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A terapia antineoplásica tradicional apresenta algumas limitações que podem ser superadas através da utilização dos lipossomas. Estes nanossistemas de carreamento possibilitam o direcionamento de fármacos e reduzem efeitos secundários. Alguns peptídeos catiônicos sintetizados na pele de anuros apresentam atividade citotóxica seletiva (microorganismos e/ou tumores). Neste sentido, espécies do gênero Phyllomedusa secretam as dermaseptinas. Objetivou-se neste estudo, avaliar a citotoxicidade in vitro da dermaseptina 01 (DS 01) livre e encapsulada em lipossomas unilamelares pequenos (SUVs) em células tumorais humanas. Os lipossomas foram preparados pelo método de hidratação do filme lipídico seguido de sonicação. Foram produzidas formulações neutras e catiônicas, convencionais e furtivas. A citotoxicidade foi analisada em células tumorais de pulmão (NCI-H292), cólon (HT-29) e laringe (HEp-2), pelo ensaio de redução do sal tetrazólio (MTT) em placas de 96 poços. Os lipossomas foram submetidos a testes de estabilidade acelerada e em longo prazo. Em NCI-H292, a DS 01 livre apresentou efeito citostático médio de 35,6%. A encapsulação do peptídeo em lipossomas convencionais neutros aumentou o efeito, ao contrário dos furtivos. Para HT-29 e HEp-2, a DS 01 livre inibiu o crescimento celular em aproximadamente 50%, em média. A encapsulação em lipossomas catiônicos potencializou o efeito; os lipossomas convencionais inibiram na faixa de 80% e os furtivos, mais que 95% para as duas linhagens celulares. A DS 01, um peptídeo catiônico antimicrobiano, apresentou efeito citotóxico in vitro para células tumorais humanas que foi potencializado com a nanoencapsulação...

The conventional anticancer therapies show some limitations that can be overcome by using liposomes. This type of nanocarriers allows preferential targeting of drugs and reduces undesirable secondary effects. Some cationic peptides synthesized by the skin of anurans exhibit selective cytotoxicity (to pathogens and/or tumors). Species of Phyllomedusa secrete dermaseptins (DSs). The aim of this study was to assess the in vitro cytotoxicity of free and small unilamellar vesicle (SUV)-encapsulated dermaseptin 01 (DS 01) in various human tumor cells. Liposomes were prepared by lipid film hydration followed by sonication. Neutral and cationic, conventional and stealth liposomes were produced. Cytotoxicity was analyzed in lung (NCI-H292), colon (HT-29) and larynx (HEp-2) cancer cells, by the tetrazolium reduction method (MTT) carried out in 96-well microplates. Liposomes were tested for accelerated and long-term stability. In NCI-H292, free DS 01 showed a medium cytostatic effect of 36.5%. The conventional neutral liposome encapsulation of peptide increased this effect, whereas the stealth did not. In HT-29 and HEp-2, free DS 01 inhibited the cell growth by approximately 50% on average. The cationic liposome encapsulation was synergic, inhibition being about 80% in conventional and higher than 95% in stealth liposomes for both celllines. Thus, DS 01, an antimicrobial cationic peptide, showed in vitro cytotoxicity to human tumor cells that was potentiated by nanoencapsulation...

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BACKGROUND: Cleidocranial dysplasia (CCD) is a dominantly inherited autosomal disease characterized by typical bone defects including short stature, persistently open or delayed closure of the cranial sutures, and hypoplastic or aplastic clavicles. Oral features are frequent and include supernumerary teeth, delayed eruption or impaction of the permanent teeth, and malocclusion. Heterozygous mutations in RUNX2 gene, which encodes a transcription factor essential for osteoblast differentiation, were identified as the etiological cause of CCD. OBJECTIVE AND METHODS: Herein, we performed physical and radiographic examination and screening for RUNX2 mutations in 11 patients from five families with CCD. RESULTS: All patients demonstrated the classical phenotypes related to CCD. Families whose affected members had several dental alterations such as multiple impacted and supernumerary teeth demonstrated heterozygous missense mutations (R190Q and R225Q) that impair the runt domain of RUNX2. On the other hand, CCD patients from families with low frequency of dental abnormalities showed no mutation in RUNX2 or mutation outside of the runt domain (Q292fs→X299). CONCLUSION: The current findings suggest a correlation between dental alterations and mutations in the runt domain of RUNX2 in CCD patients. Further clinical and genetic studies are needed to clarify the relationship between phenotypes and genotypes in CCD and to identify other factors that might influence the clinical features of this uncommon disease.

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Aunque se ha denunciado ampliamente la dificil aplicabilidad de las clasificaciones psiquiátricas a la atención primaria, hasta el momento son escasas las investigaciones destinadas a definir y sistematizar las demandas reales con respecto a dichos sistemas nosológicos. Recientemente, ha visto la luz la versión revisada para atención primaria del capítulo de trastornos mentales y del comportamiento de la CIE-10. La nueva herramienta es el resultado de un proceso de elaboración desarrollado primordialmente por un grupo de 971 médicos de atención primaria coordinados por 55 psiquiatras. El proyecto se organizó en tres fases: a) evaluación de la versión actual y recogida de propuestas de modificación; b) definición de objetivos para una versión optimizada, y c) redacción de una propuesta de texto revisado. El resultado es un texto más asimilable a una guía diagnóstica y terapéutica que a un mero sistema de codificación, más adaptado al papel que los médicos de atención primaria están en condiciones de desempeñar en cada trastorno, más actualizado (especialmente en el apartado del tratamiento) y más específico en muchos aspectos

Although the difficulty of applying psychiatric classifications to primary care has been widely criticized, there have been few investigations up to now to define and systematize the real demands in regards to these nosological systems. Recently, the revised version of the Mental and Behavior Disorders Chapter of the ICD 10 has been published. The new tool is the result of an elaboration process mainly developed by a group of 971 primary care physicians coordinated by 55 psychiatrists. The project was organized into three phases: a) evaluation of the current version and collection of proposals for change; b) definition of objectives for an optimized version; and c) writing a proposal of revised text. The result is a text that is more assimilable to a diagnostic and therapeutic guide than a mere coding system, more adapted to the role that the primary care physician can play in each disorder, more up-dated (especially in the treatment section) and more specific in many aspects

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The buildup of layer-by-layer (LBL) films from chitosan and the azodye Ponceau-S (PS) was investigated under various experimental conditions, and the resulting films were used in optical storage experiments. The kinetics for the writing process in optical storage was faster for LBL films prepared at low pHs, probably because the films had a larger free volume for isomerization of the chromophores. The nanostructured nature of the LBL films also affected the crystallinity of chitosan, which was considerably decreased in this type of film as chitosan became protonated because of the electrostatic interactions between adjacent layers.

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Layer-by-layer (LBL) films of chitosan alternated with an azopolymer, PS119, have been used for optical storage and fabrication of surface-relief gratings. The optical properties stem from the trans-cis-trans isomerization cycles undergone by the azochromophore, with a kinetics for writing the birefringence pattern that is much slower than in the spin-coated or cast films of azopolymers. The long writing times, of the order of 100 s, are due to the electrostatic interactions between adjacent chitosan and PS119 layers. Such interactions are also responsible for other features in the LBL films, namely the increase in the amount of adsorbed material when the pH of the preparation solution is decreased and the large residual birefringence after the writing laser is switched off. Gratings could be inscribed with s-polarized but not with p-polarized light, indicating a mass transport process associated with photodegradation.

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BACKGROUND: Asthma morbidity and mortality have been increasing. Data of asthma and respiratory mortality rates in Brazil are scarse. METHODS: We studied asthma and respiratory disease mortality rates in the state of So Paulo (capital and country side) from 1970 to 1996, as its relation with sales of drugs usually used in asthma treatment. RESULTS: Asthma mortality in the 5-34-year age group has doubled in the state of So Paulo (0.2 deaths/100,000 inhabitants in 1970 to 0.4 in 1996), mainly by its increase in the capital. The greatest increase was observed in the population of up to 15 years of age. The sales of inhaled anti-inflammatory drugs are proportionally very low and reflect a greater concern about the treatment of acute exacerbations. CONCLUSION: We believe that the institution of a public health supply to the whole population could provide better conditions for the control of those indexes.

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As modificacoes ultra-sonicas que ocorrem na placenta, nas ultimas semanas de prenhez, foram estudadas com equipamento com escala de cinza, tempo real e sonda de 3,5mHz. Foram classificados quatro tipos basicos de imagem placentar e estudou-se sua distribuicao entre 31 e 42 semanas.Conclui-se pela existencia de cronologia significante destas modificacoes, pois o numero de placentas com calcificacoes visiveis no bolo placentar progressivamente maior a medida que aumentou a idade gestacional. Sao feitas consideracoes sobre as possibilidades do uso da placentrografia ultra-sonica na estimativa de maturidade fetal

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Havera alguma validade em mantermos nossos pacientes esquizofrenicos sob o uso continuo de neurolepticos, ou essa e mais uma das inquestionaveis tradicoes medicas? Muitos fatores contribuem para dificultar a avaliacao do tratamento neuroleptico de manutencao na esquizofrenia. Entre os principais incluem-se a questao do diagnostico psiquiatrico, as duvidas quanto a etiologia desta doenca o conceito de cura em psiquiatria, alem das influencias do contexto socio-economico-politico em que esta inserida a pratica medica. Uma revisao da literatura nao conduz ao estabelecimento de regras definidas de como usar os neurolepticos, sendo encontradas todas as matizes de opiniao, quanto a seu uso a longo prazo, desde a elegia ate a detracao. Apesar das controversias, podem ser demarcados alguns criterios para orientar o planejamento de um esquema terapeutico, levando-se em consideracao tanto os fatores clinicos como os componentes culturais e economicos da realidade do paciente

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Monografia apresentada pelo autor na posse da cadeira de Pediatria, da Sociedade Portuguesa de Beneficência do Rio de Janeiro, cujo patrono é o Dr. Aloysio de Castro. Tece comentários sobre a vida e obra do biografado, destacando sua importância para o desenvolvimento da medicina brasileira. (JGC)

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