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1.
Journal of Neurology - Determining the cause of acute ischemic stroke is crucial for patient management, particularly for preventing future stroke. In recent years, carotid web (CW), a...  相似文献   
2.
The interactions of naked and surface-modified poly(D,L-lactic acid) (PLA) nanocapsules (NC), where polyethyleneglycol (PEG) was adsorbed or covalently attached, have been studied with a macrophage-like cell line. The fluorescent oil marker, DiD, was successfully encapsulated in NCs in order to follow their interactions with cells. The cell-associated fluorescence obtained with PEG-PLA NC was about 3- to 13-fold lower than that obtained with naked-PLA NC. The effects of PEG chain length, its content as a percentage of total polymer and NC concentration in the culture medium were evaluated. PEG-PLA NC showed dramatically reduced fluorescence association with cells during an 18 h incubation compared with naked-PLA NC, showing that covalent attachment of PEG is important for the persistence of low uptake. The best results in reducing cell-associated fluorescence were obtained with a surface-modified PEG-PLA NC bearing a chain with 20000 MW. Increasing the percentage of PEG produced a reduction in marker association for a given PEG chain length. Moreover, when the PEG-containing poloxamer was simply adsorbed, marker association was dependent on the extent of dilution and the type of serum in the culture medium. Serum proteins, especially immunoglobulins, increased cell-associated fluorescence for PEG-adsorbed NC, but had very little effect on PEG-PLA NC. Marker association was only partially inhibited in the presence of cytochalasin B. The mechanisms of cell-NC interaction depended on the characteristics of the NC surface in each formulation. When the NC was physically separated from cells no diffusion of fluorescent marker in aqueous medium occurred. Nevertheless, collision-mediated transfer of DiD from NC to J774 cells was a non-negligible route of marker transfer, mainly for naked NC. However, this collision-mediated transfer was reduced for the PEG-PLA NC probably due to the restricted contact between NC and cells afforded by PEG steric hindrance at the surface.  相似文献   
3.

Background

Nanocapsules, as a delivery system, are able to target drugs and other biologically sensitive molecules to specific cells or organs. This system has been intensively investigated as a way to protect bioactives drugs from inactivation upon interaction with the body and to ensure the release to the target. However, the mechanism of improved activity of the nanoencapsulated molecules is far from being understood at the cellular and subcellular levels. Epidemiological studies suggest that dietary polyunsaturated fatty acids (PUFA) can reduce the morbidity and mortality from breast cancer. This influence could be modulated by the oxidative status of the diet and it has been suggested that the anti-proliferative properties of docosahexaenoic acid (DHA) are enhanced by pro-oxidant agents.

Methods

The effect of encapsulation of PUFA on breast cancer cell proliferation in different oxidative medium was evaluated in vitro. We compared the proliferation of the human breast cancer cell line MDA-MB-231 and of the non-cancer human mammary epithelial cell line MCF-10A in different experimental conditions.

Results

DHA possessed anti-proliferative properties that were prevented by alpha-tocopherol (an antioxidant) and enhanced by the pro-oxidant hydrogen peroxide that confirms that DHA has to be oxidized to exert its anti-proliferative properties. We also evaluated the anti-proliferative effects of the 4(RS)-4-F4t-neuroprostane, a bioactive, non-enzymatic oxygenated metabolite of DHA known to play a major role in the prevention of cardiovascular diseases. DHA-loaded nanocapsules was less potent than non-encapsulated DHA while co-encapsulation of DHA with H2O2 maintained the inhibition of proliferation. The nanocapsules slightly improves the anti-proliferative effect in the case of 4(RS)-4-F4t-neuroprostane that is more hydrophilic than DHA.

Conclusion

Overall, our findings suggest that the sensitivity of tumor cell lines to DHA involves oxidized metabolites. They also indicate that neuroprostane is a metabolite participating in the growth reducing effect of DHA, but it is not the sole. These results also suggest that NC seek to enhance the stability against degradation, enhance cellular availability, and control the release of bioactive fatty acids following their lipophilicities.
  相似文献   
4.
The aim of our work was to examine the relationship between modifications of the surface of nanocapsules (NC) by adsorption or covalent grafting of poly(ethylene oxide) (PEG), and changes in their phospholipid (PL) content on complement activation (C3 cleavage) and on uptake by macrophages. The physicochemical characterization of the NC included an investigation of their properties, such as surface charge, size, hydrophilicity, morphology and homogeneity. This is the first time that such properties have been correlated with biological interactions for NC, a novel carrier system with a structure more complex than nanospheres. C3 crossed immunoelectrophoresis revealed the reduced activation for NC with longer PEG chain and higher density, although all formulations induced C3 cleavage to a lesser or greater extent. NC bearing PEG covalently bound to the surface were weaker activators of complement than plain PLA [poly(D,L-lactide)] NC or nanospheres (NS). Furthermore, the fluorescent/confocal microscopy of J774A1 cells in contact with NC reveal a dramatically reduced interaction with PEG-bearing NC. However, the way in which PEG was attached (covalent or adsorbed) seemed to affect the mechanism of uptake. Taken together, these results suggest that the low level of protein binding to NC covered with a high density of 20kDa PEG chains is likely to be due to the steric barriers surrounding these particles, which prevents protein adsorption and reduces their interaction with macrophages.  相似文献   
5.
Several classes of antifungal have been employed in candidiasis treatment, but patients with advanced immunodeficiency can present unsatisfactory results after therapy. In these cases, high doses of drugs or the use of multiple agents are sometimes used, and hence increasing the risk of serious side effects. Considering theses difficulties, the encapsulation of antifungal agents in nanoparticulate carriers has been used with the objective of modifying the pharmacokinetic of drugs resulting in more efficient treatments with less side effects. The purpose of this work was the preparation, characterization and the investigation of the release profiles of radiolabeled fluconazole nanocapsules. The size, homogeneity and zeta potential of NC preparations were determined with a Zetasizer 3000HS. The morphology and the structural organization were evaluated by atomic force microscopy (AFM). The release study in vitro of NC was evaluated in physiologic solution with or without 70% mouse plasma. The labeling yield of fluconazole with 99mTc was 94% and the radiolabeled drug was stable within 24h period. The encapsulation percentage of 99mTc-fluconazole in PLA-POLOX NC and PLA-PEG NC was approximately of 30%. The average diameter calculated by photon correlation spectroscopy (PCS) varied from 236 to 356 nm, while the average diameter determined by AFM varied from 238 to 411 nm. The diameter/height relation decreased significantly when 25% glutaraldehyde was used for NC fixation on mica. The zeta potential varied from -55 to -69 nm and surface-modified NC showed lower absolute values than conventional NC. The in vitro release of 99mTc-fluconazole in plasma medium of the conventional and surface-modified NC was greater than in saline. The drug release in plasma medium from conventional NC was faster than for surface-modified NC. The results obtained in this work suggest that the nanocapsules containing fluconazole could be used to identify infectious foci, due to the properties, such as size, zeta potential and controlled release of (99m)Tc-fluconazole. The surface-modified nanocapsules could constitute a long-circulating intravenous formulation of fluconazole for treating sepsis caused by disseminated form of candidiasis. However, in vivo studies should be considered and are under investigation.  相似文献   
6.
In the last year there was happened a series of adolescent deaths in the province of Salta that might be related to a dangerous game known as "the choking game". It has been practiced over many years in different countries around the world and consists of provoking brain hypoxia for some seconds by different techniques to obtain an instant of ecstasy and pleasure. We consider relevant that health providers know about this practice and so be able to recognize through signs and symptoms when an adolescent might be playing this game.  相似文献   
7.
8.
Mutation of the von Hippel–Lindau (VHL) tumor suppressor protein at codon 200 (R200W) is associated with a disease known as Chuvash polycythemia. In addition to polycythemia, Chuvash patients have pulmonary hypertension and increased respiratory rates, although the pathophysiological basis of these symptoms is unclear. Here we sought to address this issue by studying mice homozygous for the R200W Vhl mutation (VhlR/R mice) as a model for Chuvash disease. These mice developed pulmonary hypertension independently of polycythemia and enhanced normoxic respiration similar to Chuvash patients, further validating VhlR/R mice as a model for Chuvash disease. Lungs from VhlR/R mice exhibited pulmonary vascular remodeling, hemorrhage, edema, and macrophage infiltration, and lungs from older mice also exhibited fibrosis. HIF-2α activity was increased in lungs from VhlR/R mice, and heterozygosity for Hif2a, but not Hif1a, genetically suppressed both the polycythemia and pulmonary hypertension in the VhlR/R mice. Furthermore, Hif2a heterozygosity resulted in partial protection against vascular remodeling, hemorrhage, and edema, but not inflammation, in VhlR/R lungs, suggesting a selective role for HIF-2α in the pulmonary pathology and thereby providing insight into the mechanisms underlying pulmonary hypertension. These findings strongly support a dependency of the Chuvash phenotype on HIF-2α and suggest potential treatments for Chuvash patients.  相似文献   
9.
OBJECTIVE: Estimates of vaccination costs usually provide only point estimates at national level with no information on cost variation. In practice, however, such information is necessary for programme managers. This paper presents information on the variations in costs of delivering routine immunization services in three diverse districts of Peru: Ayacucho (a mountainous area), San Martin (a jungle area) and Lima (a coastal area). METHODS: We consider the impact of variability on predictions of cost and reflect on the likely impact on expected cost-effectiveness ratios, policy decisions and future research practice. All costs are in 2002 prices in US dollars and include the costs of providing vaccination services incurred by 19 government health facilities during the January-December 2002 financial year. Vaccine wastage rates have been estimated using stock records. FINDINGS: The cost per fully vaccinated child ranged from 16.63-24.52 U.S. Dollars in Ayacucho, 21.79-36.69 U.S. Dollars in San Martin and 9.58-20.31 U.S. Dollars in Lima. The volume of vaccines administered and wastage rates are determinants of the variation in costs of delivering routine immunization services. CONCLUSION: This study shows there is considerable variation in the costs of providing vaccines across geographical regions and different types of facilities. Information on how costs vary can be used as a basis from which to generalize to other settings and provide more accurate estimates for decision-makers who do not have disaggregated data on local costs. Future studies should include sufficiently large sample sizes and ensure that regions are carefully selected in order to maximize the interpretation of cost variation.  相似文献   
10.
The encapsulation of active pharmaceutical ingredients (APIs) within drug delivery systems such as polymeric nanoparticles (PNPs) vastly improves the therapeutic efficiency of the incorporated APIs. PNPs synthesized using amphiphilic block copolymers are efficient drug delivery systems as the hydrophobic block facilitates the encapsulation of lipophilic components and the hydrophilic block constitutes the hairy corona of the PNP that stabilizes the nanocarriers against aggregation in solution. Poly(styrene-alt-maleic acid) (SMA) is an attractive polymer for the hydrophilic corona of PLA-based nanoparticles as it allows for post polymerization functionalization and aids in the prevention of NP aggregation. The synthesis of a novel PLA-b-SMA block copolymer, via sequential ring opening polymerization (ROP) and reversible addition–fragmentation chain transfer (RAFT) polymerization, is presented. PLA macro-CTAs, synthesized via ROP, can be chain extended via RAFT copolymerization of styrene and maleic anhydride to yield PLA-b-SMAnh and via RAFT polymerization of N-vinylpyrrolidone to yield PLA-b-PVP block copolymers. Controlled hydrolysis of the anhydride moieties converts PLA-b-SMAnh into PLA-b-SMA. Monodisperse PLA-b-SMA and PLA-b-PVP nanoparticles (NPs) ranging in diameter between 60 and 220 nm are prepared. The lipophilic fluorescent dye DiI is encapsulated within the NPs successfully and these fluorescent NPs are used in a preliminary cell uptake study.  相似文献   
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