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121.
《Journal of liposome research》2013,23(4):318-326
AbstractThe aim was to investigate the potential of proliposomes to improve the permeability of tenofovir, anti-HIV, for oral delivery. Tenofovir was incorporated into phosphatidylcholine proliposomes and their absorption was determined in Caco-2 cell cultures grown on Transwell inserts using aqueous drug solutions as reference. Five batches of proliposomes were prepared with different stearylamine levels and characterized in terms of vesicular morphology, drug encapsulation efficiency (EEF), drug leakage, vesicular sizing and surface charges. Cytotoxicity of the reconstituted liposomes was evaluated by the MTT assay. The obtained results showed that increasing the incorporated percentage of stearylamine led to an increase in drug encapsulation, a slower drug leakage and larger liposomes formed. Compared to the drug solutions at corresponding concentrations, the proposed formulations showed a positive relationship (R2?=?0.9756) for the influence of increasing the stearylamine percentage on reduction of mitochondrial activity. Regarding the drug permeability, enhancements of apparent permeability by 16.5- and 5.2-folds were observed for proliposomes formulations with 5% and 15% stearylamine, respectively. A good correlation was observed between the Caco-2 and dialysis models that might indicate passive diffusion as well as paracellular transport as suggested mechanisms for drug absorption. Cationic proliposomes offered a potential formulation to improve the permeation of tenofovir. 相似文献
122.
123.
W.C. Mahaney D.H. Krinsley C.C.R. Allen J. Ditto K. Langworthy A.D. Batchelor 《Geomicrobiology journal》2013,30(1):27-41
The presence of Mn-Fe nodules in the epipedons (surface horizons) of paleosols of presumed Upper Neogene age in the northwestern Venezuelan Andes have been interpreted as products of inorganic oxidation and reduction processes operating over the full range of glacial and interglacial cycles that affected paleosol morphogenesis. New microscopic/chemical data from combined SEM-EDS-FIB analyses of representative Mn-Fe nodules indicate microbes play an important role in Mn/Fe precipitation leading to their genesis in alpine Mollisols (Argiustolls). Although the prevailing new data are based mainly on fossil forms of filamentous bacteria and fungi and other biogenic pseudomorphs that may represent the former resident bacteria, the presence of extant microbes must await field experiments/collection, followed by a molecular microbiology approach to determine the biological drivers of metal precipitation. As in other terrestrial niche environments, microbes are seen here to play a role, perhaps a key one, in the morphogenesis of paleosols of importance in upper Neogene paleoenvironmental reconstruction. 相似文献
124.
Trefoil factor peptides are highly conserved secreted molecules characterized by heat and enzymatic digestion resistance. Intestinal trefoil factor 3 (TFF3) protects and repairs the gastrointestinal mucosa and restores normal intestinal permeability, which is dependent on the integrity of the tight junction (TJ) barrier and the TJ associated proteins claudin-1, zona occludens-1 (ZO-1) and occludin. Despite the important role of intestinal barrier dysfunction in the pathogenesis of inflammatory bowel diseases, the underlying mechanisms and associated molecules remain unclear. In the present study, we show that TFF3 and toll-like receptor 2 (TLR2) are functionally linked and modulate intestinal epithelial permeability via a mechanism that involves the PI3K/Akt pathway. We used the Caco-2 cell model to show that TLR2 and TFF3 inhibit the IL-1β induced increase in permeability and release of proinflammatory cytokines, and that this effect is mediated by activation of PI3K/Akt signaling. TLR2 silencing downregulated the expression of TFF3 and overexpression of TLR2 and TFF3 increased the levels of phospho-Akt. TFF3 overexpression significantly upregulated the expression of ZO-1, occludin and claudin-1 and this effect was abrogated by inhibition of the PI3K/Akt pathway. Taken together, our results indicate that TLR2 signaling selectively enhances intestinal TJ barrier integrity through a mechanism involving TFF3 and the activation of the PI3K/Akt pathway. 相似文献
125.
Lisa Dalla Via Aída N. García-Argáez Arianna Adami Silvia Grancara Pamela Martinis Antonio Toninello Daniela Belli Dell’Amico Luca Labella Simona Samaritani 《Bioorganic & medicinal chemistry》2013,21(22):6965-6972
A convenient synthetic route and the characterization of complexes trans-[PtCl2(L)(PPh3)] (L = Et2NH (2), (PhCH2)2NH (3), (HOCH2CH2)2NH) (4) are reported. The antiproliferative activity was evaluated on three human tumor cell lines. The investigation on the mechanism of action highlighted for the most active complex 4 the capacity to affect mitochondrial functions. In particular, both the induction of the mitochondrial permeability transition phenomenon and an aspecific membrane damage occurred, depending on concentration. 相似文献
126.
《Molecular membrane biology》2013,30(3-4):95-106
AbstractStallion sperm exhibits great male-to-male variability in survival after cryopreservation. In this study, we have investigated if differences in sperm freezability can be attributed to membrane phase and permeability properties. Fourier transform infrared spectroscopy (FTIR) was used to determine supra and subzero membrane phase transitions and characteristic subzero membrane hydraulic permeability parameters. Sperm was obtained from stallions that show differences in sperm viability after cryopreservation. Stallion sperm undergoes a broad and gradual phase transition at suprazero temperatures, from 30–10°C, whereas freezing-induced dehydration of the cells causes a more severe phase transition to a highly ordered gel phase. Sperm from individual stallions showed significant differences in post-thaw progressive motility, percentages of sperm with abnormal cell morphology, and chromatin stability. The biophysical membrane properties evaluated in this study, however, did not show clear differences amongst stallions with differences in sperm freezability. Cyclodextrin treatment to remove cholesterol from the cellular membranes increased the cooperativity of the suprazero phase transition, but had little effects on the subzero membrane phase behavior. In contrast, freezing of sperm in the presence of protective agents decreased the rate of membrane dehydration and increased the total extent of dehydration. Cryoprotective agents such as glycerol decrease the amount of energy needed to transport water across cellular membranes during freezing. 相似文献
127.
Mitochondria isolated from engineered mice lacking Cyclophilin D (CypD), a component of the Permeability Transition Pore (PTP) complex, can still undergo a Ca2?+?-dependent but Cyclosporin A-insensitive permeabilization of the inner membrane. Higher Ca2?+? concentrations are required than for wild-type controls. The characteristics of the pore formed in this system were not known, and it has been proposed that they might differ substantially from those of the normal PTP. To test this hypothesis, we have characterized the PTP of isogenic wild-type and CypD? mouse liver mitochondria in patch clamp experiments, which allow biophysical characterization. The pores observed in the two cases, very similar to those of rat liver mitochondria, are indistinguishable according to a number of criteria. The only clear difference is in their sensitivity to Cyclosporin A. CypD is thus shown to be an auxiliary, modulatory component of the “standard” PTP, which forms and has essentially the same properties even in its absence. The observations suggest that Ca2?+?, CypD, and presumably other inducers and inhibitors act at the level of an activation or assembly process. Activation is separate and upstream of the gating observable on a short or medium-term time scale. Once the pore is activated, its molecular dynamics and biophysical properties may thus be predicted not to depend on the details of the induction process. 相似文献
128.
《Molecular membrane biology》2013,30(6):197-206
AbstractFTIR and cryomicroscopy have been used to study mouse embryonic fibroblast cells (3T3) during freezing in the absence and presence of DMSO and glycerol. The results show that cell volume changes as observed by cryomicroscopy typically end at temperatures above ?15°C, whereas membrane phase changes may continue until temperatures as low as ?30°C. This implies that cellular dehydration precedes dehydration of the bound water surrounding the phospholipid head groups. Both DMSO and glycerol increase the membrane hydraulic permeability at subzero temperature and reduce the activation energy for water transport. Cryoprotective agents facilitate dehydration to continue at low subzero temperatures thereby decreasing the incidence of intracellular ice formation. The increased subzero membrane hydraulic permeability likely plays an important role in the cryoprotective action of DMSO and glycerol. In the presence of DMSO water permeability was found to be greater compared to that in the presence of glycerol. Two temperature regimes were identified in an Arrhenius plot of the membrane hydraulic permeability. The activation energy for water transport at temperature ranging from 0 to ?10°C was found to be greater than that below ?10°C. The non-linear Arrhenius behavior of Lp has been implemented in the water transport model to simulate cell volume changes during freezing. At a cooling rate of 1°C min-1, ~5% of the initial osmotically active water volume is trapped inside the cells at ?30°C. 相似文献
129.
《Molecular membrane biology》2013,30(2):59-68
Dimethyl sulphoxide is a widely used agent in cell biology. It is well known as a cryoprotectant, cell fusogen and a permeability enhancing agent. These applications depend, to a greater or lesser extent, on the effect of dimethyl sulphoxide on the stability and dynamics of biomembranes. The aim of this review is to examine progress of the research which has been directed towards studies of the interactions between dimethyl sulphoxide and membranes, particularly that with the lipid components of cell membranes, as seen in its effects on model membrane systems. Models are proposed to explain the mechanism whereby dimethyl sulphoxide may mediate its effects on biological functions by its effects on the stability and properties of the membrane lipid matrix. 相似文献
130.
G. C. H. Yang, K. Fried and P. H. Levine Detection of medullary thyroid microcarcinoma using ultrasound‐guided fine needle aspiration cytology Objective: Compared with incidental papillary thyroid microcarcinoma (microPTC), incidental medullary thyroid microcarcinoma (microMTC) is clinically more significant. The objective of the present study was to summarize our experience in detecting microMTCs. Methods: From 1995 to 2011, there were 10 825 thyroid fine needle aspirates (FNAs) guided using high‐resolution ultrasound with on‐site preparation and evaluation by a cytopathologist. Of the 140 microcarcinomas detected, 132 were microPTCs and eight were microMTCs, which are the subject of the present study. Results: All eight cases were incidentalomas and none of the five women and three men, age 37–70 years, had a family history of MTC. One patient had two FNAs at an interval of 10 months, two had a single lymph node metastasis and one had a 0.1‐cm tumour nodule near the main tumour. Four of five plasmacytoid cell microMCTs had irregular borders; two round cell and one rectangular cell tumours had smooth borders. In contrast, 17 larger MTCs diagnosed in the same period included seven plasmacytoid, four giant cell and six spindle cell types. All five plasmacytoid microMTCs were correctly diagnosed on FNA, but the round cell and rectangular cell tumours were undercalled as follicular lesions. Sampling of colloid from adjacent follicles was noted in microMTCs. Two were diagnosed on histology following recommended surgery and one was diagnosed on recommended repeat FNA. Conclusions: US‐guided FNA of thyroid lesions is a powerful tool in the detection of microMTCs, provided that cytopathologists are alerted to the pitfalls described in the present study. 相似文献