Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Environmental influences on the new surfactant-stabilized bubbles, ST68, were investigated. We have developed a new surfactant-based contrast agent ST68, which is prepared by insonating buffered mixtures of Span 60 and Tween 80 in the presence of either air, PFC, or SF(6) gas. The effect of dilution, shear, and sonication on size distribution of ST68 showed that PFC-containing bubbles (ST68-PFC) were most stable. ST68-PFC bubbles lasted more than 15 min with approximately 30 dB backscatter enhancement in degassed phosphate-buffered saline, (pH 7.4), and air bubbles lasted approximately 3 s, suggesting the effects of diffusion. Additionally, it was found that the ionic strength of the suspending medium (for example, PBS), did not have any effect on ST68 bubbles containing SF(6) or PFC, but had a dramatic impact on bubbles containing air.
 ...
PMID:Influence of environmental conditions on a new surfactant-based contrast agent: ST68. 1085 25

The effects of the adjuvant QS-21 in various formulations on immediate pain on injection after intramuscular injection were evaluated in three Phase I clinical trials in healthy adults. Each trial was designed as a double-blind, randomized, four-way or five-way cross-over study with each subject acting as his/her own control. In the first trial, four formulations designed to evaluate the effect of QS-21 or pH (over a range of 6--7.2) were evaluated: phosphate-buffered saline at pH 6.0 or 7.2, and 50 microg of QS-21 in phosphate-buffered saline at pH 6.0 or 7.2. Thirty-three volunteers received each of the four intramuscular injections in random order separated by approximately 1 week. The volunteers assessed the immediate injection pain from 0 to 10 (none to most pain). The data indicate that the presence of QS-21, but not pH, is associated with transient injection site pain. The second trial, which utilized the same design as the first trial, evaluated formulations of QS-21 in various excipients. Fifteen volunteers received phosphate-buffered saline, QS-21/PBS, QS-21/aluminum hydroxide, and QS-21/4 mg/ml of polysorbate 80. Polysorbate 80, but not aluminum hydroxide, reduced the mean pain score compared to QS-21/PBS. The third trial evaluated formulations of QS-21 in additional excipients. Fifteen volunteers received aluminum hydroxide (without QS-21), QS-21/PBS, QS-21/0.72% benzyl alcohol, QS-21/30 mg/ml of hydroxypropyl-beta-cyclodextrin, and QS-21/8-mg/ml of polysorbate 80. Benzyl alcohol, cyclodextrin, and the higher concentration of polysorbate 80 reduced the pain scores associated with QS-21. Hence, QS-21 is associated with injection pain in simple buffer formulations, but it is possible to improve the acceptability of QS-21-containing formulations through reformulation with certain excipients.
 ...
PMID:Three double-blind, randomized trials evaluating the safety and tolerance of different formulations of the saponin adjuvant QS-21. 1142 71

A novel procedure has been developed for the encapsulation of peptide antigens in poly(lactide-co-glycolide) (PLGA) microspheres, which employs trifluoro-acetic acid (TFA) as a carrier solvent for both the polymer and antigen. The antigen/polymer solution is emulsified in mineral oil containing sorbitan trioleate (Span 85) as an emulsifier and a low level of cottonseed oil to extract the TFA. Fluoresceinisothiocyanate-labelled bovine serum albumin (FITC-BSA) was used as a model antigen to characterize the microencapsulation. Microspheres were of the desired size (<10 microm) for targeting to antigen-presenting cells, and released the model antigen slowly after an initial burst release (11%) in PBS/0.02% Tween 80 at 37 degrees C. Subsequently, a potential peptide vaccine, designated MVFMF2, for the human T-lymphotropic virus type 1 (HTLV-1 ) was encapsulated at 4.7% loading using the novel oil-in-oil method. In vivo immune responses were examined in rabbits immunized with (i) encapsulated MVFMF2 together with encapsulated adjuvant (N-acetyl-glucosamine-3yl-acetyl-L-alanyl-D-isoglutamine, nor-MDP, (ii) encapsulated MVFMF2 without adjuvant, and (iii) free peptide with adjuvant. Inoculation of the encapsulated peptide produced an antibody response similar to that of the free peptide emulsified in adjuvant. Moreover, the elevated immune response elicited by the encapsulated peptide was observed without multiple booster immunizations and irrespective of whether an adjuvant was used. Additionally, the antibodies raised against both free and encapsulated MVFMF2 had similar affinities, as judged by competitive enzyme-linked immunosorbant assay (ELISA), indicating that the encapsulated peptide retained a significant fraction of its epitopes. Hence, these results demonstrate that peptide vaccines can be encapsulated in PLGA microspheres using a common carrier solvent for both the peptide and polymer, which produces a desirable immune response in the absence of an adjuvant.
 ...
PMID:Microencapsulation of a synthetic peptide epitope for HTLV-1 in biodegradable poly(D,L-lactide-co-glycolide) microspheres using a novel encapsulation technique. 1150 71

Determination of the kinetics of water-soluble degradation products inside poly(lactide-co-glycolide) (PLGA) delivery systems during polymer degradation is important to evaluate the polymer microclimate conditions, particularly microclimate pH changes for optimization of encapsulated drug stability. A pre-derivatization high-performance liquid chromatography (HPLC) method was developed for separation and quantification of water-soluble acid impurities and degradation products in PLGA. Thin PLGA films (approximately 200 microm) were incubated in PBS/0.02% Tween 80, pH 7.4, for 6 weeks. Water-soluble monomers and oligomers were obtained from polymer films after repeated CHCl(3)/H(2)O extraction and then derivatized into bromophenacyl esters. With the common chromophore, the esters were separated and quantified by HPLC with increased ultraviolet (UV) sensitivity at 254 nm. The total amount of water-soluble acids in the extract was validated by potentiometric titration with tetrabutyl ammonium hydroxide. During the first 3 weeks of incubation of PLGA 50:50 (inherent viscosity = 0.63 dL/g), the principal water-soluble acids in the polymer were glycolic, lactic, and lactoyllactic acids, and an unknown oligomer. After 4 weeks of incubation, a large fraction of higher molecular weight oligomers was observed. Pre-derivatization HPLC can be used to accurately measure water-soluble acid distribution, and may be invaluable to examine the degradation behavior of PLGAs, including the underlying mechanism of polymer microclimate pH development.
 ...
PMID:Determination of water-soluble acid distribution in poly(lactide-co-glycolide). 1470 90

For understanding the relationship between the increased incidence of sudden cardiac death and air pollution, we examined the effects of intratracheal instillation of diesel exhaust particles (DEP) on acute myocardial ischemia/reperfusion-induced arrhythmia in rats. The animals received 1 mg DEP 24-48 h before the ischemia/reperfusion (DEP-pretreated group, DEP-PRE), and were subjected to 3 successive brief ischemia/reperfusion (3 min ischemia followed by 5 min reperfusion) procedures. These were to make the animals tolerant to ischemia/reperfusion-related myocardial deterioration. Thereafter the animals were subjected to a 10-min ischemia followed by a 30-min reperfusion. In the experiments, an increased mortality was observed in the DEP-PRE group compared to the vehicle (0.05% Tween 80-PBS)-treated group. Forty-six percent of the animals in DEP-PRE died during the first 3-min reperfusion period. The animals of other groups were intratracheally instilled with DEP at the beginning of ischemia/reperfusion experiment, or were pretreated with polyethylene glycol-conjugated superoxide dismutase (1000 IU kg(-1), iv). In these animals, incidences of both arrhythmia and mortality were similar to those in the animals treated with the vehicle. In experiments to investigate the effects of DEP on the biochemical and hematological parameters, neutrophil count was elevated by a higher dose (5 mg) of DEP at 24 h after the intratracheal instillation, and oxygen radical production, which was induced by 12-O-tetradecanoylphorbol 13-acetate, was enhanced at 72 h. These results indicate that intratracheal DEP instillation exacerbates short-period ischemia/reperfusion-induced arrhythmia. Delivery and activation of peripheral neutrophils and oxygen radicals produced in neutrophils might participate in this exacerbation. This is the first article that demonstrates the arrhythmogenicity of DEP using intratracheal instillation in rats.
 ...
PMID:Delayed exacerbation of acute myocardial ischemia/reperfusion-induced arrhythmia by tracheal instillation of diesel exhaust particles. 1537 Nov 83

The objective of this study is the incorporation of adenoviral vectors into a microparticulate system adequate for mucosal delivery. Microencapsulation of the vectors was accomplished by ionotropic coacervation of chitosan, using bile salts as counter-anion. The process was optimized in order to promote high encapsulation efficiency, with a minimal loss of viral infectivity. The maintenance of sterility during all the encapsulation procedure was also taken into account. The principle relies on the simple addition of a solution containing adenoviral vectors to a solution of neutralized chitosan, under stirring. Some surfactants were added to the chitosan solution, to improve the efficiency of this process, such as Tween 80, and Pluronic F68 at 1% (w/v). Encapsulation efficiency higher than 84% was achieved with formulations containing sodium deoxycholate as counter-anion and Pluronic F68 as dispersant agent. The infectivity of the adenoviral vectors incorporated into microparticles was assessed by release assays in PBS and by direct inoculation in 293 and Caco-2 cells. The release in aqueous media was negligible but, when in contact with monolayers of the cells, an effective release of bioactive adenovirus was obtained. Our work shows that encapsulation in microparticles, not only appear to protect the adenovirus from the external medium, namely from low pH, but can also delay their release that is fully dependent on cell contact, an advantage for mucosal vaccination purposes. The formulations developed are able to maintain AdV infectivity and permit a delayed release of the bioactives that is promoted by digestion in situ of the microparticles by the cell monolayers. The onset of delivery is, that way, host-controlled. In view of these results, these formulations showed good properties for mucosal adenovirus delivery.
 ...
PMID:Encapsulation of adenoviral vectors into chitosan-bile salt microparticles for mucosal vaccination. 1675 53

The aim of this work was to develop a stable injectable formulation of the antimalarial drug halofantrine (Hf) based on nanocapsules (NC) prepared from biodegradable polymers with Miglyol 810N as the oily core. Poly(D,L-lactide) PLA and its copolymers with poly(ethyleneglycol) (PLA-PEG) were used together with the surfactants poloxamer 188 and lecithin to yield NC with different surface properties. Highly efficient loading of the free base form of Hf was obtained; zeta potential measurements indicated that a part of the associated Hf was at the NC surface, interacting with the lecithin. NC were 150-250 nm in diameter and more stable on storage than nanoemulsions formed from oil and lecithin without polymer. The most stable NC, showing minimal size changes and flocculation, were those with a high density of 20-kDa PEG chains covalently grafted at the surface. Hf release from NC occurred mainly by partition with the external medium. In PBS, even when Tween 80 was added, release was limited to 20% of the total content, whatever the formulation. Addition of serum to the medium allowed complete and rapid release from PLA NC stabilized with adsorbed poloxamer 188, because of the high affinity of Hf for lipoproteins. However, the presence of covalently grafted PEG chains at the surface limited release by providing a hydrophilic steric barrier at the particle surface. A dense coverage with long PEG chains provided the best reduction of release. Such systems could constitute a long-circulating intravenous formulation of Hf for treating severe malaria.
 ...
PMID:Surface-modified and conventional nanocapsules as novel formulations for parenteral delivery of halofantrine. 1704 36

Terminal restriction fragment length polymorphism (T-RFLP) is a molecular technique used for comparative analysis of microbial community structure and dynamics. We evaluated three sampling methods for recovering bacterial community DNA associated with intestinal mucosa of mice (i.e. mechanical agitation with PBS, hand washing with PBS containing Tween 80, and direct DNA extraction from mucosal plugs). In addition, the utility of two methods (i.e. Klenow fragment and mung-bean nuclease) to reduce single-stranded DNA artifacts was tested. T-RFLP analysis indicated that diverse communities of bacteria are associated with mucosa of the ileum, cecum, and descending colon of mice. Although there was no significant difference in bacterial community structure between the mechanical agitation and direct DNA extraction methods regardless of intestinal location, community diversity was reduced for the hand wash method in the colon. The use of Klenow fragment and mung-bean nuclease have been reported to eliminate single-stranded DNA artifacts (i.e. pseudo-T-restriction fragments), but neither method was beneficial for characterizing mucosa-associated bacterial communities of the mouse cecum. Our study showed that the mechanical agitation and direct plug extraction methods yielded equivalent bacterial community DNA from the mucosa of the small and large intestines of mice, but the latter method was superior for logistical reasons. We also applied a combination of different statistical approaches to analyze T-RFLP data, including statistical detection of true peaks, analysis of variance for peak number, and group significance test, which provided a quantitative improvement for the interpretation of the T-RFLP data.
 ...
PMID:Characterization of mucosa-associated bacterial communities of the mouse intestine by terminal restriction fragment length polymorphism: Utility of sampling strategies and methods to reduce single-stranded DNA artifacts. 1946 63

Methoxy poly(ethylene glycol)-block-oligo(l-aspartic acid)-block-poly(epsilon-caprolactone) with four aspartic acid groups was synthesized with a molecular weight and M(w)/M(n) of 8930 and 1.22. Polymeric micelles were formed by dialysis and stabilized by electrostatic interactions between the carboxylic acid groups and calcium cations. The critical micelle concentration of mPEG-Asp-PCL was determined to be 0.078 mg/mL. At 0.02 mg/mL, the dissociation of micelles without ionic stabilization formed an opaque, phase-separated solution, while the stabilized micelles under the same conditions showed structural stability through ionic stabilization. The paclitaxel-loading and efficiency were 8.7% and 47.6%, respectively, and the drug loading increased the mean diameter from 73.0 nm to 87 nm, which was increased further to 96 nm after ionic fixation. Rapid releases of approximately 65% of the encapsulated paclitaxel from a non-stabilized micelle and 45% from a stabilized micelle were observed in the first 24h at pH 7.4 in a PBS solution containing 0.1 wt% Tween 80. The stabilized micelles then showed a sustained, slow release pattern over a couple of weeks, while the profile from the non-stabilized micelles reached a plateau at approximately 75% after 50h. The enhanced micelle stability independent of concentration through ionic stabilization opens a way for preparing long circulating delivery systems encapsulating water-insoluble drugs.
 ...
PMID:Stabilized polymeric micelles by electrostatic interactions for drug delivery system. 1973 30

The need for the precise and reliable collection of potential biothreat contaminants has motivated research in developing a better understanding of the variability in biological surface sampling methods. In this context, the objective of this work was to determine parameters affecting the efficiency of extracting Bacillus anthracis Sterne spores from commonly used wipe sampling materials and to describe performance using the interfacial energy concept. In addition, surface thermodynamics was applied to understand and predict surface sampling performance. Wipe materials were directly inoculated with known concentrations of B. anthracis spores and placed into extraction solutions, followed by sonication or vortexing. Experimental factors investigated included wipe material (polyester, cotton, and polyester-rayon), extraction solution (sterile deionized water [H(2)O], deionized water with 0.04% Tween 80 [H(2)O-T], phosphate-buffered saline [PBS], and PBS with 0.04% Tween 80 [PBST]), and physical dissociation method (vortexing or sonication). The most efficient extraction from wipes was observed for solutions containing the nonionic surfactant Tween 80. The increase in extraction efficiency due to surfactant addition was attributed to an attractive interfacial energy between Tween 80 and the centrifuge tube wall, which prevented spore adhesion. Extraction solution significantly impacted the extraction efficiency, as determined by statistical analysis (P < 0.05). Moreover, the extraction solution was the most important factor in extraction performance, followed by the wipe material. Polyester-rayon was the most efficient wipe material for releasing spores into solution by rank; however, no statistically significant difference between polyester-rayon and cotton was observed (P > 0.05). Vortexing provided higher spore recovery in H(2)O and H(2)O-T than sonication, when all three wipe materials and the reference control were considered (P < 0.05).
 ...
PMID:Parameters affecting spore recovery from wipes used in biological surface sampling. 2129 45


1 2 3 Next >>