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21.
The protein kinase C inhibitor H-7 (2-20 microM) inhibited dose-dependently the infectivity of the vesicular stomatitis virus on cultured human fibroblasts. Electron microscopy showed that H-7 inhibited the viral entry. H-7 also inhibited the infectivity of four other enveloped viruses, herpes simplex I, turkey herpes, vaccinia and Sindbis. Similar results were obtained using staurosporine (2.5 nM), tamoxifen (40 microM), phloretin (140 microM), or W-7 (40 microM). However, the infectivity of non-enveloped viruses (e.g. poliomyelitis I) was not inhibited by H-7. These results show that protein kinase C is critically involved in the infectivity of enveloped viruses, most probably at the level of viral entry (receptor-mediated endocytosis). 相似文献
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Melanie Köllmer Carmen Popescu Prashanth Manda Leon Zhou Richard A. Gemeinhart 《AAPS PharmSciTech》2013,14(4):1333-1340
Pharmaceutical excipients contain reactive groups and impurities due to manufacturing processes that can cause decomposition of active drug compounds. The aim of this investigation was to determine if commercially available oral disintegrating tablet (ODT) platforms induce active pharmaceutical ingredient (API) degradation. Benzocaine was selected as the model API due to known degradation through ester and primary amino groups. Benzocaine was either compressed at a constant pressure, 20 kN, or at pressure necessary to produce a set hardness, i.e., where a series of tablets were produced at different compression forces until an average hardness of approximately 100 N was achieved. Tablets were then stored for 6 months under International Conference on Harmonization recommended conditions, 25°C and 60% relative humidity (RH), or under accelerated conditions, 40°C and 75% RH. Benzocaine degradation was monitored by liquid chromatography–mass spectrometry. Regardless of the ODT platform, no degradation of benzocaine was observed in tablets that were kept for 6 months at 25°C and 60% RH. After storage for 30 days under accelerated conditions, benzocaine degradation was observed in a single platform. Qualitative differences in ODT platform behavior were observed in physical appearance of the tablets after storage under different temperature and humidity conditions. 相似文献
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The diffusion of small molecules through polymers is important in many areas of polymer science, such as gas barrier and separation membrane materials, polymeric foams, and in the processing and properties of polymers. Molecular simulation techniques have been applied to study the diffusion of oxygen and carbon dioxide as small molecule penetrants in models of bulk amorphous poly(ethylene terephthalate) (PET) and related alkylene and isomeric polyesters. A bulk amorphous configuration with periodic boundary conditions made into a unit cell whose dimensions were determined for each of the simulated polyesters in the cell having the experimental density. The diffusion coefficients for O 2 and CO 2 were determined via NVE molecular dynamics simulations using the Dreiding 2.21 molecular mechanics force field over a range of temperatures (300, 500 and 600 K) using up to 3 ns simulation time. We have focussed on the influence of the temperature, polymer dynamics, number of CH 2 groups, density and free volume distribution on the diffusion properties. Correlation of diffusion coefficients with free volume and number of CH 2 groups was found. 相似文献
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Magali Moreau Timothy Westlake Giulio Zampogna George Popescu Miaoying Tian Christos Noutsos Sorina Popescu 《The Plant journal : for cell and molecular biology》2013,76(4):603-614
Salicylic acid (SA) is a small phenolic molecule with hormonal properties, and is an essential component of the immune response. SA exerts its functions by interacting with protein targets; however, the specific cellular components modulated by SA and critical for immune signal transduction are largely unknown. To uncover cellular activities targeted by SA, we probed Arabidopsis protein microarrays with a functional analog of SA. We demonstrate that thimet oligopeptidases (TOPs) constitute a class of SA‐binding enzymes. Biochemical evidence demonstrated that SA interacts with TOPs and inhibits their peptidase activities to various degrees both in vitro and in plant extracts. Functional characterization of mutants with altered TOP expression indicated that TOP1 and TOP2 mediate SA‐dependent signaling and are necessary for the immune response to avirulent pathogens. Our results support a model whereby TOP1 and TOP2 act in separate pathways to modulate SA‐mediated cellular processes. 相似文献
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Laura Cristina Ceafalan Tudor Emanuel Fertig Teodora Cristina Gheorghe Mihail Eugen Hinescu Bogdan Ovidiu Popescu Jens Pahnke Mihaela Gherghiceanu 《Journal of cellular and molecular medicine》2019,23(2):819-827
The blood‐brain barrier (BBB) is essential for a functional neurovascular unit. Most studies focused on the cells forming the BBB, but very few studied the basement membrane (BM) of brain capillaries in ageing. We used transmission electron microscopy and electron tomography to investigate the BM of the BBB in ageing C57BL/6J mice. The thickness of the BM of the BBB from 24‐month‐old mice was double as compared with that of 6‐month‐old mice (107 nm vs 56 nm). The aged BBB showed lipid droplets gathering within the BM which further increased its thickness (up to 572 nm) and altered its structure. The lipids appeared to accumulate toward the glial side of the BM. Electron tomography showed that the lipid‐rich BM regions are located in small pockets formed by the end‐feet of astrocytes. These findings suggest an imbalance of the lipid metabolism and that may precede the structural alteration of the BM. These alterations may favour the accretion of abnormal proteins that lead to neurodegeneration in ageing. These findings warrant further investigation of the BM of brain capillaries and of adjoining cells as potential targets for future therapies. 相似文献