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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of perfusion medium composition on the two important biopharmaceutical parameters drug solubility and permeability was determined for ibuprofen. Eight commonly used buffers were examined. Equilibrium solubility, buffer capacity profiles and permeability coefficients, using the in situ rat gut perfusion model, were determined for each medium at 37 degrees C. The solubility of ibuprofen differed sixfold over the range of buffer systems studied. The differences in solubility were associated with different pHs of the buffers when saturated with drug and also the presence of micelles and divalent ions. The solubility of ibuprofen in FeSSIF was significantly higher than predicted from the pH due to micellisation, while that in Krebs was significantly lower due to ibuprofen-calcium salt formation. Buffer capacities varied over a 40-fold range. The pK(a) values of the buffer components were determined from the buffer capacity versus pH profiles and were in good agreement with the thermodynamic values when corrected for temperature and ionic strength. Smaller, but statistically significant differences in P(app) values for ibuprofen were also observed between some of the buffers. During perfusion, pHs of the perfusate samples gradually changed over time towards a median value of approximately 6.5. HBSS gave a P(app) approximately 50% greater than that observed in PBS 7.4. Physicochemical factors such as medium pH, buffer capacity and osmolarity should be considered when determining the P(app) values of ionisable compounds. Care needs to be exercised when comparing P(app) values from different laboratories as buffer composition can have a significant effect on both solubility and permeability of a drug, whose ionisation is substantially changed over the pH range of the buffers. Despite the high amount ionised, ibuprofen appears to be well absorbed and it can be classified as a highly permeable drug.
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PMID:Effect of buffer media composition on the solubility and effective permeability coefficient of ibuprofen. 1259 36

In this study photo-control of the non-biospecific interaction between endothelial cell membranes and photo-cation generatable water-soluble polymers were examined. The water-soluble polymers contained triphenylmethane leucohydroxide (malachite green) groups (contents: 0.4 and 1.6 mol%), which dissociate into triphenylmethyl cations and counter hydroxide ions upon ultraviolet light (UV) irradiation, and were prepared by free radical copolymerization of diphenyl(4-vinylphenyl)methane leucohydroxide and acrylamide. The nature and magnitude of the interaction was quantitatively assessed by direct luminescence measurement of the intracellular calcium ion concentration using a calcium-sensitive photoprotein, aequorin. When a PBS buffer of the photoreactive copolymers were added, prior to UV irradiation, to a PBS suspension of cultured bovine endothelial cells loaded with aequorin, no detectable elevation of Ca(2+) was measured. In contrast, cationic copolymers, derived from the photoreactive copolymers after UV irradiation at a wavelength of 290<lambda<410 nm, induced an immediate transient increase in the cytosolic free Ca(2+) concentration due to a Ca(2+) inflow from the extracellular space into the cells, which may be due to non-biospecific transmembrane stimulation. Longer UV irradiation exposures of the copolymers and higher concentrations of the polymers, with higher contents of the photodissociable group, resulted in more Ca(2+) inflow with little cellular damage. The photo-cation generatable copolymers developed here made possible to control the non-biospecific interaction with endothelial cell membranes by UV irradiation condition, and composition and amount of the copolymer.
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PMID:Photo-control of the interaction between endothelial cells and photo-cation generatable water-soluble polymers. 1271 45

Ion-exchange microspheres (MS) designed as a drug delivery system for embolization coupling ability to occlude vessels and chemotherapy were used to evaluate a manufacturing process allowing to control the drug release rate through reduction of diffusion rate of the drug within the particle by impregnation of calcium alginate inside the porous MS. Impregnation was performed by diffusion of sodium alginate inside DEAE-Trisacryl(R) MS, dispersion of the MS in deionised water and gelling alginate by adding CaCl(2) to the dispersed MS. Studied parameters were alginate concentration, alginate diffusion time and calcium concentration. Indomethacin was loaded into the MS by eluting an aqueous indomethacin solution through a chromatographic column packed with impregnated MS. Indomethacin loading was reduced by alginate. Swelling studies showed indomethacin loading enhanced the hydrophobicity of MS while impregnation had no effect. This had an incidence on indomethacin release rate, which was assessed using the rapid elution of PBS through loaded impregnated MS packed in a column. Indomethacin loading reduced its own rate of release. MS impregnated with 2% w/v alginate gelled with a 40 mM calcium solution presented the lower release rate. This work indicated the manufacturing conditions to display a calcium alginate matrix effect on indomethacin release from DEAE-Trisacryl MS.
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PMID:Indomethacin release from ion-exchange microspheres: impregnation with alginate reduces release rate. 1512 Aug 94

Therapeutic angiogenesis is the growth of blood vessels from a pre-existing vasculature for clinical applications such as treating myocardial and limb ischemia. Vascular endothelial growth factor (VEGF) is a potent signal transduction molecule that acts specifically on vascular endothelial cells. Encapsulation of VEGF in a polymer matrix not only protects protein against enzymatic degradation in the body, but also allows proteins to be released at a controllable rate into a localized area. In this study, VEGF was encapsulated in calcium alginate beads by the extrusion/external gelation method, and was subsequently released in PBS and in serum media. The objective was to optimize VEGF encapsulation yield and obtain VEGF release at a constant rate from alginate matrices in vitro. The incorporation of low concentrations of VEGF and NaCl can increase encapsulation yield to 97%. The rate of VEGF release from alginate beads was higher in serum than in PBS, which was due to the capacity of the serum in reducing the electrostatic interaction between alginate and VEGF. The presence of CaCl(2) in the release supernatant can shield the alginate interaction with VEGF, and a constant release rate of 6 ng/ml/day may be sustained for 14 days. These results suggest that the alginate-VEGF delivery system may be useful in the development of vascular tissue engineering and wound healing applications.
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PMID:Sustained delivery of vascular endothelial growth factor with alginate beads. 1512 Sep 2

Wool keratin sponges were reported to be useful scaffolds for long-term and high-density cell cultivation (J. Biotechnol. 93 (2002) 165). The hybrid of the keratin sponges with calcium phosphate materials gave the additional function. Two rapid fabrication methods for calcium phosphate hybrid biomaterials were described. Firstly, the CaP-precipitated sponges were obtained by only the immersion of the carboxyl-sponges, chemically introduced with high amount of carboxyl groups on the sponges, in calcium and phosphate ions containing buffers such as PBS(+) for only 1-3 days. Neither sponge, introduced with amino or amido groups or non-treated, gave significant calcium phosphate precipitation. The carboxyl-sponges were mimics of matrix gamma-carboxyglutamic acid protein, which is responsible for osteoblast calcification. Secondly, the hydroxyapatite particle suspension was added onto carboxyl-sponges to fabricate trapped sponge. The trapped hydroxyapatite particles might interact with keratin protein of the sponge walls. Preliminary experiments measuring the expression of alkaline phosphatase, early osteoblast differentiation marker, suggested that both hybrid sponges, CaP-precipitated and trapped sponges, alter the differentiation pattern of preosteoblasts, MC3T3-E1.
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PMID:Rapid fabrication of keratin-hydroxyapatite hybrid sponges toward osteoblast cultivation and differentiation. 1526 71

A calcium-dependent lectin (chiletin) was isolated from oyster haemolymph by mannose elution from Sepharose CL-6B followed by anion exchange chromatography. Chiletin was predominantly composed of 12 and 24 kDa bands when examined with SDS-PAGE under reducing and non-reducing conditions, respectively. Larger molecular weight bands of 36 and 50 kDa were also variably present under reducing conditions. The NH2-terminal sequence of the 24 kDa band was determined and was not homologous to any known protein from the databases searched. Isolated chiletin was composed of multiple isomers approximately 12 kDa in size and ranging in pI from 5.2 to 6.0. Rabbit antiserum was raised to a synthetic peptide coupled to keyhole limpet hemocyanin and the size of the chiletin subunits was confirmed by Western blot. Two and five different conformational aggregates of chiletin were resolved in oyster haemolymph using size exclusion chromatography in 8 M urea and PBS, respectively. The largest aggregate obtained from size exclusion in 8 M urea was estimated to be greater than 640 kDa. The ability of whole haemolymph and isolated chiletin to agglutinate sheep red blood cells was inhibited by galactose and mannose. Chiletin was identified by immunohistochemistry to be most consistently present in the auricle, followed by the digestive gland, however staining was seen sporadically in haemocytes, gastrointestinal epithelium and interstitial connective tissue cells.
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PMID:Isolation and partial characterization of a calcium-dependent lectin (chiletin) from the haemolymph of the flat oyster, Ostrea chilensis. 1531 12

Carbonated hydroxyapatite (CHA) coatings were applied onto titanium implants by using a biomimetic precipitation method. Different antibiotics were incorporated into the CHA coatings and their release and efficacy against bacteria growth were studied in vitro. The following antibiotics were used within this study: cephalothin, carbenicillin, amoxicillin, cefamandol, tobramycin, gentamicin and vancomycin. Increased concentrations of antibiotics in the coating solution led to a higher quantity of antibiotic incorporated into the CHA coating. Some antibiotics were better incorporated than others depending on their chemical structure. Antibiotics, containing carboxylic groups such as cephalothin, carbenicillin and cefamandol, were better incorporated than antibiotics lacking these groups. A bacterial inhibition test on Staphylococcus aureus bacteria showed inhibition of growth for all antibiotics that were released from the CHA coating. A release test was conducted in phosphate buffer saline PBS at pH 7.4 and 37 degrees C and showed that antibiotics containing carboxylic groups like cephalothin were slower released from the CHA coating than others. These results suggest that certain antibiotics are able to bind/chelate with calcium, resulting in a better incorporation into the CHA coating and a slower release. Antibiotics incorporated in CHA coatings on titanium implants might be used to prevent post-surgical infections and to promote bone-bonding of orthopedic devices.
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PMID:Incorporation of different antibiotics into carbonated hydroxyapatite coatings on titanium implants, release and antibiotic efficacy. 1534 86

A possible alternative for immunosuppression is a microencapsulation technique using hydrogels, which have been utilized for cell immobilization and drug delivery systems. Angiogenesis is crucial for delivery of the metabolic products to the host tissues as well as to supply oxygen and nutrients to cells. The local delivery of angiogenic growth factors, such as VEGF and basic FGF, has been recently studied to enhance angiogenesis on peripheral tissue of graft. In this study, we evaluated sustained VEGF release with a model using hydrogels coated with chitosan and heparin in vitro. We fabricated calcium alginate gels and chitosan-coated calcium alginate gels. Heparinized chitosan-coated calcium-induced alginate hydrogel beads were prepared by soaking chitosan-coated calcium alginate gels in heparin solution. We compared the stability and VEGF release manner between three kinds of hydrogels. To compare the stability, 5 mL of each hydrogel was incubated with 20 mL PBS under the rotational culture. Compression forces were measured using a rheometer. The amount of VEGF released from the gels was measured by ELISA. The heparin-coated chitosan alginate hydrogels showed the highest surface stability among the three hydrogels. VEGF from the heparinized gel was released in sustained manner up to 10 days in vitro. Chitosan-coated alginate gels released 90% of loaded VEGF within 5 days. These results suggest that local delivery of VEGF using a heparinized hydrogel may provide a long-term supply of angiogenic growth factor that might induce new vessel formation in vivo.
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PMID:Sustained release of vascular endothelial growth factor from calcium-induced alginate hydrogels reinforced by heparin and chitosan. 1556 Dec 82

The development of diagnostic tests to differentiate between vaccinated animals and those infected with Mycobacterium bovis is required so that test and slaughter control strategies can continue alongside vaccination. In this work, the peptide antigen, ESAT-6, p45, derived from the N-terminal sequence of the ESAT-6 protein, was adsorbed onto a range of microparticulate and nanoparticulate substrates to enhance the in vitro immune response of blood lymphocytes previously sensitised to M. bovis. Two types of hydroxyapatite (HA) nanoparticles (both approximately 300 nm in linear dimension), carbonate hydroxyapatite nanospheres (CHA, approximately 50 nm), two sizes of polystyrene nanospheres ( approximately 500 and 40 nm), calcium carbonate microparticles (0.3-1.0 microm) and glass microspheres (1.0-3.0 microm) were incubated in a solution of the peptide in PBS. Peptide adsorption increased on the nanoparticle carriers in the order HA (2.5+/-0.12%w/w), CHA (4.9+/-0.12) polystyrene (500 nm, 6.8+/-0.15%, 40 nm, 9.2+/-0.07) and these systems exhibited fairly low levels of desorption (approximately 10-15% peptide release) over a 24-h incubation period in PBS at 37 degrees C. HA, CHA and polystyrene carriers with adsorbed peptide were subsequently tested in the BOVIGAM assay to investigate the efficiency of the immune response of blood lymphocytes in terms of interferon-gamma (IFN-gamma) production. A general elevation of IFN-gamma production resulted for particle-bound peptide relative to free peptide at high peptide concentrations (>10 microg/ml). Only HA-adsorbed peptide resulted in consistently higher immune responses at low peptide concentration (<0.1 microg/ml) compared with the free peptide, indicating that peptide antigens adsorbed to hydroxyapatite nanoparticles may be useful, in diagnostic assays, for differentiating between tuberculosis (TB)-infected and vaccinated animals.
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PMID:Improving peptide-based assays to differentiate between vaccination and Mycobacterium bovis infection in cattle using nanoparticle carriers for adsorbed antigens. 1568 Oct 78

Although ischemia has been shown to disrupt cell adhesion, the underlying molecular mechanism is unknown. In these studies, we adapted a model of ischemia-reperfusion to normal rat kidney (NRK) cells, examined disruption of the cadherin/catenin complex, and identified a role for matrix metalloproteinases (MMPs) in ischemia-induced cleavage of cadherins. In NRK cells, ischemia was induced by applying a thin layer of PBS solution supplemented with calcium and magnesium and a layer of mineral oil, which restricts exposure to oxygen. NRK cells exhibited extracellular 80-kDa and intracellular 40-kDa E-cadherin fragments after 4 h of ischemia, and at 6 h the expression of full-length E-cadherin decreased. While no fragments of N-cadherin, alpha-catenin, and gamma-catenin were observed at any time point, the detectable levels of these proteins decreased during ischemia. Ischemia was detected by an increase in pimonidazole adducts, as well as an increase in glucose transporter-1 protein expression. Ischemia did not decrease cell number, but there was a decrease in ATP levels. In addition, there was no evidence of cleaved caspase 3 or 9 during 6 h of ischemia. The MMP inhibitors GM-6001 and TAPI-O inhibited cleavage and/or loss of E- and N-cadherin protein expression. Tissue inhibitors of metalloproteinases (TIMP)-3 and to a lesser extent TIMP-2, but not TIMP-1, inhibit ischemic cleavage and/or loss of E- and N-cadherin. These results demonstrate that ischemia induces a selective metalloproteinase-dependent cleavage of E-cadherin and decrease in N-cadherin that are associated with a disruption of junctional contacts.
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PMID:Ischemia-induced cleavage of cadherins in NRK cells: evidence for a role of metalloproteinases. 1576 36


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