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At least 973 records · Page 54Linked to original sources
PubMed2001

The in vitro evaluation of 'azo containing polysaccharide gels' for colon delivery.

This study reports on 'azo-polysaccharide gels', more specifically azo-inulin and azo-dextran gels, for colon drug delivery. Compared with azo-hydrogels which can be only degraded by reduction of the azo-groups, this study evaluates whether, in vitro, azo-polysaccharide gels can be degraded through both reduction of the azo-groups in the crosslinks as well as enzymatic break down of the polysaccharide backbone. The azo-polysaccharide gels were synthesized by radical crosslinking of a mixture of methacrylated inulin or methacrylated dextran and N,N'-bis(methacryloylamino)azobenzene (B(MA)AB) and were characterized by dynamic mechanical analysis and swelling measurements. Azo-dextran gels could be obtained from methacrylated dextran having low degree of substitution but not from lowly substituted methacrylated inulin. Increasing the amount of B(MA)AB resulted in denser azo-inulin and azo-dextran networks. Compared with their swelling in dimethylformamide, all azo-dextran gels became more swollen in water while azo-inulin gels shrank upon exposure to water, indicating a more hydrophobic character of the azo-inulin gels. Break down of the inulin and dextran chains in the azo-polysaccharide gels by inulinase and dextranase, respectively, was observed. However, the degradation of azo-dextran gels by dextranase seemed to be more pronounced than the degradation of the azo-inulin gels by inulinase. In rat caecal content medium, reduction of the azo function in azo-inulin gels was not observed. This may be attributed to a low partitioning of nicotinamide-adenine dinucleotide phosphate (NADP(+)) in the gels.

Algorithms↗
PubMed1996

Modeling polysaccharides: present status and challenges.

The most recent tools that have been developed for modeling the three-dimensional features of polysaccharides and carbohydrate polymers are presented. The presentation starts with a description of the conformations of the monosaccharides, and of the flexible rings such as in the case of five-membered rings, and a thorough description of the conformational space that is available for a disaccharide unit, either in vacuo or in an aqueous phase. The extension to the modeling of the parent polysaccharides is addressed, based on the assumption that owing to the size and relative rigidity of the intervening monosaccharides units, the rotations at a particular linkage can be, under some conditions, considered as independent of nearest neighbor interactions. Appropriate modeling techniques are described that can provide insights into the dimensions of the chain in a solution which is best described as a random coil accompanied by the occurrence of local "helical" regions. With the help of such descriptors such as helical parameters, the ordered state of polysaccharide strands can be readily characterized. The generation of double or triple helices can be then attempted in order to explore the occurrence of such multi-stranded arrangements that may be energetically stable. The final step in the determination of the structure of polysaccharides in the ordered state, is the investigation of the interactions of different helices. This may lead to either the best arrangement(s) between two polymeric chains, or to the prediction of the dimensions, and the symmetry of a three-dimensional lattice. Some of the tools which have been developed should allow automatic scarches for meaningful correlations between structures and functions, through exploratory data analysis. Structure-function or structure-property correlation could be then used to model changes arising from structural alterations. This would open the field of polysaccharide engineering.

Carbohydrate Conformation↗
PubMed2000

Reduced antibody response to revaccination with meningococcal serogroup A polysaccharide vaccine in adults.

Widespread use of meningococcal A and C polysaccharide (MACP) vaccines has raised concerns about induction of hyporesponsiveness to these polysaccharides. Immunological hyporesponsiveness to C polysaccharide has been clearly documented in infants, children and adults but only limited data from Gambian children are available for A polysaccharide. We investigated whether a second dose of MACP, given 6 months after an initial dose affected the immunological response as measured by the serum bactericidal assay (SBA) and enzyme-linked immunosorbent assay (ELISA), to serogroup A meningococci in young adults (university students, n=36). Serogroup A SBA responses 1 month following the second dose of MACP (geometric mean titre (GMT) 103.6, 95% CI 45.6-235.1) were approximately one third of the levels observed 1 month post first dose (GMT 281.9, 95% CI 134.9-581.4). The serogroup A-specific IgG levels post second dose (GMC 21.2, 95% CI 15.3-29.4) were also significantly lower at an average of three-quarters the level post first dose (GMC 28.7, 95% CI 20.8-39.7). This confirms that revaccination with MACP vaccine, 6 months following the initial dose, results in a reduced immunological response to A polysaccharide in adults. Repeated vaccination with MACP vaccine may be ineffective and development and use of meningococcal serogroup A conjugate vaccines should be encouraged.

Adolescent↗
PubMed2001

Rapid and complete adsorption of unconjugated protein from protein-polysaccharide conjugate vaccines.

We have developed a rapid and inexpensive approach to remove unconjugated protein from protein-polysaccharide conjugate vaccines, without using gel filtration or ultrafiltration. We employ porous particles that adsorb the protein, whether bound or free, but with a pore size that allows only the unconjugated protein to enter the particle. Using limited amounts of media there is preferential binding of the unconjugated protein over the high molecular weight protein-polysaccharide conjugate. Adsorption of the unconjugated protein is rapid, with greater than 90% recovery of the conjugate. The approach is applicable to both neutral and charged polysaccharides and is not dependent on the chemistry used to make the conjugate vaccine. We have used this method to prepare tetanus toxoid-polysaccharide conjugates and found their immunogenicity in mice comparable to conjugates prepared using gel filtration. The method described can be used to reduce the cost and increase the yields of protein-polysaccharide conjugate vaccines.

Adsorption↗
PubMed1997

The synthesis of Streptococcus pneumoniae polysaccharide-tetanus toxoid conjugates and the effect of chain length on immunogenicity.

To study the relationship between length of pneumococcal polysaccharide and immunologic performance in rabbits we took well defined fragments of the capsular polysaccharides of S. pneumoniae types 3, 6A, 18C, 19F and 23F and pneumococcal C-polysaccharide and linked them terminally by reductive amination to tetanus toxoid. Contrary to other reports we found little variation in antibody titers with increasing length. In general the opsonophagocytic titers determined using activated HL60 cells and rabbit peritoneal cells correlated well with the antibody titers except for that of type 3, which despite the presence of high polysaccharide antibody titers gave unexpectedly low opsonophagocytic titers. The C-polysaccharide-conjugate was also immunogenic when injected in both rabbits and mice but gave low opsonophagocytic titers. It was demonstrated that opsonophagocytosis was solely dependent on the presence of phosphoryl choline-specific antibody and that the induction of these antibodies was species dependent.

Animals↗
PubMed1997

Urinary excretion of sulfated polysaccharides administered to Wistar rats suggests a renal permselectivity to these polymers based on molecular size.

Sulfated polysaccharides were administered to Wistar rats and their elimination from the blood as well as their urinary excretion were evaluated. Sulfated polysaccharides with differences in molecular mass, charge density and molecular structure were obtained from algae, marine invertebrates and vertebrates. A simple methodology based on the metachromatic property of these polysaccharides with 1,9-dimethylmethylene blue was used to estimate their concentration in urine and blood. Renal permselectivity to these macromolecules was based on molecular size, but the upper limit of molecular mass for excretion of a sulfated polysaccharide in urine varies among polymers with different structures. For dextran sulfates the upper limit is approximately 8 kDa. Chondroitin 4- and 6-sulfates were excreted as fragments of approximately 30 kDa, which is smaller than the injected polysaccharide. This suggests that they were degraded enzymatically in vivo. Large synthetic polymers (dextran sulfate > 8 kDa) were not excreted in urine, but slowly disappeared from the blood. Evaluation of their tissue distribution after intravenous administration indicated that these molecules are preferentially accumulated in the kidney.

Animals↗
PubMed1979

Electron microscopic cytochemistry of polysaccharides in bacteria Xanthomonas fuscans, the cause of the bean fuscous blight.

High resolution cytochemical staining of polysaccharides in the cells of the bean fuscous blight bacteria Xanthomonas fuscans (Burkholder) Bur. revealed extensive deposits of a periodic acid-oxidizable compound in the cytoplasm, which accumulated at the onset of polysaccharide excretion and occupied a substantial part of the cell volume. In the course of subsequent culture growth the intracellular polysaccharides gradually disappeared and polysaccharide microfibrils were visualized in the medium. Our observations indicate that the exuded phytopathogenic polysaccharides may be synthetized in the cytoplasm of the bacteria.

Cytoplasm↗
PubMed2003

Mitogenic and comitogenic activities of polysaccharides from some European herbaceous plants.

From the leaves of Plantago lanceolata, the green parts of Rudbeckia fulgida, the aerial parts of Salvia officinalis and the roots of Valeriana officinalis, crude polysaccharides have been isolated by extraction with water and further purified and fractionated by various techniques. The water-soluble polysaccharides obtained were examined for their immunomodulatory activities using the in vitro mitogenic and comitogenic rat thymocyte tests. The results indicate that in spite of the considerable differences in chemical composition and structural properties, the tested polysaccharides exhibited similar significant immunomodulatory properties with a particularly high adjuvans activity in the case of the Rudbeckia and Salvia polysaccharides. The pectic polysaccharide-rich complex from Valeriana was shown to also stimulate the immune function of bone marrow cells.

Adjuvants, Immunologic↗
PubMed1996

The cpsABCDE genes involved in polysaccharide production in Streptococcus salivarius ssp. thermophilus strain NCBF 2393.

A 4074-bp EcoRI fragment of Streptococcus salivarius ssp. thermophilus (S. thermophilus) chromosomal DNA containing genes involved in exocellular polysaccharide (EPS) was identified and cloned. The nucleotide sequence of this fragment was determined and found to contain one partial and four complete open reading frames. These were designated cpsA, cpsB, cpsC, cpsD and cpsE and encoded proteins of > 130, 243, 230, 246 and 455 amino acids, respectively, that showed homology with the genes of the cps cluster, involved in polysaccharide biosynthesis, in Streptococcus pneumoniae Type 19F. The cpsA gene is predicted to encode a transcriptional regulator, while cpsC and cpsD are predicted to encode proteins involved in polysaccharide polymerization and export. The cpsE gene is likely to encode the phosphate-prenyl glycosyl-1-phosphate transferase catalyzing the first step in polysaccharide biosynthesis in S. thermophilus. Southern blot analysis revealed that cpsE is found only in polysaccharide producing strains of S. thermophilus.

Amino Acid Sequence↗
PubMed2001

Polysaccharides in colon-specific drug delivery.

Natural polysaccharides are now extensively used for the development of solid dosage forms for delivery of drug to the colon. The rationale for the development of a polysaccharide based delivery system for colon is the presence of large amounts of polysaccharidases in the human colon as the colon is inhabited by a large number and variety of bacteria which secrete many enzymes e.g. beta-D-glucosidase, beta-D-galactosidase, amylase, pectinase, xylanase, beta-D-xylosidase, dextranase, etc. Various major approaches utilizing polysaccharides for colon-specific delivery are fermentable coating of the drug core, embedding of the drug in biodegradable matrix, formulation of drug-saccharide conjugate (prodrugs). A large number of polysaccharides have already been studied for their potential as colon-specific drug carrier systems, such as chitosan, pectin, chondroitin sulphate, cyclodextrin, dextrans, guar gum, inulin, amylose and locust bean gum. Recent efforts and approaches exploiting these polysaccharides in colon-specific drug delivery are discussed.

Administration, Oral↗
PubMed2002

Regulation of elastase-type endopeptidase activity, MMP-2 and MMP-9 expression and activation in human dermal fibroblasts by fucose and a fucose-rich polysaccharide.

Tissue loss during ageing and age-dependent pathologies are the result of a disturbed regulation of proteolytic activities. Elastase-type endopeptidases, especially MMP-2 and -9, play an important role in this respect. Dermal fibroblast cultures and skin explant cultures were used in order to measure the efficiency of fucose and fucose-rich polysaccharides to downregulate the elastase-type endopeptidase activity. Fucose and fucose-rich polysaccharides were shown to downregulate this elastase-type activity, the basic activity and also the hyaluronan or kappa-elastin-stimulated activity. In skin explant cultures, we could demonstrate that fucose and fucose-rich polysaccharides produced an inhibition of the activation of the pro-form to the active form of MMP-9. Here, we show that mono-, di-, oligo- and polysaccharides acting on the elastin-laminin receptor and/or on the fucose-mannose receptor are efficient inhibitors of such enzymes by downregulating elastase-type endopeptidase activity, both at the level of their biosynthesis and at the level of the activation of the pro-enzymes. Fucose and fucose-rich polysaccharide preparations were shown to be efficient modulators of MMP-2 and MMP-9, activity with potential therapeutic applications in age-related pathologies accompanied by tissue loss.

Child, Preschool↗
PubMedDate not supplied

Studies on skin aging. Preparation and properties of fucose-rich oligo- and polysaccharides. Effect on fibroblast proliferation and survival.

Skin aging represents an important chapter of connective tissue aging and concerns an organ of vital importance. Here we describe the preparation as well as the biological properties of fucose-rich oligo- and polysaccharides (FROPs), composed of polymers of a trisaccharide containing galactose, acetyl galacturonic acid and fucose, from the original high molecular weight bacterial polysaccharide (Fucogel), Solabia, France). Using endoglycosidases, oligo- and polysaccharides were prepared and characterized by physical and chemical procedures. The non-reducing end-groups comprise equal amounts of galactose and fucose. The here-described biological properties are: stimulation of cell proliferation of cultured human skin fibroblasts, protection of cells against ascorbate-induced cytotoxicity due to the release of reactive oxygen species (ROS). Properties elsewhere described concern the inhibition of matrix metallo-proteinases 2 and 9 (MMP-2 and MMP-9), their expression and activation. Using fluorescein isothiocyanate (FITC)-labeled polysaccharides, their interaction with cell membranes and also their penetration and accumulation in cells, especially in the cell nucleus could be demonstrated, probably via cell-membrane receptor-mediated mechanisms. We describe some of the symptoms of skin aging and show, that the here-described polysaccharide preparations are susceptible to slow down some of the cellular and molecular mechanisms involved, partly by the mediation of the above-mentioned receptors, partly by acting directly on the regulation of gene expression.

Ascorbic Acid↗
PubMed1994

Detection of pneumococcal polysaccharide antigens in the urine of patients with bacteraemic and non-bacteraemic pneumococcal pneumonia.

Countercurrent-immunoelectrophoresis (CIE) was used to detect pneumococcal capsular polysaccharide and C-polysaccharide (C-Ps) antigens in urine. The neutral capsular polysaccharides of types 7F and 14 were detected by coagglutination. We found pneumococcal polysaccharide in urine with the same frequency in two groups of patients, i.e. a non-bacteraemic pneumonia group (68%) and a group of patients with pneumococcal bacteraemia (66%). C-Ps was detected in the urine of two patients (4%) and, therefore, this test has no value in the diagnosis of pneumococcal infections. Since there is no sensitive, non-invasive, single procedure for the diagnosis of non-bacteraemic pneumococcal pneumonia we conclude that attempts to detect pneumococcal capsular polysaccharide by CIE in combination with coagglutination (types 7F and 14) may be a useful diagnostic supplement in the search for the etiological agent in pneumonia in adults until new, more sensitive diagnostic methods have been developed.

Adult↗
PubMed1994

Expression of capsular polysaccharide determines serum resistance in Escherichia coli K92.

The amount of capsular polysaccharide expression has been shown to be the major determinant of serum resistance in Escherichia coli K1. E. coli K92, like K1, is a polymer of sialic acid molecules. It differs from K1 by containing both alpha (2.8) and alpha (2.9) linkages. Four strains of E. coli K92 were tested for serum resistance. Three strains were serum-resistant (50% normal human serum), one strain was moderately serum-sensitive. The serum-resistant strains expressed significantly more capsular polysaccharide than did the serum-sensitive strain. For each of the serum-resistant strains, six mutants were isolated by selection for resistance against infection with a K92-specific bacteriophage. All of the mutants expressed less capsular polysaccharide than the respective wild-type strains. All mutants were more sensitive to serum killing than the wild-type strains. In all groups, the mutants with lowest expression of capsular polysaccharide were highly serum-sensitive. Changes of outer membrane proteins or lipopolysaccharide patterns that were present in some mutants did not correlate with serum resistance properties of the mutants. Furthermore, it was investigated whether the presence of active serum had an influence on capsule expression. In the serum-sensitive strain, the presence of serum induced a significant and concentration-dependent increase of capsule expression. Serum had no effect on capsule expression by the serum-resistant strains. We conclude from the data that the expression of K92 capsular polysaccharide determines serum resistance in the strains examined.

Bacterial Capsules↗
PubMed1998

X-ray diffraction of food polysaccharides.

The morphologies of food polysaccharides described in this chapter illustrate the power of x-ray fiber diffraction in conjunction with computer modeling and sophisticated refinement techniques. On the other hand, the lack of information on structures such as xanthan reflects the inadequacy of the experimental techniques used to date. But the demands from academic and industrial sectors to investigate the molecular interactions in multicomponent systems, including protein-protein, protein-polysaccharide, polysaccharide-polysaccharide, and other complexes, are high and growing, because they have important food applications. These complexes are structurally more difficult than those solved in the past 40 years and it is improbable that any chosen system will be amenable for crystallographic investigation, crystals or fibers. Modern research facilities that include two-dimensional area detectors, millisecond exposures with synchrotron x-ray radiation, interactive computer graphics, sophisticated molecular dynamics calculations, unbelievably fast and inexpensive computers, and our own intellectual abilities are indispensable tools for the future of structural science in general and food polysaccharides in particular.

Carbohydrate Conformation↗
PubMed1990

Influence of larval schistosomes on polysaccharide synthesis in albumin glands of Biomphalaria glabrata.

An in vitro bioassay was used to examine [14C]glucose incorporation into polysaccharides in albumen glands (AGs) of susceptible M-line Biomphalaria glabrata infected with the NMRI strain of Schistosoma mansoni. Polysaccharide and galactogen synthesis were unaffected by larval trematode infection in AGs of snails at days 14, 21, and 28 post-infection (p.i.) when compared to uninfected controls. Further experiments were conducted to determine if daughter sporocysts, hypothesized to be primary mediators of parasitic castration in this system, were able to exert direct effects on synthetic activity of uninfected AGs via haemolymph-borne molecules or in vitro culture-generated larval excretory-secretory (ES) products. When AGs were incubated in the presence of infected snail haemolymph, significant differences in quantities of polysaccharides and galactogen were detected only in test organs incubated in day 28 p.i. haemolymph. Daughter sporocyst ES products generated during the first 48 h of culture caused a significant reduction in polysaccharide and galactogen synthesis in test organs. When ES products from days 3 to 6 of in vitro culture were tested similarly, no significant differences in either polysaccharide or galactogen synthesis were observed between control and test organs. These data demonstrate that daughter sporocysts are able to modulate a specific aspect of the reproductive activity of the snail host through haemolymph-borne molecules of host or parasite origin, or directly through in vitro culture-generated ES products.

Analysis of Variance↗
PubMed2004

LC/MS characterization of meningococcal depolymerized polysaccharide group C reducing endgroup and internal repeating unit.

Hydrogen peroxide has been used to cleave the native Neisseria meningiditis polysaccharide (PS) from mega-Dalton molecular weight to a smaller size (approximately 20 kDa) depolymerized polysaccharide. The polysaccharide was examined after partial peroxide depolymerization to verify the presence of the carboxyl group at position 1 and the intactness of the internal sialic acid repeating units. The reducing end group of meningococcal polysaccharide type C was also examined after derivatization by L-tyrosine hydrazide. Partial peroxide depolymerization did not result in loss of the position 1 carboxyl group at the reducing end of the polysaccharide. In addition, no loss of structural integrity was noted for the internal sialic repeat units.

Carboxylic Acids↗
PubMedDate not supplied

Synthesis of ultrasmall superparamagnetic iron oxides using reduced polysaccharides.

Investigation into the effect of the reducing sugar of dextran on formation and stability of dextran-coated ultrasmall superparamagnetic iron oxides (USPIO) has demonstrated that reduction of the terminal reducing sugar can have a significant effect on particle size, coating stability, and magnetic properties. Four aspects of polysaccharide-coated USPIO particle synthesis were investigated: (i) the effect reduction of the terminal polysaccharide sugar has upon polysaccharide usage, particle size, stability, and magnetic susceptibility; (ii) the effect an exogenous reducing sugar can have upon particle synthesis; (iii) the effect the molecular weight of the reduced polysaccharide has on particle synthesis; and (iv) the effectiveness of reduced and native dextrans in stabilizing a preformed magnetic sol. For low molecular weight dextrans (MW 20,000 x 10(-6) cgs). Similar results were obtained with a 12 kDa pullulan. The effect of polysaccharide molecular weight on particle size was studied, wherein higher molecular weight reduced dextrans produced larger particles. The effectiveness of the reduced and native dextrans in stabilizing a preformed magnetic sol was compared. Reduced dextrans were found to be superior for stabilizing the magnetic sol. The observed effects of reduction of the terminal sugar in dextran compared with the native dextran were modeled using the Langmuir adsorption isotherm. A good fit of experimental data with this model was found.

Dextrans↗