•Polysaccharides have physical and chemical properties suitable for drug delivery systems.•Polysaccharides provide a range of drug stabilization, delivery and release mechanisms.•Polysaccharide drug ...delivery systems are biocompatible, biodegradable and non-toxic.•Particle-based drug delivery systems are easily constructed from polysaccharides.•Polysaccharide particles can deliver protein, oligonucleotide and small molecule drug forms.
This review investigates the significant role polysaccharide particles play in functional drug delivery. The importance of these systems is due to the wide variety of polysaccharides and their natural source meaning that they can provide biocompatible and biodegradable systems with a range of both biological and chemical functionality valuable for drug delivery. This functionality includes protection and presentation of working therapeutics through avoidance of the reticuloendothelial system, stabilization of biomacromolecules and increasing the bioavailability of incorporated small molecule drugs. Transport of the therapeutic is also key to the utility of polysaccharide particles, moving drugs from the site of administration through mucosal binding and transport and using chemistry, size and receptor mediated drug targeting to specific tissues. This review also scrutinizes the methods of synthesizing and constructing functional polysaccharide particle drug delivery systems that maintain and extend the functionality of the natural polysaccharides.
The chronic phase of HIV infection is marked by pathological activation of the immune system, the extent of which better predicts disease progression than either plasma viral load or CD4(+) T cell ...count. Recently, translocation of microbial products from the gastrointestinal tract has been proposed as an underlying cause of this immune activation, based on indirect evidence including the detection of microbial products and specific immune responses in the plasma of chronically HIV-infected humans or SIV-infected Asian macaques. We analyzed tissues from SIV-infected rhesus macaques (RMs) to provide direct in situ evidence for translocation of microbial constituents from the lumen of the intestine into the lamina propria and to draining and peripheral lymph nodes and liver, accompanied by local immune responses in affected tissues. In chronically SIV-infected RMs this translocation is associated with breakdown of the integrity of the epithelial barrier of the gastrointestinal (GI) tract and apparent inability of lamina propria macrophages to effectively phagocytose translocated microbial constituents. By contrast, in the chronic phase of SIV infection in sooty mangabeys, we found no evidence of epithelial barrier breakdown, no increased microbial translocation and no pathological immune activation. Because immune activation is characteristic of the chronic phase of progressive HIV/SIV infections, these findings suggest that increased microbial translocation from the GI tract, in excess of capacity to clear the translocated microbial constituents, helps drive pathological immune activation. Novel therapeutic approaches to inhibit microbial translocation and/or attenuate chronic immune activation in HIV-infected individuals may complement treatments aimed at direct suppression of viral replication.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Occult hypovolaemia is a key factor in the aetiology of postoperative morbidity and may not be detected by routine heart rate and arterial pressure measurements. Intraoperative gut hypoperfusion ...during major surgery is associated with increased morbidity and postoperative hospital stay. We assessed whether using intraoperative oesophageal Doppler guided fluid management to minimize hypovolaemia would reduce postoperative hospital stay and the time before return of gut function after colorectal surgery.
This single centre, blinded, prospective controlled trial randomized 128 consecutive consenting patients undergoing colorectal resection to oesophageal Doppler guided or central venous pressure (CVP)-based (conventional) intraoperative fluid management. The intervention group patients followed a dynamic oesophageal Doppler guided fluid protocol whereas control patients were managed using routine cardiovascular monitoring aiming for a CVP between 12 and 15 mm Hg.
The median postoperative stay in the Doppler guided fluid group was 10 vs 11.5 days in the control group P<0.05. The median time to resuming full diet in the Doppler guided fluid group was 6 vs 7 for controls P<0.001. Doppler patients achieved significantly higher cardiac output, stroke volume, and oxygen delivery. Twenty-nine (45.3%) control patients suffered gastrointestinal morbidity compared with nine (14.1%) in the Doppler guided fluid group P<0.001, overall morbidity was also significantly higher in the control group P=0.05.
Intraoperative oesophageal Doppler guided fluid management was associated with a 1.5-day median reduction in postoperative hospital stay. Patients recovered gut function significantly faster and suffered significantly less gastrointestinal and overall morbidity.
Motivation: Artemis and Artemis Comparison Tool (ACT) have become mainstream tools for viewing and annotating sequence data, particularly for microbial genomes. Since its first release, Artemis has ...been continuously developed and supported with additional functionality for editing and analysing sequences based on feedback from an active user community of laboratory biologists and professional annotators. Nevertheless, its utility has been somewhat restricted by its limitation to reading and writing from flat files. Therefore, a new version of Artemis has been developed, which reads from and writes to a relational database schema, and allows users to annotate more complex, often large and fragmented, genome sequences. Results: Artemis and ACT have now been extended to read and write directly to the Generic Model Organism Database (GMOD, http://www.gmod.org) Chado relational database schema. In addition, a Gene Builder tool has been developed to provide structured forms and tables to edit coordinates of gene models and edit functional annotation, based on standard ontologies, controlled vocabularies and free text. Availability: Artemis and ACT are freely available (under a GPL licence) for download (for MacOSX, UNIX and Windows) at the Wellcome Trust Sanger Institute web sites: http://www.sanger.ac.uk/Software/Artemis/ http://www.sanger.ac.uk/Software/ACT/ Contact: artemis@sanger.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.
Graphene oxide (GO) nanosheets were attached to the polyamide selective layer of thin film composite (TFC) forward osmosis (FO) membranes through a poly l-Lysine (PLL) intermediary using either ...layer-by-layer or hybrid (H) grafting strategies. Fourier transform infrared spectroscopy, zeta potential, and thermogravimetric analysis confirmed the successful attachment of GO/PLL, the surface modification enhancing both the hydrophilicity and smoothness of the membrane’s surface demonstrated by water contact angle, atomic force microscopy, and transmission electron microscopy. The biofouling resistance of the FO membranes determined using an adenosine triphosphate bioluminescence test showed a 99% reduction in surviving bacteria for GO/PLL-H modified membranes compared to pristine membrane. This antibiofouling property of the GO/PLL-H modified membrane was reflected in reduced flux decline compared to all other samples when filtering brackish water under biofouling conditions. Further, the high density and tightly bound GO nanosheets using the hybrid modification reduced the reverse solute flux compared to the pristine, which reflects improved membrane selectivity. These results illustrate that the GO/PLL-H modification is a valuable addition to improve the performance of FO TFC membranes.
A decade of research has sought to identify circulating endothelial progenitor cells (EPC) in order to harness their potential for cardiovascular regeneration. Endothelial outgrowth cells (EOC) most ...closely fulfil the criteria for an EPC, but their origin remains obscure. Our aim was to identify the source and precursor of EOC and to assess their regenerative potential compared to mature endothelial cells. EOC are readily isolated from umbilical cord blood (6/6 donors) and peripheral blood mononuclear cells (4/6 donors) but not from bone marrow (0/6) or peripheral blood following mobilization with granulocyte‐colony stimulating factor (0/6 donors). Enrichment and depletion of blood mononuclear cells demonstrated that EOC are confined to the CD34+CD133−CD146+ cell fraction. EOC derived from blood mononuclear cells are indistinguishable from mature human umbilical vein endothelial cells (HUVEC) by morphology, surface antigen expression, immunohistochemistry, real‐time polymerase chain reaction, proliferation, and functional assessments. In a subcutaneous sponge model of angiogenesis, both EOC and HUVEC contribute to de novo blood vessel formation giving rise to a similar number of vessels (7.0 ± 2.7 vs. 6.6 ± 3.7 vessels, respectively, n = 9). Bone marrow‐derived outgrowth cells isolated under the same conditions expressed mesenchymal markers rather than endothelial cell markers and did not contribute to blood vessels in vivo. In this article, we confirm that EOC arise from CD34+CD133−CD146+ mononuclear cells and are similar, if not identical, to mature endothelial cells. Our findings suggest that EOC do not arise from bone marrow and challenge the concept of a bone marrow‐derived circulating precursor for endothelial cells. STEM CELLS2013;31:338–348
ACT: the Artemis comparison tool Carver, Tim J.; Rutherford, Kim M.; Berriman, Matthew ...
Bioinformatics,
08/2005, Letnik:
21, Številka:
16
Journal Article
Recenzirano
Odprti dostop
The Artemis Comparison Tool (ACT) allows an interactive visualisation of comparisons between complete genome sequences and associated annotations. The comparison data can be generated with several ...different programs; BLASTN, TBLASTX or Mummer comparisons between genomic DNA sequences, or orthologue tables generated by reciprocal FASTA comparison between protein sets. It is possible to identify regions of similarity, insertions and rearrangements at any level from the whole genome to base-pair differences. ACT uses Artemis components to display the sequences and so inherits powerful searching and analysis tools. ACT is part of the Artemis distribution and is similarly open source, written in Java and can run on any Java enabled platform, including UNIX, Macintosh and Windows. Availability: ACT is freely available (under a GPL licence) for download from the Sanger Institute web site, http://www.sanger.ac.uk Contact: artemis@sanger.ac.uk
Inulin-based hydrogels are useful carriers for the delivery of drugs in the colon-targeted system and in other biomedical applications. In this project, inulin hydrogels were fabricated by ...crosslinking oxidized inulin with adipic acid dihydrazide (AAD) without the use of a catalyst or initiator. The physicochemical properties of the obtained hydrogels were further characterized using different techniques, such as swelling experiments, in vitro drug release, degradation, and biocompatibility tests. The crosslinking was confirmed with Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), and differential scanning calorimetry (DSC). In vitro releases of 5-fluorouracil (5FU) from the various inulin hydrogels was enhanced in acidic conditions (pH 5) compared with physiological pH (pH 7.4). In addition, blank gels did not show any appreciable cytotoxicity, whereas 5FU-loaded hydrogels demonstrated efficacy against HCT116 colon cancer cells, which further confirms the potential use of these delivery platforms for direct targeting of 5-FU to the colon.
Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of ...the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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