The Interaction of Large Bowel Microflora with the Colonic Mucus Barrier

The colonic mucus barrier is the first line of defence that the underlying mucosa has against the wide range of potentially damaging agents of microbial, endogenous, and dietary origin that occur within the colonic lumen. The functional component of mucus is the secreted, polymeric glycoprotein mucin. The mucus barrier can either act as an energy source or a support medium for growth to the intestinal microflora. The mucus barrier appears to effectively partition the vast number of microbial cells from the underlying epithelium. The normal functionality and biochemistry of this mucus barrier appears to be lost in diseases of the colorectal mucosa. Germ-free animal studies have highlighted the necessity of the presence of the colonic microflora to drive the maturation of the colonic mucosa and normal mucus production. A number of by-products of the microflora have been suggested to be key luminal drivers of colonic mucus secretion

Dynamic Modelling of a Two-link Flexible Manipulator System Incorporating Payload

This paper presents dynamic modelling of a twolink flexible manipulator based on closed-form equations of motion. The kinematic model is based on standard frame transformation matrices describing both rigid rotation and modal displacement, under small deflection assumption. The Lagrangian approach is used to derive the dynamic model of the structure. Links are modelled as Euler-Bernoulli beams with proper clamped-mass boundary conditions. A dynamic model of the system, incorporating structural damping, hub inertia and payload, is developed using finite assumed mode methods. Explicit equations of motions are detailed by assuming two modes of vibration for each link. Moreover, effects of payload on the response of the flexible manipulator are discussed. Extensive results that validate the theoretical derivation are presented in the time and frequency domains

The immunoregulatory and allergy-associated cytokines in the aetiology of the otitis media with effusion.

Inflammation in the middle ear mucosa, which can be provoked by different primary factors such as bacterial and viral infection, local allergic reactions and reflux, is the crucial event in the pathogenesis of otitis media with effusion (OME). Unresolved acute inflammatory responses or defective immunoregulation of middle inflammation can promote chronic inflammatory processes and stimulate the chronic condition of OME. Cytokines are the central molecular regulators of middle ear inflammation and can switch the acute phase of inflammation in the chronic stage and induce molecular-pathological processes leading to the histopathological changes accompanying OME. In this review we present cytokines identified in otitis media, immunoregulatory [interleukin (IL)-2, IL-10, transforming growth factor-beta]) and allergy associated (IL-4, IL-5, granulocyte-macrophage colony-stimulating factor), as crucial molecular regulators, responsible for chronic inflammation in the middle ear and the chronic condition of OME

Alginate as a protease inhibitor in vitro and in a model gut system; selective inhibition of pepsin but not trypsin

Alginates are widely used in the food and medical industries, including as a Gastro-Oesophagul Reflux treatment. This work investigates the inhibitory effects of alginate on the reflux aggressors trypsin and pepsin and the role of alginate-substrate binding, pH and alginate structure on inhibition. Alginates were shown to reduce pepsin activity by up to 53.9% (±9.5SD) in vitro. Strong positive correlation between alginate mannuronate residue frequency and levels of pepsin inhibition was observed. Limited inhibition of trypsin was shown. Viscometric observations of pH dependent interactions between alginate and protein suggest a mechanism whereby pH dependent ionic interactions reduce substrate availability to enzyme at acidic pH. To understand how dietary protein digestion is affected by alginate, proteolytic digestion was investigated in an in vitro model of the upper digestive tract. Significant inhibition of proteolysis was shown in the gastric phase of digestion, but not the small intestinal phase

Acceptability of alginate enriched bread and its effect on fat digestion in humans

Lifestyle interventions and physical activity remain the cornerstone of obesity management, as pharmacological therapies (orlistat) are associated with gastrointestinal (GI) side effects. Combining orlistat with fibers can reduce side effects, improving compliance. Therefore, a fiber that inhibits lipase without side effects could help treat obesity. The aims of the present work were to assess whether alginate enriched bread could inhibit fat digestion, and assess the acceptability of alginate bread and its effect on GI wellbeing. A double-blind, randomised, controlled cross-over pilot study (NCT03350958) assessed the impact of an alginate bread meal on; lipid content in ileal effluent and circulating triacylglycerol levels. This was compared against the same meal with non-enriched (control) bread. GI wellbeing and acceptability of alginate bread was compared to control bread through daily wellbeing questionnaires and food diaries (NCT03477981). Control bread followed by alginate bread were consumed for two weeks respectively. Consumption of alginate bread reduced circulating triacylglycerol compared to control (2% reduction in AUC) and significantly increased lipid content in ileal effluent (3.8 g ± 1.6 after 210 min). There were no significant changes to GI wellbeing when comparing alginate bread to control bread. A significant increase in the feeling of fullness occurred with alginate bread compared to baseline and the first week of control bread consumption. This study showed that sustained consumption of alginate enriched bread does not alter GI wellbeing and can decrease lipolysis, increasing lipid leaving the small intestine. Further studies are required to demonstrate that reduced fat digestion through the action of alginate can reduce fat mass or body weight

Biological activity of alginate and its effect on pancreatic lipase inhibition as a potential treatment for obesity

Alginates are classed as a dietary fibre and have been shown to inhibit digestive enzymes in vitro, and therefore could be used as an obesity treatment. The current study aims to assess whether alginate in a bread vehicle maintains its inhibition properties despite cooking and digestion, and may therefore be used as a potential treatment for obesity. After 180 min in a model gut that replicates digestion in the mouth, stomach and small intestines alginate bread (AB), control bread (CB), CB with Manucol® DM alginate, free DM alginate and model gut solution were collected. DM, LFR 5/60 and SF200 were heated at 37 °C and 200 °C, with DM also heated at 50, 100 and 150 °C. Samples from the model gut and heated alginate were assessed for molecular size and inhibition properties using viscosity, gel filtration and a lipase turbidity assay. AB does not significantly increase viscosity in the model gut. Viscosity of alginate reduces beyond 100 °C, although alginate retains its inhibition properties up to 150 °C. Cooking into the bread does not reduce the molecular size of the alginate or affect its inhibition properties. These data demonstrate the robustness of alginates lipase inhibition despite the cooking process and digestion. Therefore adding alginate to a bread vehicle may have the potential in the treatment for obesity

Molecular phylogeny of Burkholderia pseudomallei from a remote region of Papua New Guinea

Background The island of New Guinea is located midway between the world's two major melioidosis endemic regions of Australia and Southeast Asia. Previous studies in Papua New Guinea have demonstrated autochthonous melioidosis in Balimo, Western province. In contrast to other regions of endemicity, isolates recovered from both environmental and clinical sources demonstrate narrow genetic diversity over large spatial and temporal scales. Methodology/Principal Findings We employed molecular typing techniques to determine the phylogenetic relationships of these isolates to each other and to others worldwide to aid in understanding the origins of the Papua New Guinean isolates. Multi-locus sequence typing of the 39 isolates resolved three unique sequence types. Phylogenetic reconstruction and Structure analysis determined that all isolates were genetically closer to those from Australia than those from Southeast Asia. Gene cluster analysis however, identified a Yersinia-like fimbrial gene cluster predominantly found among Burkholderia pseudomallei derived from Southeast Asia. Higher resolution VNTR typing and phylogenetic reconstruction of the Balimo isolates resolved 24 genotypes with long branch lengths. These findings are congruent with long term persistence in the region and a high level of environmental stability. Conclusions/Significance Given that anthropogenic influence has been hypothesized as a mechanism for the dispersal of B. pseudomallei, these findings correlate with limited movement of the indigenous people in the region. The palaeogeographical and anthropogenic history of Australasia and the results from this study indicate that New Guinea is an important region for the further study of B. pseudomallei origins and dissemination

Whole-genome sequencing of Burkholderia pseudomallei isolates from an unusual melioidosis case identifies a polyclonal infection with the same multilocus sequence type

Twelve Burkholderia pseudomallei isolates collected over a 32-month period from a patient with chronic melioidosis demonstrated identical multilocus sequence types (STs). However, whole-genome sequencing suggests a polyclonal infection. This study is the first to report a mixed infection with the same ST

Mucin Gene Expression in Reflux Laryngeal Mucosa: Histological and In Situ

Objectives/Hypothesis. To determine if laryngopharyngeal reflux alters mucin gene expression in laryngeal mucosa. Methods. In situ hybridization was employed to study the expression of the 8 well-characterised mucin genes MUC1-4, 5AC, 5B, 6, and 7 in reflux laryngeal mucosa from laryngeal ventricles, posterior commissures, and vocal folds compared to control/normal laryngeal mucosa. Results. MUC1-5 genes are expressed in normal and reflux laryngeal mucosa. MUC1, 3 and 4 are expressed in respiratory and squamous mucosa whereas MUC2 and 5AC are expressed in respiratory mucosa only. MUC3, 4 and 5AC are downregulated in reflux mucosa. MUC5AC expression is significantly reduced in the 3 mucosal sites and when mucosal type was taken into account, this remains significant in combined laryngeal and ventricular mucosa only. Conclusions. MUC3, 4 and 5AC expression is downregulated in laryngopharyngeal reflux. This may be due to laryngeal mucosal metaplasia and/or alteration of mucin gene expression in the preexisting mucosa. Altered mucin gene expression might predispose laryngeal mucosa to the damaging effect of reflux