detergent-insoluble forms, particularly in SH-SY5YG93A cells. Among the insoluble forms a covalent SOD dimer was identified. These altered SOD forms are probably responsible for proteasome activation and endoplasmatic reticulum stress response verified in transfected cells. In conclusion, SOD1 over-expression was sufficient to increase intracellular immature and oligomerized SOD1 forms and basal oxidation and the G93A mutation enhanced these processes.

Made available in DSpace on 2016-08-10T10:38:40Z (GMT). No. of bitstreams: 1 ALEANDRO GERALDO ALVES.pdf: 687501 bytes, checksum: 815caf3ef15e76a3ef410c769760c097 (MD5) Previous issue date: 2011-08-11 / Amyotrophic lateral sclerosis (ALS) is a multifactorial disease that affects motor neurons. In most cases, the disease is sporadic, however, 5 to 10% of patients have a familial history (FALS). Among patients with FALS, 12 to 23% present with mutations in the SOD1 gene. Objectives: To present a systematic review about the mutations described in SOD1 gene in patients with FALS. Methods: The databases used in this study included PubMed, ISI Web of Science and Cochrane Library Virtual Health. After reading the abstracts, 71 articles were selected and systematically reviewed on this study. Results: The largest number of publications was found in 1997, and Japan was the country with the majority of published studies on the subject, with 23 articles. The majority of the mutations were described in éxons four and five of SOD1 gene, and A4V, I113T, I144F, D90A and L38V were the most commonly mutation described. More than 156 mutations in the SOD1 gene have been cataloged in patients with ALS-F and these data are deposited in ALS GENETICS ONLINE DATABASE, a database that contains specific information on mutations associated with amyotrophic lateral sclerosis. However, the articles reviewed in this study described 103 mutations. Conclusions: Several mutations in the SOD1 gene have been described in patients with ALS-F, however, the relationship between such mutations and the pathogenesis of ALS-F remains unclear, as well as the relationship between mutations and disease progression. Further studies are necessary in order to better explain such relationship. / A esclerose amiotrófica lateral (EAL) é uma doença multifatorial que afeta os neurônios motores. Na maioria dos casos, a doença é esporádica, entretanto, 5 a 10% dos pacientes apresentam história familiar (EAL-F). Dentre os pacientes com EAL-F, 12 a 23% apresentam mutações no gene SOD1. O objetivo deste trabalho foi realizar uma revisão sistemática acerca das mutações descritas no gene SOD1 em pacientes com EAL-F. As bases de dados consultadas incluíram Pubmed, ISI Web of Science e Cochrane Biblioteca Virtual em Saúde. Após a revisão dos resumos, 71 artigos foram selecionados descrevendo mutações no gene SOD1 em pacientes com EAL-F. O ano que apresentou o maior número de publicações foi 1997 e o Japão foi o país que mais publicou sobre o assunto, aparecendo em 23 artigos. O maior número de mutações foi descrito nos éxons 4 e 5 do gene SOD1 e as mutações A4V, I113T, I144F, D90A e L38V foram as mais comumente citadas. Até o momento 156 mutações no gene SOD1 já foram catalogadas em pacientes com EAL-F e esses dados encontram-se depositados no ALS ONLINE GENETICS DATABASE, um banco de dados que contém informações específicas sobre mutações associadas à esclerose amiotrófica lateral. Entretanto, os artigos revisados neste estudo descrevem 103 destas mutações. As causas relacionadas às mutações no gene SOD1 permanecem incertas, assim como a relação entre tais mutações e a evolução da doença, portanto, muito ainda deve ser estudado acerca desse tema.

<p>Amyotrophic lateral sclerosis is a fatal, progressive neurodegenerative disease with unknown ethiology. The aim of this study was to increase understanding of the pathophysiological mechanisms of dying motor neurons and wasting muscle tissue in this particular disorder.</p><p>Quantitative receptor autoradiographic methodology was applied on cervical spinal cord sections from patients with ALS to evaluate the specific binding of the acetylcholine transporter ³H-vesamicol in motor neurons. Despite a significant reduction of the number of ventral motor neurons in ALS, the ³H-vesamicol binding was not reduced in ALS compared to control cases, which suggests an increased metabolic activity in remaining motor neurons.</p><p>Motor neurons dying in ALS might go through apoptosis (programmed cell death), so immunohistochemical and TUNEL techniques were applied on thoracic spinal cord from ALS patients to evaluate the possibility of an apoptotic process. The increased Bax expression indicates an apoptotic process and further, motor neurons were TUNEL-positive, indicating DNA degradation caused by programmed cell death.</p><p>Muscle biopsies were obtained from ALS patients, and mRNA levels for the neurotrophic factors GDNF and BDNF were measured and compared to control subjects. GDNF levels were increased in muscle tissue in ALS whereas BDNF levels were unaltered.</p><p>Levels of GDNF and BDNF were also measured in cerebrospinal fluid from ALS patients and controls using ELISA methodology. Levels of BDNF were unaltered in ALS cornpared to controls. GDNF however was not detectable in controls whereas 12 out of 15 ALS patients had measurab1e levels of GDNW. A marked upregulation of endogenous GDNF and GDNF mRNA in ALS CSF and muscle respectively is of special interest in relation to clinical trials where GDNF is administered to this group of patients.</p>

Amyotrophic lateral sclerosis is a fatal, progressive neurodegenerative disease with unknown ethiology. The aim of this study was to increase understanding of the pathophysiological mechanisms of dying motor neurons and wasting muscle tissue in this particular disorder. Quantitative receptor autoradiographic methodology was applied on cervical spinal cord sections from patients with ALS to evaluate the specific binding of the acetylcholine transporter 3H-vesamicol in motor neurons. Despite a significant reduction of the number of ventral motor neurons in ALS, the 3H-vesamicol binding was not reduced in ALS compared to control cases, which suggests an increased metabolic activity in remaining motor neurons. Motor neurons dying in ALS might go through apoptosis (programmed cell death), so immunohistochemical and TUNEL techniques were applied on thoracic spinal cord from ALS patients to evaluate the possibility of an apoptotic process. The increased Bax expression indicates an apoptotic process and further, motor neurons were TUNEL-positive, indicating DNA degradation caused by programmed cell death. Muscle biopsies were obtained from ALS patients, and mRNA levels for the neurotrophic factors GDNF and BDNF were measured and compared to control subjects. GDNF levels were increased in muscle tissue in ALS whereas BDNF levels were unaltered. Levels of GDNF and BDNF were also measured in cerebrospinal fluid from ALS patients and controls using ELISA methodology. Levels of BDNF were unaltered in ALS cornpared to controls. GDNF however was not detectable in controls whereas 12 out of 15 ALS patients had measurab1e levels of GDNW. A marked upregulation of endogenous GDNF and GDNF mRNA in ALS CSF and muscle respectively is of special interest in relation to clinical trials where GDNF is administered to this group of patients.

New biomarkers are needed to improve knowledge about pathophysiology, in order to provide earlier correct diagnosis and to follow disease progression of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). The aim of this thesis was to find new biomarkers for these diseases. First, increased serum levels and unchanged levels in postmortal spinal cord of vascular endothelial growth factor (VEGF) were demonstrated. VEGF was not detected in cerebrospinal fluid (CSF) in ALS. Second, increased levels of fibroblast growth factor 2 were found in the CSF and serum of ALS patients. Both studies used enzyme-linked immunoassays. Third, a proteomics method for CSF analysis was explored, based on tryptic digestion and subsequent separation and detection of the peptides by on-line liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry. ALS-specific patterns were observed. Four out of five samples were correctly assigned, but no single protein biomarker could be identified. Fourth, [11C](L)-deprenyl-D2 (DED) positron emission tomography (PET) demonstrated increased retention in the pons and white matter in ALS. DED binds to monoamino oxidase B, which in the brain is primarily located in astrocytes. Thus evidence was provided that astrocytosis may be detected in vivo in ALS. Fifth, normal [11C]-PIB binding in five nondemented patients with PD was reported, in contrast to previous findings of increased retention in Alzheimer's disease reflecting amyloid aggregation. Finally, the combined use of fluorodeoxyglucose and L-[β 11C]-DOPA PET for the differential diagnosis of parkinsonian syndromes was evaluated. PET provided support for the clinical diagnosis in 62 out of 75 patients, and served to exclude suspected diagnoses in another five patients.

La fitorremediación es una técnica de descontaminación de ecosistemas que aprovecha la capacidad de las plantas para acumular sustancias tóxicas en su interior sin que afecten severamente a su ciclo vital. Dicha técnica presenta un bajo impacto medioambiental, convirtiéndose en una alternativa a los métodos clásicos, más agresivos y costosos. En lo referente a metales pesados, las plantas inducen la síntesis intracelular de fitoquelatinas (PC), ligandos tiólicos que complejan los metales y los almacenan en orgánulos celulares de bajo metabolismo como las vacuolas. A pesar de las investigaciones realizadas hasta la fecha, el mecanismo de actuación de las fitoquelatinas no está totalmente establecido, incluida la secuencia de formación y la estequiometria final de los complejos PC-M. Por esta razón, resulta de gran interés estudiar estos procesos de complejación, pues sus conclusiones pueden ayudar a entender la fitorremediación y a optimizar su aplicación. Las investigaciones recogidas en esta tesis se sustentan -como metodología básica- en el análisis quimiométrico mediante MCR-ALS de los datos obtenidos de valoraciones complexométricas registradas por técnicas electroanalíticas, concluyendo con la proposición de modelos de complejación para el sistema en estudio. La elección del plomo como metal complejante se debe a su alta toxicidad y dispersión en el medio ambiente, así como por suponer un paso más en el uso de dicha metodología, pues el estudio de los sistemas PC/Pb(II) presentan problemas que la dificultan. Estos problemas son, principalmente, el desplazamiento lateral de las señales voltamperométricas que produce un decrecimiento en la linealidad de los datos obtenidos, y la presencia de señales anódicas que favorece un fuerte solapamiento entre los picos de las diferentes especies químicas; ambos problemas comprometen la aplicación del método MCR-ALS y el correcto examen de los resultados. El objetivo de esta tesis adquiere así una doble vertiente. Por un lado, para solucionar dichos problemas y, de alguna forma, ampliar la aplicabilidad de MCR-ALS a eventuales sistemas más complejos, se estudian nuevas adaptaciones metodológicas (análisis MCR-ALS de matrices espectro-voltamperométricas), herramientas (programa shiftfit, que corrige el desplazamiento de potencial de las señales voltamperométricas) y metodologías experimentales (uso de electrodos alternativos al de mercurio). Por otro lado, se procura la consecución de resultados para los propios sistemas PC/Pb(II) estudiados, es decir, la determinación de modelos de complejación lo bastante completos y sólidos para servir de apoyo a los resultados de los estudios in vivo o in vitro. Los trabajos publicados y la explicación de los resultados están organizados en tres bloques: • El primer bloque (artículo 11.1) recoge la aproximación inicial al estudio de la complejación de fitoquelatinas y ligandos relacionados con plomo utilizando la metodología básica. Los resultados ponen de relieve la relativa solvencia del procedimiento, así como el verdadero alcance de los problemas que se describen en el capítulo 5. • El segundo bloque recopila los resultados de la aplicación de las nuevas metodologías y herramientas propuestas para solucionar las insuficiencias o ambigüedades de los modelos de complejación obtenidos en el artículo anterior. Estas metodologías son el análisis quimiométrico conjunto de valoraciones registradas por polarografía y dicroísmo circular (11.2), la formulación del programa shiftfit que corrige el movimiento lateral de señales polarográficas, es decir, la falta de un valor fijo del potencial de pico (11.3) y, finalmente, el uso del electrodo de película de bismuto (BiFE) con la intención de minimizar el solapamiento que producen las señales anódicas (11.4). • Tras la aplicación de estas metodologías a sistemas sencillos, en el tercer bloque se aplican a sistemas con plomo (11.5 y 11.6), incluyendo la comparación de los diferentes modelos de complejación obtenidos en los artículos 11.1 y 11.5 para el sistema PC3/Pb(II). / Phytoremediation is a decontamination technique that takes profit by the plants ability to accumulate toxic substances without affecting severely their vital cycles. This technique presents the advantatges of being cheap and non-destructive to ecological systems. Regarding heavy metals, plants induce the intracellular synthesis of phytochelatins (PC), Cys-rich polypeptides that complex metals and storage them in cellular organelles of limited metabolism as vacuoles. Despite the research achieved to date, the mechanism of actuation of phytochelatins is not entirely established, including the sequence of formation and the final stoichiometry of the PC-M complexes. By this reason, it is of great interest to study these complexation processes, reaching conclusions that would be able to help the optimization of phytoremediation. The investigations collected in this doctoral thesis are held -as basic methodology- in the chemometric analysis through MCR-ALS of the data obtained from complexometric titrations carried out by voltammetric techniques. This methodology concludes with the proposition of complexation models for the systems under study, but when lead is used as complexing metal, PC/Pb(II) systems present problems that make it more difficult. Mainly, these problems are the lateral movement of the voltammetric signals (producing a decrease in the linearity of the data), and the presence of anodic signals that propitiate a strong overlapping between peaks of different chemical species; both troubles compromise the MCR-ALS application and the correct investigation of the results. To solve the aforementioned problems -and that way to increase the applicability of MCR-ALS to more complex systems-, some new tools have been applied for the first time: • Methodologic adaptations as the MCR-ALS simultaneous analysis of spectro- and electrochemical data (row-wise CD-DPP augmented matrices) to differenciate real chemical species from physicochemical or kinetic phenomena of the diffusion layer. • Chemometric programs as shiftfit that corrects the potential shift of the polarographic signals to obtain a matrix of corrected voltammograms with an increased linearity. • The use of the bismuth film electrode (BiFE) for complexation studies, to minimize the overlapping produced by the anodic signals.

<p>In this research project the question is raised whether it is possible to detect and analyse differences between incidental and intentional vocabulary acquisition within a traditional, systematic teaching setting of German as an L3. The ten par-ticipating Swedish students at the upper secondary level worked with two differ-ent German newspaper articles in two different ways. One set of lessons focused mainly on textual content (incidental learning) while the other involved both dis-cussions about the contents of the text and explicit vocabulary practice (inten-tional learning). The students were later tested on four separate occasions using a self-report-test involving 16 pre-tested words. The two main research questions are: How many of the encountered words will the students recall and what depth of knowledge does this recall represent? Results point to a very limited vocabu-lary acquisition through incidental learning compared to the acquisition through intentional learning which gave a higher score. The overall tendency is for ac-quired vocabulary knowledge to change over time and more so if intentionally acquired. This raises a further question: How much and what kind of work in-volving texts is needed in the classroom for long lasting vocabulary acquisition, incidental or intentional, to take place? Furthermore the results indicate that the self-report test used in the research project shows deficiencies regarding validity as well as reliability issues, which puts further focus on the test methods used in educationally applied vocabulary acquisition research.</p>

Diss. (sammanfattning) Umeå : Umeå universitet, 2009. / Härtill 5 uppsatser. Även tryckt utgåva.

Lipids are important for structural and physiological functions of neuronal cell membranes. They exhibit a range of biological effects many are bioactive lipid mediators derived from polyunsaturated fatty acids such as sphingolipids, fatty acid ethanolamides (FA-EA) and endocannabinoids (EC). These lipid mediators and oxysterols elicit potent bioactive functions in many physiological and pathological processes of the brain and neuronal tissues. They have been investigated for biomarker discovery of ageing, neuroinflammation and neurodegenerative disorders. The n-3 fatty acids EPA and DPA are thought to exhibit a range of neuroprotective effects many of which are mediated through production of such lipid mediators. The aims of this study were to evaluate the effects of n-3 EPA and n-3 DPA supplementation on RBC membranes and in this way assess dietary compliance and to investigate brain sphingomyelin species of adult and aged rats supplemented with n-3 EPA and n-3 DPA to evaluate the effects and benefits on age-related changes in the brain. Furthermore, to study the effects of lithium on the brain FA-EAs and ECs to further understand the neuroprotective effects of lithium neuroprotective action on neuroinflammation as induced by LPS. Finally to examine if circulating oxysterols are linked to the prevalence of ALS and whether RBC fatty acids are markers of this action in relation to age and disease stages. These analytes were extracted from tissue samples and analysed with GC, LC/ESI-MS/MS and GC-MS. It was found that aged rats exhibited a significant increase in brain AA and decrease in Σn-3 and Σn-6 PUFAs when compared to adult animals. The observed increase of brain AA was reversed following n-3 EPA and n-3 DPA supplementation. Sphingomyelin was significantly increased when aged animals were supplemented with n-3 DPA. LPS treatment following lithium supplementation increased LA-EA and ALA-EA, while it decreased DHA-EA. Both oxysterols 24-OH and 27-OH increased in ALS patients and SOD1-mice. Eicosadienoic acid was different in ASL-patients compared to aged SOD1-mice. These studies demonstrated that dietary intake of n-3 EPA and n-3DPA significantly altered RBC fatty acids and sphingolipids in rat brain. They suggest that n-3 DPA can be a potential storage form for EPA, as shown by retro-conversion of n-3 DPA into EPA in erythrocyte membranes, ensuring supply of n-3 EPA. Also, n-3 EPA and n-3 DPA supplementation can contribute to an increase in brain sphingomyelin species with implications for age effects and regulation of brain development. Effects of lithium highlight novel anti-neuroinflammatory treatment pathways. Both 24-hydroxycholesterol and eicosadienoic acid may be used as biomarkers in ALS thereby possibly helping to manage the progressive stages of disease.