Polycationic peptides from diatom biosilica that direct silica nanosphere formation.
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Diatom cell walls are regarded as a paradigm for controlled production of nanostructured silica, but the mechanisms allowing biosilicification to proceed at ambient temperature at high rates have remained enigmatic. A set of polycationic peptides (called silaffins) isolated from diatom cell walls were shown to generate networks of silica nanospheres within seconds when added to a solution of silicic acid. Silaffins contain covalently modified lysine-lysine elements. The first lysine bears a polyamine consisting of 6 to 11 repeats of the N-methyl-propylamine unit. The second lysine was identified as epsilon-N,N-dimethyl-lysine. These modifications drastically influence the silica-precipitating activity of silaffins. (+info)
Review article: alginate-raft formulations in the treatment of heartburn and acid reflux.
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Alginate-based raft-forming formulations have been marketed word-wide for over 30 years under various brand names, including Gaviscon. They are used for the symptomatic treatment of heartburn and oesophagitis, and appear to act by a unique mechanism which differs from that of traditional antacids. In the presence of gastric acid, alginates precipitate, forming a gel. Alginate-based raft-forming formulations usually contain sodium or potassium bicarbonate; in the presence of gastric acid, the bicarbonate is converted to carbon dioxide which becomes entrapped within the gel precipitate, converting it into a foam which floats on the surface of the gastric contents, much like a raft on water. Both in vitro and in vivo studies have demonstrated that alginate-based rafts can entrap carbon dioxide, as well as antacid components contained in some formulations, thus providing a relatively pH-neutral barrier. Several studies have demonstrated that the alginate raft can preferentially move into the oesophagus in place, or ahead, of acidic gastric contents during episodes of gastro-oesophageal reflux; some studies further suggest that the raft can act as a physical barrier to reduce reflux episodes. Although some alginate-based formulations also contain antacid components which can provide significant acid neutralization capacity, the efficacy of these formulations to reduce heartburn symptoms does not appear to be totally dependent on the neutralization of bulk gastric contents. The strength of the alginate raft is dependant on several factors, including the amount of carbon dioxide generated and entrapped in the raft, the molecular properties of the alginate, and the presence of aluminium or calcium in the antacid components of the formulation. Raft formation occurs rapidly, often within a few seconds of dosing; hence alginate-containing antacids are comparable to traditional antacids for speed of onset of relief. Since the raft can be retained in the stomach for several hours, alginate-based raft-forming formulations can additionally provide longer-lasting relief than that of traditional antacids. Indeed, clinical studies have shown Gaviscon is superior to placebo, and equal to or significantly better than traditional antacids for relieving heartburn symptoms. Alginate-based, raft-forming formulations have been used to treat reflux symptoms in infants and children, and in the management of heartburn and reflux during pregnancy. While Gaviscon is effective when used alone, it is compatible with, and does not interfere with the activity of antisecretory agents such as cimetidine. Even with the introduction of new antisecretory and promotility agents, alginate-rafting formulations will continue to have a role in the treatment of heartburn and reflux symptoms. Their unique non-systemic mechanism of action provides rapid and long-duration relief of heartburn and acid reflux symptoms. (+info)
Accumulation of a polyisoprene-linked amino sugar in polymyxin-resistant Salmonella typhimurium and Escherichia coli: structural characterization and transfer to lipid A in the periplasm.
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Polymyxin-resistant mutants of Escherichia coli and Salmonella typhimurium accumulate a novel minor lipid that can donate 4-amino-4-deoxy-l-arabinose units (l-Ara4N) to lipid A. We now report the purification of this lipid from a pss(-) pmrA(C) mutant of E. coli and assign its structure as undecaprenyl phosphate-alpha-l-Ara4N. Approximately 0.2 mg of homogeneous material was isolated from an 8-liter culture by solvent extraction, followed by chromatography on DEAE-cellulose, C18 reverse phase resin, and silicic acid. Matrix-assisted laser desorption ionization/time of flight mass spectrometry in the negative mode yielded a single species [M - H](-) at m/z 977.5, consistent with undecaprenyl phosphate-alpha-l-Ara4N (M(r) = 978.41). (31)P NMR spectroscopy showed a single phosphorus atom at -0.44 ppm characteristic of a phosphodiester linkage. Selective inverse decoupling difference spectroscopy demonstrated that the undecaprenyl phosphate group is attached to the anomeric carbon of the l-Ara4N unit. One- and two-dimensional (1)H NMR studies confirmed the presence of a polyisoprene chain and a sugar moiety with chemical shifts and coupling constants expected for an equatorially substituted arabinopyranoside. Heteronuclear multiple-quantum coherence spectroscopy analysis demonstrated that a nitrogen atom is attached to C-4 of the sugar residue. The purified donor supports in vitro conversion of lipid IV(A) to lipid II(A), which is substituted with a single l-Ara4N moiety. The identification of undecaprenyl phosphate-alpha-l-Ara4N implies that l-Ara4N transfer to lipid A occurs in the periplasm of polymyxin-resistant strains, and establishes a new enzymatic pathway by which Gram-negative bacteria acquire antibiotic resistance. (+info)
A novel fluorescent silica tracer for biological silicification studies.
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BACKGROUND: Biological silica production has drawn intense attention and several molecules involved in biosilicification have been identified. Cellular mechanisms, however, remain unknown mainly due to the lack of probes required for obtaining information on live specimens. RESULTS: The fluorescence spectra of the compound 2-(4-pyridyl)-5-((4-(2-dimethylaminoethylaminocarbamoyl)methoxy)phenyl)oxazole (PDMPO) are affected by the presence of >3.2 mM silicic acid. Increase in intensity and shift in the fluorescence coincide with the polymerization of Si. The unique PDMPO-silica fluorescence is explored here to visualize Si deposition in living diatoms. The fluorophore is selectively incorporated and co-deposited with Si into the newly synthesized frustules (the outer silica shells) showing an intense green fluorescence. CONCLUSIONS: We suggest that a fluorescence shift is due to an interaction between PDMPO and polymeric silicic acid. PDMPO is an excellent probe for imaging newly deposited silica in living cells and has also a potential for a wide range of applications in various Si-related disciplines, including biology of living organisms as diatoms, sponges, and higher plants, clinical research (e.g. lung fibrosis and cancer, bone development, artificial bone implantation), and chemistry and physics of materials research. (+info)
Aluminum-dependent regulation of intracellular silicon in the aquatic invertebrate Lymnaea stagnalis.
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Silicon is essential for some plants, diatoms, and sponges but, in higher animals, its endogenous regulation has not been demonstrated. Silicate ions may be natural ligands for aluminum and here we show that, in the freshwater snail (Lymnaea stagnalis), intracellular silicon seems specifically up-regulated in response to sublethal aluminum exposure. X-ray microanalysis showed that exposure of snails to low levels of aluminum led to its accumulation in lysosomal granules, accompanied by marked up-regulation of silicon. Increased lysosomal levels of silicon were a specific response to aluminum because cadmium and zinc had no such effect. Furthermore, intra-lysosomal sulfur from metallothionein and other sulfur-containing ligands was increased after exposure to cadmium and zinc but not aluminum. To ensure that these findings indicated a specific in vivo response, and not ex vivo formation of hydroxy-aluminosilicates (HAS) from added aluminum (555 microg/liter) and water-borne silicon (43 microg/liter), two further studies were undertaken. In a ligand competition assay the lability of aluminum (527 microg/liter) was completely unaffected by the presence of silicon (46 microg/liter), suggesting the absence of HAS. In addition, exogenous silicon (6.5 mg/liter), added to the water column to promote formation of HAS, caused a decrease in lysosomal aluminum accumulation, showing that uptake of HAS would not explain the loading of aluminum into lysosomal granules. These findings, and arguments on the stability, lability, and kinetics of aluminum-silicate interactions, suggest that a silicon-specific mechanism exists for the in vivo detoxification of aluminum, which provides regulatory evidence of silicon in a multicellular organism. (+info)
A phase separation model for the nanopatterning of diatom biosilica.
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Diatoms are encased in an intricately patterned wall that consists of amorphous silica. Species-specific fabrication of this ornate biomineral enables taxonomists to identify thousands of diatom species. The molecular mechanisms that control this nanofabrication and generate the diversity of patterns is not well understood. A simple model is described, in which repeated phase separation events during wall biogenesis are assumed to produce self-similar silica patterns in smaller and smaller scales. On the basis of this single assumption, the apparently complex patterns found in the valves of the diatom genus Coscinodiscus can be predicted. Microscopic analysis of valves in statu nascendi from three different Coscinodiscus species supports the conclusions derived from the model. (+info)
Simple procedure for the removal of nonspecific inhibitors of rubella virus hemagglutination.
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The adsorption of serum lipoproteins onto an insoluble matrix of colloidal silicic acid results in the removal of nonspecific inhibitors of rubella virus hemagglutinin. The procedure can be performed in 15 min at room temperature. Comparative studies using both the dextran sulfate-CaCl2 and heparin-MnCl2 methods for removal of inhibitors demonstrated that the colloidal silicic acid procedure yielded identical hemagglutination inhibition titers. In addition, it is technically feasible to read titers below 1:8. (+info)
Pantoprazole maintenance therapy prevents relapse of erosive oesophagitis.
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OBJECTIVES: To compare the safety and efficacy of pantoprazole with ranitidine for the maintenance of endoscopically documented healed (grade 0 or 1) erosive oesophagitis. METHODS: Patients (371) were randomly assigned to receive pantoprazole 10, 20 or 40 mg or ranitidine 150 mg. Endoscopies were performed after 1, 3, 6 and 12 months or when symptoms suggesting relapse (grade = 2) developed. Gastric biopsies were obtained at baseline and on at least one postbaseline visit. Symptom-free days and Gelusil use were assessed. RESULTS: Pantoprazole was significantly (P < 0.001) more effective in maintaining erosive oesophagitis healing. After 12 months, 33%, 40%, 68% and 82% of patients remained healed for the ranitidine and pantoprazole 10, 20 and 40 mg groups, respectively. Daytime and night-time heartburn were eliminated in > 90% of days for the pantoprazole 40 mg group. Gelusil use was significantly lower with pantoprazole 20 and 40 mg than with ranitidine (P < 0.02) during the first 9 months. CONCLUSIONS: Twelve months of maintenance therapy with pantoprazole (10-40 mg once daily) was superior to ranitidine (150 mg twice daily) in maintaining erosive oesophagitis healing. Pantoprazole 40 mg provided the most consistent efficacy and was well tolerated. (+info)