Risk of multiple sclerosis after optic neuritis in patients with normal baseline brain MRI

When assessing and managing a patient with optic neuritis (ON), the risk of future development of multiple sclerosis (MS) is an important issue, as this can be the first presentation of the disease. Although the presence of lesions on baseline brain MRI is the strongest predictor of MS conversion, some patients with normal imaging also develop MS. We aimed to estimate MS risk in patients with ON and a normal baseline MRI and identify individuals with higher risk of conversion. We performed a retrospective study including patients with idiopathic ON and normal baseline brain MRI who presented to our hospital over an 8year period. Of a total of 42 patients, 10 converted to MS: five during the first follow-up year, seven during the first 2years and all of the patients within the first 5years, with a 5year MS conversion rate of 23.8%. MS conversion rates were significantly higher in patients with history of previous symptoms suggestive of demyelination (p=0.002), cerebrospinal fluid oligoclonal bands unmatched in serum (p=0.004) and incomplete visual acuity recovery (⩽6/12) after 1year (p=0.002). Lower conversion rates were found in patients with optic disc edema (p=0.022). According to these results, a significant proportion of patients with idiopathic ON and a normal baseline brain MRI will develop MS, with a higher risk during the first 5years. Therefore, in the presence of factors in favor of MS conversion, close follow-up, including semestral medical consultations and yearly brain MRI, can be recommended. Early immunomodulatory treatment may be individually considered as it can delay conversion and reduce new lesion development rate

Deformed Skyrme Crystals

The Skyrme crystal, a solution of the Skyrme model, is the lowest energy-per-charge configuration of skyrmions seen so far. Our numerical investigations show that, as the period in various space directions is changed, one obtains various other configurations, such as a double square wall, and parallel vortex-like solutions. We also show that there is a sudden "phase transition" between a Skyrme crystal and the charge 4 skyrmion with cubic symmetry as the period is gradually increased in all three space directions.Comment: 13 pages, 6 figures. To be published in JHE

LAS INCAPACIDADES FÍSICAS DE PACIENTES CON ACCIDENTE VASCULAR CEREBRAL: ACCIONES DE ENFERMERÍA

This paper addresses physical disabilities resulting from a cerebrovascular accident (CVA). Objectives: To identify the profile of physical disabilities resulting from CVA in the published literature and to discuss nursing interventions in advising the patients and their families in regards to the resulting disabilities. Methodology: Narrative review that used the same description in all databases, selecting papers between 1997 and 2007. Analyzed by categories of different physical disabilities. Results: 112 publications were found, 11 were selected. Three categories of disabilities have been created, according to predominance: Motor Disability (55%); Dysphasia (36%), and Aphasia (9%). Discussion: These disabilities have a high potential for interfering in daily activities generating a high degree of patient dependence on a care giver. The nurse ought to advise about the complications of immobility, dysphasia and aphasia. Conclusion: Life after effusion requires planning and nurse orientation addressed at minimizing the effects of physical disabilities for the patient.Este artículo trata de las discapacidades físicas causadas por un accidente vascular cerebral (AVC). Objetivos: identificar el perfil de las discapacidades físicas como una secuela del AVC presente en artículos y discutir las acciones de enfermería en la orientación del enfermo y su familia acerca de las discapacidades. Metodología: revisión narrativa que ha empleado los mismos descriptores en todas las bases electrónicas, seleccionando artículos entre los años de 1997 a 2007 y analizados por categorías a partir de las diferentes discapacidades físicas encontradas. Resultados: encontradas 112 publicaciones, seleccionadas 11. Se han construido tres categorías de discapacidades de acuerdo con la predominancia: discapacidad motora (55%), disfagia (36%) y afasia (9%). Discusión: todas tienen un alto potencial de interferir en las actividades cotidianas provocando alto grado de dependencia del enfermo para un cuidador. El enfermero debe orientar acerca de las complicaciones de inmovilidad, disfagia y afasia. Conclusión: La supervivencia tras el derrame exige orientaciones de enfermería dirigidas a limitar los efectos que las discapacidades tienen para el paciente.Este artigo trata das incapacidades físicas decorrentes de um acidente vascular cerebral (AVC). Objetivos: identificar o perfil das incapacidades físicas como seqüela de AVC presentes nas publicações e discutir as ações de enfermagem na orientação do paciente e família em relação às incapacidades. Metodologia: revisão narrativa que usou os mesmos descritores em todas as bases eletrônicas, selecionando artigos entre os anos de 1997 a 2007. Analisados por categorias a partir das diferentes incapacidades físicas encontradas. Resultados: encontrados 112 publicações, selecionados onze. Foram estruturadas três categorias: incapacidade motora (55%), disfagia (36%) e afasia (9%). Discussão: são incapacidades que tem um alto potencial de interferir nas atividades cotidianas gerando alto grau de dependência do paciente para com um cuidador. O enfermeiro deve orientar sobre as complicações da imobilidade, disfagia e afasia. Conclusão, a sobrevida após o AVC requer planejamento e orientações de enfermagem direcionadas a limitar o efeito das incapacidades físicas para o paciente

Sequential and resonant field emission from nano-structured cathodes

The attempt to integrate two electron transport mechanisms, by computing the field emission (FE) current as a superposition of both resonant and sequential branches, is reported. A quantum object through which the tunnelling occurs is modelled as a one-dimensional (1D) potential well separated from the substrate by a potential barrier. Results show that the proposed model is useful in the interpretation of real I-V diagrams of FE through composite vacuum interfaces and in evaluating the amount of coherence in the related tunnelling processes

Environmental Exposure, Obesity, and Parkinson’s Disease: Lessons from Fat and Old Worms

BACKGROUND: A common link has been exposed, namely, that metal exposure plays a role in obesity and in Parkinson's disease (PD). This link may help to elucidate mechanisms of neurotoxicity. OBJECTIVE: We reviewed the utility of the nematode, Caenorhabditis elegans, as a model organism to study neurodegeneration in obesity and Parkinson's disease (PD), with an emphasis on the neurotransmitter, dopamine (DA). DATA SOURCES: A PubMed literature search was performed using the terms "obesity" and any of the following: "C. elegans," "central nervous system," "neurodegeneration," "heavy metals," "dopamine" or "Parkinson's disease." We reviewed the identified studies, including others cited therein, to summarize the current evidence of neurodegeneration in obesity and PD, with an emphasis on studies carried out in C. elegans and environmental toxins in the etiology of both diseases. DATA EXTRACTION AND DATA SYNTHESIS: Heavy metals and DA have both been linked to diet-induced obesity, which has led to the notion that the mechanism of environmentally induced neurodegeneration in PD may also apply to obesity. C. elegans has been instrumental in expanding our mechanism-based knowledge of PD, and this species is emerging as a good model of obesity. With well-established toxicity and neurogenetic assays, it is now feasible to explore the putative link between metal- and chemical-induced neurodegeneration. CONCLUSIONS: One side effect of an aging population is an increase in the prevalence of obesity, metabolic disorders, and neurodegenerative orders, diseases that are likely to co-occur. Environmental toxins, especially heavy metals, may prove to be a previously neglected part of the puzzle

Effects of iron-ore mining and processing on metal bioavailability in a tropical coastal lagoon

In water systems, water quality and geochemical properties of sediments determine the speciation of trace metals, metal transport, and sediment-water exchange, influencing metal availability and its potential effects on biota. Studies from temperate climates have shown that iron-ore mining and tailing wastewaters, besides being a source of trace metals, usually show high levels of dissolved ions and particulate suspended matter, thus having the potential of indirectly changing metal bioavailability. For the first time in the tropics, we identified the effects of iron-ore mining and processing on metal bioavailability in a coastal lagoon. With an extensive sampling scheme, we investigated the potential sources of metals; the links among metal levels in water, sediments, and invertebrates; and the contrasting effects on metal speciation and bioavailability. The metals Fe, Mn, Al, Cr, Zn, Cu, Ni, Pb, Cd, Hg, and As were measured in water, sediments (surface and profiles), and invertebrates from Mãe-Bá Lagoon and in the sites directly influenced by the mining operations (tailing dams and nearby rivers). In addition, samples from two other lagoons, considered pristine, were analyzed. The study area is located in the southeast of Brazil (Iron Quadrangle Region and a coastal area of Espírito Santo State). General water characteristics included pH, dissolved organic carbon, alkalinity, and anion composition. Water metal speciation was assessed by a speciation model (Chemical Equilibria in Aquatic Systems). Grain-size distribution, organic carbon, carbonate, and acid volatile sulfide (AVS) were determined in sediments. Statistical methods included comparison of means by Mann-Whitney test, ordination and correlation analyses, and analysis of regression for geochemical normalization of metals with grain size. The dissolved metal concentrations, the total metal levels in sediments, and the normalization based on the fine sediment fraction showed that the mining operations constitute potential sources of Fe, Mn, Cr, Cu, Ni, Pb, As, and Hg to Mãe-Bá Lagoon. However, trace metal availability was reduced because of increased pH, hardness, and sulfide content (356 μmol/g) in the sites influenced by the mining. The lagoon showed similar water chemistry as in the mining sites, with metal bioavailability further decreased by the presence of dissolved organic carbon and chloride. Although AVS levels in the lagoon were low (0.48-56 μmol/g), metal bioavailability was reduced because of the presence of organic matter. Metal levels in invertebrates confirmed the predicted low metal bioavailability in Mãe-Bá Lagoon. The lagoon was considered moderately contaminated only by Hg and As. The iron-ore mining and processing studied here constitute potential sources of metal pollution into the tropical lagoon. Contrary to expectations, however, it also contributes to reducing the overall metal bioavailability in the lagoon. These findings are believed to be useful for evaluating metal exposure in a more integrated way, identifying not only the sources of pollution but also how they can affect the components involved in metal speciation and bioavailability in water systems, leading to new insights

Cytotoxic T cells and mycobacteria

How the immune system kills Mycobacterium tuberculosis is still a puzzle. the classical picture of killing due to phagocytosis by activated macrophages may be only partly correct. Based on recent evidence, we express here the view that cytotoxic T lymphocytes also make an important contribution and suggest that DNA vaccines might be a good way to enhance this. (C) 2001 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.Univ São Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP, BrazilUniv São Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Bromatol & Toxicol, BR-14049 Ribeirao Preto, SP, BrazilUniversidade Federal de São Paulo, Dept Microbiol & Immunol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol & Immunol, São Paulo, BrazilWeb of Scienc

A DNA vaccine against tuberculosis based on the 65 kDa heat-shock protein differentially activates human macrophages and dendritic cells

Abstract\ud \ud \ud \ud Background\ud \ud A number of reports have demonstrated that rodents immunized with DNA vaccines can produce antibodies and cellular immune responses presenting a long-lasting protective immunity. These findings have attracted considerable interest in the field of DNA vaccination. We have previously described the prophylactic and therapeutic effects of a DNA vaccine encoding the Mycobacterium leprae 65 kDa heat shock protein (DNA-HSP65) in a murine model of tuberculosis. As DNA vaccines are often less effective in humans, we aimed to find out how the DNA-HSP65 stimulates human immune responses.\ud \ud \ud \ud Methods\ud \ud To address this question, we analysed the activation of both human macrophages and dendritic cells (DCs) cultured with DNA-HSP65. Then, these cells stimulated with the DNA vaccine were evaluated regarding the expression of surface markers, cytokine production and microbicidal activity.\ud \ud \ud \ud Results\ud \ud It was observed that DCs and macrophages presented different ability to uptake DNA vaccine. Under DNA stimulation, macrophages, characterized as CD11b+/CD86+/HLA-DR+, produced high levels of TNF-alpha, IL-6 (pro-inflammatory cytokines), and IL-10 (anti-inflammatory cytokine). Besides, they also presented a microbicidal activity higher than that observed in DCs after infection with M. tuberculosis. On the other hand, DCs, characterized as CD11c+/CD86+/CD123-/BDCA-4+/IFN-alpha-, produced high levels of IL-12 and low levels of TNF-alpha, IL-6 and IL-10. Finally, the DNA-HSP65 vaccine was able to induce proliferation of peripheral blood lymphocytes.\ud \ud \ud \ud Conclusion\ud \ud Our data suggest that the immune response is differently activated by the DNA-HSP65 vaccine in humans. These findings provide important clues to the design of new strategies for using DNA vaccines in human immunotherapy.We thank Dr. Carlos Rodrigo ZárateBladés for helpful suggestions during the course of the studies. We also thank Mrs. Izaíra T. Brandão and Mrs. Ana P. Masson for technical assistance. This study was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Programa Nacional de DST/AIDS do Ministério da Saúde and Conselho Nacional de Pesquisa (CNPq).We thank Dr. Carlos Rodrigo Zárate-Bladés for helpful suggestions during the course of the studies. We also thank Mrs. Izaíra T. Brandão and Mrs. Ana P. Masson for technical assistance. This study was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Programa Nacional de DST/AIDS do Ministério da Saúde and Conselho Nacional de Pesquisa (CNPq)

Comparison of different delivery systems of DNA vaccination for the induction of protection against tuberculosis in mice and guinea pigs

The great challenges for researchers working in the field of vaccinology are optimizing DNA vaccines for use in humans or large animals and creating effective single-dose vaccines using appropriated controlled delivery systems. Plasmid DNA encoding the heat-shock protein 65 (hsp65) (DNAhsp65) has been shown to induce protective and therapeutic immune responses in a murine model of tuberculosis (TB). Despite the success of naked DNAhsp65-based vaccine to protect mice against TB, it requires multiple doses of high amounts of DNA for effective immunization. In order to optimize this DNA vaccine and simplify the vaccination schedule, we coencapsulated DNAhsp65 and the adjuvant trehalose dimycolate (TDM) into biodegradable poly (DL-lactide-co-glycolide) (PLGA) microspheres for a single dose administration. Moreover, a single-shot prime-boost vaccine formulation based on a mixture of two different PLGA microspheres, presenting faster and slower release of, respectively, DNAhsp65 and the recombinant hsp65 protein was also developed. These formulations were tested in mice as well as in guinea pigs by comparison with the efficacy and toxicity induced by the naked DNA preparation or BCG. The single-shot prime-boost formulation clearly presented good efficacy and diminished lung pathology in both mice and guinea pigs