In vitro, heparin and antithrombotic drugs specifically stimulate the synthesis of an antithrombotic heparan sulfate proteoglycan (HSPG) produced by endothelial cells. The putative heparin binding site(s) that may be related to this phenomenon were investigated. In the preceding article, using various heparin probes, it was shown that the heparin does not bind to the endothelial cell surface, but only to the extracellular matrix. The present study demonstrated that, when the cells were exposed to heparin at 37 degrees C, the heparin was internalized and with time was localized in lysosomes. However, endocytosis of heparin was not required for the stimulation of HSPG synthesis. The requirement for heparin degradation in the stimulus of HSPG synthesis was also investigated. When the cells were incubated with chloroquine, a lysosomotropic amine that raises the lysosomal pH thus inhibiting enzymatic degradation of internalized compounds, stimulation of HSPG synthesis was still observed. These combined results indicate that neither internalization nor degradation of heparin is required for stimulation of HSPG synthesis, and suggests that its binding to the extracellular matrix could be responsible for this effect.
O desenvolvimento de vacinas envolve a necessidade de se controlar todos os eventos adversos, visando monitorar a segurança do produto sob investigação de forma ágil e acurada. Objetivo: Esta pesquisa desenvolve um artefato destinado a reduzir o tempo de relato dos Eventos Adversos em um ensaio clínico para desenvolvimento de vacinas. Metodologia: Utilizou-se o Design Science Research como técnica condutora da investigação, com a finalidade de estabelecer um artefato destinado a encontrar uma solução para o problema apresentado no objetivo. Utilizou-se técnicas do Lean e do Six sigma como ferramentas de melhoria no processo de relato de Eventos Adversos, em um ensaio clínico fase 3 para desenvolvimento de uma vacina. Resultados: Como resultado da pesquisa, o artefato proposto proporcionou uma redução do tempo médio do relato de Evento Adverso de 30 dias para 6 dias, e redução do desvio padrão de 33 dias para 6 dias. Desta forma, o tempo total no processo de relato do Evento Adverso passou a apresentar-se em conformidade com o protocolo do centro de pesquisas, proporcionando agilidade no processo, garantindo maior segurança, e qualidade de informação, aos colaboradores envolvidos. Conclusão: A combinação de ferramentas do Lean e Six sigma associado com ferramentas de controle como a carta controle, o Kanban e aplicação de formulário no padrão de Check List se apresentou como estratégia adequada para a gestão do tempo de relato de Evento Adverso, podendo ser um recurso satisfatório para otimização de processos em pesquisa clínica ou outros na área de saúde.
Autologous hematopoietic stem cell transplantation (HSCT) has proved efficient to treat hematological malignancies. However, some patients fail to mobilize HSCs. It is known that the microenvironment may undergo damage after allogeneic HSCT. However little is known about how chemotherapy and growth factors contribute to this damage. We studied the stromal layer formation (SLF) and velocity before and after HSC mobilization, through long-term bone marrow culture from 22 patients and 10 healthy donors. Patients' SLF was similar at pre- (12/22) and post-mobilization (9/20), however for controls this occurred more at pre-mobilization (9/10; p=0.03). SLF velocity was higher at pre than post-mobilization in both groups. Leukemias and multiple myeloma showed faster growth of SLF than lymphomas at post-mobilization, the latter being similar to controls. These findings could be explained by less uncommitted HSC in controls than patients at post-mobilization. Control HSCs may migrate more in response to mobilization, resulting in a reduced population by those cells.
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