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

A new model for in vitro evaluation of an activity of antibacterial agents released from delivery systems containing antibiotics or antiseptics was developed. The model was composed of two layers of agar gel of two different concentrations in PBS. In the upper gel, the wells were cut and filled with polyurethane sponges saturated with bacterial broth culture. The sponges were then covered with tested dressings containing antibacterial agent. The model was tested by using two bacterial strains, Pseudomonas aeruginosa or Staphylococcus aureus and experimental collagen dressing with doxycyclin, amikacin, or with silver sulfadiazine. The number of colony-forming units (CFU) in the polyurethane sponges was significantly lower under the dressings with antibacterial agents as compared to the control (the same dressing without antimicrobials) during 3 days of observation. The new in vitro model can be recommended for examination of different antibacterial delivery systems instead of experimentally infected wounds in laboratory animals or instead of the other in vitro models.
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PMID:A simple in vitro model to test the efficacy of antimicrobial agents released from dressings. 891 24

We performed an open, prospective, randomized clinical trial in 51 patients receiving mechanical ventilation for more than 72 h, in order to evaluate the impact of using either invasive (protected specimen brush [PSB] and bronchoalveolar lavage [BAL] via fiberoptic bronchoscopy) or noninvasive (quantitative endotracheal aspirates [QEA]) diagnostic methods on the morbidity and mortality of ventilator-associated pneumonia (VAP). Patients were randomly assigned to two groups: Group A patients (n = 24) underwent QEA, PSB, and BAL; Group B patients (n = 27) underwent only QEA cultures. Empiric antibiotic treatment was given according to the attending physician and was modified according to the results of cultures and sensitivity in Group A using PSB and BAL results and in Group B based upon QEA cultures. Bacteriologic cultures were done quantitatively for EA, PSB, and BAL. Thresholds of > or = 10(5), > or = 10(3), and > or = 10(4) CFU/ml were used for QEA, PSB, and BAL, respectively. Microbial cultures from Group A patients were positive in 16 (67%) BAL samples, 14 (58%) PSB samples, and 16 (67%) QEA samples. In Group B patients, QEA microbial cultures yielded positive results in 20 of 27 (74%) samples. In Group A, there was total agreement between culture results of the three techniques on 17 (71%) occasions. In five (21%) cases, QEA coincided with either BAL or PBS. In only two (8%) cases, QEA cultures did not coincide with either PSB or BAL. No cases of positive BAL or PSB cultures had negative QEA cultures. Initial antibiotic treatment was modified in 10 (42%) patients from Group A and in four (16%) patients from Group B (p < 0.05). The observed crude mortality rate was 11 of 24 (46%) in Group A, and 7 of 27 (26%) in Group B, whereas the adjusted mortality rates (observed crude minus predicted at admission) for Groups A and B were 29 and 10%, respectively. There were no statistically significant differences when comparing crude and adjusted mortality rates of Groups A and B. There were no differences in mortality between both groups when comparing pneumonia, considering together Pseudomonas aeruginosa and Acinetobacter spp. (Group A, 33% versus Group B, 27%). There were no differences between Groups A and B with regard to ICU stay duration and total duration of mechanical ventilation. In this pilot study, the impact of bronchoscopy was to lead to more frequent antibiotic changes with no change in mortality. Further studies with larger population samples are warranted to confirm these findings.
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PMID:Impact of invasive and noninvasive quantitative culture sampling on outcome of ventilator-associated pneumonia: a pilot study. 947 43

Unmethylated bacterial DNA containing a high frequency of the CpG motif, is mitogenic and induces T-cell independent, murine B-cell proliferation. These stimulatory effects are also induced by synthetic oligonucleotides that contain one or more unmethylated CpG dinucleotides (CpG oligo). Such mitogenicity is not seen with highly methylated vertebrate DNA, which has a lower prevalence of the CpG motif than bacterial DNA. Due to their stimulatory effects, CpG oligo have been proposed for use as vaccine adjuvants. In order to determine if a synthetic CpG oligo that was stimulatory for B-cell proliferation could augment the murine antibody response to protective bacterial polysaccharide epitopes (Pseudomonas aeruginosa LPS-O polysaccharide side chain; high-molecular-weight polysaccharide or high-MW PS), BALB/c mice were injected with mitogenic doses of CpG oligo simultaneously with high-MW PS, and antibody titers were measured by ELISA weekly for 4 weeks. Controls received PBS, a nonstimulatory control oligo plus PS, CpG alone, or PS alone. Despite evidence of B-cell mitogenicity and an increase in total IgM in CpG oligo-treated mice, CpG oligo treatment plus PS significantly decreased the high-MW PS antibody response compared to PS alone. The blunting of the anti-PS antibody response could be eliminated by vaccinating the animals with PS prior to CpG oligo. We conclude that despite in vitro and in vivo evidence of B-cell proliferation, this CpG oligo reduces PS-specific antibody responses in an animal model when given simultaneously with a bacterial polysaccharide. Based on results in this model, oligonucleotides containing stimulatory unmethylated CpG dinucleotides may not be useful adjuvants when given simultaneously with bacterial PS vaccines.
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PMID:Mitogenic synthetic polynucleotides suppress the antibody response to a bacterial polysaccharide. 960 13

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen that can be found in individuals in which the immune system has been suppressed by HIV/AIDS or chronic alcoholism. We evaluated the role of inducible nitric oxide synthase (NOS II) as a modulator of lung concentrations of P. aeruginosa in normal rats and rats given a single dose of ethanol (ETOH). Rats were pretreated with either sterile saline (PBS, 0.1 ml/kg, i.v.) or the NOS II inhibitor L-N6-iminoethyl lysine (LNIL, 10 mg/kg, i.v.) 15 min before intraperitoneal administration of either PBS (4.5 ml/kg) or ETOH (4.5 g/kg). Thirty min after administration of PBS or ETOH the rats were placed in inhalation chambers and exposed to 45 min of an aerosol containing P. aeruginosa (5 x 10(4) colony forming units, CFU). A group of rats (n = 5-6/treatment/time period) were killed immediately (0 hr) or 4 hr after inhalation of P. aeruginosa. The lungs were homogenized and the P. aeruginosa were grown in nutrient broth to determine the number of viable CFU remaining in the lung. The NOS II and TNFalpha mRNA and protein content lung alveolar macrophages (AM) and neutrophils (PMN) were measured with RT-PCR and Western blot. The concentration of nitrate and nitrite anion in the bronchoalveolar lavage fluid (BALf) and ex vivo incubates of PMN were also measured. The CFU of P. aeruginosa present in the lungs of the four groups of rats at 0 hr did not differ. The CFU of P. aeruginosa in the lung increased (p < 0.05) in rats pretreated with ETOH when compared with that obtained from rats pretreated with PBS. However, pretreatment of rats with LNIL decreased (p < 0.05) the 4 hr lung content of P. aeruginosa. Coadministration of LNIL and ETOH to rats augmented the CFU of P. aeruginosa in lungs to amounts which did not differ from that of rats pretreated with ETOH. Inhalation of P. aeruginosa increased NOS II mRNA and protein in rat AM and PMN. Pretreatment of rats with ETOH alone, or in combination with LNIL, inhibited P. aeruginosa-induced NOS II transcription and translation and AM and PMN nitrate and nitrite generation whereas pretreatment with LNIL alone only inhibited nitrate and nitrite generation. Pretreatment of rats with ETOH suppressed P. aeruginosa stimulated PMN recruitment into the lung whereas LNIL enhanced (p < 0.05) P. aeruginosa-stimulated PMN recruitment into the lung. ETOH-induced increases of the lung content of P. aeruginosa were associated with increased PKC delta isozyme in the membrane of the PMN but could not be explained by altered plasma concentrations of hydrocortisone or ETOH. The data demonstrate that selective inhibition of NOS II-derived NO by LNIL decreases the lung content of P. aeruginosa whereas ETOH inhibits the lung clearance of P. aeruginosa. Speculatively, the difference between these effects of LNIL and ETOH may result from differences in drug-induced changes in lung recruitment of PMN.
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PMID:Ethanol inhibits lung clearance of Pseudomonas aeruginosa by a neutrophil and nitric oxide-dependent mechanism, in vivo. 1023 11

Drug-impregnated polyelectrolyte complex (PEC) sponge composed of chitosan and sodium alginate was prepared for wound dressing application. The morphological structure of this wound dressing was observed to be composed of a dense skin outer layer and a porous cross-section layer by scanning electron microscopy (SEM). Equilibrium water content and release of silver sulfadiazine (AgSD) could be controlled by the number of repeated in situ PEC reactions between chitosan and sodium alginate. The release of AgSD from AgSD-impregnated PEC wound dressing in PBS buffer (PH = 7.4) was dependent on the number of repeated in situ complex formations for the wound dressing. The antibacterial capacity of AgSD-impregnated wound dressing was examined in agar plate against Pseudomonas aeruginosa and Staphylococcus aureus. From the behavior of antimicrobial release and the suppression of bacterial proliferation, it is thought that the PEC wound dressing containing antimicrobial agents could protect the wound surfaces from bacterial invasion and effectively suppress bacterial proliferation. In the cytotoxicity test, cellular damage was reduced by the controlled released of AgSD from the sponge matrix of AgSD-medicated wound dressing. In vivo tests showed that granulation tissue formation and wound contraction for the AgSD plus dihydroepiandrosterone (DHEA) impregnated PEC wound dressing were faster than any other groups.
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PMID:Polyelectroylte complex composed of chitosan and sodium alginate for wound dressing application. 1035 65

ABA-type block copolymers (abbreviated as LEL) composed of poly(L-leucine) (PLL) as the A component and poly(ethylene glycol) (PEG) as the B component were synthesized by ring-opening polymerization of L-leucine N-carboxyanhydride initiated by primary amino group located at both ends of PEG chain. A silver sulfadiazine (AgSD)-impregnated wound dressing of sponge type was prepared by the lyophilization method. Morphological structure of this wound dressing by scanning electron microscopy was observed to be composed of a dense skin layer and a porous inner layer. Equilibrium water content of LEL wound dressing increased with an increase in PEG content in the block copolymer due to the hydrophilicity of PEG. AgSD release from AgSD-impregnated wound dressing in PBS buffer (pH = 7.4) was dependent on PEG content in the block copolymer. Release of AgSD was increased in proportion to the PEG content in the copolymer. Antibacterial capacity of AgSD-impregnated wound dressing was examined in agar plate against Pseudomonas aeruginosa and Staphylococcus aureus. It was found that the suppression of bacterial proliferation in the wound dressing was dependent upon the PEG content. In cytotoxicity test, cell damage did not occur by the release of AgSD from the LEL sponge matrix of AgSD-medicated wound dressing. In in vivo test, granulous tissue formation and wound contraction for the AgSD- and dehydroepiandrosterone-impregnated LEL-2 wound dressing were faster than for any other groups.
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PMID:Possibility of wound dressing using poly(L-leucine)/poly(ethylene glycol)/poly(L-leucine) triblock copolymer. 1063 95

The alarming increase in the incidence of allergic diseases in the past decade has led to a clear call for more effective treatment. Recently, we reported on the construction of a chimeric protein for targeted elimination of cells expressing FcepsilonRI receptors. This chimeric protein, designated Fc2'-3-PE40, is composed of a Fc fragment of mouse IgE attached to a truncated form of Pseudomonas exotoxin. The Fc2'-3-PE40 chimeric protein was found to be highly cytotoxic to mouse mast cell lines and primary mouse mast cells. We now demonstrate that Fc2'-3-PE40 successfully prevents the development of passive cutaneous anaphylaxis reaction (PCA) in mice. Treatment with Fc2'-3-PE40 for 7 days prevented the PCA reaction in mice by 80% compared with that in control mice given only PBS. Fc2'-3-PE40M, the mutated, enzymatically inactive analogue of Fc2'-3-PE40, did not display this activity. Fc2'-3-PE40 was also effective when given as a single dose 16 h before antigen exposure, resulting in complete inhibition of the PCA reaction. Moreover, treatment with Fc2'-3-PE40 did not cause mast cell degranulation, as the serum histamine values of mice treated with Fc2'-3-PE40 were within the range obtained for control, untreated mice. Thus, the Fc2'-3-PE40 chimeric protein offers a novel approach to the treatment of allergic disorders.
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PMID:Targeted Fc2'-3-PE40 chimeric protein abolishes passive cutaneous anaphylaxis in mice. 1069 9

To determine the prevalence of capsular polysaccharide (CP) types of Staphylococcus aureus isolated from bovine mastitic milk in Korea, the protective effect of the conjugates, composed of microencapsulated S. aureus clinical isolate type 8 CP bound to Pseudomonas aeruginosa exotoxin A (ETA) was evaluated in mice. Of 107 S. aureus isolates, serotype 5 and 8 accounted for only 26 or 24.2%. When serotype 336 antiserum was employed, fifty of the remaining 81 isolates were typed as 336, 26 reacted with two serotypes, and 5 were nontypeable. Mice challenged with the same strain used for immunization had fewer S. aureus cells in their kidneys than mice challenged with the heterologous strain. But the magnitudes of difference on bacterial clearance were similar in both groups, indicating that the significance of this result remains to be determined. Mice immunized with the conjugate elicited an antibody response 3 days post injection, which persisted for 13 days of the observation period after second injection in some mice. The mice immunized with the CP8-ETA conjugates developed antibodies significantly higher than those immunized with CP-Freund's adjuvant or PBS. In in vivo bacterial challenge experiment, the survival rate of mice immunized with CPS-ETA conjugate was significantly higher than that of mice immunized with PBS. It was suggested that CP8-ETA vaccine had a potential to protect mice against experimental S. aureus bacteremia.
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PMID:Prevalence of capsular polysaccharide (CP) types of Staphylococcus aureus isolated from bovine mastitic milk and protection of S. aureus infection in mice with CP vaccine. 1119 54

The crystal structure and growth kinetics of melt-crystallized poly(butylene succinate-co-14 mol % ethylene succinate) [P(BS-co-14 mol % ES)] copolyester have been investigated at a wide crystallization temperature range of 30 to 90 degrees C. By means of wide-angle X-ray diffraction (WAXD), the copolyester composed of BS and ES units has been identified to have the same crystal structure with that of poly(butylene succinate) (PBS) homopolymer, suggesting that only PBS sequences crystallize while that the ES units are in an amorphous form. On the basis of secondary nucleation theory, two regimes of II and III have been observed and their transition temperature is around 80 degrees C. The spherulitic morphologies of P(BS-co-14 mol % ES) copolyester developed from banded spherulites to the normal ones without banding extinction patterns as the crystallization temperature increased. The melting behavior of P(BS-co-14 mol % ES) copolyester under different conditions has been studied by differential scanning calorimetry (DSC). Four melting peaks and one exothermal peak on the melting curves were observed during heating process, and their origination is discussed. The enzymatic degradation was carried out on the melt-crystallized P(BS-co-14 mol % ES) thin film by an extracellar PHB depolymerase from Pseudomonas stutzeri and the morphologies of lamellar crystals before and after degradation have been examined by atomic force microscopy (AFM). The results have indicated that enzymatically degradable ES units exist on the surface of lamellar crystals and are hydrolyzed by the enzyme, while that the crystalline cores composed of PBS chains are not degraded.
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PMID:Crystallization, melting, and enzymatic degradation of biodegradable poly(butylene succinate-co-14 mol % ethylene succinate) copolyester. 1174 88

To increase the local concentration of tamoxifen in estrogen receptor (ER) positive breast cancer, we have developed and characterized nanoparticle formulation using poly(epsilon -caprolactone) (PCL). The nanoparticles were prepared by solvent displacement method using acetone-water system. Particle size analysis, scanning electron microscopy, zeta potential measurements, and differential scanning calorimetry (DSC) were used for nanoparticle characterization. Biodegradation studies were performed in the presence and absence of Pseudomonas lipase in phosphate-buffered saline (PBS, pH 7.4) at 37 degrees C. Tamoxifen loading over different concentrations was analyzed by high-performance liquid chromatography (HPLC) and the optimum loading concentration was determined. In vitro release studies were performed in 0.5% (w/v) sodium lauryl sulfate (SLS) containing PBS at 37 degrees C. Cellular uptake and distribution of fluorescent-labeled nanoparticles was examined in MCF-7 breast cancer cells. SEM micrographs and Coulter analysis showed nanoparticles with spherical shape and uniform size distribution (250-300 nm), respectively. Zeta potential analysis revealed a positive surface charge of +25 mV on the tamoxifen-loaded formulation. Being hydrophobic crystalline polyester, PCL did not degrade in PBS alone, but the degradation was enhanced by the presence of lipase. The maximum tamoxifen loading efficiency was 64%. Initial burst release of tamoxifen was observed, probably due to significant surface presence of the drug on the nanoparticles. A large fraction of the administered nanoparticle dose was taken up by MCF-7 cells through non-specific endocytosis. The nanoparticles were found in the perinuclear region after 1 h. Results of the study suggest that nanoparticle formulations of selective ER modulators, like tamoxifen, would provide increased therapeutic benefit by delivering the drug in the vicinity of the ER.
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PMID:Biodegradable poly(epsilon -caprolactone) nanoparticles for tumor-targeted delivery of tamoxifen. 1243 41


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