Low Molecular Weight Sodium Alginate Research Articles

Dietary Sodium Alginate Effect on Growth, Digestion, Body Composition, Antioxidant Capacity, and Mucous Immune Response in Yellowfin Sea Bream, Acanthopagrus latus

Abstract In the present study, the effects of dietary supplementation of low molecular weight sodium alginate on growth, body composition, anti-oxidant enzymes, digestive enzymes, and immune response in yellowfin sea bream juvenile (Acanthopagrus latus) were investigated. Fish (n=180) were divided into 3 groups with 3 replicates and received dietary treatments including basal diet without sodium alginate (control treatment), basal diet containing 5 g sodium alginate per kg diet (0.5% treatment), and 10 g sodium alginate per kg diet (1% treatment) for 8 weeks. The results showed that the final weight, weight gain, specific growth rate, condition factor, feed conversion, and protein efficiency ratios did not reveal a significant improvement compared to the control treatment (P>0.05). The obtained results indicated that dietary sodium alginate did not affect body composition (P>0.05). The activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in the groups fed on 0.5 and 1% sodium alginate showed a significant increase (P<0.05) compared to the control group. But, the activity of lipid peroxidation (MDA) in the groups fed on 0.5 and 1% sodium alginate showed a significant decrease (P<0.05) compared to the control group. The digestive enzymes increased significantly (P<0.05) by supplementation of sodium alginate, compared to the control group. Mucus lysozyme and complement activity were not significantly different (P>0.05). Overall, it can be concluded that feeding of yellowfin sea bream on the diet supplemented with 0.5 and 1 percent sodium alginate for a period of 8 weeks does not enhance the non-specific immune response and growth. Nonetheless, sodium alginate improved the activity of the antioxidant and digestive enzymes, indicating the positive effects of sodium alginate on enzymatic responses.

Does Dietary Sodium Alginate with Low Molecular Weight Affect Growth, Antioxidant System, and Haemolymph Parameters and Alleviate Cadmium Stress in Whiteleg Shrimp (Litopenaeus vannamei)?

Decreasing low molecular weight can improve the digestibility and availability of ingredients such as sodium alginate. This study aimed to test the four dosages of low molecular weight sodium alginate (LMWSA) (0%: Control, 0.05%: 0.5 LMWSA, 0.10%: 1.0 LMWSA, and 0.2%: 2.0 LMWSA) in whiteleg shrimp (Litopenaeus vannamei) (3.88 ± 0.25 g) for eight weeks. After finishing the trial, shrimp were exposed to cadmium (1 mg/L) for 48 h. While feed conversion ratio (FCR) improved in shrimp fed dietary 2.0 LMWSA (p < 0.05), there was no significant difference in growth among treatments. The results showed a linear relation between LMWSA level and FCR, and glutathione S-transferase (GST) before; and malondialdehyde (MDA), glutathione (GSH), GST, and alanine transaminase (ALT) after cadmium stress (p < 0.05). The GST, MDA, ALT, and aspartate transaminase (AST) contents were changed after stress but not the 2.0 LMWSA group. The survival rate after stress in 1.0 LMWSA (85.23%) and 2.0 LMWSA (80.20%) treatments was significantly higher than the Control (62.05%). The survival rate after stress negatively correlated with GST and ALT, introducing them as potential biomarkers for cadmium exposure in whiteleg shrimp. Accordingly, the 2.0 LMWSA treatment had the best performance in the abovementioned parameters. As the linear relation was observed, supplementing more levels of LMWSA to reach a plateau is recommended.

Preparation of low-molecular-weight sodium alginate by ozonation

Low-molecular-weight sodium alginate (LMWSA) has been reported to possess unique physicochemical properties and bioactivities. There is little information available about degradation of sodium alginate by ozonation. Effect of ozonation on molecular weight, molecular weight distribution, color change, M/G ratio, and chemical structure of sodium alginate was investigated. The molecular weight of sodium alginate decreased from 972.3 to 76.7 kDa in the 80-min period of ozonation at 25 °C. Two different degradation-rate constants were calculated. Molecular weight distribution of the LMWSA changed appreciably. Ozonation cannot lead to color change of LMWSA. The M/G ratio of LMWSA was not altered significantly, compared with that of the original alginate. The FT-IR and 13C NMR spectra indicated the chemical structure of LMWSA obtained by ozonation was not altered appreciably. New insight into the ozonation of alginate will be promisingly opened up. Ozonation of sodium alginate can be a alternative for production of LMWSA.

Influence of dietary sodium alginate and Pediococcus acidilactici on liver antioxidant status, intestinal lysozyme gene expression, histomorphology, microbiota, and digestive enzymes activity, in Asian sea bass (Lates calcarifer) juveniles

A 42-day study was conducted to determine the effect of incorporating dietary low molecular weight sodium alginate (LMWSA), extracted from the brown algae, Undaria pinnatifida and Macrocystis pyritera, and Pediococcus acidilactici MA 18/5 M (PA), Lallemand Animal Nutrition S.A., Blagnac, France, on growth performance, antioxidant defense activity, intestinal lysozyme gene (LYZ) expression, histo-morphology, microbiota, and digestive enzymes activity of Asian sea bass (Lates calcarifer) juveniles. Six experimental diets were formulated including: Diet (1) a basal diet (Control), Diet (2) 5 g LMWSA kg−1 diet, Diet (3) 10 g LMWSA kg−1 diet, Diet (4) 0.9 × 107 CFU PA g−1 diet, Diet (5) 5 g LMWSA kg−1 diet + 0.9 × 107 CFU PA g−1 diet, and Diet (6) 10 g LMWSA kg−1 diet + 0.9 × 107 CFU PA g−1 diet were fed to Asian sea bass, L. calcarifer (12.0 ± 0.2 g). The results showed that fish fed PA alone (Diet 4) and the combination of both supplements (Diet 5) had the greatest weight gain. Fish fed Diet 6 and those fed Diet 1 (Control) had the highest and lowest villus height, apparent villus surface and crypt depth, respectively. Fish fed diets administered with PA (Diet 4) or synbiotics (Diets 5 and 6) showed higher total viable and lactic acid bacteria counts than all the other groups. The evaluated digestive enzymes activities including total protease, trypsin, lipase, and α-amylase remarkably increased by administration of LMWSA or its combination with PA. Moreover, liver antioxidant enzymes activities including superoxide dismutase, catalase, and Glutathione S-transferase pronouncedly enhanced following the administration of LMWSA or its combination with PA. Supplementing diet with blends of 10 g kg−1 of LMWSA and PA (Diet 6) more pronouncedly enhanced c-type and g-types LYZ expression in comparison with those fed 5 g kg−1 of LMWSA and PA (Diet 5). Based on the results obtained, it can be claimed incorporating diet with LMWSA and PA separately or in symbiotic form had promising results as functional feed additives in juvenile Asian sea bass L. calcarifer.

Dietary supplementation with low molecular weight sodium alginate improves growth, haematology, immune reactions and resistance againstAeromonas hydrophilainClarias gariepinus

A few studies have illustrated the effects of sodium salt derived from alginic acid on different fish species. However, little is known about the effect of sodium alginate on catfish (Clarias gariepinus). Therefore, this study was performed to assess the use of low molecular weight sodium alginate (LMWSA) in C. gariepinus. A total of 180 apparently healthy C. gariepinus with a mean body weight of 45 g were randomly divided into three equal groups (D1, D2 and D3). D1 the control group received a control diet, while D2 and D3 received 1% and 3% LMWSA, respectively, for 8 weeks. A challenge test against Aeromonas hydrophila was performed on 15 randomly selected catfish for 15 days. At the end of the experiment, catfish in D3 that received a diet of 3% LMWSA showed significant increases in the final body weight, weight gain and thermal-unit growth coefficient compared with those in D2 and D1. There was a significant decrease in the erythrogram in D1 after the 4-day pathogen challenge. A leucogram revealed leucocytosis, heterophilia and lymphocytosis in catfish in D2 and D3 compared with those in D1. After the 4-day challenge, the following changes took place: lysozyme, nitric oxide, phagocytic activity and the respiratory burst were significantly elevated in catfish that received LMWSA and were more pronounced in D3 than in D1. The mortalities of catfish have been stopped after pathogen challenge from 8-day in D1 and D2 where at 6-day in D3. Thus, administration of 1% and 3% LMWSA enhances the growth, immune response and resistance of C. gariepinus against A. hydrophila.

Free Radicals Scavenging Activities of Low Molecular Weight Sodium Alginate (LMWSA) from Sargassum polycystum, Produced by Thermal Treatment

In this study, the effects of alginate from Sargassum polycystum molecular reduction by thermal heating on DPPH anti radical scavenging activity were investigated. Raw alginate as the control treatment was heated at 140 o C in a laboratory oven for different time courses 1.5, 4.5, and 7.5 hours. The assessment of molecular weight, UV-visible and FT-IR spectroscopic studies were applied. By heat treatment, molecular weight of polymer was decreased in a time-dependent manner, though there is no significant difference between 4.5 h and 7.5 h samples. The UV-visible spectroscopic studies pointed that there was a new absorption band between 250 and 290 nm in alginate heated treatments. The higher antiradical scavenging activity were reached from 1.5 h and 4.5 h treatments (19.83% and 20.07%). Interestingly, the antiradical scavenging activity of the longest heating treatment (7.5 h) was reduced (16.85%), similar to the raw alginate (17.89%). Prolonged heat treatments influenced the antioxidant activity and reduced the ability of donate electrons or hydrogen atoms to inactivate this radical action.

Combined effects of dietary low molecular weight sodium alginate and Pediococcus acidilactici MA18/5M on growth performance, haematological and innate immune responses of Asian sea bass (Lates calcalifer) juveniles

Six weeks feeding trial was conducted to examine the effects of dietary administration of low molecular weight sodium alginate (LMWSA) and Pediococcus acidilactici MA 18/5M (PA) on humoral and mucosal immune responses, haematological parameters and growth performance, of Lates calcarifer juveniles. Fish (12.0 ± 0.2 g) were fed experimental diets as follows: Control (diet 1, basal diet), 5 g kg−1 LMWSA (diet 2), 10 g kg−1 LMWSA (diet 3), 0.9 × 107 CFU g−1 PA (diet 4), 5 g kg−1 LMWSA + 0.9 × 107 CFU g−1 PA (Diet 5), and 10 g kg−1 LMWSA + 0.9 × 107 CFU g−1 PA (Diet 6). Results indicated a significant (P < 0.05) increase in innate immune parameters including serum lysozyme, bactericidal, hemolytic and respiratory burst activities as well as mucosal immune responses including lysozyme and bactericidal activities, when diet was supplemented with immunostimulants. Moreover, the combined effects of LMWSA with PA resulted in more pronounced immunological responses compared to the control and singular administration. Red and white blood cell counts significantly increased with either singular or combined administration of LMWSA and PA compared with the control group (P < 0.05). The singular administration of PA and combined supplementation of 5 g kg−1 LMWSA with PA significantly increased growth performance and feed intake compared with other experimental groups (P < 0.05). These results indicated that combined administration of LMWSA and PA can be considered as beneficial feed additive and immunostimulant in L. calcarifer juveniles.

The effects of dietary kefir and low molecular weight sodium alginate on serum immune parameters, resistance against Streptococcus agalactiae and growth performance in Nile tilapia (Oreochromis niloticus)

The present study evaluates the effects of dietary kefir and low molecular weight sodium alginate (LWMSA) (singular or combined) on non-specific immune response, disease resistance and growth performance of Nile tilapia (Oreochromis niloticus). Fish with average weight of 18.60 ± 0.04 g were supplied and randomly stocked in sixteen glass tanks (150 L) at density of 20 fish per tank. Fish were fed experimental diets as follows: 0 g kg−1 LMWSA (Control, Diet 1), 10 g kg−1 LMWSA (Diet 2), 40 g kg−1 kefir (Diet 3), and 10 g kg−1 LMWSA + 40 g kg−1 kefir (Diet 4) for 50 days. At the end of the feeding trial, serum lysozyme (SL), phagocytosis (PI), respiratory burst (RB), and alternative complement (ACH50) activities as well as growth performance were measured. Singular and combined administration of kefir and low molecular weight sodium alginate (LMWSA) significantly increased serum SL, PI, RB, and ACH50 activities compared control group (P < 0.05); the highest innate immune responses were observed in fish fed combinational diet (kefir + LMWSA) (P < 0.05). The results of experimental challenge revealed significantly higher resistance against Streptococcus agalactiae in fish fed supplemented diets and the highest post challenge survival rate was observed in synbiotic diet (P < 0.05). Similar results obtained in case of growth parameters. Feeding on supplemented diet significantly improved SGR and FCR and the highest growth parameters was observed in fish fed synbiotic diet (P < 0.05). These finding revealed that combined administration of dietary kefir and LMWSA can be considered for improving immune response, disease resistance and growth performance of Nile tilapia.

Effect of depolymerized sodium alginate on Salmonella Typhimurium infection in human enterocyte-like HT-29-Luc cells and BALB/c mice

Depolymerized low-molecular-weight sodium alginate (LM-NA) has been developed as functional component for beverages. Solubility of LM-NA is far higher than that of general high-molecular-weight sodium alginate (HM-NA). To evaluate the effects of the alginates on infection of food related pathogens, the adhesion and invasion of Salmonella Typhimurium in human enterocyte-like HT-29-Luc cells and the infection in BALB/c mice were studied. Both the alginates (0.1% w/v) inhibited the adhesion and invasion in HT-29-Luc cells by 70–80%. Dietary intake of both alginates (2% w/v) reduced the infection in the liver of BALB/c mice from 5.0 to 4.4 log CFU/g tissue. Drinking water containing LM-NA (2.5% w/v) also reduced the infection in the liver from 5.5 to 4.6 log CFU/g tissue and in the spleen from 4.6 to 3.6 log CFU/g tissue. These results suggest that LM-NA can exert positive immunomodulatory effects and would be useful as a functional food material.

Combined administration of low molecular weight sodium alginate boosted immunomodulatory, disease resistance and growth enhancing effects of Lactobacillus plantarum in Nile tilapia (Oreochromis niloticus)

The present study investigates the effects of combined or singular administration of low molecular weight sodium alginate (LWMSA) and Lactobacillus plantarum on innate immune response, disease resistance and growth performance of Nile tilapia (Oreochromis niloticus). Three hundred and twenty fish were supplied and randomly stocked in sixteen glass tanks (150 L) assigned to four treatments as follows: 0 g kg−1 LMWSA (Control, Diet 1), 10 g kg−1 LMWSA (Diet 2), 108 CFU g−1L. plantarum (Diet 3), and 10 g kg−1 LMWSA + 108 CFU g−1L. plantarum (Diet 4). Following 30 and 60 days of the feeding trial, serum lysozyme, phagocytosis, respiratory burst and alternative complement activities as well as growth performance parameters (specific growth rate, feed conversion ratio) were measured. Serum lysozyme, phagocytosis, respiratory burst, and alternative complement activities of fish were significantly stimulated by both LMWSA and L. plantarum diets, however, the highest innate immune response were observed in fish fed synbiotic diet. At the end of the experiment, eight fish per replication were randomly selected for a challenge test against Streptococcus agalactiae. The survival rate of the fish fed supplemented diets was significantly greater than the control treatment and the highest post challenge survival rate was observed in synbiotic diet. Furthermore, SGR and FCR were significantly improved in fish fed supplemented diets after 60 days and the highest growth performance was observed in fish fed synbiotic diet. These results suggest combined LMWSA and L. plantarum can be considered as a promising immunostimulant and growth enhancer in Nile tilapia diet.

Effects of low molecular weight sodium alginate on growth performance, immunity, and disease resistance of tilapia, Oreochromis niloticus.

Present study was carried out to evaluate the effects of low molecular weight sodium alginate (LMWSA) as potential prebiotic source on growth performance, innate immunity and disease resistance of tilapia, Oreochromis niloticus. Three hundred twenty fish were divided into four treatments and fed following diets 0 (T1- Control), 10 (T2), 20 (T3) and 30 (T4) gkg(-1) LMWSA for period of 60 days. A Completely Randomized Design with four replications was applied. At the end of experiment, fish in each replication were weighed and specific growth rate (SGR) and feed conversion ratio (FCR) were calculated. Five randomly selected fish were used for innate immune response measurement. Another ten fish were randomly selected for challenge test against Streptococcus agalactiae for a period of 18 days. The lysozyme, complement, phagocytosis, and respiratory burst activities were detected after 60 days of feeding trial and after challenge test. The results indicated that fish fed diet 10gkg(-1) LMWSA significantly improved SGR and FCR after 60 days of feeding trial. The lysozyme, phagocytosis, respiratory burst, and complement activities were significantly higher in fish fed LMWSA diets compared to control. Fish fed 10gkg(-1) LMWSA had greatest values compared to fish fed 20 and 30gkg(-1) LMWSA. The survival rate of O.niloticus was significantly improved in fish fed LMWSA diets after challenge with S.agalactiae for 18 days. However, no significant difference in survival rate was observed among LMWSA supplemented diets. It is indicated that fish fed 10, 20 and 30gkg(-1) LMWSA diets can stimulate growth performance, innate immunity and disease resistance in tilapia against S.agalactiae.

Preventative Effects of Sodium Alginate on Indomethacin-induced Small-intestinal Injury in Mice.

Recent advances in diagnostic technologies have revealed that nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious mucosal injury in the upper and lower gastrointestinal tract (including the small intestine). A drug to treat NSAID-induced small-intestinal injury (SII) is lacking. Sodium alginate is a soluble dietary fiber extracted from brown seaweed and its solution has been used as a hemostatic agent to treat gastrointestinal bleeding due to gastric ulcers. Whether sodium alginate has therapeutic effects on NSAID-induced SII and its mechanism of action are not known. Here, we investigated if administration of two forms (high-molecular-weight (HMW) and low-molecular-weight (LMW)) of sodium alginate could ameliorate indomethacin-induced SII. Pretreatment with HMW sodium alginate or LMW sodium alginate before indomethacin administration improved ulceration and the resultant intestinal shortening was associated with reduced histological severity of mucosal injury and ameliorated mRNA expression of inflammation-related molecules in the small intestine. We found that mRNAs of secretory Muc2 and membrane-associated Muc1, Muc3 and Muc4 were expressed in the small intestine. mRNA expression of Muc1-4 was increased in indomethacin-induced SII, and these increases were prevented by sodium alginate. Thus, administration of sodium alginate could be a therapeutic approach to prevent indomethacin-induced SII.

Generation of scaffold-supported microtissues inside cell-instructive hydrogels

Event Abstract Back to Event Generation of scaffold-supported microtissues inside cell-instructive hydrogels Sílvia J. Bidarra1, 2, Aureliana Sousa1, 2, Ana L. Torres1, 2, 3 and Cristina Barrias1, 2 1 i3S - Instituto de Inovação e Investigação em Saúde, Portugal 2 INEB – Instituto de Engenharia Biomédica, Portugal 3 ICBAS – Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal Introduction: Cell-based therapies are important tools for regenerative medicine. Yet, clinical trials have not yet demonstrated consistent therapeutic benefits, which has been attributed to poor survival/engraftment of transplanted cells, usually administered as single-cell suspensions. Some of the experienced failures may be related to the way cells are delivered, and not to a lack of intrinsic therapeutic potential, pointing to the urgent need for improved cell delivery strategies. A promising approach is the use of cell-aggregates, or microtissues, where cell-cell/cell-matrix interactions are preserved, improving survival, retention and pro-regeneration properties[1]. This work describes a bioengineering approach to generate scaffold-supported microtissues inside molecularly designed cell-instructive hydrogels. Materials and Methods: In situ forming alginate hydrogel matrices loaded with mesenchymal stem cells (MSC) were prepared by internal gelation as described previously[2],[3]. To produce hydrogels with tailored composition and stiffness, pre-gel solutions were prepared using binary mixtures of low and high molecular weight sodium alginate, at different polymer concentrations and various densities of alginate-grafted cell-adhesion RGD peptides. Hydrogels viscoelastic properties were characterized by oscillation rheometry. Cell behavior along in vitro culture was characterized at different levels, namely in terms of viability, spatial rearrangement, proliferation, osteogenic differentiation and production of endogenous ECM and angiogenic factors. The angiogenic potential was also evaluated in vivo, using the CAM assay. Results and Discussion: MSC aggregation and microtissue formation occurred only in more compliant matrices (G’≤120 Pa), independently of the presence/amount of cell-adhesion RGD ligands. Fibronectin assembly stabilized cell-cell contacts within aggregates, even in non-adhesive matrices. However, MSC were only able to substantially contract the artificial matrix when RGD was present. Compliant matrices facilitated MSC proliferation and supported osteogenic differentiation, even in the absence of RGD. Cell interactions with the artificial matrix appear to become less important over time, as cells produced their own ECM. Yet, the intrinsic properties of the artificial matrix and the initial cell-matrix interactions were critical determinates of cell fate. After one week of culture, hydrogels with aggregated MSC expressed significantly higher amounts of pro-angiogenic factors (VEGF) in vitro, and showed higher angiogenic capacity in vivo (CAM assay), as compared to freshly-prepared hydrogels with individually dispersed cells. Conclusions: MSC entrapped within rationally designed alginate hydrogels can be induce to aggregate and form microtissue-like structures, which present interesting therapeutic features. This work provided new clues to the design of cell-instructive 3D matrices and established a new biomaterial-driven strategy to generate scaffold-supported microtissues. FCT/MEC through National Funds co-financed by FEDER through the PT2020 Partnership Agreement under the 4293 Unit I&D; FCT project IF/00939/2013/CP1179/CT000; FCT fellowships (SFRH/BPD/80571/2011 to SJB; SFRH/BPD/90047/2012 to AS; SFRH/BD/94306/2013 to ALT); CCB Research position (IF2013, FCT).

Biodegradable Ocular Inserts for Sustained Delivery of Brimonidine Tartarate: Preparation and In Vitro/In Vivo Evaluation

The bioavailability of therapeutic agents from eye drops is usually limited due to corneal barrier functions and effective eye protective mechanisms. Therefore, the current study aims to enhance ocular bioavailability of brimonidine, a potent antiglaucoma drug, through the preparation of ocular inserts. Solvent casting technique was employed to prepare the inserts using polyvinylpyrrolidone K-90 (PVP K-90) as film-forming polymer blended with different viscosity grades of bioadhesive polymers namely hydroxypropyl methycellulose, carbopol, sodium alginate, and chitosan. The prepared ocular inserts were evaluated for various physicochemical parameters, swelling behavior, and in vitro release patterns. Sodium alginate-based ocular inserts revealed the most sustainment in drug release (99% at 6 h), so it was selected for further modifications via coating it, on one side or dual sides, using hydrophobic film composed of either ethylcellulose or Eudragit RSPO. The obtained in vitro release results for the modified ocular inserts revealed that ethylcellulose is superior to Eudragit RSPO in terms of brimonidine release sustainment effect. Ocular inserts composed of 7% PVP K-90, 1.5% low molecular weight sodium alginate with or without ethylcellulose coat were able to sustain the in vitro release of brimonidine. Their therapeutic efficacy regarding intraocular pressure (IOP) lowering effect when inserted in albino rabbits eyes showed superior sustainment effect compared with that of brimonidine solution. Furthermore, due to both the mucoadhesive property and the drug sustainment effect, the one-side-coated ocular insert showed more IOP lowering effect compared with that of its non-coated or dual-side-coated counterpart.

Lyophilised wafers as a drug delivery system for wound healing containing methylcellulose as a viscosity modifier

Lyophilised wafers have potential as drug delivery systems for suppurating wounds. A dual series of wafers made from low molecular weight sodium alginate (SA) and xanthan gum (XG) respectively, modified with high molecular weight methylcellulose (MC) were produced. The swelling and flow properties of these wafers on model suppurating surfaces were both qualitatively and quantitatively investigated. The wafers instantaneously adhered to the surfaces, absorbing water and transforming from glassy, porous solids to highly viscous gels. The rate at which this occurred varied for the series studied with clear distinctions between the behaviour of SA and XG systems. For SA wafers there was a distinct relationship between the flow-rate and MC content. Increased amounts of MC decreased the rate at which the SA wafers flowed across a model gelatine surface. Flow rheometry was used to quantify the effect of increased MC content on both series of wafers and for the SA series, highlighted a substantial increase in apparent viscosity as a function of incremental increases in MC content. These results reflected those from the gelatine model. Observations of the reluctance of a swollen, unmodified XG wafer to flow compared with the relative ease of unmodified, low molecular weight SA was attributed to the yield stress characteristic of xanthan gels. XG is known to exhibit complex, loosely bound network structures in solution via the association of helical backbone structures. The inclusion of sodium fluorescein as a visible model for a soluble drug highlighted the potential of lyophilised wafers as useful drug delivery systems for suppurating wounds.

Inhibitory effects of laminaran and low molecular alginate against the putrefactive compounds produced by intestinal microflora in vitro and in rats

The inhibitory effects of laminaran and low molecular weight sodium alginate (MW = 49,000) against formation of ammonia, indole compounds and phenol compounds, putrefactive and harmful compounds, induced by human fecal microflora, were examined in vitro. Laminaran was fermented to acetate, propionate, n-butyrate and lactate. The alginate was fermented to acetate and propionate. Both of these polysaccharides inhibited formation of the putrefactive compounds. In the case of rats fed diet containing 2% (w/w) laminaran or low molecular alginate, the fermentation pattern agreed with that of the in vitro experiment. Laminaran suppressed indole, p-cresole and sulfide, significantly. These putrefactive compounds, in rats fed low molecular alginate, also tended to be lower. These results suggest that the fermentation of laminaran by intestinal bacteria suppresses the putative risk markers for colon cancer.

Cellular Response to Transforming Growth Factor-β1 and Basic Fibroblast Growth Factor Depends on Release Kinetics and Extracellular Matrix Interactions

The extracellular matrix plays an important role in growth factor biology, serving as a potential platform for rapid growth factor mobilization or a sink for concentrated sequestration. We now demonstrate that when a growth factor binds reversibly to the matrix, its effects are augmented by this interaction, and when the factor is absorbed irreversibly to the extracellular matrix, it becomes sequestered. These findings call into question the notion that all growth factors are best presented to cells and tissues in a sustained and controlled fashion. In our studies, we examined basic fibroblast growth factor (bFGF) and transforming growth factor-beta1 (TGF-beta1) release kinetics from synthetically fabricated microsphere devices and naturally synthesized extracellular matrix. While the sustained release of bFGF was up to 3.0-fold more potent at increasing vascular endothelial and smooth muscle cell proliferation than bolus administration, the reverse was true for TGF-beta1. A bolus of TGF-beta1 inhibited vascular cells up to 3.8-fold more efficiently than the same amount of TGF-beta1 if control-released. Both growth factors bound to the extracellular matrix, but only bFGF was released in a controlled fashion (2.8%/day). Contact with the extracellular matrix and subsequent release enhanced bFGF activity such that it was 86% more effective at increasing smooth muscle cell numbers than equal amounts of growth factor diluted from frozen stock. TGF-beta1 remained tightly adherent. The small amount of TGF-beta1 released from the extracellular matrix was approximately 30% less effective than bolus administration at inhibiting vascular endothelial and smooth muscle cell growth. Sustained growth factor release may be the preferable mode of administration, but only when a similar mode of metabolism is utilized endogenously.