96 research outputs found
Desordens temporomandibulares e dores orofaciais: uma abordagem sobre as dores polpar e periodontal
Este trabalho, orientado para o aluno iniciante em "Desordens temporomandibulares e dor oro-facial; Diagnóstico" foi elaborado para proporcionar uma parcela de informação revisada e atualizada em complementação a uma série de conferências sob o título de "Dor no consultório - o que fazer?" (Diretório Acadêmico Othon Silva - FO/UFRGS - 1990) Considerando o fato de que uma boa parte das dores somáticas profundas na região oro-facial têm origens dentárias, achamos justificável a abordagem de: 1 - um resumo dos fatores envolvidos na etiologia e percepção das dores polpares e periodontais, e 2 - uma descrição suscinta dos mecanismos que embasam a transmissão das dores de origem dentária e sua modulação, tanto periférica como central. Não são aqui discutidas, devido a suas características muitas vezes multidisciplinares, especialmente nos casos de dores crônicas, as oportunidades terapêuticas múltiplas atualmente à disposição do clínico. Algumas serão só citadas. Para facilitar ao aluno interessado a oportunidade de um maior acesso às fontes de referência atualizadas, aquelas consideradas mais importantes são citadas ao final do trabalho e numeradas no texto. Os autores
Acetylcholinesterase inhibitory activity of oxazole derivatives
Comunicação oral sob a forma de painelAlzheimer’s disease (AD) is the most common form of dementia among persons over 65 years of age. It is a brain neurodegenerative disorder characterised by loss of memory and cognition. Current treatment is symptomatic, with the major therapeutic strategy based on the “cholinergic hypothesis”, specifically acetylcholinesterase (AChE) inhibition. Tacrine (THA) was the first and one of the few drugs approved in the last decade for the treatment of AD. However, due to the important adverse effects, such as hepatotoxicity, it is no longer widely used. Therefore, more potent and less aggressive THA analogues are necessary. This prompted us to evaluate the AChE inhibitory activity of new oxazole derivatives (compounds 1-5), presenting a pyridine ring (compounds 2,3) or a benzene ring (compounds 4,5) in the molecule (1). The biological activity of the compounds was evaluated by measuring the AChE inhibitory activity by an adaptation of the method reported by Ellman et al (2). The reaction rates were compared and the percent of inhibition by the test compounds was calculated. Assays were performed in quadruplicate in at least two independent experiments, and THA was used as a reference compound. At the maximum soluble concentrations, compounds 1 and 2 inhibited AChE activity by nearly 50%, while the inhibition by the derivative 3 was only around 30%. In contrast, the oxazolo-derivatives 4 and 5 were devoid of any inhibitory activity, which we can speculate to be due to the absence of the N atom in the benzene ring in these compounds. Collectively, these preliminary findings point to a potential interest of precursor 1 and THA-derivative 2 for AD therapeutics, although structural modifications are needed to improve the solubility of the compounds, which is an essential step to enhance their activity.
References:
1. Carreiras MC, Eleutério A, Marco-Contelles J, unpublished results.
2. Ellman, G. L. et al. Biochem. Pharmacol. 1961; 7: 88-95.Financial support: Centro de Estudos de Ciências Farmacêuticas, Centro de Patogénese Molecular – UBMBE and Instituto de Química Orgánica General – CSIC
Analysis of flood warning and evacuation efficiency by comparing damage and life-loss estimates with real consequences related to the São Francisco tailings dam failure in Brazil
Economic damage and life-loss estimates provide important
insights for the elaboration of more robust alerts and effective emergency
planning. On the one hand, accurate damage analysis supports decision-making
processes. On the other hand, the comparison of different flood alert
scenarios through modeling techniques is crucial for improving the
efficiency of alert and evacuation systems design. This work evaluates the
use of flood damage and life-loss models in floods caused by tailings dams
through the application of these models in the real case of the São
Francisco dam failure, which occurred in January 2007 in the city of
Miraí in Brazil. The model results showed great agreement with
observed damage and loss of life. Furthermore, different simulations were
done in order to measure the impact of increasing and decreasing alert
system efficiency on life-loss reduction. The simulated scenarios exploring
the inefficiency of flood alert and evacuation revealed that life loss could
have reached the maximum rate of 8.7 % of the directly exposed population
when considering the more pessimistic and uncertain scenario instead of the
actual null life loss achieved. The results of this work indicate that the
models could represent both the observed accident and different
alert and evacuation efficiency impacts. It highlights the importance of
developing and implementing robust alert and evacuation systems and
regulations in order to reduce flood impacts.</p
Biomass and leaf area in Eucalyptus clones in crop-livestock-forestry systems: implications for pruning.
Resumo
CONTROLADOR LÓGICO PROGRAMÁVEL UTILIZANDO PIC 18F4550
Desde a criação dos relés eletromecânicos os processos industriais vêm se modernizando, principalmente após a descoberta dos microprocessadores que impulsionaram o desenvolvimento dos controladores lógicos programáveis. Os controladores tornaram os processos produtivos flexíveis do ponto de vista de manutenção, expansão e principalmente aumentando a qualidade dos produtos e qualidade de vida dos envolvidos, já que esta tecnologia vem retirando os homens de processos insalubres e tornando estes processos inteligentes e independentes. A cada dia os controladores ficam mais poderosos e consequentemente mais caros, o que vem tornando estes dispositivos inviáveis para processos simples e com baixo valor agregado. Este fato motivou o desenvolvimento de um controlador de baixo custo de produção e de fácil implementação para profissionais que atuam nestes processos mais simples. Para o desenvolvimento deste trabalho foi utilizado o Microcontrolador PIC18F4550. Depois de concluídas as simulações foi observada a possibilidade de se aumentar os módulos de entrada e saída do controlador, o que torna seu custo beneficio ainda maior
Rifabutin encapsulated in liposomes exhibits increased therapeutic activity in a model of disseminated tuberculosis
Tuberculosis (TB) is a leading cause of death amongst infectious diseases. The low permeation of antimycobacterial agents and their difficult access to infected macrophages necessitate long-term use of high drug doses. Liposomes preferentially accumulate in macrophages, increasing the efficacy of antibiotics against intracellular parasites. In the present work, several rifabutin (RFB) liposomal formulations were developed and characterised and their in vivo profile was compared with free RFB following intravenous administration. With the RFB liposomal formulations tested, higher concentrations of the antibiotic were achieved in liver, spleen and lungs 24h post administration compared with free RFB. The concentration of RFB in these organs was dependent on the rigidity of liposomal lipids. The liposomal RFB formulation prepared with dipalmitoyl phosphatidylcholine:dipalmitoyl phosphatidylglycerol (DPPC:DPPG) was the most effective and was selected for biological evaluation in a mouse model of disseminated TB. Compared with mice treated with free RFB, mice treated with the DPPC:DPPG RFB formulation exhibited lower bacterial loads in the spleen (5.53 log(10) vs. 5.18 log(10)) and liver (5.79 log(10) vs. 5.41 log(10)). In the lung, the level of pathology was lower in mice treated with encapsulated RFB. These results suggest that liposomal RFB is a promising approach for the treatment of extrapulmonary TB in human immunodeficiency virus co-infected patients.This work was supported by grants from FCT (POCTI/FCB/36416/99) and from the Health Services of FCG. Fellowships were granted by FCT (SFRH/BD/9624/2002- GABBA Program to A. Cruz and SFRH/BD/15911/2005 to A.G. Fraga
Unconstrained mining of transcript data reveals increased alternative splicing complexity in the human transcriptome
Mining massive amounts of transcript data for alternative splicing information is paramount to help understand how the maturation of RNA regulates gene expression. We developed an algorithm to cluster transcript data to annotated genes to detect unannotated splice variants. A higher number of alternatively spliced genes and isoforms were found compared to other alternative splicing databases. Comparison of human and mouse data revealed a marked increase, in human, of splice variants incorporating novel exons and retained introns. Previously unannotated exons were validated by tiling array expression data and shown to correspond preferentially to novel first exons. Retained introns were validated by tiling array and deep sequencing data. The majority of retained introns were shorter than 500 nt and had weak polypyrimidine tracts. A subset of retained introns matching small RNAs and displaying a high GC content suggests a possible coordination between splicing regulation and production of noncoding RNAs. Conservation of unannotated exons and retained introns was higher in horse, dog and cow than in rodents, and 64% of exon sequences were only found in primates. This analysis highlights previously bypassed alternative splice variants, which may be crucial to deciphering more complex pathways of gene regulation in human.info:eu-repo/semantics/publishedVersio
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