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

VIVÊNCIAS LÚDICAS DE PRÉ-ESCOLARES NASCIDOS COM MUITO BAIXO PESO / PLAYFUL EXPERIENCES OF PRESCHOOL CHILDREN WHO ARE BORN WITH VERY LOW BIRTHWEIGHT

Introdução: O brincar é constituído de valores e normas culturais representativos das relações sociais estabelecidas no processo de integração da criança na comunidade. As vivências lúdicas além das influências culturas dependem do ambiente e de características das crianças. Objetivo: Avaliar vivências lúdicas de crianças em idade pré-escolar nascidas com muito baixo peso. Métodos: Pesquisa do tipo estudo de casos, com amostra constituída por 36 crianças que foram acompanhadas no Ambulatório de Seguimento do Hospital Universitário da Universidade Federal do Maranhão. Dois instrumentos foram utilizados: Entrevista Inicial com os Pais e Avaliação do Comportamento Lúdico (adaptada por Sant'anna et al., 2008). Os dados foram processados nos programas de bioestatística Epi Info® 3.4.1 e SPSS® 16.0. Resultados: Verificou-se que o extremo baixo peso e o desenvolvimento atípico influenciam a atitude lúdica; o prazer e a curiosidade foram características mais frequentes nas brincadeiras, e senso de humor e gosto pelo desafio foram atitudes menos presentes nas crianças do estudo. Conclusão: Pais de crianças com baixo peso ao nascer devem ser orientados precocemente em relação às necessidades específicas relacionadas à importância das vivências lúdicas.Palavras-chave: Recém-nascido de baixo peso. Criança. Crescimento e Desenvolvimento.AbstractIntroduction: Playing is comprised of cultural norms and values which represent the social relationships established in the integration process of the child in the community. Playful experiences as well as the cultural values depend on characteristics of the environment and children. Objective: To evaluate playful experiences of preschool children who are born with very low birth weight. Methods: Case-control study with 36 children who were followed up in the University Hospital of Federal University of Maranhão. Two instruments were used: initial interview with parents and evaluation of playful behavior (adapted by Sant'anna et al., 2008). The statistical programs Epi Info® 3.4.1 and SPSS® 16.0 were used for data processing. Results: We found that the extremely low birth weight and atypical development influence the playful attitude. Pleasure and curiosity were features more frequent seen in the games. Sense of humor and taste for challenge attitudes were less prevalent. Conclusion: Parents of children with low birth weight should be advised early in relation to the specific needs related to the importance of playful experiences.Keywords: Newborns with low birth weight. Child. Growth and Development

Neuropsychological assessment and differential diagnosis of infectious parasitic and degenerative dementias

Submitted by Erika Demachki ([email protected]) on 2014-10-20T16:34:20Z No. of bitstreams: 2 Dissertação - Vania Lúcia Dias Soares - 2010.pdf: 2719926 bytes, checksum: 1c97489df4974bad588171364647d4d2 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Approved for entry into archive by Jaqueline Silva ([email protected]) on 2014-10-20T17:09:31Z (GMT) No. of bitstreams: 2 Dissertação - Vania Lúcia Dias Soares - 2010.pdf: 2719926 bytes, checksum: 1c97489df4974bad588171364647d4d2 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Made available in DSpace on 2014-10-20T17:09:31Z (GMT). No. of bitstreams: 2 Dissertação - Vania Lúcia Dias Soares - 2010.pdf: 2719926 bytes, checksum: 1c97489df4974bad588171364647d4d2 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2010-06-08Neuropsychological assessment and differential diagnosis between infective and degenerative dementias.. There are no studies comparing the neuropsychological profile of patients with parasitic infectious dementia (DIP) and other forms of primarily degenerative dementia. The objectives were to compare the neuropsychological deficits present in three groups of patients with dementia and a normal control group in relation to the DIP group. For this purpose, we prospectively evaluated 130 individuals with dementia from Dementia Unit, Hospital das Clinicas, Federal University of Goias and from the Tropical Diseases Hospital, Goiânia, aged above 18 years, divided in the following groups: infectious dementia (DIP), Alzheimer's disease (AD) , frontotemporal lobar degeneration(DLFT) , parkinsonism plus (PP) and normal controls. All underwent extensive neuropsychological assessment, addressing all cognitive domains (verbal and visual memory, attention, executive functions, gnosis, praxis, visuospatial skills, language). The productions were transcribed into tables and quantified by specific tests (Stroop, Trail Making A / B, Cancelation Test, Maze, Digit Span, Rey Figure, RAVLT, Logical Memory, Verbal Fluency, Hooper and Proverbs from WAIS). The DIP group generally presented with severe neuropsychological deficits present in multiple cognitive domains, and possibly even higher than those presented by primarily degenerative dementia in the elderly. These cognitive deficits can signal that the functional and / or lesional disturbances in DIP group undertake extensive brain areas or even that are impaired basic neuropsychological functions (attention, executive functions) that support the other functions with which are interdependent (memory, visuospatial functions). The DIP group had a higher run time, and committed more errors in the bell cancellation test than the control group (p <0.001), indicating deficits in selectivity and planning suggestive of involvement of fronto-subcortical areas. Overall, the DIP group had a performance in memory tasks higher than the AD group, equal to the DLFT group and lower than the PP group, suggesting the presence of heterogeneous hippocampal pathology in DIP group. The results emphasize that the neuropsychological assessments aid in the differential diagnosis of dementia and the topographic location of lesions associated with the predominant profile of cognitive dysfunction.A avaliação neuropsicológica constitui importante suporte no diagnóstico diferencial entre as diversas formas de demência. Ainda não existem estudos comparando o perfil neuropsicológico de pacientes com demência infecto-parasitária (DIP) e outras formas de demência primariamente degenerativa. Os objetivos desta pesquisa foram comparar as alterações neuropsicológicas presentes em quatro grupos de pacientes com demência em relação ao grupo de pacientes com DIP e comparar o perfil neuropsicológico do grupo DIP com um grupo controle constituído por sujeitos saudáveis, pontuando os elementos neuropsicológicos diferenciadores entre eles. Para tanto, foram avaliados prospectivamente 130 indivíduos portadores de demência do ambulatório de Demências do Hospital das Clínicas da Universidade Federal de Goiás e do Hospital de Doenças Tropicais, Goiânia, com idade acima de 18 anos divididos no seguintes grupos:demência infecto parasitária (DIP), doença de Alzheimer (DA), degeneração lobar frontotemporal (DLFT) , parkinsonismo plus (PP) e controles normais. Todos realizaram avaliação neuropsicológica extensa, contemplando todos os domínios cognitivos (memória verbal e visual, atenção, funções executivas, gnosias, praxias, habilidades vísuo-espaciais, linguagem). As produções foram transcritas em tabelas e quantificadas por meio de testes específicos (Stroop, Trail Making A/B, Sinos, Labirinto, Dígitos, Figura Rey, RAVLT, Memória Lógica, Fluência Verbal, Hooper e Provérbios do WAIS). O grupo DIP apresentou desempenho cognitivo prejudicado em praticamente todos os domínios, quando comparado ao grupo controle normal. O grupo DIP apresentou maior tempo de execução e cometeu muito mais erros no teste de cancelamento dos sinos que o grupo controle (p < 0,001), indicando déficits na seletividade e no planejamento sugestivos de comprometimento de áreas fronto-subcorticais. No geral, o grupo DIP apresentou desempenho em tarefas de memória superior ao grupo DA, igual ao grupo DLFT e inferior ao grupo PP e controle, sugerindo a presença heterogênea de patologia hipocampal no grupo DIP. Os resultados ressaltam que as avaliações neuropsicológicas auxiliam no diagnóstico diferencial das demências e na localização topográfica das lesões associadas ao perfil predominante de disfunções cognitivas