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1.
In Silico Biol ; 14(1-2): 101-121, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32597796

RESUMO

A dynamical model of the pathophysiological behaviors of IL18 and IL10 cytokines with their receptors is tested against data for the case of early sepsis. The proposed approach considers the surroundings (organs and bone marrow) and the different subsystems (cells and cyctokines). The interactions between blood cells, cytokines and the surroundings are described via mass balances. Cytokines are adsorbed onto associated receptors at the cell surface. The adsorption is described by the Langmuir model and gives rise to the production of more cytokines and associated receptors inside the cell. The quantities of pro and anti-inflammatory cytokines present in the body are combined to give global information via an inflammation level function which describes the patient's state. Data for parameter estimation comes from the Sepsis 48 H database. Comparisons between patient data and simulations are presented and are in good agreement. For the IL18/IL10 cytokine pair, 5 key parameters have been found. They are linked to pro-inflammatory IL18 cytokine and show that the early sepsis is driven by components of inflammatory character.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Citocinas/imunologia , Sepse/tratamento farmacológico , Adjuvantes Imunológicos/farmacologia , Anti-Inflamatórios/uso terapêutico , Citocinas/metabolismo , Citocinas/uso terapêutico , Feminino , Humanos , Inflamação , Interleucina-10/metabolismo , Interleucina-18/metabolismo , Masculino , Modelos Imunológicos , Sepse/imunologia , Sepse/metabolismo , Choque Séptico/tratamento farmacológico , Choque Séptico/imunologia , Choque Séptico/metabolismo , Resultado do Tratamento
2.
J Nanosci Nanotechnol ; 6(9-10): 3187-92, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17048535

RESUMO

Generally nanocapsules suspensions are a colloidal system in a metastable state, there is aggregation due to attraction and repulsion forces between particles. The objective of this work was to bring the role of the polymeric membrane in the protection of the active drug against damaging caused by external agents and to select the monomer which leads to obtain stable formulation with the highest possible payload of the active drug. The stability testing involving visual aspect, particle size measurement, transmission electron microscopy (TEM) examination, and drug loss was conduced after 6 months of storage at different temperatures (4, 25, and 45 degrees C). The colloidal suspensions of nanocapsules were obtained using the combined interfacial polycondensation and spontaneous emulsification, the technique was used to encapsulate alpha-tocopherol using polyurethanes polymers. It is a one step procedure: An organic phase composed of a water miscible solvent (acetone), lipophilic monomer (Isophorone diisocyanate IPDI), oil, and a lipophilic surfactant, is injected in an aqueous phase containing hydrophilic monomer (diol with various molecular weight: 1,2-ethanediol (ED), 1,4-butanediol (BD), and 1,6-hexanediol (HD)) and hydrophilic emulsifying agent. The water miscible solvent diffuses to the aqueous phase, the oil precipitates as nano-droplets, and the two monomers react at the interface, forming a membrane around the nanoemulsion leading to nanocapsules. A good physical stability of suspensions corresponds to absence of symptoms such as sedimentation or agglomeration, significant size change and alpha-tocopherol degradation due to external agents such as oxygen, temperature, and ultraviolet (UV) irradiation. The size of nanocapsules before storage was about 232 +/- 3, 258 +/- 29, and 312 +/- 4 nm for ED, BD, and HD, respectively. After 6 months of storage, polyurethanes nanocapsules possess good stability against aggregation at 4 and 25 degrees C. Comparing results obtained using different monomers, it reveals that the polyurethane based on HD offers good protection of alpha-tocopherol against damaging caused by the temperature and UV irradiation.


Assuntos
Coloides/química , Portadores de Fármacos/química , Excipientes/química , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Poliuretanos/química , Tocoferóis/química , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/efeitos da radiação , Cápsulas/química , Cápsulas/efeitos da radiação , Coloides/efeitos da radiação , Difusão , Portadores de Fármacos/efeitos da radiação , Estabilidade de Medicamentos , Excipientes/efeitos da radiação , Tamanho da Partícula , Poliuretanos/efeitos da radiação , Temperatura , Tocoferóis/administração & dosagem , Tocoferóis/efeitos da radiação , Raios Ultravioleta
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