Tempol ameliorates murine viral encephalomyelitis by preserving the blood-brain barrier, reducing viral load, and lessening inflammation

Multiple sclerosis (MS) is a progressive inflammatory and/or demyelinating disease of the human central nervous system (CNS). Most of the knowledge about the pathogenesis of MS has been derived from murine models, such as experimental autoimmune encephalomyelitis and vital encephalomyelitis. Here, we infected female C57BL/6 mice with a neurotropic strain of the mouse hepatitis virus (MHV-59A) to evaluate whether treatment with the multifunctional antioxidant tempol (4-hydroxy-2,2,6,6-tetramethyl-1-piperidinyloxy) affects the ensuing encephalomyelitis. In untreated animals, neurological symptoms developed quickly: 90% of infected mice died 10 days after virus inoculation and the few survivors presented neurological deficits. Treatment with tempol (24 mg/kg, ip, two doses on the first day and daily doses for 7 days plus 2 mM tempol in the drinking water ad libitum) profoundly altered the disease outcome: neurological symptoms were attenuated, mouse survival increased up to 70%, and half of the survivors behaved as normal mice. Not Surprisingly, tempol substantially preserved the integrity of the CNS, including the blood-brain barrier. Furthermore, treatment with tempol decreased CNS vital titers, macrophage and T lymphocyte infiltration, and levels of markers of inflammation, such as expression of inducible nitric oxide synthase, transcription of tumor necrosis factor-alpha and interferon-gamma, and protein nitration. The results indicate that tempol ameliorates murine viral encephalomyelitis by altering the redox status of the infectious environment that contributes to an attenuated CNS inflammatory response. overall, our study supports the development of therapeutic strategies based on nitroxides to manage neuroinflammatory diseases, including MS. (C) 2009 Elsevier Inc. All rights reserved.

Adsorption of 4-aminopyridine on Co and Ag electrodes probed by SERS

The adsorption of 4-aminopyridine (4-AP) on Co and Ag electrodes in acid or alkaline solutions of KCl and KI electrolyte salts were monitored by the Surface-enhanced Raman Spectroscopy (SERS) technique. The SERS intensity for the Ag electrode was in 2 orders of magnitude higher than for the Co electrode, due to the enhancement of the Raman cross-section on Ag by the surface-plasmon excitation. In acidic chloride medium (pH 4), the SERS results for Ag electrodes indicate that the protonated form of 4-AP (4-APH(+)) adsorbs in the potential range of -0.1 to -0.6 V (Ag broken vertical bar AgCl broken vertical bar KCl sat) through hydrogen-bonding between 4-APH(+) and Cl(-) adsorbed on the electrode surface: at more negative potentials the neutral form 4-AP is the predominant adsorbed species. For Co electrode in the same medium, only bands due to neutral 4-AP were observed in the spectra at -0.8 and -0.9 V. For more negative potentials bands assigned to both 4-AP and 4-AP surface complex are observed, with the lasts being enhanced, as the potentials are turned more negative. In alkaline chloride medium (pH 13), for less negative potentials the bands assigned to free 4-AP were observed in the spectra of both Ag and Co surfaces. For more negative potentials, only bands assigned to the 4-AP surface complex were observed. For 0.1 mol L(-1) KI acidic or alkaline solutions, bands assigned to 4-AP and 4-APH(+) were observed in a wider potential range than in chloride solutions. An adsorption scheme of 4-AP on Ag and Co is proposed for acidic and alkaline solutions. (C) 2010 Elsevier B.V. All rights reserved.

Livskvalitet och fatigue vid Multipel Skleros : en systematisk litteraturstudie

Syftet med denna systematiska litteraturstudie var att beskriva hur livskvaliteten påverkas hos personer med Multipel Skleros (MS) och vad som kan göras för att öka livskvaliteten. I syftet ingick även att beskriva hur personer med MS upplever fatigue som är ett av huvudsymtomen av sjukdomen samt vad som kan göras för att lindra följderna av fatigue. Artiklarna har sökts i databaserna Elin@Dalarna och Cinahl, tillgängliga via Högskolan Dalarnas proxyserver och granskats med hjälp av en granskningsmall för att säkerställa att de var av en god kvalitet. Sökord som användes var: “multiple sclerosis”, “quality of life”, “nursing” och “fatigue”. Av de artiklar som användes i resultatet var 10 kvantitativa, fyra kvalitativa i en användes båda ansatserna. Resultatet visade att personer med MS generellt sett har en sämre livskvalitet än den övriga befolkningen. Mycket av patienternas livskraft går åt till att bara klara av det dagliga livet. Många personer med MS upplever en stor frustration relaterad till att vilja men inte kunna. Ofta har den försämrade livskvaliteten sin orsak i det sociala livet. Fatigue har ofta en stor påverkan på livet för personer med MS. Det finns en mängd varierande icke farmakologiska behandlingsmetoder som med fördel kan användas för att öka livskvaliteten och minska följderna av fatigue. Exempel på dessa är kylväst, träning och yoga.

Sjuksköterskans omvårdnadsåtgärder vid Multipel Skleros : En systematisk litteraturstudie

Föreliggande systematiska litteraturstudies syfte var att inhämta information om och evidensgradera sjuksköterskans omvårdnadsåtgärder hos patienter med MS. Artiklar söktes ur databasen Electronic Libary Information Navigator (ELIN) via biblioteket på Högskolan Dalarna. Sökorden ”multiple sclerosis” och ”quality of life” användes. Artiklarna kvalitetsgranskades efter granskningsmallar med 28 bedömningskriterier därefter evidensgraderades artiklarna med hjälp av en tillämpad granskningsskala (Batshevani, 2008). Av dessa var 17 artiklar användbara i resultatet för vidare granskning. I resultaten framkom fyra evidensbaserade omvårdnadsåtgärder vid MS: information och undervisning om urinvägsproblem, information om träning och dess betydelse, koordinering av samarbete och insatser i omvårdnadsarbetet med andra yrkeskategorier inom hälso- och sjukvården samt information och undervisning om trötthet. Av dessa omvårdnadsåtgärder hade information och undervisning om urinvägsproblem samt information om träning och dess betydelse inte tidigare tagits nämnvärd hänsyn till. Resultatet i föreliggande studie kan hjälpa sjuksköterskor att öka förståelsen och se unika behov hos MS patienter och att ha med sig dessa kunskaper i utförandet, utvecklandet och stödjandet av omvårdnaden hos dessa patienter för att öka eller bevara livskvaliteten. Resultatet i föreliggande studie diskuterades utifrån Virginia Hendersons omvårdnadsteoretiska modell där sjuksköterskans specifika funktion och mål för omvårdnaden är att främja hälsa, välbefinnande och tillfrisknande vilket kan leda till en ökad livskvalitet hos patienter med MS.

Att leva med Multipel Skleros : En litteraturstudie

Syfte: Syftet med litteraturöversikten var att sammanställa aktuell forskning som beskriver hur det är att leva med Multipel Skleros (MS). Metod: Vetenskapliga artiklar söktes i databaserna Cinahl och PubMed. Tolv artiklar med kvalitativ ansats valdes ut och kvalitetsgranskades enligt Högskolan Dalarnas granskningsmall för kvalitativa studier. Huvudresultat: Resultatet visade att leva med MS innebar upplevelser av att identiteten och självbilden påverkades och känslor av att inte vilja uppfattas som annorlunda. Det fanns en rädsla över förlorad självständighet och att vara beroende av andra människor. Personer som levde med MS kände en trötthet som gjorde det nödvändigt att planera och prioritera i vardagen för att energin skulle räcka till. Sjukdomens oförutsägbara förlopp ledde till känslor av att leva i en ovisshet som gjorde framtidsplaner svåra. Att leva med sjukdomen kunde även innebära att få ett nytt sätt att se på livet, där små saker uppskattades mer och inte togs för givet. Många levde med ett hopp om förbättring och en andlighet som i många fall blivit starkare. Slutsats: Litteraturöversikten kan ge sjuksköterskan en förståelse för hur det är att leva med MS. Därmed kan bättre förutsättningar skapas för att ge en god omvårdnad till personer med MS utifrån individuella behov.

Incorporação da questão de gênero pelas políticas públicas na esfera local de governo

O presente relatório apresenta os resultados de pesquisa sobre a incorporação da perspectiva de gênero por políticas públicas promovidas por governos subnacionais no Brasil. Analisam-se não apenas programas que se dirigem especificamente à mulher, mas também iniciativas governamentais em diversas áreas e setores, procurando verificar em que medida a questão de gênero foi integrada aos programas de governo. Utilizou-se como material empírico banco de dados do Gestão Pública e Cidadania, programa de premiação e disseminação de iniciativas inovadoras de governos subnacionais, relativo ao Ciclo de 1996, o qual inclui atividades e programas governamentais nas mais diversas áreas. A análise sugere que, no caso de iniciativas dirigidas especificamente à mulher, ao lado de programas tradicionais - sobretudo os de saúde materno-infantil - tem surgido uma série de iniciativas e respondem a demandas de movimentos de mulheres relativas a temas críticos como violência doméstica, prostituição infantil, planejamento familiar, geração de trabalho e renda, sexualidade entre outros. No caso das demais políticas, há duas observações a fazer: a)em que pese a inexistência de preocupação com a temática de gênero no início dos programas, ocorre, em algumas iniciativas, a incorporação da perspectiva de gênero, ao longo da implantação da política; b) parte significativa dos programas que incorporam gênero responde a questões postas por movimentos de gênero ou por mulheres que integram a clientela dos programas, constituindo, portanto, respostas a uma agenda formulada com a participação das mulheres.

Modulatory effects of tuberculosis vaccines on experimental autoimmune encephalomyelitis

Although BCG is the only accepted vaccine against tuberculosis (TB), its protective ability is very limited. Therefore, many new vaccines are being evaluated. Our group has been working on DNAhsp65 - a genetic construction containing the hsp65 gene from Mycobacterium leprae. In previous experimental works, we demonstrated that both DNAhsp65 alone or associated with BCG, in a prime-boost regimen, were effective to control TB. A possible deleterious effect related to autoimmunity needed to be tested because hsp65 is highly homologous to the correspondent mammalian protein. In this investigation we tested the effect of a previous immunization with DNAhsp65 alone or associated with BCG in a rat model of multiple sclerosis. Female Lewis rats were immunized with three doses of DNAhsp65 or primed with BCG followed by two DNAhsp65 boosters. The animals were, then, immunized with myelin associated with complete Freund's adjuvant to develop experimental autoimmune encephalomyelitis (EAE). The following parameters were evaluated: weight loss, clinical score, central nervous system (CNS) inflammation and anti-myelin immune response. No deleterious effect was associated with these immunizations schedules. Immunized animals equally lost weight, the clinical scores were similar and CNS inflammation did not increase. Interestingly, both procedures determined decreased inflammation in the brain and lumbar spinal cord. This was concurrent with a modulatory effect over cytokine production by peripheral lymphoid organs. Cell cultures from spleen and lymph nodes in vitro stimulated with myelin produced less IFN-gamma and IL-10, respectively. This phenomenon was more clear in rats immunized with the genetic vaccine alone than with the prime-boost strategy. Together the results suggest that these strategies for TB prophylaxis would not accelerate or aggravate multiple sclerosis, being therefore, safe in this aspect. In addition, they indicate that these vaccination regimens have a potential anti-inflammatory activity that could be better explored in the future.

Immunization with pVAXhsp65 Decreases Inflammation and Modulates Immune Response in Experimental Encephalomyelitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

O transplante de células-tronco hematopoéticas como opção no tratamento de doenças não hematológicas

Nesta revisão são abordadas as doenças em que existem dados e perspectivas do uso de transplante de células-tronco hematopoéticas em suas diversas modalidades. São apresentados também os aspectos referentes aos regimes de condicionamento empregados, e sua relação com toxicidade e taxa de mortalidade ligadas ao transplante. São apresentadas as doenças autoimunes e particularizados dados específicos do lúpus eritematoso sistêmico, esclerose sistêmica e esclerose múltipla e diabetes mellitus tipo 1. A base do procedimento nas doenças autoimunes é a reprogramação imunológica. Aparentemente o procedimento tem sua indicação nas doenças em que os tratamentos convencionais de imunossupressão tenham falhado, e o dano orgânico não tenha sido definitivo, mas tenha chance de ocorrer caso não seja realizado o transplante. A modalidade aparentemente indicada no momento deve ser o transplante de células-tronco autogênico com regimes de condicionamento não mieloablativo para se obter sobrevivência estimada em mais de 50% em todas as doenças, com baixa toxicidade e com mortalidade nula ligada ao transplante. São apresentados também os resultados nos tumores sólidos, que são discutíveis, e particularidades no câncer de mama. A aparente indicação para os tumores sólidos é transplante de células-tronco alogênico e se baseia no tratamento intensivo com doses mieloablativas com a finalidade de se induzir o efeito enxerto contra o tumor. Os regimes não mieloablativos são preconizados com a finalidade de redução da toxicidade e indução de imunossupressão, sendo os dados insuficientes e discutíveis, o que obriga a introdução de novas estratégias terapêuticas baseadas na terapia imune e celular.

Abordagem initial do paciente com mielopatia aguda não compressiva

Acute myelopathy are characterized by spinal cord dysfunction, developing sensitive, motor and autonomic signs and symptons. Since they are relatively rare, there are some difficulties to early diagnosis and to the beginning of the treatment. So, literature was reviewed to describe the main aetiologies of acute non compressive myelopathy: 1) demyelinating diseases; 2) systemic disease; 3) parainfectious; 4) delayed radiation myelopathy; 5) vascular myelopathy; 6) idiopatic and 7) vitamin B12 deficiency. Besides, we suggest an algorithm to initial approach of these patients and further aethiologic investigation. © Copyright Morelra Jr. Editora.

Qualidade de vida em portadores de esclerose múltipla

Multiple sclerosis (MS) is a chronic disease which may exert significant effects on the life of patients. Traditional outcome measures in MS lack in consider the effects of the disease on health-related quality of life (HRQoL). The goal of this study is to measure HRQoL in MS patients in the city of Uberlân-dia, State of Minas Gerais, Brazil. The Brazilian version of the SF-36 was applied in 23 MS patients and in 69 subjects of general population (blood donors) in Uberlândia. MS patients scored lower in all SF-36 scales than do the general population, principally in physical function domains. Patients with EDSS scores ≤3.5 had higher mean scores in four domains than do the patients with EDSS scores ≥4.0, and lower in all domains than control group. Depressive symptoms and heat intolerance showed correlation with SF-36 domains and components. In conclusion, MS patients have a significant negative impact on all HRQoL domains measured by SF-36, compared with general population, even in the stages with lower disability.

Model to increase the lateral line length of drip irrigation systems

Non-pressure compensating drip hose is widely used for irrigation of vegetables and orchards. One limitation is that the lateral line length must be short to maintain uniformity due to head loss and slope. Any procedure to increase the length is appropriate because it represents low initial cost of the irrigation system. The hypothesis of this research is that it is possible to increase the lateral line length combining two points: using a larger spacing between emitters at the beginning of the lateral line and a smaller one after a certain distance; and allowing a higher pressure variation along the lateral line under an acceptable value of distribution uniformity. To evaluate this hypothesis, a nonlinear programming model (NLP) was developed. The input data are: diameter, roughness coefficient, pressure variation, emitter operational pressure, relationship between emitter discharge and pressure. The output data are: line length, discharge and length of the each section with different spacing between drippers, total discharge in the lateral line, multiple outlet adjustment coefficient, head losses, localized head loss, pressure variation, number of emitters, spacing between emitters, discharge in each emitter, and discharge per linear meter. The mathematical model developed was compared with the lateral line length obtained with the algebraic solution generated by the Darcy-Weisbach equation. The NLP model showed the best results since it generated the greater gain in the lateral line length, maintaining the uniformity and the flow variation under acceptable standards. It had also the lower flow variation, so its adoption is feasible and recommended.

Persistent inflammation in the CNS during chronic EAE despite local absence of IL-17 production

Experimental autoimmune encephalomyelitis (EAE) is an artificially induced demyelination of the central nervous system (CNS) that resembles multiple sclerosis in its clinical, histopathological, and immunological features. Activated Th1 and Th17 cells are thought to be the main immunological players during EAE development. This study was designed to evaluate peripheral and local contribution of IL-17 to acute and chronic EAE stages. C57BL/6 mice were immunized with MOG plus complete Freund's adjuvant followed by pertussis toxin. Mice presented an initial acute phase characterized by accentuated weight loss and high clinical score, followed by a partial recovery when the animals reached normal body weight and smaller clinical scores. Spleen cells stimulated with MOG produced significantly higher levels of IFN-γ during the acute period whereas similar IL-17 levels were produced during both disease stages. CNS-infiltrating cells stimulated with MOG produced similar amounts of IFN-γ but, IL-17 was produced only at the acute phase of EAE. The percentage of Foxp3+ Treg cells, at the spleen and CNS, was elevated during both phases. The degree of inflammation was similar at both disease stages. Partial clinical recovery observed during chronic EAE was associated with no IL-17 production and presence of Foxp3+ Treg cells in the CNS. © 2013 Sofia Fernanda Gonçalves Zorzella-Pezavento et al.

Efeito da vacina gênica para tuberculose(pVAXhsp65) na encefalite autoimune experiemtal

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeito modulador de estratégias vacinais para tuberculose na encefalite autoimune experimental (EAE)

Pós-graduação em Doenças Tropicais - FMB