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)

Microporous materials have been produced by gradual precipitation from solutions of poly(epsilon-caprolactone) (PCL) in acetone induced by solvent extraction across a semi-permeable PCL membrane which is formed in situ at the polymer solution/non-solvent interface. Microparticulates of hydroxyapatite and inulin polysaccharide, respectively, were incorporated in precipitation cast PCL matrices to illustrate potential applications in hard tissue repair and macromolecular drug release. Microporous PCL and HA filled PCL materials were found to provide a favourable surface for attachment and growth of primary human osteoblasts in cell culture. The in vitro degradation characteristics of microporous PCL and inulin/PCL materials in PBS at 37 degrees C were monitored over 45 months. Microporous PCL demonstrated zero weight loss, minor changes in molecular weight characteristics and a fairly constant indentation resistance of around 1 MN/m2. Inulin-loaded PCL materials exhibited a total weight loss of approximately 17% after 12 months in PBS. The indentation resistance decreased by 50% from an initial value of 28 MN/m2 in the first 2 months and then remained stable. Precipitation cast materials based on PCL are expected to be useful for formulating long-term, controlled release devices for bioactive molecules such as growth factors and hormones and extended-residence supports for cell growth and tissue development.
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PMID:Precipitation casting of polycaprolactone for applications in tissue engineering and drug delivery. 1458 19

We previously showed that S-adenosylmethionine (SAM) induces movement impairments similar to those observed in Parkinson's disease (PD) apparently by prenylated protein methylation; 5 kDa molecules being methylated and the symptoms being inhibited by prenylcysteine (PC) analogs. In the present study, we explore the biochemical mechanism of action of the PC analogs. N-acetylgeranylcysteine (AGC), N-acetylfarnesylcysteine (AFC), N-acetylgeranylgeranylcysteine (AGGC), farnesylthioacetic acid (FTA), farnesyl-2-ethanesulfonic acid (FTE) and farnesylsuccinic acid (FMS), but not farnesylthiotriazole (FTT) and farnesylthiolactic acid (FTL), inhibited the SAM-induced motor impairments. Incubation of the respective analogs with rat brain membranes containing prenylated protein methyltransferase (PPMTase) resulted in the methylation of AGC, AFC and AGGC. FTA, FTE, FMS and FTT, but not FTL, inhibited the enzyme activity. A single injection of the active analogs remained effective for at least 3 days against repeated injections of 1 micromol SAM. Amphetamine-induced hyperactivity in rats was inhibited by SAM but potentiated by FTE. During 60 min, the movement time for amphetamine-treated rats was 1477 s compared with 633 and 1664 s for amphetamine+SAM- and amphetamine+FTE-treated rats, respectively. The total distance for amphetamine+FTE-treated rats was 82% higher than for amphetamine. The horizontal activity was 30,728 (amphetamine), 15,430 (FTE), 18,526 (amphetamine+SAM), 41,736 (amphetamine+FTE) and 7004 (SAM) as compared to the PBS control (4726). The intricate relationship between the actions of SAM, which speeds up prenylated protein methylation and impairs movement, amphetamine, which increases synaptic dopamine levels and movement, and the PC analogs, which prevent the SAM-induced movement impairments, suggests a SAM-induced defect on dopamine signaling as the likely cause of the symptoms. The data reveal that interaction of PC analogs with PPMTase may not be an indicator of anti-PD-like activity.
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PMID:Inhibition mechanism of S-adenosylmethionine-induced movement deficits by prenylcysteine analogs. 1464 42

VEGF-A is a major angiogenesis and permeability factor. Its cellular effects, which can be used as targets in anti-angiogenesis therapy, have mainly been studied in vitro using endothelial cell cultures. The purpose of the present study was to further characterize these effects in vivo in vascular endothelial cells and pericytes, in an experimental monkey model of VEGF-A-induced iris neovascularization. Two cynomolgus monkeys (Macaca fascicularis) received four injections of 0.5 microg VEGF-A in the vitreous of one eye and PBS in the other eye. After sacrifice at day 9, eyes were enucleated and iris samples were snap-frozen for immunohistochemistry (IHC) and stained with a panel of antibodies recognizing endothelial and pericyte determinants related to angiogenesis and permeability. After VEGF-A treatment, the pre-existing iris vasculature showed increased permeability, hypertrophy, and activation, as demonstrated by increased staining of CD31, PAL-E, tPA, uPA, uPAR, Glut-1, and alphavbeta3 and alphavbeta5 integrins, VEGF receptors VEGFR-1, -2 and -3, and Tie-2 in endothelial cells, and of NG2 proteoglycan, uPA, uPAR, integrins and VEGFR-1 in pericytes. Vascular sprouts at the anterior surface of the iris were positive for the same antigens except for tPA, Glut-1, and Tie-2, which were notably absent. Moreover, in these sprouts VEGFR-2 and VEGFR-3 expression was very high in endothelial cells, whereas many pericytes were present that were positive for PDGFR-beta, VEGFR-1, and NG2 proteoglycan and negative for alpha-SMA. In conclusion, proteins that play a role in angiogenesis are upregulated in both pre-existing and newly formed iris vasculature after treatment with VEGF-A. VEGF-A induces hypertrophy and loss of barrier function in pre-existing vessels, and induces angiogenic sprouting, characterized by marked expression of VEGFR-3 and lack of expression of tPA and Tie-2 in endothelial cells, and lack of alpha-SMA in pericytes. Our in vivo study indicates a role for alpha-SMA-negative pericytes in early stages of angiogenesis. Therefore, our findings shed new light on the temporal and spatial role of several proteins in the angiogenic cascade in vivo.
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PMID:In vivo angiogenic phenotype of endothelial cells and pericytes induced by vascular endothelial growth factor-A. 1468 16

A highly sensitive analytical method for evaluation of poly(L-lactide) (PLA), poly(epsilon-caprolactone) (PCL), poly(beta-hydroxybutyrate) (PHB), and poly(butylene succinate) (PBS) degradability was developed using coated cellulose paper, prepared by penetration and adhesion of these plastics into/onto the cellulose paper. Enzymatic degradability of the obtained plastic coated papers was evaluated using various commercial proteases and lipases. PLA coated paper was highly susceptible to subtilisin and mammalian enzymes, alpha-chymotrypsin, elastase and trypsin. To our knowledge, this is the first report on the degradation of PLA coated paper using subtilisin and mammalian enzymes. Almost all lipase preparations degraded PCL and PHB coated papers but not PBS coated paper. The biodegradability of plastic coated paper was greater than that of plastic powder. The penetration of plastic into cellulose paper by coating improved the plastic degradability, and can be regulated easily.
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PMID:A new method for the evaluation of biodegradable plastic using coated cellulose paper. 1546 96

The substrate specificity of alpha-chymotrypsin and other serine proteases, trypsin, elastase, proteinase K and subtilisin, towards hydrolysis of various polyesters was examined using poly(L-lactide) (PLA), poly(beta-hydroxybutyrate) (PHB), poly(ethylene succinate) (PES), poly(ethylene adipate) (PEA), poly(butylene succinate) (PBS), poly(butylene succinate-co-adipate) (PBS/A), poly[oligo(tetramethylene succinate)-co-(tetramethylane carbonate)] (PBS/C), and poly(epsilon-caprolactone) (PCL). alpha-Chymotrypsin could degrade PLA and PEA with a lower activity on PBS/A. Proteinase K and subtilisin degraded almost all substrates other than PHB. Trypsin and elastase had similar substrate specificities to alpha-chymotrypsin.
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PMID:Hydrolysis of polyesters by serine proteases. 1592 50

Reducing the blood supply of tumors is one modality to combat cancer. The objective of this study was to evaluate such an approach in the treatment of localized murine AML (acute myelogenous leukemia). For this purpose we designed an experimental model in which leukemic cells were embedded in 1% agar discs before subcutaneous implantation in C57Bl female mice. The C-1498 AML cell line (Frederick Inst., NCI, MD, USA) was used. Thirty experimental mice received on alternate days injections of 5 x 2.5 microg anti-VEGF (vascular endothelial growth factor) and 5 x 2.5 microg anti-Flk-1 (VEGFR2) antibodies to the site of cell implantation over a period of 10 d. Fifteen control mice received daily PBS injections. All mice were sacrificed 16 d after AML implantation. Of the 30 experimental animals, macroscopic examination showed in 21 animals (70%) small sized, pale tumors (0.5 g); in six mice (20%) the tumors were replaced completely by necrotic tissue, while in three mice (10%), there were large (2.5 g), highly vascularized tumors. In all 15 control mice large highly vascularized tumors were seen. A separate group of mice was studied for total survival following AML implantation. While 12 mice in the control group not treated with antibodies survived for 16 d post-implantation, survival was prolonged in 15 antibody treated mice by approximate 30 d to a total survival time of 48 d. Tumor specimens were processed for histology, immunohistochemistry (IHC) for CD31 endothelial cell antigen, and tube-like formation assay. The small, pale tumors of antibody treated animals consisted of degenerate hyaline material with remnant nests of leukemic cells, whereas large tumors showed sheets of leukemic cells and numerous blood vessels. Specimens processed for CD31 antigen showed scarce or absence of blood vessels in the small, pale tumors in contrast to intensive staining from a rich network of blood vessels in the large, highly vascularized tumors. Tube-like formation assays disclosed rudimentary Grade 1 endothelial cell tubes in the small, pale tumors as opposed to polygonal Grade 4 tube formation in control animals. In conclusion, this murine model of localized AML allows assessment of anti-angiogenic tumor regression. Anti-angiogenic antibodies against VEGF and Flk-1 have therapeutic effects in murine AML.
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PMID:Anti-angiogenic effects and regression of localized murine AML produced by anti-VEGF and anti-Flk-1 antibodies. 1594 9

Microporous, poly(epsilon-caprolactone) (PCL) matrices were loaded with progesterone by precipitation casting using co-solutions of PCL and progesterone in acetone. Progesterone loadings up to 32% w/w were readily achieved by increasing the drug content of the starting PCL solution. The kinetics of steroid release in PBS at 37 degrees C over 10 days could be described effectively by a diffusional release model although the Korsmeyer-Peppas model indicated the involvement of multiple release phenomena. The diffusion rate constant (D) increased from 8 to 24 microg/mg matrix/day0.5 as the drug loading increased from 3.6 to 12.4% w/w. A total cumulative release of 75%-95% indicates the high efficiency of steroid delivery. Increasing the matrix density from 0.22 to 0.39 g/cm3, by increasing the starting PCL solution concentration, was less effective in changing drug release kinetics. Retention of anti-proliferative activity of released steroid was confirmed using cultures of breast cancer epithelial (MCF-7) cells. Progesterone released from PCL matrices into PBS at 37 degrees C over 14 days retarded the growth of MCF-7 cells by a factor of at least 3.5 compared with progesterone-free controls. These findings recommend further investigation of precipitation-cast PCL matrices for delivery of bioactive molecules such as anti-proliferative agents from implanted, inserted or topical devices.
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PMID:Precipitation casting of drug-loaded microporous PCL matrices: incorporation of progesterone by co-dissolution. 1599 8

A novel poly(epsilon-caprolactone)/calcium sulfate system was prepared and characterized in order to enhance calcium sulfate (gypsum) performance as bone graft substitute overcoming its brittleness and fast resorption rate. A poly(epsilon-caprolactone) (PCL) photo-crosslinkable derivative (PCLf) was synthesized by reaction of a low molecular weight PCL diol with methacryloyl chloride and confirmed by FT-IR and 1H NMR analyses. An injectable and easy mouldable mixture of PCLf and calcium sulfate hemi-hydrate (PCLf/CHS) was obtained. Thermal analyses and solvent extraction proved the occurrence of PCLf photo-crosslinking, even in the presence of CHS, in a time suitable for clinical applications. Swelling studies demonstrated that the encapsulation of the inorganic filler increases network hydrophilicity making it more permeable to water. Scanning electron microscopy, performed on crosslinked PCLf/CHS and on the same material after incubation in a PBS solution, showed the feasibility to obtain, in situ, gypsum entrapped into a degradable polymeric network. In vitro cytotoxicity tests, performed according to ISO 10993-5, proved that the developed system was not cytotoxic supporting its potential use in tissue engineering as a new, injectable, photocurable bone graft material. SEM micrograph of calcium sulfate di-hydrate (gypsum) entrapped in the PCL network.
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PMID:A novel injectable poly(epsilon-caprolactone)/calcium sulfate system for bone regeneration: synthesis and characterization. 1624 68

Microporous, poly(epsilon-caprolactone) (PCL) matrices were loaded with the aminoglycoside antibiotic, gentamicin sulphate (GS) using the precipitation casting technique by suspension of powder in the PCL solution prior to casting. Improvements in drug loading from 1.8% to 6.7% w/w and distribution in the matrices were obtained by pre-cooling the suspension to 4 degrees C. Gradual release of approximately 80% of the GS content occurred over 11 weeks in PBS at 37 degrees C and low amounts of antibiotic were measured up to 20 weeks. The kinetics of release could be described effectively by the Higuchi model with the diffusion rate constant (D) increasing from of 1.7 to 5.1 microg/mg matrix/day(0.5) as the drug loading increased from 1.4% to 8.3% w/w. GS-loaded PCL matrices retained anti-bacterial activity after immersion in PBS at 37 degrees C over 14 days as demonstrated by inhibition of growth of S. epidermidis in culture. These findings recommend further investigation of precipitation-cast PCL matrices for delivery of hydrophilic molecules such as anti-bacterial agents from implanted, inserted or topical devices.
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PMID:Delivery of the antibiotic gentamicin sulphate from precipitation cast matrices of polycaprolactone. 1632 55

The biodegradable poly(butylene succinate)/poly(epsilon-caprolactone) (PBS/PCL) microcapsules containing indomethacin were prepared by emulsion solvent evaporation method. The morphologies, thermal properties, and release behaviors of PBS/PCL microcapsules were investigated. As a result, the microcapsules exhibited porous and spherical form in the presence of gelatin as a surfactant. From the DSC result, the PBS/PCL microcapsules showed the two exothermic peaks meaning the melting points of PCL and PBS. The results of FT-IR and DSC proved that the PBS and PCL were mixed so that the PBS/PCL microcapsules were composed of two wall-forming materials. And the release rate of indomethacin from the microcapsules was decreased with increasing the PCL content. It was noted that an addition of PCL on the PBS led to the decrease of pore size in the PBS/PCL microcapsules.
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PMID:Release behaviors of porous poly(butylene succinate)/poly(epsilon-caprolactone) microcapsules containing indomethacin. 1641 77


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