Efeitos dos ácidos propiônico e metilmalônico sobre o imunoconteúdo da subunidade de alto peso molecular dos neurofilamentos em fatias de córtex cerebral de ratos

As acidemias orgânicas são desordens metabólicas caracterizadas, bioquimicamente, pelo acúmulo de um ou mais ácidos orgânicos e, clinicamente, por disfunções neurológicas graves. Os ácidos propiônico (PA) e metilmalônico (MMA) são metabólitos presentes, em altas concentrações, nos tecidos e fluídos biológicos de pacientes afetados pelas acidemias propiônica e metilmalônica, respectivamente. Os neurofilamentos (NFs) são proteínas do citoesqueleto neuronal formados pela polimerização de três subunidades, denominadas: NF de alto peso molecular (NFH), NF de médio peso molecular (NF-M) e NF de baixo peso molecular (NF-L), com pesos moleculares aparentes de 200, 150 e 68 kDa, respectivamente. Essas proteínas são amplamente fosforiladas, sendo que seu nível de fosforilação está relacionado com a polimerização dos NFs e com a regulação das interações entre os constituintes do citoesqueleto. Neste trabalho fizemos um estudo ontogenético dos efeitos in vitro do PA e do MMA 2,5 mM sobre a imunorreatividade da subunidade NF-H em fatias de córtex cerebral de ratos de 9, 12, 17, 21 e 60 dias de idade. Para tanto utilizamos uma abordagem metodológica baseada na imunodetecção da NF-H com dois anticorpos diferentes: o anticorpo monoclonal anti NF-200 clone NE14 que se liga somente a epítopos fosforilados da NF-H e, portanto, reconhece a NF-H fosforilada; e o anticorpo monoclonal anti NF-200 clone N52 que reconhece a NF-H total, independentemente do nível de fosforilação. Nossos resultados mostraram que os metabólitos induzem alterações na imunorreatividade da NF-H presente na fração citoesquelética de maneira dependente do estágio de desenvolvimento do animal Considerando o conjunto de dados obtidos com os anticorpos NE14 e N52 na fração citoesquelética, podemos dizer que o tratamento das fatias de córtex cerebral de ratos de 9 dias aumentou o nível de fosforilação sem alterar o imunoconteúdo total; em ratos de 12 e 17 dias de vida levou a um acúmulo da subunidade NF-H na fração citoesquelética e que esta proteína está na forma fosforilada; e finalmente, em ratos de 21 e 60 dias de vida os metabólitos não alteraram os parâmetros estudados. Mostramos, também, que o acúmulo da NF-H provocado pelos metabólitos em ratos de 12 e 17 dias de vida não decorreu de um aumento na síntese da proteína, mas, provalvelmente devido a um desequilíbrio na relação NF-H solúvel/NF-H polimerizada, que favoreceu a forma polimerizada. Finalmente, mostramos um possível envolvimento de mecanismos de neurotransmissão GABAérgica e glutamatérgica para os efeitos observados em ratos de 12 e 17 dias de idade, respectivamente. Considerando que a fosforilação é um mecanismo importante para a regulação da dinâmica de polimerização dos NFs e das interações com outros componentes do citoesqueleto, sugerimos que uma desorganização na sua homeostase possa causar uma neurodegeneração, que é característica dos pacientes portadores das acidemias propiônica e metilmalônica.

O filtro sensorial P50 em transtornos neuropsiquiátricos e a sua modulação por cafeína

O paradigma do P50 é uma técnica eletrofisiológica útil na investigação da neurobiologia básica subjacente aos defeitos de processamento sensorial que caracterizam algumas doenças mentais, mais tradicionalmente associados à esquizofrenia. Nessa tese replica-se e amplia-se o estudo do filtro sensorial P50 em algumas condições neurológicas e psiquiátricas. Foram replicados os achados de perda de supressão na esquizofrenia, na doença de Parkinson e no transtorno de estresse pós-traumático (avaliando pioneiramente vítimas de violência urbana). O filtro sensorial P50 em populações com transtorno de pânico, com transtorno obsessivo-compulsivo e na doença de Machado-Joseph, uma ataxia cerebelar, foi avaliado pela primeira vez. Em todas estas patologias documentou-se uma perda da supressão do P50. Também se investigou os efeitos da modulação do filtro sensorial por cafeína (a substância psicoativa mais consumida no mundo todo, um antagonista não-seletivo dos receptores de adenosina do tipo A1 e A2A), administrada por via oral a 24 voluntários saudáveis em diferentes doses (100, 200 e 400 mg e placebo). As doses de 200mg e 400 mg reduziram a supressão do P50. O efeito da cafeína foi independente do gênero e do uso habitual de cafeína. Usuários (n=15) mostraram valores basais diferentes quando comparados aos não usuários (n=9), com amplitudes S2 menores. Os resultados obtidos com a teofilina, num estudo prévio, e com a cafeína foram reanalizados, mostrando uma perda transitória de supressão do P50 mais pronunciada à direita, sugerindo uma alteração no padrão de lateralização do filtro sensorial P50 mediada pelo uso de metil-xantinas. Estes achados reforçam a participação da adenosina na modulação do filtro sensorial P50 e indicam que a ingestão de cafeína deva ser controlada neste tipo de estudo. Dessa forma, demonstra-se que uma supressão do P50 alterada é um achado pouco específico. Uma vez que a supressão do P50 pode ser alterada por uma situação habitual como o uso de bebidas que contém cafeína, é possível que a perda da supressão não seja necessáriariamente ruim, mesmo que ela esteja potencialmente associada a uma vulnerabilidade maior para doenças neuropsiquiátricas.

O exame neurológico do recém-nascido pré-termo não complicado: avaliação pela escala de saint-anne dargassies, e screening pelas escalas de amiel-barrier-shnider modificada e prechtl ao termo

This study compared the evolution of posture, tone and neonatal reflexes in preterm infants without clinical or neurological complications before and after the age of term using the scale of Saint-Anne Dargassies. To reach the age of the term, was applied Scales Amiel-Barrier-Shnider changed and the Prechtl, traditionally used in the evaluation of term newborns, looking for possible changes to the term, while also evaluating the sensitivity of these scales. We studied 20 non-complicated preterm infants, both sexes aged 32-36 weeks, born in Januário Cicco Maternity School, from August 2006 to August 2007. Was applied to the scale of Saint-Anne Dargassies every two weeks until reach the term, and the range of Amiel-Barrier-Shnider changed and the Prechtl, after reaching 39 and 41 weeks. The evaluation result of articular angles was subjected to the test of Friedman ANOVA, significant differences between the three measurements of the scale of Saint-Anne Dargassies only for angles heel-to-ear to term. Neonatal reflexes changed in the period of prematurity were the cardinal points reflexes, Moro reflexes, cross extensions reflex and the automatic walking reflexes. The posture was the parameter which remained unchanged in the three scales. Considering a significance level of 5% by applying Cochran Q Test, it was found that the scale of Saint-Anne Dargassies is more sensitive to detect suspects. With this methodology and the results it was possible to prepare a manuscript: The neurological examination of non-complicated preterm newborns using the Sanit-Anne Dargssies Scale from birth to term: normal or altered? In which we describe that despite the good clinical condition, the RNP show changes in tone and neonatal reflexes. These data are important because though non-complicated RNP need further attention its maturation process, enabling us to detect and intervene early. With these results we can build a scale simplified neurological assessment made with items found most altered during the application of three scales. The development of this project has a multidisciplinary approach, because it involved Paediatric Neurologist, Physiotherapist and Neonatologist, as recommended by PPGCSA

A prática de atividade física de crianças e adolescentes com e sem epilepsia

The epilepsy is one of the neurological disorders more common in the pediatric period, and which interferes significantly in the psycho and social life of children and teenagers. The objective of this study was analyzing the practice of sedentary practices, physicals, traditional infant fun and games of children and teenagers with and without epilepsy. The study was prospective, transversal descriptive, done with 60 children and teenagers with epilepsy (Epileptic Group - EG) patients from Pediatric Neurology Clinic of the Centre Integrated Health Lineu Araújo and 60 children and teenagers without epilepsy (Control Group - CG) students from municipal public school, both of the two groups paired with the same age (age group 7 to 14 years) of both the genders (female = 25/41,6% and male = 35/58,3%) of the Teresina city Piauí. It was done two pattern questionnaires, one applied to children and teenagers of the EG and CG to identify the sedentary activities, physical and traditional infant games and other to the parents/responsible of the EG about the clinical and demographic information. The results permitted the elaboration of two manuscripts: a) the first one titled The Practice of Sedentary and Physical Activities of Children and Teenagers with Epilepsy which showed significant difference in the sedentary activities of playing with car toy (p=0,021) to the EG and reading to the CG (p=0,001); in the physical activities the school physical education (p=0,001) and riding a bike (p=0,014) to the CG; b) the second one The Practice of Infant Games and Fun the children and teenagers with and without Epilepsy in this one the playing with marble presented significant difference (p=0,016) to the CG, despite the girls of the two groups don t do this activity. Observing the distribution of frequencies, it was verified that in the play catch-up and hide-and-seek and burn the EG plays more than the CG both in female and male gender. The girls of the EG play less skip, 60 while the boys of the two groups don t play. Elastic jump the girls of the two groups play in a same frequency and the boys don t participate of this fun. The seizures were found to occur during: soccer (23,3%); hide-and-seek (6,6%) and running (3,3%). In the sedentary activities, seizures were reported to occur: resting and watching TV (18,3%), sleeping (36,0%); sitting (13,3%) and lying down (11,7%). Our results showed that the epileptic group and the controls group engage in the same activities, although the epileptic group participates less than the controls. Although the EG had presented a bigger percentage of generalized attacks, they don t occur during the practice of formal physical activities. The research was developed by a multidisciplinary team, and this contributed a lot to the realization of this study

Marcadores genéticos associados com a resposta inflamatória na meningite bacteriana

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Caracteres físico-químicos e citológicos do liquor de cães em diferentes fases da cinomose

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

Retrospective study of thoracolumbar ventral fenestration through intercostal thoracotomy and paracostal laparotomy in the dog

Foram analisados os resultados da fenestração ventral dos discos toracolombares em 29 cães agrupados segundo a raça, sexo, peso, idade, graus de déficits neurológicos, duração dos sinais, discos intervertebrais envolvidos, tempo para recuperação e porcentagem de sucesso. A raça Dachshund representou 55,18% (n = 16), cães sem raça definida, 13,8% (n = 4), Poodle e Basset Hound e Cocker Spaniel Inglês 6,89% cada (n = 6), e Pastor Alemão, Beagle e Pinscher, 3,45% cada (n = 3), sendo 51,72%, machos e 48,28%, fêmeas, com idade média de 68,03 meses. O grau de déficits neurológicos correspondeu a: 13,8% dos cães pertencentes ao GI (dor), 41,8% ao GII (paresia), 27,6% ao GIII (paraplegia com dor profunda presente) e 17,2% ao GIV (paraplegia com dor profunda ausente). Os sinais clínicos variaram em duração entre 2 e 60 dias, correspondendo às médias de 18,5 (GI), 12,3 (GII), 8,28 (GIII) e 4,2 dias (GIV). A porcentagem de discos intervertebrais acometidos foi: T10/11 (10,81%), T11/12 (24,33%), T12/13 (40,55%), T13/L1 (16,21%) e L1/2, L2/3 e L3/4, 2,7% cada. O tempo médio de recuperação, em dias, foi: 16 (GI), 19,1 (GII), 20,6 (GIII) e 30,6 (GIV), onde 100% dos animais dos grupos I, II e III recuperaram ambas as funções neurológicas e motoras. O grupo IV apresentou 80% de sucesso. Conclui-se que a fenestração ventral produz excelentes resultados pós-operatórios desde que bem selecionados os casos.

O púlpito como cátedra: retórica e educação nos sermões do Pe. Antônio Vieira (1608-1697)

This work aims to analyze the relationship among culture, education and rhetoric on the sermons of the Priest Antonio Vieira (1608-1697). It discusses the presence of oratory on the Western teaching since its Greek origins until the formation of the Ratio Studiorum in 17th-century. Brazilian society is defined as baroque and the rhetoric arises as element essential in the elaboration of the social imaginary speeches and, occupying as an essencial element in the elaboration of discursese and social imaginaries, occupying the centre of controversies, about questions like reason and the faith, ethics and the politics, the nature of the Indian and African peoples, even over the own construction of the modern subject. In this context the vieira´s preaching discharges the functions of kerigma (preaching), didachê (education) and politics (action). The research consisted in a finicky reading over five of these sermons that were returned in the presence of different audiences. The pulpit was the cathedra where Vieira used his sermons as a manner of social mobilization that aimed not only teaching a determined knowledge of reality, but altering cruel situations like Indian and poor people slavery in his epoch. Education by Vieira consist in a tension between utopian hopes and urgencies of practice. The rhetorical tradition affirms the interdependence of technical ethics and politics aspects. To know is not enough is necessary to convince and to move, realizating passage from theorical to practical liverly. It presupposes still the preoccupation with the solidity of argumentation and of reasoning, a wide cultural formation, the requirement of a civic ethics and, mainly, the adequacy between content and the specifics of audience

Acidentes de Trabalho : análise em profissionais de enfermagem que atuam nas unidades de terapia intensiva e urgência Natal/RN

It is a descriptive-exploratory research, with a quantitative approach, aiming to characterize typical occupational accident suffered by the professionals from nursery group, in the Intensive Care Units and Emergency in a hospital in Natal-RN, trying to identify the factors that contribute to those accidents; to identify some information taken by those professionals related to the accident risks; to know the procedures taken after each accident. This sample is composed by 176 professionals that are 44 nurses and 132 nursing technicians/auxiliaries, collected from March to April 2010. The results related to the personal characterization of the nursery group showed that 31 (18.61%) are between the 36-40 years of age; 148 (84.09%) females and 96 (55.68%) had finished High School. Related to the professional characterization, 53 (30.11%) are nurses, and 123 (69.88%) nursing technicians and auxiliaries; 44 (25.00%) are working as nurses, and 132 (75.00%) as nursing technicians and auxiliaries; 45 (25.56%) are working in the nursery area between 15 to 20 years and 11 months; 53 (30.11%) are in this institution between 10 to 14 years and 11 months; 79 (44.88%) work in the ICU; 55 (31.25%) are working in this area from 1 to 4 years and 11 months; 110 (62.50%) like to work in this area; 161 (91.47%) work 30 to 40 hours per week; 90 (51,13%) have another employment. Related to knowledge about typical occupational accident, 167 (94.88%) said they know about it; 96 (54.54%) know the accident rules; 103 (58.52%) think it is important to talk about this subject in the nursery courses; 92 (52.27%) said this subject is important to be discussed in the work and 372 (87.73%) think education is necessary to reduce accident. Related to the data about accidents, 104 (59.09%) have suffered typical occupational accident, among them 69 (39.20%) have suffered it once; 47 (36.19%) did not register any accident; 60 (57.69%) were caring some patient during the accident; 47 (45.19%) of them occurred in the ICU; 50 (48.07%) professionals were working during the night period; 69 (66.34%) have suffered perforation; 86 (82.69%) had upper limbs affected; 64 (61.53%) were affected by needle; about the reason of the accident, 89 (60.54%) said it occurred due to carelessness. Related to the accident evolution, 88 (85.57%) did not need to remain off work after accident; 13 (81.25%) remained off work during 15 days; 87 (83.65%) had no sequelae and for 101 (97.11%) it was not necessary rehabilitation. We conclude that typical occupational accident can occur with young workers who admit a knowledge about the subject, however they do almost nothing to prevent it. We believe this research has contributed to the characterization of this kind of accident suffered by the nursery group of a public hospital in Natal, and it can stimulate the creation and reformulation of personal protection against typical occupational accident suffered by nursery professionals

Conhecimento do enfermeiro sobre as ações de vigilância epidemiológica no Hospital Universitário Onofre Lopes, Natal, RN

This is an exploratory descriptive study with quantitative approach, aiming to verify the nurses' knowledge concerning the epidemiological surveillance activities at the Onofre Lopes hospital (HUOL), in Natal, Rio Grande do Norte. The study was performed with 63 nurses from the hospital and the data were collected through a questionnaire. All data were analyzed using descriptive statistics. The results were discussed and organized into four sections: nurses' knowledge on hospital epidemiological surveillance; procedures of the professional nurse through compulsory notification diseases; difficulties found by nurses to register the compulsory notification diseases and suggestions of strategies to joint epidemiological surveillance service with the care practices of nurses. The results showed that 55.55% of nurses know the main action of epidemiological surveillance, compulsory notification of diseases, and that 42.86% reported to the Hospital Epidemiology Center , while 57.14% did not allocate the information for this service. Most nurses found it difficult to perform notification for not knowing its flow; for the surveillance service does not operate 24 hours and for vagueness on diagnostic of disorders. Suggestions of strategies to improve the quality of epidemiological information are focused on training of nurses in hospital epidemiological surveillance; working in partnership with the surveillance center; diffusion of information on surveillance and conducting a daily active search. It comes to conclusion that most nurses don't notify the Surveillance Center about Compulsory Notification Diseases and it wasn't observed the incorporation of integrality values between the hospital surveillance and all nurses, since this principle guides the actions of health services based on dialogue, listening, ethical commitment, sharing of knowledge among professionals of various services and respect towards other professionals. Therefore, the integrality gap in the actions of the nurses studied, as well as in the surveillance service does not mobilize the potential of such services to changes in the sense of achievement of practices aimed at a special attention model that combines preventive and corrective actions, proposed and desired by SUS. Through the difficulties presented, it becomes important to recommend educational processes with strategy to transform the conducts, besides proposing actions under the principle of integrality provide responses agile and effective, as the purpose of VE hospital emergency care by the current epidemic

Modelo arquitetural de comunicação para monitoramento de pacientes baseado em middleware, computação móvel e ubíqua

Hospital Automation is an area that is constantly growing. The emergency of new technologies and hardware is transforming the processes more efficient. Nevertheless, some of the hospital processes are still being performed manually, such as monitoring of patients that is considered critical because it involves human lives. One of the factors that should be taken into account during a monitoring is the agility to detect any abnormality in vital signs of patients, as well as warning of this anomaly to the medical team involved. So, this master's thesis aims to develop an architecture to automate this process of monitoring and reporting of possible alert to a professional, so that emergency care can be done effectively. The computing mobile was used to improve the communication by distributing messages between a central located into the hospital and the mobile carried by the duty

Influência da adição de carga na marcha em esteira de crianças com paralisia cerebral hemiparética espástica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Associação entre polimorfismos em enzimas de reparo de DNA e ocorrência de meningite bacteriana.

Despite advances in vaccine development and therapy, bacterial meningitis (BM) remains a major cause of death and long-term neurological disabilities. As part of the host inflammatory response to the invading pathogen, factors such as reactive oxygen species are generated, which may damage DNA and trigger the overactivation of DNA repair mechanisms. It is conceivable that the individual susceptibility and outcome of BM may be in part determined by non synonymous polymorphisms that may alter the function of crucial BER DNA repair enzymes as PARP-1, OGG-1 and APE-1. These enzymes, in addition to their important DNA repair function, also perform role of inflammatory regulators. In this work was investigated the non synonymous SNPs APE-1 Asn148Glu, OGG-1 Ser326Cys,PARP-1 Val762Ala, PARP-1 Pro882Leu and PARP-1 Cys908Tyr in patients with bacterial meningitis (BM), chronic meningitis (CM), aseptic meningitis (AM) and not infected (controls). As results we found increased frequency of variant alleles of PARP-1 Val762Ala (P = 0.005) and APE-1 Asn148Glu (P=0.018) in BM patients, APE-1 Asn148Glu in AM patients (P = 0.012) and decrease in the frequency of the variant allele OGG-1 Ser326Cys in patients with CM (P = 0.013), regarding the allelic frequencies in the controls. A major incidence of individuals heterozygous and/ or polymorphic homozygous in BM for PARP-1 Val762Ala (P= 0.0399, OD 4.2, 95% IC 1.213 -14.545) and PARP-1 Val762Ala/ APE-1 Asn148Glu (P = 0.0238, OD 11.111, 95% IC 1.274 - 96.914) was observed related to what was expected in a not infected population. It was also observed a major incidence of combined SNPs in the BM patients compared with the control group (P=0.0281), giving evidences that SNPs can cause some susceptibility to the disease. This combined effect of SNPs seems to regulate the principal cytokines and other factors related to BM inflammatory response and point the importance of DNA repair not only to repair activity when DNA is damaged, but to others essential functions to human organism balance.

Ativação local da rota da quinurenina por moduladores inflamatórios durante a meningite bacteriana.

Activation of the kynurenine (KYN) pathway (KP) by modulators of immune system has been observed during several neurological diseases. Here we assessed the association of chemo-/cytokine levels with the concentration of KP metabolites in cerebrospinal fluid (CSF) and plasma samples from patients with bacterial meningitis (BM). All samples were collected from 42 patients diagnosed with acute bacterial meningitis (ABM), aseptic meningitis, tuberculous meningitis and patients without infection neurological disorders. CSF and plasma concentration of metabolites from the KP was assessed by high pressure liquid chromatography (HPLC) and cytokines and chemokines by Bio-plex 200 suspension array system. Concentrations of the KP metabolites KYN and kynurenic acid (KYNA) were significantly higher in CSF of patients with ABM compared to other groups. Tryptophan (TRP), anthranilic acid (AA), 3-hydroxykynurenine (3HK) and 3-hydroxyanthranilic acid (3HAA) did not show statistical significance, although some of them presented a good accumulation during ABM. The expression of TNF-alpha, IL-6, IL-1beta, IFN-gamma, IL-10, IL-1 receptor antagonist (IL-1Ra), MIP-1alpha, MIP-1beta, MCP-1 and G-CSF was about 100-fold higher in CSF from ABM patients than other infected groups. In all CSF and plasma samples, the concentration of IL-2, IL-12(p70), IL-4, IL-8 and GM-CSF was not significant. ABM still showed significant concentrations of IL-6, IL-10, IL-1Ra and MCP-1 in plasma samples. Based on the comparison of KP metabolites concentrations between plasma and CSF samples we conclude that the activation of the tryptophan pathway upon BM occurs within the brain. This increase in KP metabolites is most due to activation of the KP by molecules as IFN-gamma and TNF-alpha in response to infection.

Efeitos da sinalização via creb sobre a sobrevivência e diferenciação meuronal

The cortical development requires a precise process of proliferation, migration, survival and differentiation of newly formed neurons to finally achieve the development of a functional network. Different kinases, such as PKA, CaMKII, MAPK and PI3K, phosphorylate the transcription factors CREB, and thus activate it, inducing CREB-dependent gene expression. In order to identify the involvement of such signaling pathways mediated by CREB over neuronal differentiation and survival, in vitro experiments of cell culture were conducted using pharmacological kinase inhibitors and genetic techniques to express different forms of CREB (A-CREB and CREB-FY) in cortical neurons. Inhibition of PKA and CaMKII decreased the length of neuronal processes (neurites); whereas inhibition of MAPK did not affect the length, but increased the number of neurites. Blockade of PI3K do not appear to alter neuronal morphology, nor the soma size changed with the kinase blockades. CREB activation (CREB-FY) along with MAPK and PI3K blockades presented a negative side effect over neuritic growth and the expression of A-CREB leaded to a significant decrease in neuronal survival after 60h in vitro and mimicked some of the effects on neuronal morphology observed with PKA and CaMKII blockade. In summary the signaling through CREB influences the morphology of cortical neurons, particularly when phosphorylated by PKA, and CREB signaling is also important for survival of immature neurons prior to the establishment of fully functional synaptic contacts. Our data contribute to understanding the role of CREB signaling, activated by different routes, on survival and neuronal differentiation and may be valuable in the development of regenerative strategies in different neurological diseases