A chemo-enzymatic method for preparation of saturated oligosaccharides from alginate and other uronic acid-containing polysaccharides.

Oligosaccharides from uronic acid-containing polysaccharides can be produced either by chemical or enzymatic degradation. The benefit of using enzymes, called lyases, is their high specificity for various glycosidic linkages. Lyases cleave the polysaccharide chain by an β-elimination reaction, yielding oligosaccharides with an unsaturated sugar (4-deoxy-l-erythro-hex-4-enepyranosyluronate) at the non-reducing end.

Difference in SII provided by initial fit and NAL-NL2 and its relation to self-reported hearing aid outcomes.

Objective: The speech intelligibility index (SII) is used to quantify the audibility of the speech. This study examined the relationship between self-reported hearing aid (HA) outcomes and the difference in aided SII (SII) calculated from the initial fit (IF) gain and that prescribed as per the second generation of National Acoustic Laboratory Non-Linear (NAL-NL2).

Design: A prospective observational study.

Structure-Activity Relationships of Low Molecular Weight Alginate Oligosaccharide Therapy against .

Low molecular weight alginate oligosaccharides have been shown to exhibit anti-microbial activity against a range of multi-drug resistant bacteria, including . Previous studies suggested that the disruption of calcium (Ca)-DNA binding within bacterial biofilms and dysregulation of quorum sensing (QS) were key factors in these observed effects. To further investigate the contribution of Ca binding, G-block (OligoG) and M-block alginate oligosaccharides (OligoM) with comparable average size DPn 19 but contrasting Ca binding properties were prepared.

Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms.

Background: The increasing prevalence of invasive fungal infections in immuno-compromised patients is a considerable cause of morbidity and mortality. With the rapid emergence of antifungal resistance and an inadequate pipeline of new therapies, novel treatment strategies are now urgently required.

Methods: The antifungal activity of the alginate oligosaccharide OligoG in conjunction with nystatin was tested against a range of spp.

Can real-ear insertion gain deviations from generic fitting prescriptions predict self-reported outcomes?

Objective: The aim of this study was to determine whether the differences in insertion gains from the first fit to generic prescriptions of hearing aids can predict the self-reported hearing aid (HA) outcomes for first-time and experienced HA users.

Design: This was a prospective observational study.

Study Sample: The study included 885 first-time and 330 experienced HA users with a valid real-ear measurement on both ears and answers to the abbreviated version of the Speech, Spatial, and Quality of Hearing (SSQ12) and the International Outcome Inventory for Hearing Aids (IOI-HA) questionnaires.

Alginate oligosaccharides enhance diffusion and activity of colistin in a mucin-rich environment.

In a number of chronic respiratory diseases e.g. cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), the production of viscous mucin reduces pulmonary function and represents an effective barrier to diffusion of inhaled therapies e.

Evaluating the alginate oligosaccharide (OligoG) as a therapy for Burkholderia cepacia complex cystic fibrosis lung infection.

OligoG has previously shown potentiation of aztreonam against Burkholderia cepacia complex (Bcc) through biofilm disruption. A randomized, double-blind, placebo-controlled cross-over design was used to evaluate safety and efficacy of inhaled OligoG as a therapy for Bcc-infected CF patients taking aztreonam. Subjects received OligoG (1050 mg daily) or matching placebo for 28-days.

Phenotypic and Genotypic Adaptations in Pseudomonas aeruginosa Biofilms following Long-Term Exposure to an Alginate Oligomer Therapy.

Chronic lung infections in cystic fibrosis (CF) evolve to generate environmentally adapted biofilm communities, leading to increased patient morbidity and mortality. OligoG CF-5/20, a low-molecular-weight inhaled alginate oligomer therapy, is currently in phase IIb/III clinical trials in CF patients. Experimental evolution of in response to OligoG CF-5/20 was assessed using a bead biofilm model allowing continuous passage (45 days; ∼245 generations).

Implementation of microbiota analysis in clinical trials for cystic fibrosis lung infection: Experience from the OligoG phase 2b clinical trials.

Culture-independent microbiota analysis is widely used in research and being increasingly used in translational studies. However, methods for standardisation and application of these analyses in clinical trials are limited. Here we report the microbiota analysis that accompanied two phase 2b clinical trials of the novel, non-antibiotic therapy OligoG CF-5/20 for cystic fibrosis (CF) lung infection.

Exploiting Mannuronan C-5 Epimerases in Commercial Alginate Production.

Alginates are one of the major polysaccharide constituents of marine brown algae in commercial manufacturing. However, the content and composition of alginates differ according to the distinct parts of these macroalgae and have a direct impact on the concentration of guluronate and subsequent commercial value of the final product. The mannuronan C-5 epimerases AlgE1 and AlgE4 were used to determine their potential value in tailoring the production of high guluronate low-molecular-weight alginates from two sources of high mannuronic acid alginates, the naturally occurring harvested brown algae (, and ) and a pure mannuronic acid alginate derived from fermented production of the mutant strain of NCIMB 10,525.

Bi-Functional Alginate Oligosaccharide-Polymyxin Conjugates for Improved Treatment of Multidrug-Resistant Gram-Negative Bacterial Infections.

The recent emergence of resistance to colistin, an antibiotic of last resort with dose-limiting toxicity, has highlighted the need for alternative approaches to combat infection. This study aimed to generate and characterise alginate oligosaccharide ("OligoG")-polymyxin (polymyxin B and E (colistin)) conjugates to improve the effectiveness of these antibiotics. OligoG-polymyxin conjugates (amide- or ester-linked), with molecular weights of 5200-12,800 g/mol and antibiotic loading of 6.

Inhaled dry powder alginate oligosaccharide in cystic fibrosis: a randomised, double-blind, placebo-controlled, crossover phase 2b study.

Background: OligoG is a low molecular-weight alginate oligosaccharide that improves the viscoelastic properties of cystic fibrosis (CF) mucus and disrupts biofilms, thereby potentiating the activity of antimicrobial agents. The efficacy of inhaled OligoG was evaluated in adult patients with CF.

Methods: A randomised, double-blind, placebo-controlled multicentre crossover study was used to demonstrate safety and efficacy of inhaled dry powder OligoG.

Effectiveness of a Community-Based Weight Management Program for Patients Taking Antidepressants and/or Antipsychotics.

Objective: This study aimed to compare weight loss (WL) outcomes for patients taking antidepressants and/or antipsychotics with those not taking psychiatric medication.

Methods: A total of 17,519 adults enrolled in a lifestyle WL intervention at the Wharton Medical Clinics in Ontario, Canada, were analyzed. Sex-stratified multivariable linear regression analysis was used to examine the association of taking antidepressants, antipsychotics, both, or neither with WL when adjusting for age, initial weight, and treatment time.

Cellulose Nanofibril Formulations Incorporating a Low-Molecular-Weight Alginate Oligosaccharide Modify Bacterial Biofilm Development.

Cellulose nanofibrils (CNFs) from wood pulp are a renewable material possessing advantages for biomedical applications because of their customizable porosity, mechanical strength, translucency, and environmental biodegradability. Here, we investigated the growth of multispecies wound biofilms on CNF formulated as aerogels and films incorporating the low-molecular-weight alginate oligosaccharide OligoG CF-5/20 to evaluate their structural and antimicrobial properties. Overnight microbial cultures were adjusted to 2.

Efficacy of High-Dose Liraglutide as an Adjunct for Weight Loss in Patients with Prior Bariatric Surgery.

Background: Bariatric surgery is the most effective long-term treatment of severe obesity. Unfortunately, many patients experience inadequate weight loss, weight plateau, or weight recidivism. We sought to determine the efficacy of high-dose liraglutide (3.

Targeted disruption of the extracellular polymeric network of biofilms by alginate oligosaccharides.

Acquisition of a mucoid phenotype by sp. in the lungs of cystic fibrosis (CF) patients, with subsequent over-production of extracellular polymeric substance (EPS), plays an important role in mediating the persistence of multi-drug resistant (MDR) infections. The ability of a low molecular weight (Mn = 3200 g mol) alginate oligomer (OligoG CF-5/20) to modify biofilm structure of mucoid (NH57388A) was studied in vitro using scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM) with Texas Red (TxRd®)-labelled OligoG and EPS histochemical staining.

Liraglutide Effects on Upper Gastrointestinal Investigations: Implications Prior to Bariatric Surgery.

Liraglutide is a glucagon-like peptide type 1 (GLP-1) analogue that is approved for long-term obesity management in North America. While bariatric surgery remains the gold standard for weight loss, an increasing number of patients are on liraglutide in the setting of ongoing workup for bariatric surgery. The presence of gastrointestinal symptoms prior to bariatric surgery may prompt testing for dysmotility, which affects surgical decision making.

Alginate Oligosaccharide-Induced Modification of the and Quorum-Sensing Systems in Pseudomonas aeruginosa.

plays a major role in many chronic infections. Its ability to readily form biofilms contributes to its success as an opportunistic pathogen and its resistance/tolerance to antimicrobial/antibiotic therapy. A low-molecular-weight alginate oligomer (OligoG CF-5/20) derived from marine algae has previously been shown to impair motility in biofilms and disrupt pseudomonal biofilm assembly.

Alginate oligosaccharides modify hyphal infiltration of Candida albicans in an in vitro model of invasive human candidosis.

Aims: A novel alginate oligomer (OligoG CF-5/20) has been shown to potentiate antifungal therapy against a range of fungal pathogens. The current study assessed the effect of this oligomer on in vitro virulence factor expression and epithelial invasion by Candida species.

Methods And Results: Plate substrate assays and epithelial models were used to assess Candida albicans (CCUG 39343 and ATCC 90028) invasion, in conjunction with confocal laser scanning microscopy and histochemistry.

A Low-Molecular-Weight Alginate Oligosaccharide Disrupts Pseudomonal Microcolony Formation and Enhances Antibiotic Effectiveness.

In chronic respiratory disease, the formation of dense, 3-dimensional "microcolonies" by within the airway plays an important role in contributing to resistance to treatment. An biofilm model of pseudomonal microcolony formation using artificial-sputum (AS) medium was established to study the effects of low-molecular-weight alginate oligomers (OligoG CF-5/20) on pseudomonal growth, microcolony formation, and the efficacy of colistin. The studies employed clinical cystic fibrosis (CF) isolates ( = 3) and reference nonmucoid and mucoid multidrug-resistant (MDR) CF isolates ( = 7).

The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption.

Concerns about acquisition of antibiotic resistance have led to increasing demand for new antimicrobial therapies. OligoG CF-5/20 is an alginate oligosaccharide previously shown to have antimicrobial and antibiotic potentiating activity. We investigated the structural modification of the bacterial cell wall by OligoG CF-5/20 and its effect on membrane permeability.

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.