Desenvolvimento de nanopartículas de quitosana para potencial administração nasal da DISBa-01, uma desintegrina recombinante do veneno da serpente Rhinocerophis alternatus

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

Emprego da tomografia computadorizada de feixe cônico na análise de alterações periapicais de origem endodôntica in vivo, e na instrumentação de canais radiculares in vitro

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Formação de biofilmes e resistência a antifúngico e biocidas em Candida parapsilosis e C. orthopsilosis isoladas de águas usadas para hemodiálise

Pós-graduação em Biociências e Biotecnologia Aplicadas à Farmácia - FCFAR

Terapia de reposição enzimática para as mucopolissacaridoses I, II e VI: recomendações de um grupo de especialistas brasileiros

As mucopolissacaridoses (MPS) são doenças genéticas raras causadas pela deficiência de enzimas lisossômicas específicas que afetam o catabolismo de glicosaminoglicanos (GAG). O acúmulo de GAG em vários órgãos e tecidos nos pacientes afetados pelas MPS resulta em uma série de sinais e sintomas, integrantes de um quadro clínico multissistêmico que compromete ossos e articulações, vias respiratórias, sistema cardiovascular e muitos outros órgãos e tecidos, incluindo, em alguns casos, as funções cognitivas. Já foram identificados 11 defeitos enzimáticos que causam sete tipos diferentes de MPS. Antes do advento de terapias dirigidas para a restauração da atividade da enzima deficiente, o tratamento das MPS tinha como principal foco a prevenção e o cuidado das complicações, aspecto ainda bastante importante no manejo desses pacientes. Na década de 80 foi proposto o tratamento das MPS com transplante de medula óssea/transplante de células tronco hematopoiéticas (TMO/TCTH) e na década de 90 começou o desenvolvimento da Terapia de Reposição Enzimática (TRE), que se tornou uma realidade aprovada para uso clínico nas MPS I, II e VI na primeira década do século 21. Os autores deste trabalho têm a convicção de que um melhor futuro para os pacientes afetados pelas MPS depende da identificação, compreensão e manejo adequado das manifestações multissistêmicas dessas doenças, incluindo medidas de suporte (que devem fazer parte da assistência multidisciplinar regular destes pacientes) e terapias específicas. Embora a inibição da síntese de GAG e o resgate da atividade enzimática com moléculas pequenas também possam vir a ter um papel no manejo das MPS, o grande avanço disponível no momento é a TRE intravenosa. A TRE permitiu modificar radicalmente o panorama do tratamento das mucopolissacaridoses I, II e VI na última década, sendo que ainda pode estender seus benefícios em breve para a MPS IV A (cuja TRE já está em desenvolvimento clínico), com perspectivas para o tratamento da MPS III A e do déficit cognitivo na MPS II através de administração da enzima diretamente no sistema nervoso central (SNC). Um grande número de centros brasileiros, incluindo serviços de todas as regiões do país, já têm experiência com TRE para MPS I, II e VI. Essa experiência foi adquirida não só com o tratamento de pacientes como também com a participação de alguns grupos em ensaios clínicos envolvendo TRE para essas condições. Somados os três tipos de MPS, mais de 250 pacientes já foram tratados com TRE em nosso país. A experiência dos profissionais brasileiros, somada aos dados disponíveis na literatura internacional, permitiu elaborar este documento, produzido com o objetivo de reunir e harmonizar as informações disponíveis sobre o tratamento destas doenças graves e progressivas, mas que, felizmente, são hoje tratáveis, uma realidade que traz novas perspectivas para os pacientes brasileiros afetados por essas condições.

Desenvolvimento de tecnologia educacional para o uso racional de energia

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação física e radiográfica de biomateriais usados para regeneração óssea

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Platelet-rich plasma (PRP): methodological aspects and clinical applications

The clinical use of platelet-rich plasma (PRP) is based on the increase in the concentration of growth factors and in the secretion of proteins which are able to maximize the healing process at the cellular level. Since PRP is an autologous biologic material, it involves a minimum risk of immune reactions and transmission of infectious and contagious diseases, and it has been widely used for the recovery of musculoskeletal lesions. Despite the great potential for applicability, the implementation of the therapeutic employment of PRP as a clinical alternative has become difficult, due to the lack of studies related to the standardization of the techniques and/or insufficient description of the adopted procedures. Therefore, it is required establish standard criteria to be followed for obtaining a PRP of high quality, as well as a larger number of studies which should establish the proper concentration of platelets for the different clinical conditions. In this context, the purpose of this review is to discuss some methodological aspects used for achieving the PRP, as well as to discuss the bioactive properties of PRP, and to point out its therapeutic use in different fields of regenerative medicine.

Bone morphogenetic proteins: promising molecules for bone healing, bioengineering, and regenerative medicine

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

Trombobectomia com anel de Vollmar e utilização do cateter de Fogarty no tratamento da trombose jugular experimental em equinos

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

Local clinical phototreatment of herpes infection in Sao Paulo

The clinical use of topical photodynamic therapy in herpes simplex lesions in Sao Paulo is presented and discussed. Although previous attempts utilising this type of approach in the USA were discontinued in the early 1970s due to several presentations of post-treatment Bowen's disease, none of the cases from the clinic presented here have displayed any complications on follow-up. In addition, lesion recrudescence periods are generally much longer than with conventional approaches. This is thought to be due to improvements in the treatment protocol, viz, use of the non-toxic photosensitisers methylene blue and Hypericum perforatum extract in place of proflavine and neutral red in the original trials, differences in photosensitisation pathway and illumination of the treatment site with red rather than fluorescent/UV light. Post-treatment cosmesis is also excellent. (C) 2012 Elsevier B.V. All rights reserved.

Production of Human Antibody Fragments Binding to Melittin and Phospholipase A2 in Africanised Bee Venom: Minimising Venom Toxicity

The hybrid created from the crossbreeding of European and African bees, known as the Africanised bee, has provided numerous advantages for current beekeeping. However, this new species exhibits undesirable behaviours, such as colony defence instinct and a propensity to attack en masse, which can result in serious accidents. To date, there is no effective treatment for cases of Africanised bee envenomation. One promising technique for developing an efficient antivenom is the use of phage display technology, which enables the production of human antibodies, thus avoiding the complications of serum therapy, such as anaphylaxis and serum sickness. The aim of this study was to produce human monoclonal single-chain Fv (scFv) antibody fragments capable of inhibiting the toxic effects of Africanised bee venom. We conducted four rounds of selection of antibodies against the venom and three rounds of selection of antibodies against purified melittin. Three clones were selected and tested by enzyme-linked immunosorbent assay to verify their specificity for melittin and phospholipase A2. Two clones (C5 and C12) were specific for melittin, and one (A7) was specific for phospholipase A2. In a kinetic haemolytic assay, these clones were evaluated individually and in pairs. The A7-C12 combination had the best synergistic effect and was chosen to be used in the assays of myotoxicity inhibition and lethality. The A7-C12 combination inhibited the in vivo myotoxic effect of the venom and increased the survival of treated animals.

delta-Lactam derivative from thermophilic soil fungus exhibits in vitro anti-allergic activity

From cultures of thermophilic soil fungus Humicola grisea var thermoidea, a delta-lactam derivative (3-(2-(4-hydroxyphenyl)-2-oxoethyl)-5,6-dihydropyridin-2( 1H)-one) that displayed anti-allergic activity was isolated, which was predicted by in silico computational chemistry approaches. The in vitro anti-allergic activity was investigated by beta-hexosaminidase release assay in rat basophilic leukaemia RBL-2H3 cells. The delta-lactam derivative exhibited similar anti-allergic activity (IC50 = 18.7 +/- 6.7 mu M) in comparison with ketotifen fumarate (IC50 = 15.0 +/- 1.3 mu M) and stronger anti-allergic activity than azelastine (IC50 = 32.0 mu M). Also, the MTT cytotoxicity assay with RBL-2H3 cells showed that delta-lactam does not display cytotoxicity at concentrations lower than 50 mu M. This study suggests that the delta-lactam derivative has the potential to be used as a lead compound in the development of anti-allergic drugs for clinical use in humans.

Structure- and ligand-based drug design approaches for neglected tropical diseases

Drug discovery has moved toward more rational strategies based on our increasing understanding of the fundamental principles of protein-ligand interactions. Structure( SBDD) and ligand-based drug design (LBDD) approaches bring together the most powerful concepts in modern chemistry and biology, linking medicinal chemistry with structural biology. The definition and assessment of both chemical and biological space have revitalized the importance of exploring the intrinsic complementary nature of experimental and computational methods in drug design. Major challenges in this field include the identification of promising hits and the development of high-quality leads for further development into clinical candidates. It becomes particularly important in the case of neglected tropical diseases (NTDs) that affect disproportionately poor people living in rural and remote regions worldwide, and for which there is an insufficient number of new chemical entities being evaluated owing to the lack of innovation and R&D investment by the pharmaceutical industry. This perspective paper outlines the utility and applications of SBDD and LBDD approaches for the identification and design of new small-molecule agents for NTDs.

Crianças com implante coclear: habilidades comunicativas e qualidade de vida

Dado o âmbito multidimensional do implante coclear, há crescente necessidade em avaliar não somente medidas clínicas de eficácia relacionadas às habilidades comunicativas, mas também aspectos mais genéricos envolvidos na efetividade do tratamento, como a qualidade de vida. OBJETIVOS: Tradução e adaptação de questionário internacional para o Português Brasileiro; análise das correlações entre fatores relacionados à qualidade de vida; análise das correlações entre qualidade de vida e medidas clínicas de resultado. MATERIAL E MÉTODO: Estudo prospectivo realizado com pais de crianças com implante coclear consistindo na aplicação de instrumentos validados para avaliar aspectos de qualidade de vida e habilidades comunicativas. RESULTADOS: A tradução e adaptação cultural do questionário foi satisfatoriamente realizada e este estudo proporciona a disponibilização do questionário em versão para o Português Brasileiro. Pelos dados obtidos, o implante coclear apresentou efeito positivo na qualidade de vida das crianças implantadas e de suas famílias. As correlações observadas para a variável comunicação demonstram uma relação direta entre comunicação oral e outras variáveis de qualidade de vida. CONCLUSÃO: Este estudo disponibiliza o questionário em versão para o Português Brasileiro. Para os pais de crianças brasileiras usuárias de implante coclear, a habilidade lexical (aquisição e uso das palavras) é a variável de maior impacto na qualidade de vida de seus filhos.

Analysis of human body kinematics using a hybrid markerless video acquisition and processing

A main objective of the human movement analysis is the quantitative description of joint kinematics and kinetics. This information may have great possibility to address clinical problems both in orthopaedics and motor rehabilitation. Previous studies have shown that the assessment of kinematics and kinetics from stereophotogrammetric data necessitates a setup phase, special equipment and expertise to operate. Besides, this procedure may cause feeling of uneasiness on the subjects and may hinder with their walking. The general aim of this thesis is the implementation and evaluation of new 2D markerless techniques, in order to contribute to the development of an alternative technique to the traditional stereophotogrammetric techniques. At first, the focus of the study has been the estimation of the ankle-foot complex kinematics during stance phase of the gait. Two particular cases were considered: subjects barefoot and subjects wearing ankle socks. The use of socks was investigated in view of the development of the hybrid method proposed in this work. Different algorithms were analyzed, evaluated and implemented in order to have a 2D markerless solution to estimate the kinematics for both cases. The validation of the proposed technique was done with a traditional stereophotogrammetric system. The implementation of the technique leads towards an easy to configure (and more comfortable for the subject) alternative to the traditional stereophotogrammetric system. Then, the abovementioned technique has been improved so that the measurement of knee flexion/extension could be done with a 2D markerless technique. The main changes on the implementation were on occlusion handling and background segmentation. With the additional constraints, the proposed technique was applied to the estimation of knee flexion/extension and compared with a traditional stereophotogrammetric system. Results showed that the knee flexion/extension estimation from traditional stereophotogrammetric system and the proposed markerless system were highly comparable, making the latter a potential alternative for clinical use. A contribution has also been given in the estimation of lower limb kinematics of the children with cerebral palsy (CP). For this purpose, a hybrid technique, which uses high-cut underwear and ankle socks as “segmental markers” in combination with a markerless methodology, was proposed. The proposed hybrid technique is different than the abovementioned markerless technique in terms of the algorithm chosen. Results showed that the proposed hybrid technique can become a simple and low-cost alternative to the traditional stereophotogrammetric systems.