Elizabeth Sumi Yamada

Neurology, Neuroscience

MD, PhD
28.40

Publications


  • No preview · Article · Feb 2016
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    ABSTRACT: Type 1 Diabetes Mellitus (Type 1 DM) affects the psychological and emotional well-being of patients and their families. This study aims to evaluate the health- related quality of life (HRQoL) of people with Type 1 DM in Brazil, a country of continental proportions, using the EuroQol questionnaires. This was a retrospective, cross-sectional, multicenter study performed by the Brazilian Type 1 Diabetes Study Group, by analyzing EuroQol scores from 3,005 participants with Type 1 DM, in 28 public clinics in Brazil. Data on demography, economical status, chronic complications, glycemic control and lipid profile were also collected. The assessment of HRQoL by the EuroQol showed that the average score assigned to general health in Brazil is markedly lower than those found in two other Type 1 DM population-based studies conducted in Europe (EQ–VAS from the Netherlands, the United Kingdom and Brazil were 80.8 ± 15.2, 75.1 ± 18.4 and 72.5 ± 22, respectively). Additionally, our data suggest that a better glycemic control could positively impact the HRQoL of people with Type 1 DM, implying that each 1 % reduction in glycated haemoglobin might lead to an increase of 1.5 points in general health status assessed by the EuroQol. This is a population-based study evaluating the HRQoL of people with Type 1 DM in Brazil. Our data indicate a worse quality of health of people with Type 1 DM in Brazil in comparison to Europe, and suggest that a better glycemic control could positively impact the HRQoL of these individuals. However, this study points to the existence of additional factors not yet evaluated that could be determinant in the HRQoL of these people.
    Full-text · Article · Dec 2015 · Health and Quality of Life Outcomes
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    DESCRIPTION: Swietenia macrophylla (mahogany) is a highly valued timber species, whereas the leaves are considered to be waste product. A total of 27 phenolic compounds were identified in aqueous extracts from mahogany leaves by comparing retention times and mass spectra data with those of authentic standards using LC-ESI-MS/MS. Polyphenols play an important role in plants as defense mechanisms against pests and pathogens and have potent antioxidant properties. In terms of health applications, interest has increased considerably in naturally occurring antioxidant sources, since they can retard the progress of many important neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. The antioxidant capacities of two aqueous extracts, M1 (decoction) and M2 (infusion), were measured using TEAC and Folin-Ciocalteau methods. Additionally, M1 was used in order to investigate its potential cytoprotective effects on an in vitro model of neurodegeneration, by using primary cerebellar cultures exposed to methyl mercury (MeHg). Under experimental sub-chronic conditions (72 h), concomitant exposure of the same cultures to MeHg and M1 extract resulted in a statistically significant increase in cell viability in all three concentrations tested (10, 50 and 100 μg/mL), strongly suggesting that due to its high content of antioxidant compounds, the M1 extract provides significant cytoprotection against the MeHg-induced in vitro neurotoxicity.
    Full-text · Research · Oct 2015
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    ABSTRACT: Background In type 1 diabetes mellitus (T1DM) management, enhancing health-related quality of life (HRQoL) is as important as good metabolic control and prevention of secondary complications. This study aims to evaluate possible regional differences in HRQoL, demographic features and clinical characteristics of patients with T1DM in Brazil, a country of continental proportions, as well as investigate which variables could influence the HRQoL of these individuals and contribute to these regional disparities. Methods This was a retrospective, cross-sectional, multicenter study performed by the Brazilian Type 1 Diabetes Study Group (BrazDiab1SG), by analyzing EuroQol scores from 3005 participants with T1DM, in 28 public clinics, among all geographical regions of Brazil. Data on demography, economic status, chronic complications, glycemic control and lipid profile were also collected. Results We have found that the North-Northeast region presents a higher index in the assessment of the overall health status (EQ-VAS) compared to the Southeast (74.6 ± 30 and 70.4 ± 19, respectively; p < 0.05). In addition, North-Northeast presented a lower frequency of self-reported anxiety-depression compared to all regions of the country (North-Northeast: 1.53 ± 0.6; Southeast: 1.65 ± 0.7; South: 1.72 ± 0.7; Midwest: 1.67 ± 0.7; p < 0.05). These findings could not be entirely explained by the HbA1c levels or the other variables examined. Conclusions Our study points to the existence of additional factors not yet evaluated that could be determinant in the HRQoL of people with T1DM and contribute to these regional disparities.
    Full-text · Article · Oct 2015 · Diabetology and Metabolic Syndrome
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    ABSTRACT: The pathogenesis of diabetic cardiomyopathy (DCM) is partially understood and is likely to be multifactorial, involving metabolic disturbances, hypertension and cardiovascular autonomic neuropathy (CAN). Therefore, an important need remains to further delineate the basic mechanisms of diabetic cardiomyopathy and to apply them to daily clinical practice. We attempt to detail some of these underlying mechanisms, focusing in the clinical features and management. The novelty of this review is the role of CAN and reduction of blood pressure descent during sleep in the development of DCM. Evidence has suggested that CAN might precede left ventricular hypertrophy and diastolic dysfunction in normotensive patients with type 2 diabetes, serving as an early marker for the evaluation of preclinical cardiac abnormalities. Additionally, a prospective study demonstrated that an elevation of nocturnal systolic blood pressure and a loss of nocturnal blood pressure fall might precede the onset of abnormal albuminuria and cardiovascular events in hypertensive normoalbuminuric patients with type 2 diabetes. Therefore, existing microalbuminuria could imply the presence of myocardium abnormalities. Considering that DCM could be asymptomatic for a long period and progress to irreversible cardiac damage, early recognition and treatment of the preclinical cardiac abnormalities are essential to avoid severe cardiovascular outcomes. In this sense, we recommend that all type 2 diabetic patients, especially those with microalbuminuria, should be regularly submitted to CAN tests, Ambulatory Blood Pressure Monitoring and echocardiography, and treated for any abnormalities in these tests in the attempt of reducing cardiovascular morbidity and mortality.
    No preview · Article · Sep 2015 · Current diabetes reviews
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    ABSTRACT: The P301S mutation in exon 10 of the tau gene causes a hereditary tauopathy. While mitochondrial complex I inhibition has been linked to sporadic tauopathies. Piericidin A is a prototypical member of the group of the piericidins, a class of biologically active natural complex I inhibitors, isolated from streptomyces spp. with global distribution in marine and agricultural habitats. The aim of this study was to determine whether there is a pathogenic interaction of the environmental toxin piericidin A and the P301S mutation. Transgenic mice expressing human tau with the P301S-mutation (P301S+/+) and wild-type mice at 12 weeks of age were treated subcutaneously with vehicle (N = 10 P301S+/+, N = 7 wild-type) or piericidin A (N = 9 P301S+/+, N = 9 wild-type mice) at a dose of 0.5 mg/kg/d for a period of 28 days via osmotic minipumps. Tau pathology was measured by stereological counts of cells immunoreative with antibodies against phosphorylated tau (AD2, AT8, AT180, and AT100) and corresponding Western blot analysis. Piericidin A significantly increased the number of phospho-tau immunoreactive cells in the cerebral cortex in P301S+/+ mice, but only to a variable and mild extent in wild-type mice. Furthermore, piericidin A led to increased levels of pathologically phosphorylated tau only in P301S+/+ mice. While we observed no apparent cell loss in the frontal cortex, the synaptic density was reduced by piericidin A treatment in P301S+/+ mice. This study shows that exposure to piericidin A aggravates the course of genetically determined tau pathology, providing experimental support for the concept of gene-environment interaction in the etiology of tauopathies.
    Full-text · Article · Dec 2014 · PLoS ONE
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    ABSTRACT: Introdução: O acidente vascular cerebral (AVC) é um dos maiores causadores de debilidades nos países desenvolvidos e em desenvolvimento. Dois fatores importantes no cuidado do AVC é a prevenção e o diagnóstico precoce. Pesquisas recentes vêm associando a patogênese do AVC à mutações nos ncRNAs, sendo o mais estudado o micro-RNA. Várias sequências de micro-RNA estão sendo descobertas. Estas foram detectáveis in situ e em sangue periférico em apresentações padronizadas especificas à natureza patogênica. Este estudo objetiva sumarizar e analisar a possibilidade do uso de micro-RNA como biomarcadores para o diagnóstico de AVC. Métodos: Foi realizado uma revisão sistemática com artigos encontrados no banco de dados online Medline (através do Pubmed) e também com as referências citadas nos artigos selecionados, todos contendo as palavras chaves “micro-RNA” e “stroke”. Dois autores realizaram a análise e a triagem dos estudos separadamente para evitar viés de seleção e perda de dados. Resultados: Foram encontrados 38 artigos, dentre os quais, após exaustiva análise, foram selecionados 12 baseados em objetivo, tipo de estudo, população, técnica adotada e resultados para análise comparativa. Conclusão: Os miRNAs podem em um futuro próximo ser utilizados como ferramenta para realização de prognóstico de AVC, assim como sub-classificar baseado em tempo e fator etiológico.
    Full-text · Conference Paper · Sep 2014
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    ABSTRACT: Both genetic and environmental factors likely contribute to the neuropathology of tauopathies, but it remains unclear how specific genetic backgrounds affect the susceptibility towards environmental toxins. Mutations in the tau gene have been associated with familial tauopathies, while annonacin, a plant-derived mitochondrial inhibitor, has been implicated in an environmental form of tauopathy. We therefore determined whether there was a pathogenic synergy between annonacin exposure and the expression of the R406W-tau mutation in transgenic mice. We found that annonacin exposure caused an increase in the number of neurons with phosphorylated tau in the somatodendritic compartment in several brain areas in R406W(+/+) mice as opposed to mice that had only the endogenous mouse tau (R406W(-/-)). Western blot analysis demonstrated a concomitant increase in total tau protein without increase in tau mRNA, but reduced proteasomal proteolytic activity in R406W(+/+), but not R406W(-/-) mice, upon annonacin-treatment. Phosphorylated tau levels exceeded the increase in total tau protein, along with increased levels of different tau kinases, foremost a striking increase in the p25/p35 ratio, known to activate the tau kinase Cdk5. In summary, we observed a synergistic interaction between annonacin exposure and the presence of the R406W-tau mutation, which resulted in reduced degradation, increased phosphorylation and redistribution of neuronal tau.
    No preview · Article · Jan 2014 · Experimental Neurology
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    Full-text · Dataset · Nov 2013
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    ABSTRACT: Five new flavonoids, 5,3'-dihydroxy-4'-methoxy-2'',2''-dimethylchromene-(5'',6'':6,7)dihydroflavonol (1), 5,3'-dihydroxy-7,4'-dimethoxy-6,8-dimethylallyl-dihydroflavonol (2), 5,3'-dihydroxy-4'-methoxy-8-allyl-2'',2''-dimethylchromene-(5'',6'':6,7) flavanone (3), 5,3'-dihydroxy-7,4'-dimethoxy-6,8-dimethylallyl-flavanone (4), 3,5,3'-trihydroxy-7,4'-dimethoxy6,8-dimethylallyl-flavanol (5), together with the stilbenes 4-methoxylonchocarpene (6) and lonchocarpene (7) were isolated from the leaves of Deguelia utilis. Their chemical structures were established on the basis of NMR (nuclear magnetic resonance) spectral data and HRESITOF-MS (electrospray ionization-high resolution time-of-flight mass spectrometry). Also, in order to investigate potential cytoprotective effects of these flavonoids, we used a fraction eluted with hexane:EtOAc containing all seven flavonoids, in an in vitro model of neurodegeneration, using hippocampal primary cultures from neonatal (PND2-P3) rats exposed to rotenone, a mitochondrial complex I inhibitor. There was a significant reduction in cell viability (19.4 ± 1.6%) when the cultures were exposed to 30 nmol L-1 rotenone for 72 h. Concomitant exposure of the cultures to the FR3 (5 µg mL-1) and 30 nmol L-1 rotenone resulted in values of cell viability similar to control groups (99.6 ± 4.8%), strongly suggesting a cytoprotective effect for this flavonoid-rich fraction.
    Full-text · Article · Oct 2012 · Journal of the Brazilian Chemical Society

  • No preview · Article · Mar 2011 · Basal Ganglia
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    ABSTRACT: The tyrant flycatchers represent a monophyletic radiation of predominantly insectivorous passerine birds that exhibit a plethora of stereotyped prey capture techniques. However, little is known about their retinal organization. Using retinal wholemounts, we estimated the total number and topography of neurons in the ganglion cell layer in the generalist yellow-bellied elaenia (Elaenia flavogaster) and the up-hover-gleaner mouse-colored tyrannulet (Phaeomyias murina) with the optical fractionator method. The mean estimated total number of neurons in the ganglion cell layer was 4,152,416 +/- 189,310 in E. flavogaster and 2,965,132 +/- 354,359 in P. murina. Topographic maps of isocounting lines revealed a similar distribution for both species: a central fovea and a temporal area surrounded by a poorly defined horizontal streak. In addition, both species had increased numbers of giant ganglion cells in the dorsotemporal retina forming an area giganto cellularis. In E. flavogaster, these giant ganglion cells were also distributed across the nasal and ventral retinal peripheries, which is in agreement with the generalist habits of this species. However, in P. murina these cells were rarely seen along the nasal and ventral peripheries, possibly reflecting a lesser need to perceive movement because this species captures stationary insects resting on foliage. Thus, we suggest that the retinas of the tyrant flycatchers in the present study show a general common pattern of neuron distribution in the ganglion cell layer irrespective of their foraging habits. We also suggest that the distribution of giant ganglion cells is indicative of the visual requirements of the species.
    Full-text · Article · May 2009 · The Journal of Comparative Neurology

  • No preview · Conference Paper · Feb 2009
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    ABSTRACT: The clinical motor dysfunction in Parkinson's disease is primarily the consequence of a progressive degeneration of dopaminergic neurons in the substantia nigra of the nigrostriatal pathway. The degeneration of this tract provokes a depletion of dopamine in the striatum, where it is required as a permissive factor for normal motor function. Despite intense investigations, no effective therapy is available to prevent the onset or to halt the progression of the neuronal cell loss. Therefore, recent years have seen research into the mechanisms of endogenous repair processes occurring in the adult brain, particularly in the substantia nigra. Neurogenesis occurs in the adult brain in a constitutive manner under physiological circumstances within two regions: the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. In contrast to these two so-called neurogenic areas, the remainder of the brain is considered to be primarily nonneurogenic in nature, implying that no new neurons are produced there under normal conditions. The occurrence of adult neurogenesis in the substantia nigra under the pathological conditions of Parkinson's disease, however, remains controversial. Here, we review the published evidence of whether adult neurogenesis exists or not within the substantia nigra, where dopaminergic neurons are lost in Parkinson's disease.
    Full-text · Article · Jan 2009 · Journal of Neural Transmission

  • No preview · Article · Jul 2008 · Planta Medica
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    ABSTRACT: To better understand the evolution of spatial and color vision, the number and spatial distributions of cones, rods, and optic nerve axon numbers were assessed in seven New World primates (Cebus apella, Saimiri ustius, Saguinus midas niger, Alouatta caraya, Aotus azarae, Calllithrix jacchus, and Callicebus moloch). The spatial distribution and number of rods and cones was determined from counts of retinal whole mounts. Optic axon number was determined from optic nerve sections by electron microscopy. These data were amassed with existing data on retinal cell number and distribution in Old World primates, and the scaling of relative densities and numbers with respect to retinal area, eye and brain sizes, and foveal specializations were evaluated. Regular scaling of all cell types was observed, with the exceptionally large, rod-enriched retina of the nocturnal owl monkey Aotus azarae, and the unusually high cone density of the fovea of the trichromatic howler monkey Alouatta caraya presenting interesting variations on this basic plan. Over all species, the lawful scaling of rods, cones, and retinal ganglion cell number is hypothesized to result from a conserved sequence of cell generation that defends retinal acuity and sensitivity over a large range of eye sizes.
    Full-text · Article · May 2008 · Visual Neuroscience
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    ABSTRACT: A neurodegenerative tauopathy endemic to the Caribbean island of Guadeloupe has been associated with the consumption of anonaceous plants that contain acetogenins, potent lipophilic inhibitors of complex I of the mitochondrial respiratory chain. To test the hypothesis that annonacin, a prototypical acetogenin, contributes to the etiology of the disease, we investigated whether annonacin affects the cellular distribution of the protein tau. In primary cultures of rat striatal neurons treated for 48 h with annonacin, there was a concentration-dependent decrease in ATP levels, a redistribution of tau from the axons to the cell body, and cell death. Annonacin induced the retrograde transport of mitochondria, some of which had tau attached to their outer membrane. Taxol, a drug that displaces tau from microtubules, prevented the somatic redistribution of both mitochondria and tau but not cell death. Antioxidants, which scavenged the reactive oxygen species produced by complex I inhibition, did not affect either the redistribution of tau or cell death. Both were prevented, however, by forced expression of the NDI1 nicotinamide adenine dinucleotide (NADH)-quinone-oxidoreductase of Saccharomyces cerevisiae, which can restore NADH oxidation in complex I-deficient mammalian cells and stimulation of energy production via anaerobic glycolysis. Consistently, other ATP-depleting neurotoxins (1-methyl-4-phenylpyridinium, 3-nitropropionic, and carbonyl cyanide m-chlorophenylhydrazone) reproduced the somatic redistribution of tau, whereas toxins that did not decrease ATP levels did not cause the redistribution of tau. Therefore, the annonacin-induced ATP depletion causes the retrograde transport of mitochondria to the cell soma and induces changes in the intracellular distribution of tau in a way that shares characteristics with some neurodegenerative diseases.
    Full-text · Article · Aug 2007 · The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
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    ABSTRACT: Fish of the genus Anableps (Anablepidae, Cyprinodontiformes) have eyes that are adapted for simultaneous aerial and aquatic vision. In this study we investigate some of the corresponding retinal specializations of the adult Anableps anableps eye using retinal transverse sections and wholemounts. The linear dimensions of the retina were found to be asymmetric with a greater representation of the dorsal compared to the ventral visual field. The total number of neurons in the ganglion cell layer of the ventral hemiretina was on average 3.6 times greater than the values obtained in the dorsal hemiretina. Isodensity contour maps revealed a prominent horizontal visual streak in the ventral hemiretina with an average peak cell density of 18,286 cells/mm(2). A second less-well-developed horizontal visual streak was also observed in the dorsal hemiretina. A sub-population of large cells with soma areas between 74 and 188 microm(2) was identified and found to be distributed evenly across both hemiretinas. Together, these results show that the sampling gain of the ventral retina is significantly greater than the dorsal segment, that retinal specializations important for mediating acute vision are present in the parts of the visual field immediately above and below the surface of the water, and that visual functions related with the large ganglion cells require more even sampling across the visual field. The relevance of these retinal specializations to the feeding and other behavioral strategies adopted by Anableps is discussed.
    Full-text · Article · Nov 2006 · Visual Neuroscience
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    ABSTRACT: A Neurobiotin-injected OFF parasol cell from midperipheral macaque retina was studied by reconstruction of serial ultrathin sections and compared with ON parasol cells studied previously. In most respects, the synaptic inputs to the two subtypes were similar. Only a few of the amacrine cell processes that provided input to the labeled OFF parasol ganglion cell dendrites made or received inputs within the series, and none of these interactions were with the bipolar cells or other amacrine cells presynaptic to the OFF parasol cell. These findings suggest that the direct inhibitory input to OFF parasol cells originates from other areas of the retina. OFF parasol cells were known to receive inputs from two types of diffuse bipolar cells. To identify candidates for the presynaptic amacrine cells, OFF parasol cells were labeled with Lucifer yellow by using a juxtacellular labeling technique, and amacrine cells known to costratify with them were labeled via immunofluorescent methods. Appositions were observed with amacrine cells containing immunoreactive calretinin, parvalbumin, choline acetylatransferase, and G6-Gly, a cholecystokinin precursor. These findings suggest that the inhibitory input to parasol cells conveys information about several different attributes of visual stimuli and, particularly, about their global properties.
    Full-text · Article · Sep 2006 · The Journal of Comparative Neurology
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    ABSTRACT: Tyrant flycatchers comprise the largest group of passerine birds of the Neotropical region but their retinal organization is unknown. The great kiskadee, Pitangus sulphuratus, is categorized as a supreme generalist and utilizes a variety of foraging strategies. The rusty margined flycatcher, Myiozetetes cayanensis, is partially frugivorous and captures insects in the air. Using retinal wholemounts, we described the topographic distribution of density and size of neurons lying in the retinal ganglion cell layer in those two species of tyrant flycatchers. Maps of neuron distribution showing isodensity contours revealed the presence of a pronounced central fovea and a temporal area in both species. Both retinal specializations were circumscribed by an inconspicuous horizontal visual streak. The highest foveal densities ranged from 48,000 to 55,000 cells/mm(2) for Pitangus sulphuratus and between 62,000 and 65,000 cells/mm(2) for Myiozetetes cayanensis. The peak density in the temporal area was around 40,000 cells/mm(2) for Pitangus sulphuratus and 46,000 cells/mm(2) for Myiozetetes cayanensis. At central, mid-peripheral and peripheral eccentricities, perikaryon size varied quite similarly in both species. A cohort of giant retinal ganglion cells with perikaryon size > 300 microm(2) was observed at the temporal periphery and defines an 'area giganto cellularis' described previously in procellariiform seabirds. This specialization is thought to be involved in movement detection and could aid the tyrant flycatchers to capture moving prey. Functionally, the presence of a fovea associated with a temporal area would allow high spatial resolution for capturing insects by the tyrant flycatchers. Nonetheless, even though both species exhibit different foraging strategies, they shared a similar topographic arrangement of neuronal density in the ganglion cell layer. This suggests that the retinal topography did not accompany changes in the foraging ecology throughout evolutionary history for these species of tyrant flycatchers.
    Full-text · Article · Jun 2006 · Brain Behavior and Evolution

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