Anastrozole and related glucuronic acid conjugate are electrophilic species.

Anastrozole (ANA), is an inhibitor of non-steroidal aromatase, widely employed for the treatment of breast cancer. However, ANA-associated liver injury cases have been documented in the application of the drug.The major purposes of the present study were to identify the structure of reactive metabolites derived from ANA and to study related metabolic pathways of ANA.We found ANA itself is an electrophilic species reactive to GSH. ANA can be metabolised to ANA-N+-glucuronide (1) catalysed by UGT1A4. An ANA GSH conjugate (2) was detected in bile and livers of rats treated with ANA. UGT1A4 participated in the phase II metabolic pathway.This work allowed us to better understand the mechanisms of the hepatotoxicity of ANA and provided new avenue to define the possible role of metabolic activation in hepatotoxicity.

Newly Developed Polyglycolic Acid Reinforcement Unified with Sodium Alginate to Prevent Adhesion.

Polyglycolic acid (PGA) mesh fabric is widely used for reinforcing injured tissues during surgeries. However, PGA induces chronic inflammation and adhesion. The purpose of this study is to develop PGA reinforcement "without PGA-induced adhesion." We developed a reinforcement fabric unified with PGA mesh and alginate foam. The antiadhesive effects of sodium alginate foam and calcium alginate foam were evaluated in rats. Sodium alginate foam unified with PGA mesh fabric exhibited strong effects that limit the extent and severity of adhesion, whereas calcium alginate foam unified with PGA mesh was less effective in preventing adhesion. In the sodium alginate group, fibroblasts and collagen fibers around implanted sites were sparse and the material degraded rapidly by macrophage ingestion. Fibroblasts and collagen fibers play a major role in adhesion formation and their excessive proliferation results in postoperative adhesion. Thus, inhibiting their increase is the key in preventing PGA-induced adhesion. The reinforcement that is composed of PGA mesh unified with sodium alginate foam strongly inhibited PGA-induced adhesion and showed excellent handling during surgery and could be easily applied with a one-step procedure.

Enhanced wound-healing performance of a phyto-polysaccharide-enriched dressing - a preclinical small and large animal study.

Alginate is a natural rich anionic polysaccharide (APS), commonly available as calcium alginate (CAPS). It can maintain a physiologically moist microenvironment, which minimises bacterial infection and facilitates wound healing at a wound site. Patients with burn injuries suffer from pain and an inflammatory response. In this study, we evaluated the CAPS dressing and traditional dressing containing carboxymethyl cellulose (CMC) for wound healing and scar tissue formation in a burn model of rat and swine. In our pilot study of a burn rat model to evaluate inflammatory response and wound healing, we found that the monocyte chemoattractant protein (MCP)-1 and transforming growth factor (TGF)-ß were up-regulated in the CAPS treatment group. Next, the burn swine models tested positive for MCP-1 in a Gram-positive bacterial infection, and there was overproduction of TGF-ß during the burn wound healing process. Rats were monitored daily for 1 week for cytokine assay and sacrificed on day 28 post-burn injury. The swine were monitored over 6 weeks. We further examined the pain and related factors and inflammatory cytokine expression in a rodent burns model monitored everyday for 7 days post-burn. Our results revealed that the efficacy of the dressing containing CAPS for wound repair post-burn was better than the CMC dressing with respect to natural wound healing and scar formation. The polysaccharide-enriched dressing exerted an antimicrobial effect on burn wounds, regulated the inflammatory response and stimulated anti-inflammatory cytokine release. However, one pain assessment method showed no significant difference in the reduction in levels of adenosine triphosphate in serum of rats after wound dressing in either the CAPS or CMC group. In conclusion, a polysaccharide-enriched dressing outperformed a traditional dressing in reducing wound size, minimising hypertrophic scar formation, regulating cytokines and maximising antimicrobial effects.

Tailored therapy guided by multichannel intraluminal impedance pH monitoring for refractory non-erosive reflux disease.

A relevant percentage of non-erosive reflux disease (NERD) is refractory to proton pump inhibitors (PPIs) treatment. Multichannel intraluminal impedance pH (MII-pH) monitoring should give useful pathophysiological information about refractoriness. Therefore, our aim was to assess whether this technique could be useful to guide a 'tailored' therapy in refractory NERD. We retrospectively recruited NERD patients undergoing MII-pH monitoring for unsuccessful treatment. All patients had undergone upper endoscopy, and those with erosive esophagitis were excluded. No patient received PPI during MII-pH monitoring. Subjects were subgrouped into three categories: acid reflux, non-acid reflux and functional heartburn. MII-pH-guided therapy was performed for 4 weeks as follows: patients with acid reflux received PPI at double dose, patients with non-acid reflux PPI at full dose plus alginate four times a day and patients with functional heartburn levosulpiride 75 mg per day. A visual analog scale (VAS) ranging from 0 to 100 mm was administered before and after such tailored therapy to evaluate overall symptoms. Responders were defined by VAS improvement of at least 40%. Sixty-nine patients with refractory NERD were selected (female-male ratio 43 : 26, mean age 47.6±15.2 years). Overall effectiveness of tailored therapy was 84% without statistical difference among subgroups (88.5% acid reflux, 92% non-acid reflux, 66.6% functional heartburn; P=0.06). Univariate analysis showed that therapy failure directly correlated with functional heartburn diagnosis (OR=4.60) and suggested a trend toward a negative correlation with smoking and a positive one with nausea. However, at multivariate analysis, these parameters were not significant. Functional heartburn experienced a lower median percent VAS reduction than acid reflux (52.5% versus 66.6%, P<0.01) even if equal to non-acid reflux (66.6%). In conclusion, a tailored approach to refractory NERD, guided by MII-pH monitoring, demonstrated to be effective and should be promising to cure symptom persistence after conventional therapy failure. Nevertheless, standardized guidelines are advisable.

Safety and Efficacy of Alginate Adhesion Barrier Gel in Compromised Intestinal Anastomosis.

BACKGROUND: For any anti-adhesive barrier developed for abdominal surgery, the use under conditions in which anastomotic healing is compromised needs to be investigated. The current study evaluates the effect of a new ultrapure alginate gel on early healing of high-risk anastomoses in the ileum and compares this with the gold standard used in clinical practice. MATERIALS AND METHODS: In 75 adult male Wistar rats, a 5 mm ileal segment was resected and continuity was restored by construction of an inverted anastomosis. Rats were divided randomly into a control group and groups receiving either alginate gel or a sodium hyaluronate carboxymethylcellulose (HA/CMC) film around the anastomosis (n = 25 each). Carprofen, given in a daily dose of 1.25 mg/kg, was used to compromise anastomotic healing. At day three, animals were killed and scored for signs of anastomotic leakage and the presence of adhesions. RESULTS: The incidence of adhesion formation was 95% in the HA/CMC film group, which was significantly higher than in the controls (64%, p = 0.010) and the alginate gel group (52%, p = 0.004). The adhesion score was nearly 40% lower in the alginate gel group compared with the HA/CMC film group. The incidence of ileal leakage in the HA/CMC film group (92%) was significantly higher than in the controls (68%, p = 0.016). Leakage rate did not differ between the alginate gel and control groups. There was no significant difference between groups in either incision bursting pressure or incision breaking strength. CONCLUSION: Ultrapure alginate gel does not interfere with repair of ileal anastomoses constructed under conditions in which chances of anastomotic dehiscence are high. The alginate gel performs better than the HA/CMC film.

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.

The therapeutic efficacy of allyl isothiocyanate in cows with bovine digital dermatitis.

Bovine digital dermatitis (BDD) is the most prevalent infectious cause of lameness in cattle. Because Treponema infection is a major etiology of BDD, the most common treatment of BDD is an antibiotic. Nonetheless, dairy cows require a withdrawal period after antibiotic treatment before their milk can be marketed. To address the problem, in this study, we tested whether 3 nonantibiotic agents (used separately)-allyl isothiocyanate (AITC), sodium alginate, and calcium hydroxide-alleviate BDD lesions in dairy cows. The AITC treatment improved the BDD lesions, whereas the sodium alginate and calcium hydroxide treatments did not. Therapeutic efficacy of AITC was similar to that of lincomycin, a topical antibiotic prescribed for BDD. These results suggest that AITC is a promising nonantibiotic agent for BDD treatment in dairy cows.

OligoG CF-5/20 normalizes cystic fibrosis mucus by chelating calcium.

The goal of this study was to determine whether the guluronate (G) rich alginate OligoG CF-5/20 (OligoG) could detach cystic fibrosis (CF) mucus by calcium chelation, which is also required for normal mucin unfolding. Since bicarbonate secretion is impaired in CF, leading to insufficient mucin unfolding and thereby attached mucus, and since bicarbonate has the ability to bind calcium, we hypothesized that the calcium chelating property of OligoG would lead to detachment of CF mucus. Indeed, OligoG could compete with the N-terminus of the MUC2 mucin for calcium binding as shown by microscale thermophoresis. Further, effects on mucus thickness and attachment induced by OligoG and other alginate fractions of different length and composition were evaluated in explants of CF mouse ileum mounted in horizontal Ussing-type chambers. OligoG at 1.5% caused effective detachment of CF mucus and the most potent alginate fraction tested, the poly-G fraction of about 12 residues, had similar potency compared to OligoG whereas mannuronate-rich (M) polymers had minimal effect. In conclusion, OligoG binds calcium with appropriate affinity without any overt harmful effect on the tissue and can be exploited for treating mucus stagnation.

Medical Treatment of Gastroesophageal Reflux Disease.

Medical treatment is effective in the majority of patients with gastroesophageal reflux disease (GERD). Lifestyle modifications are often recommended for patients with GERD, although the data supporting lifestyle recommendations are limited. Antacids are often used to treat the symptoms of GERD, but their effect is short-lived. H2-receptor antagonists and proton-pump inhibitors provide more effective options for remission of GERD symptoms and healing of esophagitis. Prokinetic medications (e.g., metoclopramide) have not been proven to help in the control of symptoms. Baclofen, which inhibits transient lower esophageal sphincter relaxations, provide an additional option for patients with persistent symptoms related to GERD; however its use is limited by side effects. Long-term medical therapy for GERD should be tailored to each patient to provide symptomatic control and maintain esophageal mucosal healing.

A Retrospective Study of Pilonidal Sinus Healing by Secondary Intention Using Negative Pressure Wound Therapy Versus Alginate or Gauze Dressings.

Pilonidal sinus (PS) disease is an inflammatory skin and subcutaneous tissue condition that presents with infection, acute abscess, chronic discharging wounds, and/or pain. Surgery with open healing by secondary intention typically is used to achieve the fastest healing time with minimal recurrence rates. A retrospective analysis was conducted of data extracted from the medical records of 73 consecutive patients who had symptomatic natal cleft PS over a 10-year period to compare use of NPWT to alginate-based/gauze daily dressing (DD) changes in terms of healing time and recurrence. Variables extracted included age, gender, PS wound diameter (small <1 cm, medium 1 cm to 3 cm, large >3 cm), and time in weeks to achieving the endpoint (epithelialization). Risk factors examined that can affect healing or recurrence of previously operated PS disease included initial drainage before excision and risk factors for impaired healing (morbid obesity as determined by body mass index [BMI] ≥35, chronic infective skin conditions, and ongoing therapy with immuno-modulating drugs or chemotherapy), and loss to follow-up. Data were collected and analyzed using the chi-squared statistic, Kaplan-Meier curves, and Cox regression models. The total time of follow-up was 390 weeks for the DD group and 311 weeks for NPWT group. Patient mean age was 26.5 ± 10.7 years, most (53, 72.6%) were male, and 12 (16.4%) had comorbidities potentially affecting healing. Nine (9) were treated with primary closure and 62 patients were treated with open healing by secondary intention (2 additional patients receiving DD were excluded from the analysis because they had small sinuses that made NPWT unfeasible). Among participants, 30 (48%) received DD and 32 had NPWT. The median time to healing was 10 weeks (95% CI: 7-17) in the DD group and 8 weeks (95% CI: 7-9) in the NPWT group (not significantly different). In patients who healed, the average time to healing was 15.0 ± 18.1 and 9.8 ± 6.3 weeks in the DD and NPWT groups, respectively (not significantly different). The PS wound recurred in 5 patients - 4 (12.5%) in the DD group and 1 (3.1%) in the NPWT group (P = .355). In univariate analysis, only the presence of comorbidities was found to significantly affect time to healing (HR 95%, CI: 0.40 [0.17-0.93]; P = .033]. Prospective, randomized controlled clinical studies are warranted.

Restoring Ovarian Endocrine Function with Encapsulated Ovarian Allograft in Immune Competent Mice.

Premature ovarian insufficiency (POI) is a major complication of cytotoxic treatments due to extreme ovarian sensitivity to chemotherapy and radiation. In pediatric cancer patients modern therapy has improved the long-term survival to over 80% in the United States. However, these cancer survivors face long-term health problems related to treatment toxicity. In female cancer survivors POI leads to sterility, along with the consequences of estrogen deficiency such as premature osteopenia, muscle wasting, accelerated cardiovascular diseases and a vast array of other health and developmental problems. These long-lasting effects are particularly significant for young girls reaching puberty. As such, restoring ovarian endocrine function is paramount in this population. In the present study, we evaluated the feasibility of restoring ovarian endocrine function in ovariectomized mice by transplanting syngeneic and allogeneic ovarian tissue encapsulated in alginate capsules or TheraCyte®. Histological analysis of the implants retrieved after 7 and 30 days' post implantation showed follicular development up to the secondary and antral stages in both syngeneic and allogeneic implants. Implantation of syngeneic and allogeneic ovarian grafts encapsulated in TheraCyte devices restored ovarian endocrine function, which was confirmed by decreased serum FSH levels from 60 to 70 ng/mL in ovariectomized mice to 30-40 ng/mL 30 days after implantation. Absence of allo-MHC-specific IgG and IgM antibodies in the sera of implanted mice with allogeneic ovarian tissue encapsulated in TheraCyte indicate that the implants did not evoke an allo-immune response, while the allogeneic controls were rejected 21 days after implantation. Our results show that TheraCyte effectively isolates the graft from immune recognition but also supports follicular growth.

Three-Arm Randomized Trial of Sodium Alginate for Preventing Radiation-Induced Esophagitis in Locally Advanced Non-Small Cell Lung Cancer Receiving Concurrent Chemoradiotherapy: The OLCSG1401 Study Protocol.

Concurrent chemoradiotherapy (CRT) is the standard of care for locally advanced non-small cell lung cancer (LA-NSCLC). However, this intensive therapy often causes severe esophagitis, which could deteriorate a patient's quality of life (QOL), leading to poor treatment compliance. Sodium alginate, approved in Japan for gastritis, is sufficiently highly viscous to remain in the esophageal mucosa, providing a protective effect in the esophagus. To investigate whether this compound has a preventive effect against severe esophagitis in patients receiving concurrent CRT, we plan a 3-arm randomized trial of sodium alginate with 2 different schedules versus water. The primary endpoint is set as the proportion of patients with grade ≥ 3 esophagitis using the Common Terminology Criteria for Adverse Events, version 4.0. With stratification by institute, performance status, and percentage of the esophageal volume receiving >35 Gy, the patients will be randomly assigned to 1 of the following groups: sodium alginate initiated concomitantly with CRT (group A), sodium alginate initiated soon after the development of extremely mild esophagitis during CRT (group B), or water administered throughout CRT (group C). Assuming that the proportion of grade ≥ 3 esophagitis would be 8% in groups A and B and 27% in group C, the required sample size would be 200 patients, with 70% power and 5% α. The secondary endpoints include QOL, the frequency of additional prescriptions of analgesics, treatment response, and survival. The results of the present study will clarify whether sodium alginate can prevent esophagitis in patients with LA-NSCLC undergoing CRT.

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.

Designing tragacanth gum based sterile hydrogel by radiation method for use in drug delivery and wound dressing applications.

Present article discusses synthesis and characterization of the sterile and pure hydrogel wound dressings which were prepared through radiation method by using polyvinyl alcohol (PVA), tragacanth gum (TG) and sodium alginate (SA). The polymer films were characterized by SEM, Cryo-SEM, FTIR, solid state C(13) NMR and XRD, TGA, and DSC. Some important biological properties such as O2 permeability, water vapor transmission rate, microbial permeability, haemolysis, thrombogenic behavior, antioxidant activity, bio-adhesion and mechanical properties were also studied. The hydrogel film showed thrombogenicity (82.43±1.54%), haemolysis (0.83±0.09%), oxygen permeability (6.433±0.058mg/L) and water vapor permeability (197.39±25.34g/m(2)/day). Hydrogel films were found biocompatible and impermeable to microbes. The release of antibiotic drug moxifloxacin occurred through non-Fickian mechanism and release profile was best fitted in Hixson-Crowell model for drug release. Overall, these results indicate the suitability of these hydrogels in wound dressing applications.

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.

An Experimental Study on the Use of Calcium Alginate to Heal Colonic Anastomoses.

BACKGROUND: Anastomotic leak is considered the major complication following abdominal surgery. In recent years, the use of a variety of sealing materials for the prevention of leaks has been analyzed. Different biomaterials have been employed as scaffolds to favour tissue repair and regeneration. Among these materials we must mention alginate, a natural polymer with different applications as temporary supporting matrix. The aim of the present study is to evaluate the behavior of both alginate-impregnated sutures and lyophilized alginate sponges in the healing process of colonic anastomes using an experimental animal model. MATERIAL AND METHODS: A preliminary study was undertaken to select the adequate scaffold. Animals (n = 45) were distributed into three groups: control (colonic anastomosis using non-continuous 5-0 Polyglactin 910 suture), suture (colonic anastomosis using suture impregnated with alginate gel at 4%) and sponge (colonic anastomosis using suture reinforced with lyophilized alginate sponge). The macroscopic and histological variables were assessed at 4, 8 and 12 days after surgical intervention. RESULTS: No statistically significant differences have been observed between the groups during the analysis of macroscopic variables. Animals with sponge implantation showed a greater degree of epithelial reepithalization, less acute and chronic inflammation and greater collagen deposit. CONCLUSIONS: The use of lyophilized alginate sponges to reinforce colonic anastomoses in an animal model reduces inflammation and promotes the earlier formation of greater collagen deposits without increasing the number of adhesions or the incidence of stenosis.

[DEVELOPMENT RESEARCH OF BIOLOGICAL DRESSING].

OBJECTIVE: To review the research progress of modern biological dressings. METHODS: The related literature at home and abroad was reviewed, analyzed, and summarized in the progress of biological dressing situation and various types of biological dressing research. RESULTS: Compared with the traditional dressing, the biological dressing can greatly promote wound healing. Biological dressings are mainly divided into the natural materials, artificial synthetic materials, and drug loaded dressings. The natural material dressings are mainly the alginate dressing, this kind of dressing can promote wound healing, which has been confirmed by a large number of studies. The artificial synthetic materials include film dressings, liquid, water colloids, gels, and foam, each has its own advantages and disadvantages, which can be chosen according to need. The drug dressing can play the role of drug loading, and further promote the wound healing; using microcapsule technology to construct the dressing and choosing Chinese medicine as drugs is the research direction of load. CONCLUSION: The experiment and clinical application of biological dressing are many types, clinical application prospect is wide, but each has its own advantages and disadvantages, further study is needed to improve its efficacy.

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.

Efficacy and Safety of Ultrapure Alginate-Based Anti-Adhesion Gel in Experimental Peritonitis.

BACKGROUND: Intra-abdominal infection may lead to adhesion and abscess formation. An adhesion barrier can reduce these complications but also aggravate intra-peritoneal infection, causing the opposite effects. The fear of infection propagation has limited clinical adhesion barrier use in a contaminated or infected abdomen. This study evaluated both adhesion and abscess reduction and infection propagation of a new ultrapure alginate-based anti-adhesive barrier gel in a rat peritonitis model. METHODS: In 64 male Wistar rats, bacterial peritonitis was induced via intra-abdominal injection of a mixture of sterile feces, 10(5) colony-forming units (CFU) of Escherichia coli, and 10(4) CFU of Bacteroides fragilis. Surgical debridement and peritoneal lavage were performed 1 h after inoculation. Animals were randomly allocated in equal numbers to a control group or an alginate gel group. Animals were sacrificed on day five post-operatively. Death and the presence and size of intra-abdominal abscesses were noted, and adhesions were scored. All outcomes were compared in the two groups. RESULTS: Seventeen rats (27%) died prematurely without any difference between the groups. Of the surviving rats in the alginate gel group, 88% developed abscesses vs. 100% of the control group. There was no significant difference in the abscess scores or incidence rates of adhesion formation between the groups. The adhesion scores were lower for the alginate gel group compared with control animals (p=0.04). CONCLUSION: Ultrapure alginate gel reduces adhesion severity but not abscesses. The gel seemed to be safe, not aggravating intra-peritoneal infection in this abdominal infection model.