931 resultados para antithrombotic agents, development for clinical use


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The use of implant-supported prosthesis to replace missing teeth became a predictable treatment. Although high success rate has been reported, implant treatment is suitable to complications, failures, and limitations such as peri-implant bone loss after implant loading. Stress evaluation on the bone-abutment-implant interface has been carried out to develop new designs of prosthetic platform and to understand the stress distribution in this interface. Several types of prosthetic platforms are available such as external and internal hexagon, Morse cone connection, and the concept of platform switching. Therefore, this study aimed to critically describe the different options of prosthetic platforms in implant dentistry, by discussing their biomechanical concepts, clinical use, and advantages and disadvantages. It was observed that all types of prosthetic platforms provided high success rate of the implant treatment by following a strict criteria of indication and limitation. In conclusion, a reverse planning of implant treatment is strongly indicated to reduce implant overload, and the use of advanced surgical-prosthetic techniques is required to obtain a long-term success of oral rehabilitations.

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

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INTRODUÇÃO: as discrepâncias entre o tamanho mesiodistal dos dentes superiores e inferiores e seus efeitos sobre a oclusão têm sido relatados há muito tempo. O método proposto por Bolton para o diagnóstico de discrepância de tamanho dentário é, inegavelmente, um dos mais difundidos no meio ortodôntico, devido à sua relativa simplicidade. Entretanto, a aplicação desse método requer cálculos matemáticos e o uso de tabelas que, muitas vezes, inviabilizam a sua utilização durante a avaliação clínica. OBJETIVO: avaliar o método proposto por Wolford, que não requer o uso de tabelas, como alternativa ao método tradicional de Bolton. MÉTODOS: a amostra foi composta por 90 pares de modelos dentários iniciais de pacientes adultos, com diferentes más oclusões. A proporção entre os dentes inferiores e superiores foi calculada para cada paciente, resultando na obtenção de dois índices (a razão total e a razão anterior). Os índices foram obtidos por meio do método originalmente proposto por Bolton e por um método alternativo, composto por duas fórmulas (uma simplificada e a variação da mesma), que foram analisadas separadamente. RESULTADOS: comparadas ao método de Bolton, as fórmulas simplificadas mostraram uma tendência de superestimar as discrepâncias dentárias inferiores (total e anterior), embora em pequena proporção. CONCLUSÕES: ambas as fórmulas do método alternativo podem ser utilizadas em substituição ao método tradicional, uma vez que mostraram diferenças médias menores que 0,58mm quando comparadas ao método de Bolton, não apresentando, portanto, significância clínica.

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The purpose was to evaluate the cytotoxicity of two novel formulations (alpha and beta) of calcium phosphate cements. Positive control, represented by a commercial hydroxyapatite cement, and negative control were included for comparative purposes. A continuous lineage of fibroblastic cells was used, and the effect of the tested materials on both cell proliferation and viability was assessed by counting cell number on hemocytometer and by the trypan blue exclusion test, respectively. Study design attempted to simulate clinical use by allowing direct and indirect contact of cells and cements. Results were analyzed by the Kruskal-Wallis test and indicated that the beta formulation was extremely cytotoxic (P < 0.001), because this material induced the greatest reduction on cell proliferation and viability. The alpha formulation behaved similarly to the positive control regarding its effect on cell proliferation and viability. Thus, it is concluded that alpha formulation has promise for further evaluation of its behavior in vivo.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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

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Myocardial reperfusion injury is associated with the infiltration of blood-borne polymorphonuclear leukocytes. We have previous described the protection afforded by annexin 1 (ANXA1) in an experimental model of rat myocardial ischemia-reperfusion (IR) injury. We examined the 1) amino acid region of ANXA1 that retained the protective effect in a model of rat heart IR; 2) changes in endogenous ANXA1 in relation to the IR induced damage and after pharmacological modulation; and 3) potential involvement of the formyl peptide receptor (FPR) in the protective action displayed by ANXA1 peptides. Administration of peptide Ac2-26 at 0, 30, and 60 min postreperfusion produced a significant protection against IR injury, and this was associated with reduced myeloperoxidase activity and IL-1 beta levels in the infarcted heart. Western blotting and electron microscopy analyses showed that IR heart had increased ANXA1 expression in the injured tissue, associated mainly with the infiltrated leukocytes. Finally, an antagonist to the FPR receptor selectively inhibited the protective action of peptide ANXA1 and its derived peptides against IR injury. Altogether, these data provide further insight into the protective effect of ANXA1 and its mimetics and a rationale for a clinical use for drugs developed from this line of research.

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The purpose of this study was to observe the clinical outcome of bone spreading and standardized dilation of horizontally resorbed bone during immediate implant placement using a "screw-type" configuration of expansion and threadformers. Fifty-three patients were included in this study, and 41 edentulous areas in anterior and posterior maxillas were treated. Sixty-eight implants were placed using an insertion torque of at least 40 Ncm. Abutments were delivered 4 to 6 months after implant placement. The overall failure percentage was 4.41% (3 failures). A retrieved analysis of I implant removed at 3 years after placement demonstrated bone resorption down to the level of the third thread. The bone spreader technique is different from Summers' osteotome, both in clinical use and in armamentarium. The main advantage of the crest-expanding technique is that it is a less invasive procedure; the facial wall expands after the medullary bone is compressed against the cortical wall. Within the limits of this preliminary study, the cumulative survival rate for this method of implant placement is 95.58% at 3 years. This study confirms that a bone spreader used in the maxilla shows an unusually low failure rate after 3 years.

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O recente avanço científico e tecnológico direcionado à identificação imuno-hematológica de produtos celulares (ex.: citocinas, interleucinas, interferons, entre outros) sintetizados por determinadas células sanguíneas, bem como na identificação de antígenos de membrana de leucócitos e células progenitoras hematopoiéticas, promoveram excepcional desenvolvimento no diagnóstico laboratorial de diversas doenças hematológicas. Somam-se a esse fato as aplicações das técnicas de biologia molecular que se tornam cada vez mais instrumentos laboratoriais de grande definição no diagnóstico e na prevenção de doenças hematológicas, notadamente aquelas de origem hereditária. O presente artigo teve o objetivo de expor as principais aplicações de novas tecnologias que deverão ser adotadas rapidamente pela moderna hematologia laboratorial, bem como a de sensibilizar os profissionais hematologistas, clínicos e laboratoriais, para a necessidade de se atualizarem numa nova ciência, a dos produtos celulares.

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JUSTIFICATIVA E OBJETIVOS: A utilização das drogas agonistas dos alfa2-adrenoceptores para controlar a pressão arterial e freqüência cardíaca, propiciar menores respostas hemodinâmicas à intubação e extubação traqueal e poupar anestésicos já está difundida na literatura desde a introdução da clonidina. O desenvolvimento de agentes providos de maior seletividade alfa2-adrenoceptora que, por isso, determinam menos efeitos adversos, como a dexmedetomidina, recentemente liberada para utilização clínica, possibilitou que ocorressem maior sedação e analgesia com o seu uso. Despertou-se, então, o interesse em sua utilização como substitutos dos opióides, conhecidos por determinarem potente analgesia e sedação. O objetivo deste trabalho foi comparar a analgesia promovida pela dexmedetomidina e pelo sufentanil, utilizados em infusões contínuas durante anestesias de procedimentos otorrinolaringológicos e de cabeça e pescoço. MÉTODO: Os 60 pacientes estudados foram divididos em dois grupos de 30: G1, recebendo sufentanil e G2, dexmedeto- midina, na indução e manutenção anestésicas. Para a manutenção da anestesia utilizaram-se, também, o óxido nitroso e o propofol, em infusão contínua alvo-controlada. Foram avaliados os parâmetros hemodinâmicos (pressões arteriais sistólica e diastólica e freqüência cardíaca), tempos de despertar e de extubação após interrupção do propofol, locais onde foram extubados os pacientes, sala de operação (SO) ou sala de recuperação pós-anestésica (SRPA), tempo de permanência na SRPA, índice de Aldrete e Kroulik e as complicações apresentadas na SO e SRPA. RESULTADOS: G1 apresentou menores valores de pressões arteriais sistólica, diastólica e freqüência cardíaca, tempos de despertar e extubação maiores, maior número de extubações na SRPA, maior tempo de permanência na SRPA, valores mais baixos para Aldrete e Kroulik na alta da SRPA e mais complicações per e pós-operatórias. CONCLUSÕES: A utilização de dexmedetomidina como analgésico per-operatório apresentou melhores resultados que a de sufentanil, nos procedimentos selecionados neste trabalho, com relação à estabilidade hemodinâmica e às condições de despertar e de recuperação anestésica.

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We have investigated if a new LEDs system has enough efficient energy to promote efficient shear and tensile bonding strength resistance under standardized tests. LEDs 470 +/- 10 nm can be used to photocure composite during bracket fixation. Advantages considering resistance to tensile and shear bonding strength when these systems were used are necessary to justify their clinical use. Forty eight human extracted premolars teeth and two light sources were selected, one halogen lamp and a LEDs system. Brackets for premolar were bonded through composite resin. Samples were submitted to standardized tests. A comparison between used sources under shear bonding strength test, obtained similar results; however, tensile bonding test showed distinct results: a statistical difference at a level of 1% between exposure times (40 and 60 seconds) and even to an interaction between light source and exposure time. The best result was obtained with halogen lamp use by 60 seconds, even during re-bonding; however LEDs system can be used for bonding and re-bonding brackets if power density could be increased.

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The crystal structures of five new non-electrophilic β-strand-templated thrombin active-site inhibitors have been determined bound to the enzyme. Four co-crystallize with hirugen and inhibitor isomorphously to produce thrombin-hirugen crystals (monoclinic, space group C2), while one co-crystallizes in the hexagonal system, space group P65. A 1,4-substituted cyclohexyl moiety is conserved at the P1 position of all the inhibitors, along with a fused hetero-bicyclic five- and six-membered ring that occupies the P2 site. Amino, amidino and aminoimidazole groups are attached to the cyclohexyl ring for recognition at the S1 specificity site, while benzylsulfonyl and diphenyl groups enhance the binding at the S3 subsite. The cyclohexyl groups at the P1 positions of three of the inhibitors appear to be in the energetically favored chair conformation, while the imidazole-substituted cyclohexyl rings are in a boat conformation. Somewhat unexpectedly, the two cyclohexyl-aminoimidazole groups bind differently in the specificity site; the unique binding of one is heretofore unreported. The other inhibitors generally mimic arginyl binding at S1. This group of inhibitors combines the nonelectrophilicity and selectivity of DAPA-like compounds and the more optimal binding features of the S1-S3 sites of thrombin for peptidic molecules, which results in highly potent (binding constants 12 nM-16 pM, one being 1.1 μM) and selective (ranging from 140 to 20 000 times more selective compared with trypsin) inhibitors of thrombin. The binding modes of these novel inhibitors are correlated with their binding constants, as is their selectivity, in order to provide further insight for the design of therapeutic antithrombotic agents that inhibit thrombin directly at the active site.

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Tuberculosis (TB) resurged in the late 1980s and now kills approximately 3 million people a year. The reemergence of tuberculosis as a public health threat has created a need to develop new anti-mycobacterial agents. The shikimate pathway is an attractive target for herbicides and anti-microbial agents development because it is essential in algae, higher plants, bacteria, and fungi, but absent from mammals. Homologs to enzymes in the shikimate pathway have been identified in the genome sequence of Mycobacterium tuberculosis. Among them, the shikimate kinase I encoding gene (aroK) was proposed to be present by sequence homology. Accordingly, to pave the way for structural and functional efforts towards anti-mycobacterial agents development, here we describe the molecular modeling of M. tuberculosis shikimate kinase that should provide a structural framework on which the design of specific inhibitors may be based. © 2002 Elsevier Science (USA). All rights reserved.

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The legacy of mining activities has typically been land 'returned to wildlife', or, at some sites, degraded to such an extent that it is unsuitable for any alternate use. Progress towards sustainability is made when value is added in terms of the ecological, social and economic well-being of the community. In keeping with the principles of sustainable development, the innovative use of flooded open pits and tailings impoundments as commercial, recreational or ornamental fish farms should be considered in some locations, as it could make a significant contribution to the social equity, economic vitality and environmental integrity of mining communities. This article highlights the growing significance of aquaculture and explores the benefits and barriers to transforming flooded pits and impoundments into aquaculture operations. Among other benefits, aquaculture may provide a much-needed source of revenue, employment and, in some cases, food to communities impacted by mine closure. Further, aquaculture in a controlled closed environment may be more acceptable to critics of fish farming who are concerned about fish escapes and viral transmissions to wild populations. Despite the potential benefits, aquaculture in flooded pits and impoundments is not without its complications - it requires a site-specific design approach that must consider issues ranging from metals uptake by fish, to the long-term viability of the aquatic system as fish habitat, to the overall contribution of aquaculture to sustainability. © 2004 United Nations. Published by Blackwell Publishing.