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Randomized, multicentre comparison of sodium alginate and cisapride in the symptomatic treatment of uncomplicated gastro-oesophageal reflux.

AIM: To assess the efficacy and tolerance of sodium alginate compared to cisapride in patients suffering from reflux symptoms, without severe oesophagitis. METHODS: A total of 353 patients with symptoms of reflux oesophagitis (average age 40 years, 51% men, 33% smokers, 43% consumers of alcoholic drinks) were selected at random--180 treated with sodium alginate (4 sachets per day) and 173 treated with cisapride (5 mg four times a day) for 1 month, with a consultation every 2 weeks. Patients with severe oesophagitis or with predominant symptoms of motor dyspepsia were not included. The principal assessment criterion was the change in the severity of the reflux symptoms as evaluated using a visual analogue scale (VAS) at 4 weeks (extremes 0-100). The secondary criteria were the VAS score at 2 weeks, the number of patients considered as treatment failures, the number of episodes of pain, the impact of the reflux on daily activities and on sleep, and an estimate of costs. The statistical analyses were planned without any knowledge of the treatments allocated and on an intention-to-treat basis. RESULTS: There was no difference between the groups at the time of randomization. There were differences in the VAS in favour of the alginate at 2 weeks (29 +/- 22 vs. 35 +/- 25, P = 0.01) at 4 weeks (13 +/- 17 vs. 20 +/- 23, P = 0.001), for the number of episodes at 4 weeks (2 +/- 2 vs. 3 +/- 4, P = 0.001), for pain interfering with daily activities (3% vs. 10%, P = 0.009), for pain disturbing sleep (2% vs. 9%, P = 0.004), and for the proportion of patients considered as treatment failures (11% vs. 24%, P < 0.001). Compliance was similar in the two groups. The average cost for 1 month was lower for alginate (130 fr.) than for cisapride (175 fr.). CONCLUSION: Sodium alginate is more effective, and costs less, than cisapride for the treatment of symptoms presented by patients suffering from reflux without severe oesophagitis.

Adult↗

Real-time PCR used to measure stress-induced changes in the expression of the genes of the alginate pathway of Pseudomonas aeruginosa.

AIMS: To measure the concentration of mRNAs transcribed from four genes involved in alginate production using real-time PCR. METHODS AND RESULTS: The mRNA concentrations in cells grown in normal and stress conditions were compared. A difference in the expression of algD, the key gene leading to overproduction of alginate, was detected between alginate-producing and non-alginate-producing strains grown under normal conditions. After growth on 3% ethanol (known to stimulate alginate production), but not after heat-shock, an increase in algD mRNA levels and a corresponding decrease in mucB (a regulatory gene) mRNA levels were detected in all strains. CONCLUSION: The quantitative results suggest that the mucB gene may have a role in recognition of stress conditions, and that having a disrupted mucA gene does not always result in a mucoid phenotype. SIGNIFICANCE AND IMPACT OF THE STUDY: Real-time PCR can be used to quantify mRNA and is a convenient method of analysing bacterial gene expression.

Alginates↗

TNF production from peripheral blood mononuclear cells in diabetic patients after stimulation with alginate and lipopolysaccharide.

Microencapsulated pancreatic Langerhans islets in calcium alginate gels have been used as an implantable bio-artificial pancreas in the treatment of diabetes mellitus, but with limited success due to overgrowth of the capsule with fibroblasts and phagocytes. The authors earlier demonstrated that alginates enriched in mannuronic acid stimulate human monocytes to produce high levels of cytokines such as tumour necrosis factor (TNF), IL-1 IL-6. In this study the authors have measured the TNF production from peripheral blood mononuclear cells (PBMC) in different groups of insulin-dependent diabetes mellitus (IDDM) patients after stimulation with different alginates and lipopolysaccharide (LPS). It was found that high G-alginate did not induce TNF production in any of the groups. High-M alginate and LPS induced a dose-dependent TNF production in all groups and the production was significantly different from unstimulated cells. The highest TNF response was found in newly diagnosed IDDM patients and the lowest was in the controls.

Adolescent↗

Iloprost in alginate decreases the thrombogenicity of expanded polytetrafluoroethylene.

Vascular prostheses of small diameter perform poorly in vivo, in part because of the high thrombogenicity of available biomaterials. This study examined the thrombogenicity of expanded polytetrafluoroethylene (ePTFE) vascular graft segments (10 mm long x 4 mm i.d.) in vitro before and after impregnation with saline, alginate, or alginate containing the stable prostacyclin analog, iloprost. Each segment was immersed in activated whole blood and the weight of the adherent thrombus was measured at specified intervals. At 6 and 7 min the saline-denucleated group accumulated significantly less thrombus than control (p < .05). Alginate alone was not significantly different from controls. The graft segments treated with alginate + iloprost accumulated significantly less thrombus (p < .05) than all other groups after 6 min. These data demonstrate that denucleation of ePTFE with iloprost in alginate dramatically decreases its in vitro thrombogenicity.

Alginates↗

The Pseudomonas syringae genome encodes a combined mannuronan C-5-epimerase and O-acetylhydrolase, which strongly enhances the predicted gel-forming properties of alginates.

Alginates are industrially important, linear copolymers of beta-d-mannuronic acid (M) and its C-5-epimer alpha-l-guluronic acid (G). The G residues originate from a postpolymerization reaction catalyzed by mannuronan C-5-epimerases (MEs), leading to extensive variability in M/G ratios and distribution patterns. Alginates containing long continuous stretches of G residues (G blocks) can form strong gels, a polymer type not found in alginate-producing bacteria belonging to the genus Pseudomonas. Here we show that the Pseudomonas syringae genome encodes a Ca(2+)-dependent ME (PsmE) that efficiently forms such G blocks in vitro. The deduced PsmE protein consists of 1610 amino acids and is a modular enzyme related to the previously characterized family of Azotobacter vinelandii ME (AlgE1-7). A- and R-like modules with sequence similarity to those in the AlgE enzymes are found in PsmE, and the A module of PsmE (PsmEA) was found to be sufficient for epimerization. Interestingly, an R module from AlgE4 stimulated Ps-mEA activity. PsmE contains two regions designated M and RTX, both presumably involved in the binding of Ca(2+). Bacterial alginates are partly acetylated, and such modified residues cannot be epimerized. Based on a detailed computer-assisted analysis and experimental studies another PsmE region, designated N, was found to encode an acetylhydrolase. By the combined action of N and A PsmE was capable of redesigning an extensively acetylated alginate low in G from a non gel-forming to a gel-forming state. Such a property has to our knowledge not been previously reported for an enzyme acting on a polysaccharide.

Alginates↗

Dietary effects of propylene glycol alginate in humans.

Following a 7-day control period, five male volunteers consumed a weight of propylene glycol alginate corresponding to 175 mg/kg body weight for 7 days, followed by 200 mg propylene glycol alginate per kg body weight for a further 16 days. Measurements before and at the end of the 23-day period of dietary supplementation showed that propylene glycol alginate had little effect on faecal parameters (pH, water content, daily wet and dry weights). The dietary transit time remained constant for three volunteers, increased for one, and decreased for one. The ingestion of propylene glycol alginate had no significant effect on (a) haematological indices, (b) plasma biochemistry parameters, (c) urinalysis parameters, (d) blood glucose and plasma insulin concentrations, (e) breath hydrogen concentrations. No allergic responses were reported by, nor observed in, any of the volunteers. The study therefore indicates that the ingestion of propylene glycol alginate at a high level for 23 days caused no adverse dietary or physiological effects; in particular, the enzymatic and other sensitive indicators of adverse toxicological effects remained unchanged.

Adult↗

Dietary effects of sodium alginate in humans.

Following a 7-day control period, five male volunteers consumed a weight of sodium alginate corresponding to 175 mg/kg body weight for 7 days, followed by 200 mg sodium alginate per kg body weight for a further 16 days. Measurements before and at the end of the 23-day period of dietary supplementation showed that sodium alginate acted as a faecal bulking agent for all volunteers, giving a significant (p less than 0.01) increase in daily wet weight, and also increases in the water content and daily dry weight, but no change in faecal pH. Although the dietary transit time remained constant for two volunteers, it decreased for two, and increased slightly for one, with little resulting change in the overall mean value. The ingestion of sodium alginate had no significant effect on (a) haematological indices, (b) plasma biochemistry parameters, (c) urinalysis parameters, (d) blood glucose and plasma insulin concentrations, (e) breath hydrogen concentrations. No allergic responses were reported by, nor observed in, any of the volunteers. The study therefore indicates that the ingestion of sodium alginate at a high level for 23 days caused no effects other than those normally associated with a polysaccharide bulking agent; in particular, the enzymatic and other sensitive indicators of adverse toxicological effects remained unchanged.

Adult↗

Evaluation of protein release from chitosan-alginate microcapsules produced using external or internal gelation.

A series of experiments was undertaken to evaluate the diffusion of a model protein, i.e. bovine serum albumin (BSA), from chitosan-alginate microcapsules produced using either internal or external gelation. Diffusion of BSA was quantified during the microcapsule manufacture processes (gelation, washing, rinsing) and during incubation in conditions simulating the pH encountered during the gastric and intestinal phases of digestion. Encapsulation of an acid phosphmonoesterase permitted in situ protein localization, providing evidence to explain results obtained with BSA. There was significantly greater protein loss from internally versus externally-gelled chitosan-alginate microcapsules during the manufacture process (37.6% versus 4.7%, respectively). Similar trends were observed during 24 h incubation in 0.1 N hydrochloric acid. Increasing alginate concentration from 2-4% (w:v) did not significantly reduce losses from internally-gelled microcapsules. Addition of 0.25 M NaCl to the gelling medium significantly increased protein diffusing during microcapsule manufacture and acid incubation from externally gelled microcapsules. In situ protein localization revealed a higher level of protein near the surface of the microcapsules of externally gelled microcapsules versus internal gelation. The above data indicate that externally-gelled microcapsules are inhomogeneous with a higher concentration of alginate near the microcapsule surface, thus reducing the porosity of the resulting microcapsules. These results suggest that the porous nature of internally-gelled chitosan-alginate microcapsules may result in low encapsulation efficiency, depending on the nature of the product being encapsulated.

Alginates↗

Effects of alginate coated on PLGA microspheres for delivery tetracycline hydrochloride to periodontal pockets.

The effects of alginate coated on tetracycline (Tc) loaded poly (D, L-lactic-co-glycolic acid) (PLGA) microspheres fabricated by double emulsion solvent evaporation technique for local delivery to periodontal pocket were investigated. Alginate coated PLGA microspheres showed smoother surface but enlarged their particle sizes compared with those of uncoated ones. In addition, alginate coated microspheres enhanced Tc encapsulation efficiency (E.E.) from 11.5 +/- 0.5% of uncoated ones to 17.9 +/- 0.5%. Moreover, all of the coated PLGA microspheres even fabricated at different conditions could prolong Tc release from 9-12 days with 50% or higher in cumulative release of Tc compared with those of uncoated ones. The swelling ratios of PLGA microspheres for alginate coated or uncoated ones, one of the possible mechanisms for enhancing Tc release for the coated ones, were measured. The results showed that 20% or higher in swelling ratio for the coated microspheres at the earlier stage of hydration (e.g. < or = 24 h) could be an important factor to result in high Tc release compared to the uncoated ones. In conclusion, alginate coated Tc loaded PLGA microspheres could enhance Tc delivery to periodontal pocket by enhancing drug encapsulated efficiency, released quantities and sustained release period compared with uncoated ones.

Alginates↗

Application of self-assembled ultra-thin film coatings to stabilize macromolecule encapsulation in alginate microspheres.

Alginate-based hydrogels have several unique properties that have enabled them to be used as a matrix for the entrapment of a variety of enzymes, proteins and cells for applications in bioprocessing, drug delivery and chemical sensing. However, control over release rates or, in some cases, stable encapsulation remains a difficult goal, especially for small particles with high surface-area-to-volume ratios. In this work, the potential to limit diffusion of macromolecules embedded in alginate spheres with nanofilm coatings was assessed. Alginate microspheres were fabricated using an emulsification process with high surfactant concentration to form beads in the size range of 2-10 microm. Using calcium chloride for ionotropic gelation, dextran was encapsulated in the gel phase by mixing with the alginate in solution. The exterior surface was then modified with polyelectrolyte coatings using the layer-by-layer self assembly technique. Leaching studies to assess retention of dextran with varying molecular weights confirmed that the application of multi-layer thin films to the alginate microspheres was effective in reducing leaching rate and total loss of the encapsulated material from the microspheres. For the best case, the rate of release for dextran of 2,000,000 Dalton molecular weight decreased from 1% h(-1) in bare microspheres to 0.1% h(-1) in polyelectrolyte-coated microspheres. The effectiveness of nanofilms reducing loss of the encapsulated macromolecules was found to vary between different polycation materials used. These studies support the feasibility of using these microsystems for development of long-term stable encapsulated systems, such as implantable biosensors.

Alginates↗

Lead absorption and excretion in rats given insoluble salts of pectin and alginate.

Exposure to environmental lead remains a widespread problem in most industrialized countries. Usage of modern agents purposed for elimination of heavy metals as well as for therapy and prevention of chronic poisoning does frequently result in toxic signs. Dietary nonstarch polysaccharides were suggested to be effective when used for this purpose. The present study was conducted to estimate metal binding capacity and effects of calcium salts of pectate and alginate on lead absorption, distribution, and removal with feces. Under in vitro conditions calcium alginate showed the highest lead-binding capacity in comparison with other agents studied. Metal binding capacity of calcium pectate was slightly lower. In rats simultaneous administration of lead acetate and suspensions containing calcium alginate or calcium pectate prevented metal absorption and significantly reduced lead accumulation in inner organs and femur. In experiments estimating lead removal from inner organs and femur in rats preliminary exposed to the heavy metal, calcium alginate and calcium pectate were the most effective agents studied in comparison with others, as indicated by reduced lead concentration in organs and femur as well as increased metal content in feces of laboratory animals. The results suggest that calcium pectate and calcium alginate may be considered perspective dietary compounds purposed for prevention and treatment of chronic lead poisoning.

Adsorption↗

A preliminary investigation of modified alginates as a matrix for gene transfection in a HeLa cell model.

Previous reports have demonstrated the effectiveness of chitosan as a transfection agent. These studies have noted the importance of polysaccharide backbone interactions with the cell surface as well as cationic groups in the transfection process. The present study focuses upon the potential utility of another polysaccharide hydrogel, alginic acid, as a transfection agent. Alginic acid was modified by carbodiimide-mediated linkage of several heterocyclic and aromatic amines to the carboxyl group of the alginate, giving the alginate polycationic characteristics through which binding to nucleic acids could be facilitated. The amines used for this modification include diaminoacridine, thionin, basic fuchsin, acridine yellow, and diaminomethyltriazine. Of all the conjugates tested, basic fuchsin-modified alginate produced the greatest increase in the transfection of a plasmid coding for beta-galactosidase into HeLa cells. These studies demonstrate that other polysaccharide hydrogels can be used as transfection agents, and the structural orientation of the cationic spacer arm is crucial for effective transfection.

Alginates↗

Sciatic nerve regeneration through alginate with tubulation or nontubulation repair in cat.

A novel material for nerve regeneration, alginate, was employed in both tubulation and nontubulation repair of a long peripheral nerve defect injury. Twelve cats underwent severing of the right sciatic nerve to generate a 50-mm gap, which was treated by tubulation repair (n = 6) or nontubulation repair (n = 6). In the tubulation group, a nerve conduit consisting of polyglycolic acid mesh tube filled with alginate sponge was implanted into the gap and the tube was sutured to both nerve stumps. In the nontubulation group, the nerve defect was repaired by a simple interpolation of two pieces of alginate sponge without any suture. The animals in both groups exhibited similar recovery of locomotor function. Three months postoperatively, successful axonal elongation and reinnervation in both the afferent and efferent systems were detected by electrophysiological examinations. Intracellular electrical activity was also recorded, which is directly indicative of continuity of the regenerated nerve and restoration of the spinal reflex circuit. Eight months after operation, many regenerated myelinated axons with fascicular organization by perineurial cells were observed within the gap, peroneal and tibial branches were found in both groups, while no alginate residue was found within the regenerated nerves. In morphometric analysis of the axon density and diameter, there were no significant differences between the two groups. These results suggest that alginate is a potent material for promoting peripheral nerve regeneration. It can also be concluded that the nontubulation method is a possible repair approach for peripheral nerve defect injury.

Alginates↗

Effect of oxygen tension and alginate encapsulation on restoration of the differentiated phenotype of passaged chondrocytes.

The implantation of laboratory-grown tissue offers a valuable alternative approach to the treatment of cartilage defects. Procuring sufficient cell numbers for such tissue-engineered cartilage is a major problem since amplification of chondrocytes in culture typically leads to loss of normal cell phenotype yielding cartilage of inferior quality. In an effort to overcome this problem, we endeavored to regain the differentiated phenotype of chondrocytes after extensive proliferation in monolayer culture by modulating cell morphology and oxygen tension towards the in vivo state. Passaged cells were encapsulated in alginate hydrogel in an effort to regain the more rounded shape characteristic of differentiated chondrocytes. These cultures were exposed to reduced (5%-i.e., physiological), or control (20%) oxygen tensions. Both alginate encapsulation and reduced oxygen tension significantly upregulated collagen II and aggrecan core protein expression (differentiation markers). In fact, after 4 weeks in alginate at 5% oxygen, differentiated gene expression was comparable to primary chondrocytes. Collagen I expression (dedifferentiation marker) decreased dramatically after alginate entrapment, while reduced oxygen tension had no effect. It is concluded that alginate encapsulation and reduced oxygen tension help restore key differentiated phenotypic markers of passaged chondrocytes. These findings have important implications for cartilage tissue engineering, since they enable the increase in differentiated cell numbers needed for the in vitro development of functional cartilaginous tissue suitable for implantation.

Alginates↗

Studies on the ability of alginate to act as a protective immunogen against infection with Pseudomonas aeruginosa in animals.

Most patients with cystic fibrosis become colonized and infected with mucoid Pseudomonas aeruginosa. The major component of the mucoid material has been identified as the polysaccharide alginic acid. The present work was undertaken to determine whether antibody to alginate is protective in a model of chronic lung infection with P. aeruginosa in rats. Bacterial clearance was associated with a rise in titers of antibody to alginate. In a number of animals a rise in antibody titers was not seen, and in fact a decrease was noted at 30 days compared with 10 days. This observation suggested the possibility of immune complex formation due to antigen excess. Evidence for immune complex deposition in tissues was obtained by immunofluorescence studies. Thus antibody to alginate may offer strain-dependent protection against chronic lung infection with P. aeruginosa in rats; however, immune complex formation should be considered as a possible consequence of immunization with alginate.

Alginates↗

The inhibitory effect of sodium alginate on antibiotic activity against mucoid and non-mucoid strains of Pseudomonas aeruginosa.

The exopolysaccharide of mucoid strains of Pseudomonas aeruginosa (MPA) is chemically similar to alginate, a common polysaccharide of seaweeds. Both polymers have been reported to decrease the diameter of the inhibition zones produced in antibiotic disc diffusion assays. In order to determine whether this phenomenon was due to reduced diffusion of the antibiotic in an agar matrix, or to inhibition of antibiotic activity by sodium alginate, we studied the effect of sodium alginate on the susceptibility of P. aeruginosa strains to antibiotics in disc diffusion assays, as well as in broth and agar dilution assays. Sodium alginate decreased the activity of the aminoglycoside antibiotics, amikacin and gentamicin, against two MPA strains and their non-mucoid derivatives in each of the assays. In broth dilution assays, increase of the calcium ion concentration likewise reduced aminoglycoside activity against P. aeruginosa, but not against Escherichia coli and Staphylococcus aureus. Sodium alginate caused no inhibition of the activity of piperacillin and carbenicillin. The reduction of aminoglycoside activity may have implications for the common failure of these antibiotics in the treatment of pulmonary infections caused by MPA in cystic fibrosis patients, but must be considered only an in-vitro phenomenon at present.

Alginates↗

Regeneration of transected spinal cord in young adult rats using freeze-dried alginate gel.

We have recently reported that freeze-dried alginate gel, which was developed in our laboratory, enhanced peripheral nerve regeneration. The purpose of this study was to examine whether alginate gel is capable of promoting nerve regeneration in the severed spinal cord of adult mammals. Using Wistar rats at 30 days of age (P30), the T9-T10 spinal cord was totally resected and alginate gel was implanted across the gap. Forty-five days after surgery myelinated and unmyelinated axons regenerated throughout the gap with remaining alginate gel. The elongated axons established electrophysiologically functional projections across the gap. In conclusion, freeze-dried alginate gel could be a promising material as an artificial nerve guide for repair of injured central nervous system.

Alginates↗

Evaluation of calcium alginate for skin graft donor sites.

Choosing the most appropriate wound dressing is of importance in optimizing healing and minimizing pain. Recent reports have suggested an improvement in wound healing with calcium alginate. To clinically evaluate this new dressing, 12 paired wounds were covered with either calcium alginate or scarlet red in seven patients with burns undergoing skin grafting. The rate of reepithelialization was assessed by optical planimetry for the calcium alginate and by time for sloughing of the scarlet red. This comparison failed to demonstrate objectively any difference in the rate of wound healing between these dressings; however, calcium alginate did significantly reduce the pain severity and was favored by the nursing personnel because of its ease of care. Thus calcium alginate does appear to have clinical advantages as a dressing for skin graft donor sites.

Alginates↗