Efficacy of ß-D-Mannuronic Acid [M2000] on the Pro-Apoptotic Process and Inflammatory-Related Molecules NFκB, IL-8 and Cd49d using Healthy Donor PBMC.

OBJECTIVE: This investigation evaluates the pro-apoptotic and anti-inflammatory effects of ß-D-mannuronic acid [M2000] compared to diclofenac, based on gene expression involved in apoptosis and inflammation process [including Bcl2, NFκB, IL-8 and Cd49d] in Peripheral Blood Mononuclear Cells [PBMCs] of healthy donors under exvivo conditions. MATERIALS: The venous blood samples of twelve healthy volunteers with aged 25-60 years were collected in heparinized tubes. The healthy volunteers were selected from no smoking group and without using illicit drugs and suffering from diabetes. The PBMCs were separated and divided into untreated and treated groups. METHODS: The PBMCs of each sample were cultured in 5 wells of culture plate, so that the first well consisted of 2×106 cells exposed by LPS-EB [1µg/ml] to stimulate PBMCs and absence of M2000 [untreated well]. The second, third, fourth and fifth wells containing 2×106 cells/well and LPS-EB, after 4 hours incubation at 37ºC, received 5, 25 and 50 µg/well of M2000 and 5 µg/well of diclofenac, respectively as treated group. RESULTS: The PBMCs were separated and RNAs were then extracted and cDNAs synthesized and gene expression levels were assessed by qRT-PCR. Furthermore, we studied whether M2000 is able to facilitate apoptosis in PBMCs. Our findings represent that the high dose of M2000 could significantly decrease the expression level of NFκB gene compared to untreated group (p < 0.0002). On the other hand, no significant change was observed in treated cells with diclofenac. All doses of M2000 could significantly augment apoptosis compared to untreated group [p < 0.0001]. Additionally, we observed the same apoptotic effects between the medium dose of M2000 and diclofenac. Besides, no significant reduction was shown in expression levels of IL8, Bcl2 and Cd49d genes in all doses of M2000 and diclofenac compared to untreated group. This experiment demonstrates M2000 as a new effective NSAID with immunosuppressive characteristics capable of stimulating apoptosis through lowering expression levels of NFκB gene, which might be probably considered as an appropriate drug for reducing the risk of developing inflammatory diseases and cancer.

Immunomodulatory effects of M2000 (ß-D-Mannuronic acid) on TNF-α, IL-17 and FOXP3 gene expression in patients with inflammatory bowel disease.

INTRODUCTION: Inflammatory bowel diseases (IBD) are immune-mediated disorders that result from an aberrant immunological response to the gut luminal antigen in genetically susceptible patients. IBD is categorized into two serotype, Crohn's diseases (CD) and ulcerative colitis (UC), both subtype are important cause of gastrointestinal diseases. The increasing rate of hospitalization, with the high economic burden experienced by the IBD patients, calls for more concerted research efforts to design a potent and affordable treatment option for the treatment of IBD. AIMS/OBJECTIVE: This research was designed to test the efficacy and potency of ß-D Mannuronic acid (M2000) and assess if it could serve as a better therapeutic option in the treatment of IBD. METHODOLOGY: Ten (10)ml of blood was aseptically collected into an EDTA container, from 24 IBD patients and 24 normal healthy controls. PBMC was isolated and stimulated with 1µg/ml of LPS in cell culture plate and incubated for 4h. The cells were later treated with 10µg/ml and 50µg/ml of ß-D Mannuronic acid (M2000) and incubated for 24h at 37°C under 5% CO2 and 100% humidity. The RNA extractions, cDNA synthesis, and QRT-PCR were performed. RESULTS: Our findings showed a significant down-regulation of TNF-α and IL-17 gene expression, while the expression of FOXP3 gene was significantly up-regulated. CONCLUSION: This result has indicated that ß-D Mannuronic acid (M2000) have immunoregulatory and anti-inflammatory effects on these cytokines that are pivotal in the pathogenesis of IBD.

Dressings and topical agents for treating pressure ulcers.

BACKGROUND: Pressure ulcers, also known as bedsores, decubitus ulcers and pressure injuries, are localised areas of injury to the skin or the underlying tissue, or both. Dressings are widely used to treat pressure ulcers and promote healing, and there are many options to choose from including alginate, hydrocolloid and protease-modulating dressings. Topical agents have also been used as alternatives to dressings in order to promote healing.A clear and current overview of all the evidence is required to facilitate decision-making regarding the use of dressings or topical agents for the treatment of pressure ulcers. Such a review would ideally help people with pressure ulcers and health professionals assess the best treatment options. This review is a network meta-analysis (NMA) which assesses the probability of complete ulcer healing associated with alternative dressings and topical agents. OBJECTIVES: To assess the effects of dressings and topical agents for healing pressure ulcers in any care setting. We aimed to examine this evidence base as a whole, determining probabilities that each treatment is the best, with full assessment of uncertainty and evidence quality. SEARCH METHODS: In July 2016 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses, guidelines and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: Published or unpublished randomised controlled trials (RCTs) comparing the effects of at least one of the following interventions with any other intervention in the treatment of pressure ulcers (Stage 2 or above): any dressing, or any topical agent applied directly to an open pressure ulcer and left in situ. We excluded from this review dressings attached to external devices such as negative pressure wound therapies, skin grafts, growth factor treatments, platelet gels and larval therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessment and data extraction. We conducted network meta-analysis using frequentist mega-regression methods for the efficacy outcome, probability of complete healing. We modelled the relative effectiveness of any two treatments as a function of each treatment relative to the reference treatment (saline gauze). We assumed that treatment effects were similar within dressings classes (e.g. hydrocolloid, foam). We present estimates of effect with their 95% confidence intervals for individual treatments compared with every other, and we report ranking probabilities for each intervention (probability of being the best, second best, etc treatment). We assessed the certainty (quality) of the body of evidence using GRADE for each network comparison and for the network as whole. MAIN RESULTS: We included 51 studies (2947 participants) in this review and carried out NMA in a network of linked interventions for the sole outcome of probability of complete healing. The network included 21 different interventions (13 dressings, 6 topical agents and 2 supplementary linking interventions) and was informed by 39 studies in 2127 participants, of whom 783 had completely healed wounds.We judged the network to be sparse: overall, there were relatively few participants, with few events, both for the number of interventions and the number of mixed treatment contrasts; most studies were small or very small. The consequence of this sparseness is high imprecision in the evidence, and this, coupled with the (mainly) high risk of bias in the studies informing the network, means that we judged the vast majority of the evidence to be of low or very low certainty. We have no confidence in the findings regarding the rank order of interventions in this review (very low-certainty evidence), but we report here a summary of results for some comparisons of interventions compared with saline gauze. We present here only the findings from evidence which we did not consider to be very low certainty, but these reported results should still be interpreted in the context of the very low certainty of the network as a whole.It is not clear whether regimens involving protease-modulating dressings increase the probability of pressure ulcer healing compared with saline gauze (risk ratio (RR) 1.65, 95% confidence interval (CI) 0.92 to 2.94) (moderate-certainty evidence: low risk of bias, downgraded for imprecision). This risk ratio of 1.65 corresponds to an absolute difference of 102 more people healed with protease modulating dressings per 1000 people treated than with saline gauze alone (95% CI 13 fewer to 302 more). It is unclear whether the following interventions increase the probability of healing compared with saline gauze (low-certainty evidence): collagenase ointment (RR 2.12, 95% CI 1.06 to 4.22); foam dressings (RR 1.52, 95% CI 1.03 to 2.26); basic wound contact dressings (RR 1.30, 95% CI 0.65 to 2.58) and polyvinylpyrrolidone plus zinc oxide (RR 1.31, 95% CI 0.37 to 4.62); the latter two interventions both had confidence intervals consistent with both a clinically important benefit and a clinically important harm, and the former two interventions each had high risk of bias as well as imprecision. AUTHORS' CONCLUSIONS: A network meta-analysis (NMA) of data from 39 studies (evaluating 21 dressings and topical agents for pressure ulcers) is sparse and the evidence is of low or very low certainty (due mainly to risk of bias and imprecision). Consequently we are unable to determine which dressings or topical agents are the most likely to heal pressure ulcers, and it is generally unclear whether the treatments examined are more effective than saline gauze.More research is needed to determine whether particular dressings or topical agents improve the probability of healing of pressure ulcers. The NMA is uninformative regarding which interventions might best be included in a large trial, and it may be that research is directed towards prevention, leaving clinicians to decide which treatment to use on the basis of wound symptoms, clinical experience, patient preference and cost.

Regeneration of rat corpora cavernosa tissue by transplantation of CD133+ cells derived from human bone marrow and placement of biodegradable gel sponge sheet.

The objective is to develop an easier technique for regenerating corpora cavernosa tissue through transplantation of human bone marrow-derived CD133 + cells into a rat corpora cavernosa defect model. We excised 2 mm × 2 mm squares of the right corpora cavernosa of twenty-three 8-week-old male nude rats. Alginate gel sponge sheets supplemented with 1 × 10 4 CD133 + cells were then placed over the excised area of nine rats. Functional and histological evaluations were carried out 8 weeks later. The mean intracavernous pressure/mean arterial pressure ratio for the nine rats (0.34258 ± 0.0831) was significantly higher than that for eight rats with only the excision (0.0580 ± 0.0831, P = 0.0238) and similar to that for five rats for which the penis was exposed, and there was no excision (0.37228 ± 0.1051, P = 0.8266). Immunohistochemical analysis revealed that the nine fully treated rats had venous sinus-like structures and quantitative reverse transcription polymerase chain reaction analysis of extracts from their alginate gel sponge sheets revealed that the amounts of mRNA encoding the nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) were significantly higher than those for rats treated with alginate gel sheets without cell supplementation (NGF: P = 0.0309; VEGF: P < 0.0001). These findings show that transplantation of CD133 + cells accelerates functional and histological recovery in the corpora cavernosa defect model.

Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2015.

As an increase in gastroesophageal reflux disease (GERD) has been reported in Japan, and public interest in GERD has been increasing, the Japanese Society of Gastroenterology published the Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009. Six years have passed since its publication, and there have been a large number of reports in Japan concerning the epidemiology, pathophysiology, treatment, and Barrett's esophagus during this period. By incorporating the contents of these reports, the guidelines were completely revised, and a new edition was published in October 2015. The revised edition consists of eight items: epidemiology, pathophysiology, diagnosis, internal treatment, surgical treatment, esophagitis after surgery of the upper gastrointestinal tract, extraesophageal symptoms, and Barrett's esophagus. This paper summarizes these guidelines, particularly the parts related to the treatment for GERD. In the present revision, aggressive proton pump inhibitor (PPI) maintenance therapy is recommended for severe erosive GERD, and on-demand therapy or continuous maintenance therapy is recommended for mild erosive GERD or PPI-responsive non-erosive GERD. Moreover, PPI-resistant GERD (insufficient symptomatic improvement and/or esophageal mucosal break persisting despite the administration of PPI at a standard dose for 8 weeks) is defined, and a standard-dose PPI twice a day, change in PPI, change in the PPI timing of dosing, addition of a prokinetic drug, addition of rikkunshito (traditional Japanese herbal medicine), and addition of histamine H2-receptor antagonist are recommended for its treatment. If no improvement is observed even after these treatments, pathophysiological evaluation with esophageal impedance-pH monitoring or esophageal manometry at an expert facility for diseases of the esophagus is recommended.

Sodium alginate prevents progression of non-alcoholic steatohepatitis and liver carcinogenesis in obese and diabetic mice.

Obesity and related metabolic abnormalities play a key role in liver carcinogenesis. Non-alcoholic steatohepatitis (NASH), which is often complicated with obesity and diabetes mellitus, is associated with the development of hepatocellular carcinoma (HCC). Sodium alginate (SA), which is extracted from brown seaweeds, is marketed as a weight loss supplement because of its high viscosity and gelling properties. In the present study, we examined the effects of SA on the progression of NASH and related liver carcinogenesis in monosodium glutamate (MSG)-treated mice, which show obesity, diabetes mellitus, and NASH-like histopathological changes. Male MSG-mice were intraperitoneally injected with diethylnitrosamine at 2 weeks of age, and, thereafter, they received a basal diet containing high- or low-molecular-weight SA throughout the experiment (16 weeks). At sacrifice, control MSG-treated mice fed the basal-diet showed significant obesity, hyperinsulinemia, steatosis and hepatic tumor development. SA administration suppressed body weight gain; improved insulin sensitivity, hyperinsulinemia, and hyperleptinemia; attenuated inflammation in the liver and white adipose tissue; and inhibited hepatic lipogenesis and progression of NASH. SA also reduced oxidative stress and increased anti-oxidant enzyme levels in the liver. Development of hepatic tumors, including liver cell adenoma and HCC, and hepatic pre-neoplastic lesions was significantly inhibited by SA supplementation. In conclusion, oral SA supplementation improves liver steatosis, insulin resistance, chronic inflammation, and oxidative stress, preventing the development of liver tumorigenesis in obese and diabetic mice. SA may have ability to suppress steatosis-related liver carcinogenesis in obese and diabetic subjects.

Exploration of alginate hydrogel/nano zinc oxide composite bandages for infected wounds.

Alginate hydrogel/zinc oxide nanoparticles (nZnO) composite bandage was developed by freeze-dry method from the mixture of nZnO and alginate hydrogel. The developed composite bandage was porous with porosity at a range of 60%-70%. The swelling ratios of the bandages decreased with increasing concentrations of nZnO. The composite bandages with nZnO incorporation showed controlled degradation profile and faster blood clotting ability when compared to the KALTOSTAT® and control bandages without nZnO. The prepared composite bandages exhibited excellent antimicrobial activity against Escherichia coli, Staphylococcus aureus, Candida albicans, and methicillin resistant S. aureus (MRSA). Cytocompatibility evaluation of the prepared composite bandages done on human dermal fibroblast cells by Alamar assay and infiltration studies proved that the bandages have a non-toxic nature at lower concentrations of nZnO whereas slight reduction in viability was seen with increasing nZnO concentrations. The qualitative analysis of ex-vivo re-epithelialization on porcine skin revealed keratinocyte infiltration toward wound area for nZnO alginate bandages.

Chemoprevention of Azoxymethane-induced Colonic Carcinogenesis in Balb/c mice Using a Modified Pectin Alginate Probiotic.

BACKGROUND: Increased intake of probiotic dietary fibre reduces colonic cancer risk. Modified citrus pectin (MCP) requires optimal bioactivity to inhibit galectin-3 (GAL-3) and vascular endothelial growth factor (VEGF). This study evaluated the preventative effect of modified pectin alginate (MCPA) probiotic microbeads on azoxymethane (AOM)-induced colonic carcinogenesis in Balb/c mice. MATERIALS AND METHODS: Optimization of AOM dose duration: 10-15 mg/kg was administered for 2-4 weeks. The optimal AOM dose was initiated prior to intake of MCPA, alginate probiotic (AP) microbeads and MCP in Balb/c mice for 16 weeks; samples were analyzed for colonic histopathology and immunohistochemistry. RESULTS: AOM at 15 mg/kg for 4 weeks induced optimal GAL-3 and VEGF immunostaining. Furthermore, MCPA treatment reduced GAL-3 expression in the colon of AOM-treated mice compared to MCP. CONCLUSION: MCPA probiotic microbeads increase bioactivity and chemopreventative effect against pre-cancerous colonic lesions and adenocarcinoma through inhibition of GAL-3 and VEGF in the Balb/c mouse model of colonic carcinogenesis.

An oral DNA vaccine against infectious haematopoietic necrosis virus (IHNV) encapsulated in alginate microspheres induces dose-dependent immune responses and significant protection in rainbow trout (Oncorrhynchus mykiss).

Administered by intramuscular injection, a DNA vaccine (pIRF1A-G) containing the promoter regions upstream of the rainbow trout interferon regulatory factor 1A gene (IRF1A) driven the expression of the infectious hematopoietic necrosis virus (IHNV) glycoprotein (G) elicited protective immune responses in rainbow trout (Oncorhynchus mykiss). However, less laborious and cost-effective routes of DNA vaccine delivery are required to vaccinate large numbers of susceptible farmed fish. In this study, the pIRF1A-G vaccine was encapsulated into alginate microspheres and orally administered to rainbow trout. At 1, 3, 5, and 7 d post-vaccination, IHNV G transcripts were detected by quantitative real-time PCR in gills, spleen, kidney and intestinal tissues of vaccinated fish. This result suggested that the encapsulation of pIRF1A-G in alginate microparticles protected the DNA vaccine from degradation in the fish stomach and ensured vaccine early delivery to the hindgut, vaccine passage through the intestinal mucosa and its distribution thought internal and external organs of vaccinated fish. We also observed that the oral route required approximately 20-fold more plasmid DNA than the injection route to induce the expression of significant levels of IHNV G transcripts in kidney and spleen of vaccinated fish. Despite this limitation, increased IFN-1, TLR-7 and IgM gene expression was detected by qRT-PCR in kidney of vaccinated fish when a 10 µg dose of the oral pIRF1A-G vaccine was administered. In contrast, significant Mx-1, Vig-1, Vig-2, TLR-3 and TLR-8 gene expression was only detected when higher doses of pIRF1A-G (50 and 100 µg) were orally administered. The pIRF1A-G vaccine also induced the expression of several markers of the adaptive immune response (CD4, CD8, IgM and IgT) in kidney and spleen of immunized fish in a dose-dependent manner. When vaccinated fish were challenged by immersion with live IHNV, evidence of a dose-response effect of the oral vaccine could also be observed. Although the protective effects of the oral pIRF1A-G vaccine after a challenge with IHNV were partial, significant differences in cumulative percent mortalities among the orally vaccinated fish and the unvaccinated or empty-plasmid vaccinated fish were observed. Similar levels of protection were obtained after the intramuscular administration of 5 µg of pIRF1A-G or after the oral administration of a high dose of pIRF1A-G vaccine (100 µg); with 70 and 56 relative percent survival values, respectively. When fish were vaccinated with alginate microspheres containing high doses of the pIRF1A-G vaccine (50 or 100 µg), a significant increase in the production of anti-IHNV antibodies was detected in serum samples of the vaccinated fish compared with that in unvaccinated fish. At 10 days post-challenge, IHNV N gene expression was nearly undetectable in kidney and spleen of orally vaccinated fish which suggested that the vaccine effectively reduced the amount of virus in tissues of vaccinated fish that survived the challenge. In conclusion, our results demonstrated a significant increase in fish immune responses and resistance to an IHNV infection after the oral administration of increasing concentrations of a DNA vaccine against IHNV encapsulated into alginate microspheres.

Evaluation of intraabdominal adhesion generating potentials of ankaferd and calcium alginate used as hemostatic agents.

AIM: The present study aimed to evaluate intra-abdominal adhesion generating potential of Ankaferd Blood Stopper (ABS), which was used as postoperative hemostatic agent in the rats that underwent surgery, in comparison with Ca-alginate. MATERIAL AND METHOD: Totally, 30 rats were randomized into 4 groups. In the control group, 1x1 cm peritoneum was removed from the right lower quadrant after cecal abrasion. In the other two study groups, the same procedure was performed after Ankaferd Blood Stopper and Ca-alginate application respectively. RESULTS were evaluated both histopathologically and by adhesion scoring methods. All results underwent statistical analysis. RESULTS: Comparing overall results, no statistically significant difference was found between the sham, control, ABS and Ca-alginate groups (p = 0.099). Paired group comparisons revealed no statistically significant difference between the sham group and the control, ABS, and Ca-alginate groups (p = 0.222, p = 0.222, and p = 0.833 respectively). It was observed that there was no statistically significant difference between the control and ABS groups (p = 0.505), but there was a statistically significant difference between the control and Ca-alginate groups with Bonferroni correction (p = 0.028). Histopathological examination revealed no statistical difference between the groups. CONCLUSION: In conclusion, intra-abdominal adhesion generating potentials of Ca-alginate and ABS were experimentally evaluated and macroscopic and microscopic comparisons revealed no significant difference between sham, control, Ca-alginate, and ABS groups (Fig. 8, Ref. 36). Text in PDF www.elis.sk. agent.

[Use of hydrogel tissues with 5-fluorouracil and sodium alginate, "COLETEX-5-FTUR," for radiomodification in cancer patients receiving radiation therapy].

Radiomodification is one of the most available and repeatable methods of amplification of the tumor damage in radiotherapy. The application of 5 FU hydrogel tissues for colorectal and breast cancer patients enables to complete the surgery, increase performance of radiation treatment, reduce the relapse frequency.

3D viability imaging of tumor phantoms treated with single-walled carbon nanohorns and photothermal therapy.

A new image analysis method called the spatial phantom evaluation of cellular thermal response in layers (SPECTRL) is presented for assessing spatial viability response to nanoparticle enhanced photothermal therapy in tissue representative phantoms. Sodium alginate phantoms seeded with MDA-MB-231 breast cancer cells and single-walled nanohorns were laser irradiated with an ytterbium fiber laser at a wavelength of 1064 nm and irradiance of 3.8 W cm(-2) for 10-80 s. SPECTRL quantitatively assessed and correlated 3D viability with spatiotemporal temperature. Based on this analysis, kill and transition zones increased from 3.7 mm(3) and 13 mm(3) respectively to 44.5 mm(3) and 44.3 mm(3) as duration was increased from 10 to 80 s. SPECTRL provides a quantitative tool for measuring precise spatial treatment regions, providing information necessary to tailor therapy protocols.

Decreasing cardiovascular risk factors in obese individuals using a combination of PGX® meal replacements and PGX® granules in a 12-week clinical weight modification program.

In this open, clinically based, weight modification program, we determined in six sedentary obese adults (five women; one male; age range 30-62 years) that the combination of a modified calorie diet plus PGX® meal replacement and PGX® supplementation resulted in a significant reduction in several cardiovascular risk factors over a 12-week time period. This included a significant improvement in lipids (-0.98 mmol/l LDL-C), reduction in average weight (-9.2 kg), mean reduction in fat (-4.1%) and an increase in fat-free mass (2.8%).

Protective effect of a new biomaterial against the development of experimental osteoarthritis lesions in rabbit: a pilot study evaluating the intra-articular injection of alginate-chitosan beads dispersed in an hydrogel.

OBJECTIVE: This study aimed to evaluate the structural benefit of a new biomaterial composed of alginate-chitosan (AC) beads dispersed in a hydrogel (H) derived from chitosan on the development of osteoarthritis (OA) in rabbit. DESIGN: OA was induced by the surgical transection of the anterior cruciate ligament in rabbits. Animals received a single intra-articular injection (900 µl) of AC beads in H hydrogel, H hydrogel alone or saline a week after surgery. OA development was followed by X-rays. Blood samples were collected throughout the study to measure biological markers (Prostaglandins E2 - PGE2 and C reactive protein - CRP). Macroscopic observation and histological evaluation of articular cartilage and synovial membrane were performed 6 weeks after surgery. RESULTS: AC beads in H hydrogel prevented from the development of OA based on the reduction of the Kellgren & Lawrence (K&L) score. It also significantly reduced the histological score of cartilage lesion severity. This effect was homogenous on every joint compartment. It was due to a significant effect on cartilage structure and cellularity scores. The injection of AC beads in H hydrogel also tended to reduce the synovial membrane inflammation. No significant variation of biological markers was noted. CONCLUSIONS: The present pilot study provides interesting and promising results for the use of AC beads in H hydrogel in animal. It indeed prevented the development of OA cartilage lesions without inflammatory signs. The potencies of this biomaterial to protect OA joint should be further documented. It could then represent a new alternative for viscosupplementation in human OA management.

Alginic acid isolated from Sargassum wightii exhibits anti-inflammatory potential on type II collagen induced arthritis in experimental animals.

The present study evaluated the anti-inflammatory potential of alginic acid isolated from the brown algae Sargassum wightii in type II collagen induced arthritic rats, a well established arthritic model that resembles more closely to human rheumatoid arthritis in its clinical, pathological, immunological and histological aspects. Type II collagen induced arthritic rats showed increased activities of inflammatory marker enzymes like cycloxygenase-2 (COX-2), lipoxygenase (5-LOX), xanthine oxidase (XO) and myeloperoxidase (MPO) along with increased concentration of rheumatoid factor (RF), ceruloplasmin and C-reactive protein (CRP). Treatment with alginic acid significantly reduced the activities of COX-2 and 5-LOX along with reduction in MPO, XO, RF and CRP. Alginic acid treatment reverted to the altered levels of hematological parameters like RBC count, WBC count and ESR in arthritic rats. Concentrations of proinflammatory cytokines like IL-1 ß, TNF α and IL-6 were significantly higher in arthritic rats which were reduced on treatment with alginic acid. Increased activities of lysosomal enzymes that manifest the systemic damage during arthritis were significantly reduced by the treatment with alginic acid which indicates the reduction in the rupture and degradation of connective tissue. Histopathology of knee joint tissues showed that extensive bone degradation and synovial hyperplasia along with infiltrating cells and treatment with alginic acid reversed the histopathological changes which indicate the protective potential of alginic acid in rheumatoid arthritis.

Effect of alginate supplementation on weight loss in obese subjects completing a 12-wk energy-restricted diet: a randomized controlled trial.

BACKGROUND: Acute studies with alginate-based preloads suggested that these strong gelling fibers may induce increased feelings of satiety and reduce energy intakes. However, the long-term efficacy and safety of alginate supplementation on body weight regulation are lacking. OBJECTIVE: The primary aim of the study was to investigate the effects in subjects of alginate supplementation in conjunction with energy restriction (-300 kcal/d) on loss of body weight and fat and, second, on metabolic risk markers in comparison with in a placebo group. DESIGN: In a parallel, double-blind, placebo-controlled study, we randomly assigned 96 obese subjects to either an energy-restricted diet plus a placebo preload supplement or an energy-restricted diet plus an alginate-based preload supplement (15 g fiber). The preload was administered as a beverage 3 times/d before main meals for a period of 12 wk. RESULTS: No differences in loss of body weight and fat between groups were shown in the intension-to-treat (ITT) analysis (P > 0.1). However, in the completer analysis (n = 80), we showed a greater weight loss with alginate (6.78 ± 3.67 kg) than with the placebo (5.04 ± 3.40 kg) (P = 0.03), which was mainly attributed to a reduction in the percentage of body fat (P = 0.03). In the ITT analysis, a larger decrease in systolic and diastolic blood pressure was shown in the placebo group than in the alginate group (P < 0.05). Plasma concentrations of glucose, insulin, C-reactive protein, and ghrelin, HOMA-IR, and lipid metabolism did not differ between treatment groups in the ITT analysis (P > 0.1). CONCLUSION: These results suggest that alginate supplementation as an adjunct to energy restriction may improve weight loss in obese subjects who complete a 12-wk dietary intervention.

Biological activities of glucosamine and its related substances.

Glucosamine (GlcN) has been widely used to treat osteoarthritis (OA) in humans. We revealed that among GlcN-derivatives (GlcN and N-acetyl-d-glucosamine) and uronic acids (d-glucuronic acid and d-galacturonic acid), only GlcN induces the production of hyaluronic acid (HA) by synovial cells and chondrocytes, and the production level is much higher (>10-fold) in synovial cells compared with chondrocytes. Moreover, GlcN increases the expression of HA-synthesizing enzymes (HAS) in synovial cells and chondrocytes. These observations indicate that GlcN likely exhibits the chondroprotective action on OA by modulating the expression of HAS and inducing the production of HA (a major component of glycosaminoglycans contained in the synovial fluid) especially by synovial cells. The pathological change of subchondral bone is implicated in the initiation and progression of cartilage damage in OA. Thus, we further determined the effect of GlcN on the bone metabolism (osteoblastic cell differentiation). The results indicated that GlcN increases the mineralization of mature osteoblasts and the expression of middle and late stage markers (osteopontin and osteocalcin, respectively) during osteoblastic differentiation, and reduces the expression of receptor activator of NF-κB ligand (RANKL), a differentiation and activation factor for osteoclasts. These observations likely suggest that GlcN has a potential to induce the osteoblastic cell differentiation and suppress the osteoclastic cell differentiation, thereby increasing bone matrix deposition and decreasing bone resorption to modulate bone metabolism in OA.

Effect of hyperbaric oxygen on mesenchymal stem cells for lumbar fusion in vivo.

BACKGROUND: Hyperbaric oxygen (HBO) therapy has been proved in improving bone healing, but its effects on mesenchymal stem cells (MSCs) in vivo is not clear. The aims of this study are to clarify whether the HBO therapy has the same enhancing effect on MSCs with regard to bone formation and maturation and to ascertain whether the transplanted MSCs survive in the grafted area and contribute to new bone formation. METHODS: Twenty-three adult rabbits underwent posterolateral fusion at L4-L5 level. The animals were divided into three groups according to the material implanted and subsequent treatment: (1) Alginate carrier (n = 6); (2) Alginate-MSCs composite (n = 11); and (3) Alginate-MSCs composite with HBO therapy (n = 6). After 12 weeks, spine fusion was examined using radiographic examination, manual testing, and histological examination. Using a PKH fluorescence labeling system, whether the transplanted MSCs survived and contributed to new bone formation in the grafted area after HBO therapy was also examined. RESULTS: The bilateral fusion areas in each animal were evaluated independently. By radiographic examination and manual palpation, union for the Alginate, Alginate-MSCs, and Alginate-MSCs-HBO groups was 0 of 12, 10 of 22, and 6 of 12 respectively. The difference between the Alginate-MSCs and Alginate-MSCs-HBO groups was not significant (P = 0.7997). The fluorescence microscopy histological analysis indicated that the transplanted PKH67-labeled MSCs survived and partly contributed to new bone formation in the grafted area. CONCLUSIONS: This study demonstrated that the preconditioned MSCs could survive and yield bone formation in the grafted area. HBO therapy did not enhance the osteogenic ability of MSCs and improve the success of spine fusion in the rabbit model. Although there was no significant effect of HBO therapy on MSCs for spine fusion, the study encourages us to research a more basic approach for determining the optimal oxygen tension and pressure that are required to maintain and enhance the osteogenic ability of preconditioned MSCs. Further controlled in vivo and in vitro studies are required for achieving a better understanding of the effect of HBO treatment on MSCs.

Reflux and cough.

Reflux is a significant contributor to cough in otolaryngology practice; cough is just one marker of its many negative effects on the upper aerodigestive tract. Reflux causes cough both by direct irritation/inflammation and by increasing sensitivities to other noxious agents. Detailed and diligent clinical evaluation, including laryngoscopy, is useful in advancing the working diagnosis of reflux-associated cough. Supplemental testing, including impedance monitoring of esophageal refluxate, can be important to evaluate for both acidic and nonacidic reflux exposure. The mainstay of treatment continues to be dietary and other lifestyle interventions and drug therapy. Although proton-pump inhibitor therapy is effective in most patients, especially those with acid reflux disease, prokinetic therapy is probably very important with those with combined acid and nonacid disease and those with pure nonacid disease. It is likely that failure to improve can be due to behavioral and drug compliance issues. Antireflux surgery can yield long-lasting positive outcomes in carefully selected patients despite the lower efficacy of treatment for primary upper aerodigestive tract symptoms (cough, hoarseness, sore throat) compared with heartburn and regurgitation.

Effect of alginate on satiation, appetite, gastric function, and selected gut satiety hormones in overweight and obesity.

Lack of control of food intake, excess size, and frequency of meals are critical to the development of obesity. The stomach signals satiation postprandially and may play an important role in control of calorie intake. Sodium alginate (based on brown seaweed Laminaria digitata) is currently marketed as a weight loss supplement, but its effects on gastric motor functions and satiation are unknown. We evaluated effects of 10 days treatment with alginate or placebo on gastric functions, satiation, appetite, and gut hormones associated with satiety in overweight or obese adults. We conducted a randomized, 1:1, placebo-controlled, allocation-concealed study in 48 overweight or obese participants with excluded psychiatric comorbidity and binge eating disorder. All underwent measurements of gastric emptying (GE), fasting, and postprandial gastric volumes (GVs), postprandial satiation, calorie intake at a free choice meal and selected gut hormones after 1 week of alginate (three capsules vs. matching placebo per day, ingested 30 min before the main meal). Six capsules were ingested with water 30 min before the GE, GV, and satiation tests on days 8-10. There were no treatment group effects on GE or volumes, gut hormones (ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY)), satiation, total and macronutrient calorie intake at a free choice meal. There was no difference detected in results between obese and overweight patients. Alginate treatment for a period of 10 days showed no effect on gastric motor functions, satiation, appetite, or gut hormones. These results question the use of short-term alginate treatment for weight loss.