Science.gov

Sample records for adherent mucus levels

  1. Adherence of bacteria to mucus collected from different parts of the reproductive tract of heifers and cows.

    PubMed

    Styková, E; Nemcová, R; Valocký, I; Novotný, F; Guba, P

    2013-11-01

    In the present study, we examined the adherence of indigenous vaginal bacteria, probiotic strains, and metritis pathogens to mucus collected from different parts of the reproductive tracts of heifers and cows and compared their adherence with the bacterial adherence to mucus collected from the stomach and large intestine of pigs. Most of the vaginal strains adhered to mucus collected from different parts of the reproductive tract and strongly adhered to gastric mucus, with the exception of Lactobacillus buchneri 24S8. Only Lactobacillus mucosae 29S8, Enterococcus faecium E21, and E. faecium EAC adhered to colonic mucus. Probiotic strains adhered strongly to mucus collected from the reproductive tract and gastric mucus but did not adhere to colonic mucus. Pathogenic strains were adherent to vaginal, uterine horn, and gastric mucus, except Escherichia coli O8:K88ab:H9 (65), Fusobacterium necrophorum, and Gardnerella vaginalis, which adhered to uterine cervix mucus. Only Kocuria kristinae and G. vaginalis adhered to uterine body mucus; E. coli O149:K88ac (EC) adhered to colonic mucus. The strains did not exhibit host specificity but rather strain specificity. The ability to adhere to mucus was a characteristic unique to each strain. To our knowledge, this is the first report regarding in vitro adherence of GRAS (Generally Regarded As Safe) lactobacilli isolated from different sources to mucus collected from different parts of the reproductive tract. PMID:24206354

  2. Modulation of Pseudomonas aeruginosa adherence to the corneal surface by mucus.

    PubMed Central

    Fleiszig, S M; Zaidi, T S; Ramphal, R; Pier, G B

    1994-01-01

    To gain access to the corneal epithelium and cause infections keratitis, bacterial pathogens must first interact with ocular surface factors that could affect bacterial adherence. In this study, we demonstrated that the mucus layer, and, in particular, the mucin fraction of mucus, modulated adherence to intact corneal epithelium of Pseudomonas aeruginosa but not that of Staphylococcus aureus or Streptococcus pyogenes. Removal of endogenous mucus from rat or rabbit eyes increased the adherence of P. aeruginosa by 3- to 10-fold. Ocular mucus obtained from rat eyes, porcine stomach mucin, or bovine submaxillary gland mucin inhibited adherence of P. aeruginosa to uninjured corneal epithelium. The mucin fraction of ocular mucus, purified by ultracentrifugation, was found to contain the inhibitory activity, and inhibition was demonstrated at concentrations of mucin as low as 35 micrograms/ml. Ocular mucin was the only material tested that inhibited adherence of P. aeruginosa to an injured cornea. However, the binding of P. aeruginosa to immobilized substrates in vitro did not predict which fraction would possess antiadherence activity: bacteria bound well to whole ocular mucus, mucin, the nonmucin fraction of ocular mucus, and dilute human tears as well as to porcine stomach mucin and bovine submaxillary gland mucin. The effectiveness of the mucin fraction of ocular mucus at inhibiting the binding of P. aeruginosa to the cornea implies that this material is a barrier that protects the surface of the eye from P. aeruginosa adherence. PMID:8168942

  3. Butyrate enemas upregulate Muc genes expression but decrease adherent mucus thickness in mice colon.

    PubMed

    Gaudier, E; Rival, M; Buisine, M-P; Robineau, I; Hoebler, C

    2009-01-01

    Colonic mucosal protection is provided by the mucus gel, mainly composed of mucins. Several factors can modulate the formation and the secretion of mucins, and among them butyrate, an end-product of carbohydrate fermentation. However, the specific effect of butyrate on the various colonic mucins, and the consequences in terms of the mucus layer thickness are not known. Our aim was to determine whether butyrate modulates colonic MUC genes expression in vivo and whether this results in changes in mucus synthesis and mucus layer thickness. Mice received daily for 7 days rectal enemas of butyrate (100 mM) versus saline. We demonstrated that butyrate stimulated the gene expression of both secreted (Muc2) and membrane-linked (Muc1, Muc3, Muc4) mucins. Butyrate especially induced a 6-fold increase in Muc2 gene expression in proximal colon. However, butyrate enemas did not modify the number of epithelial cells containing the protein Muc2, and caused a 2-fold decrease in the thickness of adherent mucus layer. Further studies should help understanding whether this last phenomenon, i.e. the decrease in adherent mucus gel thickness, results in a diminished protective function or not. PMID:18198997

  4. Helicobacter pylori in vivo causes structural changes in the adherent gastric mucus layer but barrier thickness is not compromised

    PubMed Central

    Newton, J; Jordan, N; Oliver, L; Strugala, V; Pearson, J; James, O; Allen, A

    1998-01-01

    Background—It has been proposed that a pathogenic effect of Helicobacter pylori is a weakening of the protective mucus barrier; however, this remains controversial. 
Aims—To clarify the effects of H pylori infection on the mucus gel barrier in vivo. 
Methods—Mucus gel polymeric structure and the thickness of the adherent mucus barrier were measured in endoscopic biopsy samples in subjects with and without H pylori infection. 
Results—There was a significant 18% reduction in the proportion of polymeric gel forming mucin in the adherent mucus layer in H pylori positive compared with negative subjects. There was no change in the adherent mucus thickness between H pylori positive and negative subjects without gastric atrophy (mean (SD): 104(26) µm, 106 (30) µm respectively). There was however a significant reduction in mucus thickness in those H pylori positive subjects with underlying gastric atrophy (84 (13) µm, p=0.03) compared with those without atrophy. 
Conclusions—A partial breakdown in gel forming structure of the gastric mucus barrier does occur in H pylori infection per se but this is insufficient to cause a collapse of the mucus barrier. 

 Keywords: Helicobacter pylori; gastric mucus PMID:9824571

  5. Influence of chronic nicotine intake and acute ethanol challenge on gastric mucus level and blood flow in rabbits.

    PubMed

    Luk, I S; Ho, J; Wong, W M; Yuen, S T; Luk, C T; Cho, C H

    1994-01-01

    The effects of nicotine pretreatment on ethanol-induced gastric mucosal lesions and changes of gastric mucosal mucus levels and blood flow (GBF) were studied in anaesthetized rabbits. Nicotine treatment 25 or 50 micrograms/ml drinking water did not affect the volume of water consumption during the 10-day experimental period. It did not produce gastric mucosal lesions or affect the superficial adherent mucus content. The length of mucus-containing cells and the basal GBF were also unaffected. Intragastric administration of absolute ethanol reduced GBF, this effect was not altered by nicotine. However, the alkaloid potentiated the ulcerogenic actions of ethanol both on lesion formation and mucus depletion evoked by graded oral doses of ethanol (50 or 100%, v/v). Ultrastructurally, the mucous cells were more degenerated in the animals co-treated with nicotine and ethanol. It is concluded that reductions of mucus-containing cells and adherent mucus on the gastric mucosa are likely to be the contributory factors involved in the aggravating action of nicotine on ethanol-induced gastric mucosal lesions in rabbits. PMID:7535712

  6. Cloning of a genetic determinant from Clostridium difficile involved in adherence to tissue culture cells and mucus.

    PubMed Central

    Karjalainen, T; Barc, M C; Collignon, A; Trollé, S; Boureau, H; Cotte-Laffitte, J; Bourlioux, P

    1994-01-01

    Our laboratory has previously shown that Clostridium difficile adherence to Caco-2 cells is greatly enhanced after heat shock at 60 degrees C and that it is mediated by a proteinaceous surface component. The experiments described here show that C. difficile could adhere to several types of tissue culture cells (Vero, HeLa, and KB) after heat shock. The type of culture medium (liquid or solid, with or without blood) had little effect on adhesion. To clone the adhesin gene, polyclonal antibodies against C. difficile heated at 60 degrees C were used to screen a genomic library of C. difficile constructed in lambda ZapII. Ten positive clones were identified in the library, one of which (pCL6) agglutinated several types of erythrocytes in the presence of mannose. In Western blots (immunoblots), this clone expressed in Escherichia coli a 40- and a 27-kDa protein; a 27-kDa protein has been previously identified in the surface extracts of heat-shocked C. difficile as a possible adhesin. The clone adhered to Vero, Caco-2, KB, and HeLa cells; the adherence was blocked by anti-C. difficile antibodies, by a surface extract of C. difficile, and by mucus isolated from axenic mice. Furthermore, the clone could attach ex vivo to intestinal mucus isolated from axenic mice. Preliminary studies on the receptor moieties implicated in C. difficile adhesion revealed that glucose and galactose could partially block adhesion to tissue culture cells, as did di- or trisaccharides containing these sugars, suggesting that the adhesin is a lectin. In addition, N-acetylgalactosamine, a component of mucus, and gelatin partially impeded cell attachment. Images PMID:7927694

  7. Genomic Characterization of Non-Mucus-Adherent Derivatives of Lactobacillus rhamnosus GG Reveals Genes Affecting Pilus Biogenesis

    PubMed Central

    Rasinkangas, Pia; Reunanen, Justus; Douillard, François P.; Ritari, Jarmo; Uotinen, Virva; Palva, Airi

    2014-01-01

    Lactobacillus rhamnosus GG is one of the best-characterized lactic acid bacteria and can be considered a probiotic paradigm. Comparative and functional genome analysis showed that L. rhamnosus GG harbors a genomic island including the spaCBA-srtC1 gene cluster, encoding the cell surface-decorating host-interacting pili. Here, induced mutagenesis was used to study pilus biogenesis in L. rhamnosus GG. A combination of two powerful approaches, mutation selection and next-generation sequencing, was applied to L. rhamnosus GG for the selection of pilus-deficient mutants from an enriched population. The isolated mutants were first screened by immuno-dot blot analysis using antiserum against pilin proteins. Relevant mutants were selected, and the lack of pili was confirmed by immunoelectron microscopy. The pilosotype of 10 mutant strains was further characterized by analyzing pilin expression using Western blot, dot blot, and immunofluorescence methods. A mucus binding assay showed that the mutants did not adhere to porcine intestinal mucus. Comparative genome sequence analysis using the Illumina MiSeq platform allowed us to determine the nature of the mutations in the obtained pilus-deficient derivatives. Three major classes of mutants with unique genotypes were observed: class I, with mutations in the srtC1 gene; class II, with a deletion containing the spaCBA-srtC1 gene cluster; and class III, with mutations in the spaA gene. Only a limited number of collateral mutations were observed, and one of the pilus-deficient derivatives with a deficient srtC1 gene contained 24 other mutations. This strain, PB12, can be considered a candidate for human trials addressing the impact of the absence of pili. PMID:25192985

  8. Active microrheology reveals molecular-level variations in the viscoelastic properties of Chaetopterus mucus

    NASA Astrophysics Data System (ADS)

    Weigand, William; Messmore, Ashley; Anderson, Rae

    The sea annelid, Chaetopterus Variopedatus, secretes a bioluminescent mucus that also exhibits complex viscoelastic properties. The constituents of the mucus are relatively unknown but it does play an important role in the development of the worms' parchment-like housing tubes. In order to determine how and why this mucus can exhibit material properties ranging from fluidity to rigidity we perform microrheology experiments. We determine the microscale viscoelastic properties by using optical tweezers to produce small oscillations in the mucus which allow us to determine both the linear storage and loss moduli (G',G'') along with the viscosity of the fluid. By varying the size of the microspheres (2-10 µm) and oscillation amplitude (.5-10 µm) we are able to determine the dominant intrinsic length scales of the molecular mesh comprising the mucus. By varying the oscillation frequency (1-15Hz) we determine the crossover frequency at which G' surpasses G'', to quantify the longest relaxation time of the mesh network. Initial results show a strong dependence on bead size which indicate that the dominant entanglement lengthscale of the mucus mesh is ~5 um. Microspheres of this size exhibit a wide variety of stress responses in different regions of the mucus demonstrating the substantial microscale heterogeneity of the mucus. We carry out measurements on a population of worms of varying size and age to determine mucus variability between worms.

  9. Binding of type 1-piliated Escherichia coli to vaginal mucus.

    PubMed Central

    Venegas, M F; Navas, E L; Gaffney, R A; Duncan, J L; Anderson, B E; Schaeffer, A J

    1995-01-01

    To better understand the interactions involved in bacterial adherence and the role of mucus in the pathogenesis of urinary tract infections, we developed a system to study the binding of a recombinant Escherichia coli strain, HB101/pWRS1-17, expressing type 1 pili, to vaginal mucus collected from 28 women. Bacteria bound to differing extents to all specimens examined, and preincubation of bacteria with mannose inhibited binding by 50 to 89%. Additionally, all mucus samples showed reactivity with anti-mannose antibody, and the levels of reactivity correlated with the levels of bacterial binding, suggesting that the mannose-terminal saccharides present on these glycoproteins are the receptors for the binding of type 1-piliated bacteria. Mucus specimens collected over periods of 5 days and 12 weeks exhibited significant variation in bacterial binding, indicating temporal differences in the ability of vaginal mucus to act as a receptor for type 1-piliated E. coli. The results show that vaginal mucus can bind bacteria and may thus influence the initial attachment and subsequent colonization of the vaginal and urinary tract epithelium by E. coli. PMID:7822005

  10. Ferret tracheal mucus rheology, clearability and volume following administration of substance P or methacholine.

    PubMed

    De Sanctis, G T; Rubin, B K; Ramirez, O; King, M

    1993-01-01

    We studied the effects of substances P administration on tracheal mucus viscoelasticity, water content, clearability and secretion rate. Six neutered adult male ferrets (weight 1.1-1.5 kg) were studied, on four occasions each. They were anaesthetized with ketamine and xylazine, and intubated shallowly. Control mucus (pre- and post-Ringer instillation) was compared with the mucus obtained following instillation of 200 microliters of 10(-6), 10(-5), and 10(-4) M substance P (SP), and 10(-4) M methacholine chloride as a reference. Tracheal mucus was collected by inserting a soft-bristled cytology brush to the level of the carina, and leaving it in contact with the mucosa for 30 min. After withdrawing the brush, the adherent mucus was quickly scraped off and layered with paraffin oil to prevent evaporation. The mucus was analysed for viscoelasticity by magnetic rheometry and solids content by evaporation to dryness. Mucus transportability was assessed by comparison with model gels, and also by means of the frog palate assay, which indicates how well mucus is cleared by normal ciliary action. There was a dose-related increase in mucus volume, and a dose-related decrease in mucus viscosity and elasticity, with substance P administration. Mucus transportability increased with both substance P and methacholine. The effects of 10(-4) SP and methacholine were comparable in terms of viscoelasticity and volume; with both methacholine and SP, there appeared to be an additive effect. The mucus solids content did not correlate with the viscoelastic changes for SP administration, whereas it did for methacholine. These observations suggest that the hypersecretion induced by these two agents might involve different pathways. PMID:7678818

  11. Micro- and macrorheology of mucus

    PubMed Central

    Lai, Samuel K.; Wang, Ying-Ying; Wirtz, Denis; Hanes, Justin

    2009-01-01

    Mucus is a complex biological material that lubricates and protects the human lungs, gastrointestinal (GI) tract, vagina, eyes, and other moist mucosal surfaces. Mucus serves as a physical barrier against foreign particles, including toxins, pathogens, and environmental ultrafine particles, while allowing rapid passage of selected gases, ions, nutrients, and many proteins. Its selective barrier properties are precisely regulated at the biochemical level across vastly different length scales. At the macroscale, mucus behaves as a non-Newtonian gel, distinguished from classical solids and liquids by its response to shear rate and shear stress, while, at the nanoscale, it behaves as a low viscosity fluid. Advances in the rheological characterization of mucus from the macroscopic to nanoscopic levels have contributed critical understanding to mucus physiology, disease pathology, and the development of drug delivery systems designed for use at mucosal surfaces. This article reviews the biochemistry that governs mucus rheology, the macro- and microrheology of human and laboratory animal mucus, rheological techniques applied to mucus, and the importance of an improved understanding of the physical properties of mucus to advancing the field of drug and gene delivery. PMID:19166889

  12. Screening the ability of natural feed ingredients to interfere with the adherence of enterotoxigenic Escherichia coli (ETEC) K88 to the porcine intestinal mucus.

    PubMed

    González-Ortiz, Gemma; Pérez, José Francisco; Hermes, Rafael Gustavo; Molist, Francesc; Jiménez-Díaz, Rufino; Martín-Orúe, Susana María

    2014-02-01

    The inhibition of the attachment of bacteria to the intestine by receptor analogues could be a novel approach to prevent enterotoxigenic Escherichia coli (ETEC) K88-induced diarrhoea in piglets. The objective of the present study was to screen the ability of different feed ingredients (FI) to bind to ETEC K88 (adhesion test, AT) and to block its attachment to the porcine intestinal mucus (blocking test, BT) using in vitro microtitration-based models. In the AT, wheat bran (WB), casein glycomacropeptide (CGMP) and exopolysaccharides exhibited the highest adhesion to ETEC K88 (P< 0·001). In the BT, WB, CGMP and locust bean (LB) reduced the number of ETEC K88 attached to the intestinal mucus (P< 0·001). For WB and LB, fractionation based on their carbohydrate components was subsequently carried out, and each fraction was evaluated individually. None of the WB fractions reduced the adhesion of ETEC K88 to the mucus as did the original extract, suggesting that a protein or glycoprotein could be involved in the recognition process. With regard to the LB fractions, the water-extractable material reduced the adhesion of ETEC K88 (P< 0·001) to the mucus similar to the original extract (P< 0·001), indicating, in this case, that galactomannans or phenolic compounds could be responsible for the recognition process. In conclusion, among the FI screened, the soluble extracts obtained from WB, LB and CGMP exhibited the highest anti-adhesive properties against ETEC K88 in the BT. These results suggest that they may be good candidates to be included in diets of weaned piglets for the prevention of ETEC K88-induced diarrhoea. PMID:24047890

  13. Antiretroviral regimen and suboptimal medication adherence are associated with low-level human immunodeficiency virus viremia.

    PubMed

    Konstantopoulos, Christina; Ribaudo, Heather; Ragland, Kathleen; Bangsberg, David R; Li, Jonathan Z

    2015-01-01

    Episodes of human immunodeficiency virus low-level viremia (LLV) are common in the clinical setting, but its association with antiretroviral therapy (ART) regimen and adherence remains unclear. Antiretroviral therapy adherence was evaluated in participants of the Research on Access to Care in the Homeless cohort by unannounced pill counts. Factors associated with increased risk of LLV include treatment with a protease inhibitor (PI)-based regimen (ritonavir-boosted PI vs nonnucleoside reverse-transcriptase inhibitor: adjusted hazard ratio [HR], 3.1; P = .01) and lower ART adherence over the past 3 months (HR, 1.1 per 5% decreased adherence, adjusted; P = .050). Patients with LLV may benefit from ART adherence counseling and potentially regimen modification. PMID:25884007

  14. Aggregate versus day level association between methamphetamine use and HIV medication non-adherence among gay and bisexual men

    PubMed Central

    Parsons, Jeffrey T.; Kowalczyk, William; Botsko, Michael; Tomassilli, Julia; Golub, Sarit A.

    2013-01-01

    Methamphetamine use is associated with HIV infection, especially among gay and bisexual men. Methamphetamine use contributes to disease progression both directly, by increasing viral load and damaging the immune system, and indirectly, by decreasing medication adherence. Research examining the association of methamphetamine use and non-adherence has traditionally compared groups of users and nonusers on adherence, compared methamphetamine use between participants above or below some threshold level of adherence (e.g. >90% dose adherence), or examined aggregate relationships. Using Timeline Follow-back procedures, the present study examined aggregate, threshold, and day-level associations of methamphetamine use with non-adherence in 210 HIV-positive gay and bisexual methamphetamine-using men. Methamphetamine use was not associated with adherence behavior at the aggregate-level, but methamphetamine use on a given day was associated with 2.3 times the odds of non-adherence on that day. Threshold results were equivocal. These data suggest that the methamphetamine and non-adherence relationship is complicated: non-adherence is more likely to occur on days in which methamphetamine is used, but participants reported more non-adherence days in which methamphetamine was not used. This seeming paradox generates questions about the selection of analytical techniques and has important implications for behavioral interventions targeting substance use and adherence among HIV-positive individuals. PMID:23553345

  15. Supramolecular Dynamics of Mucus

    PubMed Central

    Verdugo, Pedro

    2012-01-01

    Our purpose here is not to address specific issues of mucus pathology, but to illustrate how polymer networks theory and its remarkable predictive power can be applied to study the supramolecular dynamics of mucus. Avoiding unnecessary mathematical formalization, in the light of available theory, we focus on the rather slow progress and the still large number of missing gaps in the complex topology and supramolecular dynamics of airway mucus. We start with the limited information on the polymer physics of respiratory mucins to then converge on the supramolecular organization and resulting physical properties of the mucus gel. In each section, we briefly discuss progress on the subject, the uncertainties associated with the established knowledge, and the many riddles that still remain. PMID:23125200

  16. Difference in Effectiveness of Medication Adherence Intervention by Health Literacy Level

    PubMed Central

    Owen-Smith, Ashli A; Smith, David H; Rand, Cynthia S; Tom, Jeffrey O; Laws, Reesa; Waterbury, Amy; Williams, Andrew; Vollmer, William M

    2016-01-01

    Context: There is little research investigating whether health information technologies, such as interactive voice recognition, are effective ways to deliver information to individuals with lower health literacy. Objective: Determine the extent to which the impact of an interactive voice recognition-based intervention to improve medication adherence appeared to vary by participants’ health literacy level. Design: Promoting Adherence to Improve Effectiveness of Cardiovascular Disease Therapies (PATIENT) was a randomized clinical trial designed to test the impact, compared with usual care, of 2 technology-based interventions that leveraged interactive voice recognition to promote medication adherence. A 14% subset of participants was sent a survey that included questions on health literacy. This exploratory analysis was limited to the 833 individuals who responded to the survey and provided data on health literacy. Main Outcome Measures: Adherence to statins and/or angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers. Results: Although intervention effects did not differ significantly by level of health literacy, the data were suggestive of differential intervention effects by health literacy level. Conclusions: The differences in intervention effects for high vs low health literacy in this exploratory analysis are consistent with the hypothesis that individuals with lower health literacy may derive greater benefit from this type of intervention compared with individuals with higher health literacy. Additional studies are needed to further explore this finding. PMID:27352409

  17. Oral Drug Delivery with Polymeric Nanoparticles: The Gastrointestinal Mucus Barriers

    PubMed Central

    Ensign, Laura M.; Cone, Richard; Hanes, Justin

    2012-01-01

    Oral delivery is the most common method for drug administration. However, poor solubility, stability, and bioavailability of many drugs make achieving therapeutic levels via the gastrointestinal (GI) tract challenging. Drug delivery must overcome numerous hurdles, including the acidic gastric environment and the continuous secretion of mucus that protects the GI tract. Nanoparticle drug carriers that can shield drugs from degradation and deliver them to intended sites within the GI tract may enable more efficient and sustained drug delivery. However, the rapid secretion and shedding of GI tract mucus can significantly limit the effectiveness of nanoparticle drug delivery systems. Many types of nanoparticles are efficiently trapped in and rapidly removed by mucus, making controlled release in the GI tract difficult. This review addresses the protective barrier properties of mucus secretions, how mucus affects the fate of orally administered nanoparticles, and recent developments in nanoparticles engineered to penetrate the mucus barrier. PMID:22212900

  18. Nanoparticle diffusion in respiratory mucus from humans without lung disease

    PubMed Central

    Schuster, Benjamin S.; Suk, Jung Soo; Woodworth, Graeme F.; Hanes, Justin

    2013-01-01

    A major role of respiratory mucus is to trap inhaled particles, including pathogens and environmental particulates, to limit body exposure. Despite the tremendous health implications, how particle size and surface chemistry affect mobility in respiratory mucus from humans without lung disease is not known. We prepared polymeric nanoparticles densely coated with low molecular weight polyethylene glycol (PEG) to minimize muco-adhesion, and compared their transport to that of uncoated particles in human respiratory mucus, which we collected from the endotracheal tubes of surgical patients with no respiratory comorbidities. We found that 100 and 200 nm diameter PEG-coated particles rapidly penetrated respiratory mucus, at rates exceeding their uncoated counterparts by approximately 15- and 35-fold, respectively. In contrast, PEG-coated particles ≥ 500 nm in diameter were sterically immobilized by the mucus mesh. Thus, even though respiratory mucus is a viscoelastic solid at the macroscopic level (as measured using a bulk rheometer), nanoparticles that are sufficiently small and muco-inert can penetrate the mucus as if it were primarily a viscous liquid. These findings help elucidate the barrier properties of respiratory mucus and provide design criteria for therapeutic nanoparticles capable of penetrating mucus to approach the underlying airway epithelium. PMID:23384790

  19. Influence of carp intestinal mucus molecular size and glycosylation on bacterial adhesion.

    PubMed

    Schroers, V; Van Der Marel, M; Steinhagen, D

    2008-08-27

    The first step of the pathogenesis of many infectious diseases is the colonisation of the mucosal surface by the pathogen. Bacterial colonisation of the mucosal surface is promoted by adherence to high molecular weight mucus glycoproteins. We examined the effect of carp intestinal mucus glycoproteins on the adhesion of different bacteria. The bacteria used were 3 strains of Aeromonas hydrophila, and A. salmonicida, Edwardsiella tarda and Yersinia ruckeri. All bacteria adhered to mucus, but at varying intensities. All tested bacteria adhered best to molecules of 670 to 2000 kDa in size, less to molecules larger than 2000 kDa and weakest to molecules of 30 to 670 kDa. In general, bacteria that showed a stronger adhesion to intestinal mucus were cytotoxic to cells in vitro, and bacteria that showed a weaker adhesion to intestinal mucus did not lead to alterations of monolayers of EPC-cells. Furthermore, the involvement of glycan side chains of the glycoproteins for bacterial adhesion was analysed for one A. hydrophila strain. After cleavage of terminal sugar residues by treatment of mucus glycoproteins with different glycosidases, binding of bacteria was modulated. When mannose was cleaved off, adhesion significantly increased. Blocking of glycan receptors by incubation of bacteria with different oligosaccharides had no clear effect on bacterial binding to mucus glycoproteins. Our results suggest that bacteria interact with carbohydrate side chains of mucus glycoproteins, and that the carbohydrates of the core region are involved in bacterial binding. PMID:18924378

  20. Variability of erythrocyte and serum lithium levels correlates with therapist treatment adherence efforts and maintenance treatment outcome.

    PubMed

    Taylor, R; Mallinger, A G; Frank, E; Rucci, P; Thase, M E; Kupfer, D J

    2001-02-01

    This study investigated the relationship between psychotherapeutic interventions and pharmacologic measures of pharmacotherapy treatment adherence in patients with bipolar I disorder, as well as the relationship between these measures and treatment outcome. Subjects were participating in an ongoing maintenance treatment study. Audiotaped therapy sessions were rated for frequency of psychotherapeutic interventions related to pharmacotherapy treatment adherence. Pharmacologic measures of medication adherence were compared to the tape ratings as well as to treatment outcome. Variability in log erythrocyte (RBC) lithium-a marker of probable nonadherence to the pharmacotherapy regimen-for individual patients correlated significantly with treatment adherence interventions scale ratings. This marker of nonadherence was significantly related to maintenance treatment outcome, as was variability of the serum lithium level/dose (L/D) ratio; however, no relationship was found between treatment adherence interventions scale ratings and outcome. PMID:11120401

  1. Health Care System-level Factors Associated With Performance on Medicare STAR Adherence Metrics in a Large, Integrated Delivery System

    PubMed Central

    Nichols, Gregory A.; Dyer, Wendy; Steiner, John F.; Karter, Andrew J.; Raebel, Marsha A.

    2015-01-01

    Background: The Centers for Medicare and Medicaid Services provide significant incentives to health plans that score well on Medicare STAR metrics for cardiovascular disease risk factor medication adherence. Information on modifiable health system-level predictors of adherence can help clinicians and health plans develop strategies for improving Medicare STAR scores, and potentially improve cardiovascular disease outcomes. Objective: To examine the association of Medicare STAR adherence metrics with system-level factors. Research Design: A cross-sectional study. Subjects: A total of 129,040 diabetes patients aged 65 years and above in 2010 from 3 Kaiser Permanente regions. Measures: Adherence to antihypertensive, antihyperlipidemic, and oral antihyperglycemic medications in 2010, defined by Medicare STAR as the proportion of days covered ≥80%. Results: After controlling for individual-level factors, the strongest predictor of achieving STAR-defined medication adherence was a mean prescribed medication days’ supply of >90 days (RR=1.61 for antihypertensives, oral antihyperglycemics, and statins; all P<0.001). Using mail order pharmacy to fill medications >50% of the time was independently associated with better adherence with these medications (RR=1.07, 1.06, 1.07; P<0.001); mail order use had an increased positive association among black and Hispanic patients. Medication copayments ≤$10 for 30 days’ supply (RR=1.02, 1.02, 1.02; P<0.01) and annual individual out-of-pocket maximums ≤$2000 (RR=1.02, 1.01, 1.02; P<0.01) were also significantly associated with higher adherence for all 3 therapeutic groupings. Conclusions: Greater medication days’ supply and mail order pharmacy use, and lower copayments and out-of-pocket maximums, are associated with better Medicare STAR adherence. Initiatives to improve adherence should focus on modifiable health system-level barriers to obtaining evidence-based medications. PMID:25719517

  2. Rethinking adherence.

    PubMed

    Steiner, John F

    2012-10-16

    In 2012, the Centers for Medicare & Medicaid Services (CMS) will introduce measures of adherence to oral hypoglycemic, antihypertensive, and cholesterol-lowering drugs into its Medicare Advantage quality program. To meet these quality goals, delivery systems will need to develop and disseminate strategies to improve adherence. The design of adherence interventions has too often been guided by the mistaken assumptions that adherence is a single behavior that can be predicted from readily available patient characteristics and that individual clinicians alone can improve adherence at the population level.Effective interventions require recognition that adherence is a set of interacting behaviors influenced by individual, social, and environmental forces; adherence interventions must be broadly based, rather than targeted to specific population subgroups; and counseling with a trusted clinician needs to be complemented by outreach interventions and removal of structural and organizational barriers. To achieve the adherence goals set by CMS, front-line clinicians, interdisciplinary teams, organizational leaders, and policymakers will need to coordinate efforts in ways that exemplify the underlying principles of health care reform. PMID:23070491

  3. Functional Characterization of a Mucus-Specific LPXTG Surface Adhesin from Probiotic Lactobacillus rhamnosus GG ▿

    PubMed Central

    von Ossowski, Ingemar; Satokari, Reetta; Reunanen, Justus; Lebeer, Sarah; De Keersmaecker, Sigrid C. J.; Vanderleyden, Jos; de Vos, Willem M.; Palva, Airi

    2011-01-01

    In spite of the wealth of clinical evidence supporting the health benefits of Lactobacillus rhamnosus GG in humans, there is still a lack of understanding of the molecular mechanisms behind its probiosis. Current knowledge suggests that the health-promoting effects of this probiotic strain might be partly dependent on its persistence in the intestine and adhesion to mucosal surfaces. Moreover, L. rhamnosus GG contains mucus-binding pili that might also explain the occupation of its ecological niche as a comparatively less stringent allochthonous intestine-dwelling bacterium. To uncover additional surface proteins involved in mucosal adhesion, we investigated the adherence properties of the only predicted protein (LGG_02337) in L. rhamnosus GG that exhibits homology with a known mucus-binding domain. We cloned a recombinant form of the gene for this putative mucus adhesin and established that the purified protein readily adheres to human intestinal mucus. We also showed that this mucus adhesin is visibly distributed throughout the cell surface and participates in the adhesive interaction between L. rhamnosus GG and mucus, although less prominently than the mucus-binding pili in this strain. Based on primary structural comparisons, we concluded that the current annotation of the LGG_02337 protein likely does not accurately reflect its predicted properties, and we propose that this mucus-specific adhesin be called the mucus-binding factor (MBF). Finally, we interpret our results to mean that L. rhamnosus GG MBF, as an active mucus-specific surface adhesin with a presumed ancillary involvement in pilus-mediated mucosal adhesion, plays a part in the adherent mechanisms during intestinal colonization by this probiotic. PMID:21602388

  4. Functional characterization of a mucus-specific LPXTG surface adhesin from probiotic Lactobacillus rhamnosus GG.

    PubMed

    von Ossowski, Ingemar; Satokari, Reetta; Reunanen, Justus; Lebeer, Sarah; De Keersmaecker, Sigrid C J; Vanderleyden, Jos; de Vos, Willem M; Palva, Airi

    2011-07-01

    In spite of the wealth of clinical evidence supporting the health benefits of Lactobacillus rhamnosus GG in humans, there is still a lack of understanding of the molecular mechanisms behind its probiosis. Current knowledge suggests that the health-promoting effects of this probiotic strain might be partly dependent on its persistence in the intestine and adhesion to mucosal surfaces. Moreover, L. rhamnosus GG contains mucus-binding pili that might also explain the occupation of its ecological niche as a comparatively less stringent allochthonous intestine-dwelling bacterium. To uncover additional surface proteins involved in mucosal adhesion, we investigated the adherence properties of the only predicted protein (LGG_02337) in L. rhamnosus GG that exhibits homology with a known mucus-binding domain. We cloned a recombinant form of the gene for this putative mucus adhesin and established that the purified protein readily adheres to human intestinal mucus. We also showed that this mucus adhesin is visibly distributed throughout the cell surface and participates in the adhesive interaction between L. rhamnosus GG and mucus, although less prominently than the mucus-binding pili in this strain. Based on primary structural comparisons, we concluded that the current annotation of the LGG_02337 protein likely does not accurately reflect its predicted properties, and we propose that this mucus-specific adhesin be called the mucus-binding factor (MBF). Finally, we interpret our results to mean that L. rhamnosus GG MBF, as an active mucus-specific surface adhesin with a presumed ancillary involvement in pilus-mediated mucosal adhesion, plays a part in the adherent mechanisms during intestinal colonization by this probiotic. PMID:21602388

  5. High levels of fish oil enhance neutrophil development and activation and influence colon mucus barrier function in a genetically susceptible mouse model.

    PubMed

    Duriancik, David M; Comstock, Sarah S; Langohr, Ingeborg M; Fenton, Jenifer I

    2015-11-01

    Dietary fatty acids influence immunologic homeostasis, but their effect on initiation of colitis, an immune-mediated disease, is not well established. Previously, our laboratory demonstrated that high doses of dietary fish oil (FO) increased colon inflammation and dysplasia in a model of infection-induced colitis. In the current study, we assessed the effects of high-dose dietary FO, 6% by weight, on colon inflammation, neutrophil recruitment and function, and mucus layer integrity in a genetically susceptible, colitis-prone mouse model in the absence of infection. FO-fed SMAD3(-/-) mice had increased colon inflammation evidenced by increased numbers of systemic and local neutrophils and increased neutrophil chemoattractant and inflammatory cytokine gene expression in the colon. Mucus layer thickness in the cecum and goblet cell numbers in the cecum and colon in FO-fed mice were reduced compared to control. FO consumption affected colitis in male and female mice differently. Compared to female control mice, neutrophils from FO-fed female mice had reduced reactive oxygen species (ROS) upon ex vivo stimulation with phorbol myristate acetate while FO-fed male mice produced increased ROS compared to control-fed male mice. In summary, dietary FO impaired mucus layer integrity and was associated with colon inflammation characterized by increased neutrophil numbers and altered neutrophil function. High-dose FO may have detrimental effects in populations genetically susceptible for inflammatory bowel disease and these effects may differ between males and females. PMID:26297475

  6. Human cervical mucus: research update.

    PubMed

    Katz, D F

    1991-12-01

    Evaluation of cervical mucus is a standard for determining the fertile period in natural family planning. Cervical mucus accepts, filters, prepares, and releases sperm for successful transport to the egg and fertilization. Recent scientific advances provide answers to how the mucus regulates fertility as its physical properties change during the menstrual cycle. Transmission electron microscopy reveals small interstices between mucus macromolecules relative to a sperm head. Thus advancing sperm must push aside or cut through the microstructure. The interstices are largest in the periovulatory phase of the cycle. Small magnetic spheres, comparable with the size of a sperm head, are now being used to study the physical properties of the mucus on the scale of individual sperm. PMID:1755453

  7. Chemotaxis towards, adhesion to, and growth in carp gut mucus of two Aeromonas hydrophila strains with different pathogenicity for common carp, Cyprinus carpio L.

    PubMed

    van der Marel, M; Schroers, V; Neuhaus, H; Steinhagen, D

    2008-05-01

    Characteristics that promote bacterial colonization of the intestinal mucosal surface were examined in two strains of the common fish pathogen Aeromonas hydrophila, with different pathogenicity. The characteristics examined were chemotactic activity towards mucus, bacterial adherence to mucus and growth in mucus. Intestinal gut mucus of healthy common carp was used. The results indicate that chemotaxis is not necessary for a bacterium to become pathogenic, but it may be a necessary parameter for a bacterium to be an obligate pathogen. Adhesion also seems to be a factor influencing pathogenicity. The results suggest that higher adhesion to mucus and subsequent growth is associated with differences in pathogenicity. PMID:18355183

  8. Clearance of a Mucus Plug

    NASA Astrophysics Data System (ADS)

    Bian, Shiyao; Zheng, Ying; Grotberg, James B.

    2008-11-01

    Mucus plugging may occur in pulmonary airways in asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. How to clear the mucus plug is essential and of fundamental importance. Mucus is known to have a yield stress and a mucus plug behaves like a solid plug when the applied stresses are below its yield stress τy. When the local stresses reaches τy, the plug starts to move and can be cleared out of the lung. It is then of great importance to examine how the mucus plug deforms and what is the minimum pressure required to initiate its movement. The present study used the finite element method (FEM) to study the stress distribution and deformation of a solid mucus plug under different pressure loads using ANSYS software. The maximum shear stress is found to occur near the rear transition region of the plug, which can lead to local yielding and flow. The critical pressure increases linearly with the plug length and asymptotes when the plug length is larger than the half channel width. Experimentally a mucus simulant is used to study the process of plug deformation and critical pressure difference required for the plug to propagate. Consistently, the fracture is observed to start at the rear transition region where the plug core connects the films. However, the critical pressure is observed to be dependent on not only the plug length but also the interfacial shape.

  9. Treatment adherence in schizophrenia: a patient-level meta-analysis of combined CATIE and EUFEST studies.

    PubMed

    Czobor, Pál; Van Dorn, Richard A; Citrome, Leslie; Kahn, Rene S; Fleischhacker, W Wolfgang; Volavka, Jan

    2015-08-01

    The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) obtained a sample of 1493 chronic schizophrenia patients. The European First Episode Schizophrenia Trial (EUFEST) studied a sample of 498 patients. We have combined these two samples to study the predictors and correlates of adherence to treatment. Here we report on adherence to pharmacological treatment at the six and twelve month assessments of these trials with a combined subsample of 1154 schizophrenia patients. Individual patients׳ data were used for analyses. We used logistic regression to examine the effects of substance use, akathisia, parkinsonism, dyskinesia, hostility, and insight on pharmacological adherence. The results showed that reduced adherence to pharmacological treatment was associated with substance use (p=0.0003), higher levels of hostility (p=0.0002), and impaired insight (p<0.0001). Furthermore, poor adherence to study medication was associated with earlier discontinuation in the combined data. The clinical implications of the results point to the importance of routine assessments and interventions to address patients׳ insight and comorbid substance use and the establishment of therapeutic alliance. PMID:26004980

  10. Floating mucus aggregates derived from benthic microorganisms on rocky intertidal reefs: Potential as food sources for benthic animals

    NASA Astrophysics Data System (ADS)

    Tamura, Y.; Tsuchiya, M.

    2011-09-01

    Mucus films, flocs or foams consisting of fine sand, algae and detritus frequently occur in the surface waters of rocky intertidal reef flats during incoming tide. These masses are referred to as mucus aggregates. We examined the developmental process of mucus aggregates and their abundance, distribution, migration and trophic composition. The trophic composition of mucus aggregates was then compared to those of sediments to evaluate their potential nutritional value for benthic animals. The organic matter content, chlorophyll a concentration, microalgal density and bacteria-derived fatty acid contents of mucus aggregates were higher than those observed in sediment, suggesting that mucus aggregates contain not only high levels of organic matter but also dense concentrations of microalgae and bacteria; therefore, mucus aggregates may serve as a qualitatively more energetic food source for benthic fauna compared to sediments. Benthic diatoms were the most abundant organisms in mucus aggregates. Large numbers of diatoms were trapped in fine mineral particles and mucilage-like strings, suggesting that a portion of the mucus is secreted by these benthic microalgae. Mucus aggregate accounted for only 0.01-3.9% of the daily feeding requirements of the dominant detritivore, Ophiocoma scolopendrina (Echinodermata: Ophiuroidea) over the entire sampling area. In contrast, for the species population on the back reef, where mucus aggregates ultimately accumulate, mucus aggregates provided from 0.4 to 113.3% of food for this species. These results suggest that mucus aggregate availability varies spatiotemporally and that they do not always provide adequate food sources for O. scolopendrina populations.

  11. Event-Level Relationship between Methamphetamine Use Significantly Associated with Non-adherence to Pharmacologic Trial Medications in Event-Level Analyses

    PubMed Central

    Santos, Glenn-Milo; Vittinghoff, Eric; Santos, Deirdre; Colfax, Grant; Coffin, Phillip

    2014-01-01

    Background Methamphetamine use has been previously associated with poor medication adherence, but, to date, there have been no studies that have conducted event-level analyses on correlates of medication adherence in studies of pharmacologic agents for methamphetamine dependence. Methods We pooled data from two previous, randomized controlled trials (using bupropion and mirtazapine, respectively) for methamphetamine dependence and used a mixed effects logistic model to examine correlates of daily opening of the medication event monitoring system (MEMS) cap as a repeated measure. We explored whether periods of observed methamphetamine use via urine testing were associated with study medication adherence based on MEMS cap openings. Results We found a significant negative association between methamphetamine-urine positivity and event-level study medication adherence as measured by MEMS cap openings (AOR: 0.69; 95% CI: 0.49–0.98). In addition, age (AOR: 1.07; 95% CI: 1.02–1.11) and depressive symptoms (AOR: 0.78; 95% CI: 0.64–0.90) were significantly associated with adherence. Finally, participants were more likely to open their study medication bottles on days when they presented for in-person urine testing. Conclusions Our event-level analysis shows that methamphetamine use can be associated with reduced medication adherence as measured by MEMS cap openings in pharmacologic trials, which corroborates prior research. These findings may suggest that medication adherence support in pharmacologic trials among methamphetamine users may be needed to improve study compliance and could be targeted towards periods of time when there are more likely to not open their study medication pill bottles. PMID:25156227

  12. Human Clostridium difficile infection: altered mucus production and composition

    PubMed Central

    Engevik, Melinda A.; Yacyshyn, Mary Beth; Engevik, Kristen A.; Wang, Jiang; Darien, Benjamin; Hassett, Daniel J.; Yacyshyn, Bruce R.

    2014-01-01

    The majority of antibiotic-induced diarrhea is caused by Clostridium difficile (C. difficile). Hospitalizations for C. difficile infection (CDI) have tripled in the last decade, emphasizing the need to better understand how the organism colonizes the intestine and maintain infection. The mucus provides an interface for bacterial-host interactions and changes in intestinal mucus have been linked host health. To assess mucus production and composition in healthy and CDI patients, the main mucins MUC1 and MUC2 and mucus oligosaccharides were examined. Compared with healthy subjects, CDI patients demonstrated decreased MUC2 with no changes in surface MUC1. Although MUC1 did not change at the level of the epithelia, MUC1 was the primary constituent of secreted mucus in CDI patients. CDI mucus also exhibited decreased N-acetylgalactosamine (GalNAc), increased N-acetylglucosamine (GlcNAc), and increased terminal galactose residues. Increased galactose in CDI specimens is of particular interest since terminal galactose sugars are known as C. difficile toxin A receptor in animals. In vitro, C. difficile is capable of metabolizing fucose, mannose, galactose, GlcNAc, and GalNAc for growth under healthy stool conditions (low Na+ concentration, pH 6.0). Injection of C. difficile into human intestinal organoids (HIOs) demonstrated that C. difficile alone is sufficient to reduce MUC2 production but is not capable of altering host mucus oligosaccharide composition. We also demonstrate that C. difficile binds preferentially to mucus extracted from CDI patients compared with healthy subjects. Our results provide insight into a mechanism of C. difficile colonization and may provide novel target(s) for the development of alternative therapeutic agents. PMID:25552581

  13. Mathematical modeling of molecular diffusion through mucus

    PubMed Central

    Cu, Yen; Saltzman, W. Mark

    2008-01-01

    The rate of molecular transport through the mucus gel can be an important determinant of efficacy for therapeutic agents delivered by oral, intranasal, intravaginal/rectal, and intraocular routes. Transport through mucus can be described by mathematical models based on principles of physical chemistry and known characteristics of the mucus gel, its constituents, and of the drug itself. In this paper, we review mathematical models of molecular diffusion in mucus, as well as the techniques commonly used to measure diffusion of solutes in the mucus gel, mucus gel mimics, and mucosal epithelia. PMID:19135488

  14. Liquid crystalline order in mucus

    NASA Technical Reports Server (NTRS)

    Viney, C.; Huber, A. E.; Verdugo, P.

    1993-01-01

    Mucus plays an exceptionally wide range of important biological roles. It operates as a protective, exchange, and transport medium in the digestive, respiratory, and reproductive systems of humans and other vertebrates. Mucus is a polymer hydrogel. It is secreted as discrete packages (secretory granules) by specialized secretory cells. Mucus hydrogel is stored in a condensed state inside the secretory granules. Depending upon the architecture of their constituent macromolecules and on the composition of the solvent, polymer gels can form liquid crystalline microstructures, with orientational order being exhibited over optically resolvable distances. Individual mucin molecules consist of alternating rigid segments (heavily glycosylated; hydrophilic) and flexible segments (nonglycosylated; hydrophobic). Polymer molecules consisting of rigid units linked by flexible spacers are frequently associated with liquid crystalline behavior, which again raises the possibility that mucus could form anisotropic fluid phases. Suggestions that mucins may be self-associating in dilute solution have previously been challenged on the basis of sedimentation-equilibrium studies performed on mucus in which potential sites of association were competitively blocked with inhibitors. However, the formation of stable liquid crystalline phases does not depend on the existence of inter- or intramolecular associations; these phases can form on the basis of steric considerations alone.

  15. Fish mucus versus parasitic gnathiid isopods as sources of energy and sunscreens for a cleaner fish

    NASA Astrophysics Data System (ADS)

    Eckes, Maxi; Dove, Sophie; Siebeck, Ulrike E.; Grutter, Alexandra S.

    2015-09-01

    The cleaning behaviour of the bluestreak cleaner wrasse Labroides dimidiatus is extensively used as a model system for understanding cooperation. It feeds mainly on blood-sucking gnathiid isopods and also on the epidermal mucus of client fish; the nutritional quality of these foods, however, is unknown. The epidermal mucus of reef fish contains ultraviolet (UV)-absorbing compounds (mycosporine-like amino acids, MAAs), which are only obtained via the diet; nevertheless, while La. dimidiatus has high amounts of MAAs in its mucus, their source is unknown. Therefore, the energetic value (calories and protein estimated using carbon and nitrogen) and MAA level in gnathiids and mucus from several clients [parrotfishes, wrasses (Labridae), and a snapper (Lutjanidae)] were determined. The energetic value of mucus and gnathiids varied among fishes. Overall, carbon, nitrogen, calories, and protein per dry weight were higher in the mucus of most client species compared to gnathiids. Thus, depending on the client species, mucus may be energetically more advantageous for cleaner wrasse to feed on than gnathiids. UV absorbance, a confirmed proxy for MAA levels, indicated high MAA levels in mucus, whereas gnathiids had no detectable MAAs. This suggests that La. dimidiatus obtain MAAs from mucus but not from gnathiids. Hence, in addition to energy, the mucus of some clients also provides La. dimidiatus with the added bonus of UV-absorbing compounds. This may explain why cleaner fish prefer to feed on mucus over gnathiid isopods. The likely costs and benefits to clients of the removal of UV protecting mucus and parasitic gnathiids, respectively, and the variation in benefits gained by cleaner fish from feeding on these foods may explain some variation in cooperation levels in cleaning interactions.

  16. Mucus-penetrating nanoparticles for vaginal and gastrointestinal drug delivery

    NASA Astrophysics Data System (ADS)

    Ensign-Hodges, Laura

    A method that could provide more uniform and longer-lasting drug delivery to mucosal surfaces holds the potential to greatly improve the effectiveness of prophylactic and therapeutic approaches for numerous diseases and conditions, including sexually transmitted infections and inflammatory bowel disease. However, the body's natural defenses, including adhesive, rapidly cleared mucus linings coating nearly all entry points to the body not covered by skin, has limited the effectiveness of drug and gene delivery by nanoscale delivery systems. Here, we investigate the use of muco-inert mucus-penetrating nanoparticles (MPP) for improving vaginal and gastrointestinal drug delivery. Conventional hydrophobic nanoparticles strongly adhere to mucus, facilitating rapid clearance from the body. Here, we demonstrate that mucoadhesive polystyrene nanoparticles (conventional nanoparticles, CP) become mucus-penetrating in human cervicovaginal mucus (CVM) after pretreatment with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large MPP did not change in F127 pretreated CVM, implying there is no affect on the native pore structure of CVM. Additionally, there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for one week. Importantly, HSV virus remains adherent in F127-pretreated CVM. Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that hypotonically-induced fluid uptake could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We evaluated hypotonic formulations for delivering water-soluble drugs and for drug delivery with MPP. Hypotonic formulations markedly increased the rate at which drugs and MPP reached the epithelial surface. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that isotonic formulations

  17. Mucus-penetrating nanoparticles for vaginal and gastrointestinal drug delivery

    NASA Astrophysics Data System (ADS)

    Ensign-Hodges, Laura

    A method that could provide more uniform and longer-lasting drug delivery to mucosal surfaces holds the potential to greatly improve the effectiveness of prophylactic and therapeutic approaches for numerous diseases and conditions, including sexually transmitted infections and inflammatory bowel disease. However, the body's natural defenses, including adhesive, rapidly cleared mucus linings coating nearly all entry points to the body not covered by skin, has limited the effectiveness of drug and gene delivery by nanoscale delivery systems. Here, we investigate the use of muco-inert mucus-penetrating nanoparticles (MPP) for improving vaginal and gastrointestinal drug delivery. Conventional hydrophobic nanoparticles strongly adhere to mucus, facilitating rapid clearance from the body. Here, we demonstrate that mucoadhesive polystyrene nanoparticles (conventional nanoparticles, CP) become mucus-penetrating in human cervicovaginal mucus (CVM) after pretreatment with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large MPP did not change in F127 pretreated CVM, implying there is no affect on the native pore structure of CVM. Additionally, there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for one week. Importantly, HSV virus remains adherent in F127-pretreated CVM. Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that hypotonically-induced fluid uptake could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We evaluated hypotonic formulations for delivering water-soluble drugs and for drug delivery with MPP. Hypotonic formulations markedly increased the rate at which drugs and MPP reached the epithelial surface. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that isotonic formulations

  18. Bicarbonate and functional CFTR channel are required for proper mucin secretion and link cystic fibrosis with its mucus phenotype

    PubMed Central

    Gustafsson, Jenny K.; Ermund, Anna; Ambort, Daniel; Johansson, Malin E.V.; Nilsson, Harriet E.; Thorell, Kaisa; Hebert, Hans; Sjövall, Henrik

    2012-01-01

    Cystic fibrosis (CF) is caused by a nonfunctional chloride and bicarbonate ion channel (CF transmembrane regulator [CFTR]), but the link to the phenomenon of stagnant mucus is not well understood. Mice lacking functional CFTR (CftrΔ508) have no lung phenotype but show similar ileal problems to humans. We show that the ileal mucosa in CF have a mucus that adhered to the epithelium, was denser, and was less penetrable than that of wild-type mice. The properties of the ileal mucus of CF mice were normalized by secretion into a high concentration sodium bicarbonate buffer (∼100 mM). In addition, bicarbonate added to already formed CF mucus almost completely restored the mucus properties. This knowledge may provide novel therapeutic options for CF. PMID:22711878

  19. Role of Lactobacillus reuteri cell and mucus-binding protein A (CmbA) in adhesion to intestinal epithelial cells and mucus in vitro.

    PubMed

    Jensen, Hanne; Roos, Stefan; Jonsson, Hans; Rud, Ida; Grimmer, Stine; van Pijkeren, Jan-Peter; Britton, Robert A; Axelsson, Lars

    2014-04-01

    Lactobacillus reuteri, a symbiotic inhabitant of the gastrointestinal tract in humans and animals, is marketed as a probiotic. The ability to adhere to intestinal epithelial cells and mucus is an interesting property with regard to probiotic features such as colonization of the gastrointestinal tract and interaction with the host. Here, we present a study performed to elucidate the role of sortase (SrtA), four putative sortase-dependent proteins (SDPs), and one C-terminal membrane-anchored cell surface protein of Lactobacillus reuteri ATCC PTA 6475 in adhesion to Caco-2 cells and mucus in vitro. This included mutagenesis of the genes encoding these proteins and complementation of mutants. A null mutation in hmpref0536_10255 encoding srtA resulted in significantly reduced adhesion to Caco-2 cells and mucus, indicating involvement of SDPs in adhesion. Evaluation of the bacterial adhesion revealed that of the five putative surface protein mutants tested, only a null mutation in the hmpref0536_10633 gene, encoding a putative SDP with an LPxTG motif, resulted in a significant loss of adhesion to both Caco-2 cells and mucus. Complementation with the functional gene on a plasmid restored adhesion to Caco-2 cells. However, complete restoration of adhesion to mucus was not achieved. Overexpression of hmpref0536_10633 in strain ATCC PTA 6475 resulted in an increased adhesion to Caco-2 cells and mucus compared with the WT strain. We conclude from these results that, among the putative surface proteins tested, the protein encoded by hmpref0536_10633 plays a critical role in binding of Lactobacillus reuteri ATCC PTA 6475 to Caco-2 cells and mucus. Based on this, we propose that this LPxTG motif containing protein should be referred to as cell and mucus binding protein A (CmbA). PMID:24473252

  20. Therapeutic approaches to mucus hypersecretion.

    PubMed

    Yuta, Atsushi; Baraniuk, James N

    2005-05-01

    Mucolytic and related agents have been in use since prehistoric times. Although widely prescribed and used extensively in over-the-counter preparations, their efficacy and mechanisms of action remain in doubt. These agents belong to several distinct chemical classes. Mucolytic agents such as N-acetyl-cysteine are thiols with a free-sulfhydryl group. They are assumed to break disulfide bonds between gel-forming mucins and thus reduce mucus viscosity. Mucokinetic agents are thiols with a blocked sulfhydryl group. Expectorants such as guaifenesin increase mucus secretion. They may act as irritants to gastric vagal receptors, and recruit efferent parasympathetic reflexes that cause glandular exocytosis of a less viscous mucus mixture. Cough may be provoked. This combination may flush tenacious, congealed mucopurulent material from obstructed small airways and lead to a temporary improvement in dyspnea or the work of breathing. The roles of anticholinergic agents, DNase, and other drugs are also discussed with regard to their roles in reducing mucus production in rhinitis and other airway diseases. PMID:15842963

  1. Enumerating viruses in coral mucus.

    PubMed

    Leruste, Amandine; Bouvier, Thierry; Bettarel, Yvan

    2012-09-01

    The distribution of viruses inhabiting the coral mucus remains undetermined, as there is no suitable standardized procedure for their separation from this organic matrix, principally owing to its viscosity and autofluorescence. Seven protocols were tested, and the most efficient separations were obtained from a chemical treatment requiring potassium citrate. PMID:22729548

  2. Divergent Mechanisms of Interaction of Helicobacter pylori and Campylobacter jejuni with Mucus and Mucins

    PubMed Central

    Naughton, Julie Ann; Mariño, Karina; Dolan, Brendan; Reid, Colm; Gough, Ronan; Gallagher, Mary E.; Kilcoyne, Michelle; Gerlach, Jared Q.; Joshi, Lokesh; Rudd, Pauline; Carrington, Stephen; Bourke, Billy

    2013-01-01

    Helicobacter pylori and Campylobacter jejuni colonize the stomach and intestinal mucus, respectively. Using a combination of mucus-secreting cells, purified mucins, and a novel mucin microarray platform, we examined the interactions of these two organisms with mucus and mucins. H. pylori and C. jejuni bound to distinctly different mucins. C. jejuni displayed a striking tropism for chicken gastrointestinal mucins compared to mucins from other animals and preferentially bound mucins from specific avian intestinal sites (in order of descending preference: the large intestine, proximal small intestine, and cecum). H. pylori bound to a number of animal mucins, including porcine stomach mucin, but with less avidity than that of C. jejuni for chicken mucin. The strengths of interaction of various wild-type strains of H. pylori with different animal mucins were comparable, even though they did not all express the same adhesins. The production of mucus by HT29-MTX-E12 cells promoted higher levels of infection by C. jejuni and H. pylori than those for the non-mucus-producing parental cell lines. Both C. jejuni and H. pylori bound to HT29-MTX-E12 mucus, and while both organisms bound to glycosylated epitopes in the glycolipid fraction of the mucus, only C. jejuni bound to purified mucin. This study highlights the role of mucus in promoting bacterial infection and emphasizes the potential for even closely related bacteria to interact with mucus in different ways to establish successful infections. PMID:23716616

  3. Clinical issues of mucus accumulation in COPD

    PubMed Central

    Ramos, Frederick L; Krahnke, Jason S; Kim, Victor

    2014-01-01

    Airway mucus is part of the lung’s native immune function that traps particulates and microorganisms, enabling their clearance from the lung by ciliary transport and cough. Mucus hypersecretion and chronic productive cough are the features of the chronic bronchitis and chronic obstructive pulmonary disease (COPD). Overproduction and hypersecretion by goblet cells and the decreased elimination of mucus are the primary mechanisms responsible for excessive mucus in chronic bronchitis. Mucus accumulation in COPD patients affects several important outcomes such as lung function, health-related quality of life, COPD exacerbations, hospitalizations, and mortality. Nonpharmacologic options for the treatment of mucus accumulation in COPD are smoking cessation and physical measures used to promote mucus clearance. Pharmacologic therapies include expectorants, mucolytics, methylxanthines, beta-adrenergic receptor agonists, anticholinergics, glucocorticoids, phosphodiesterase-4 inhibitors, antioxidants, and antibiotics. PMID:24493923

  4. Mucus glycoprotein secretion by tracheal explants: effects of pollutants

    SciTech Connect

    Last, J.A.; Kaizu, T.

    1980-04-01

    Tracheal slices incubated with radioactive precursors in tissue culture medium secrete labeled mucus glycoproteins into the culture medium. We have used an in vivtro approach, a combined method utilizing exposure to pneumotoxins in vivo coupled with quantitation of mucus secretion rates in vitro, to study the effects of inhaled pollutants on mucus biosynthesis by rat airways. In addition, we have purified the mucus glycoproteins secreted by rat tracheal explants in order to determine putative structural changes that might by the basis for the observed augmented secretion rates after exposure of rats to H2SO4 aerosols in combination with high ambient levels of ozone. After digestion with papain, mucus glycoproteins secreted by tracheal explants may be separated into five fractions by ion-exchange chromatography, with recovery in high yield, on columns of DEAE-cellulose. Each of these five fractions, one neutral and four acidic, migrates as a single unique spot upon cellulose acetate electrophoresis at pH values of 8.6 and 1.2. The neutral fraction, which is labeled with (3H) glucosamine, does not contain radioactivity when Na2 35SO4 is used as the precursor. Acidic fractions I to IV are all labeled with either 3H-glucosamine or Na2 35SO4 as precursor. Acidic fraction II contains sialic acid as the terminal sugar on its oligosaccharide side chains, based upon its chromatographic behavior on columns of wheat-germ agglutinin-Agarose. Treatment of this fraction with neuraminidase shifts its elution position in the gradient to a lower salt concentration, coincident with acidic fraction I. After removal of terminal sialic acid residues with either neuraminidase or low pH treatment, the resultant terminal sugar on the oligosaccharide side chains is fucose. These results are identical with those observed with mucus glycoproteins secreted by cultured human tracheal explants and purified by these same techniques.

  5. Effect of nicotine on rectal mucus and mucosal eicosanoids.

    PubMed Central

    Zijlstra, F J; Srivastava, E D; Rhodes, M; van Dijk, A P; Fogg, F; Samson, H J; Copeman, M; Russell, M A; Feyerabend, C; Williams, G T

    1994-01-01

    Because ulcerative colitis is largely a disease of non-smokers and nicotine may have a beneficial effect on the disease, the effect of nicotine on rectal mucosa in rabbits was examined. Nicotine was given subcutaneously by an Alzet mini-pump in doses of 0.5, 1.25, and 2 mg/kg/day for 14 days to three groups of eight animals and compared with eight controls. Mean (SD) serum nicotine concentrations (ng/ml) were 3.5 (1.1), 8.8 (2.3), and 16.2 (5.2) respectively in the treated groups. The thickness of adherent mucus on rectal mucosa in controls (median 36 microns) was significantly reduced by low dose (22 microns, p = 0.0011), and increased by high dose nicotine (48 microns, p = 0.035). Incorporation of radioactive glucosamine into papain resistant glycoconjugates was unchanged, indicating that mucin synthesis was unaltered. Prostaglandins (PG) were reduced, in some cases significantly (6-keto PGF1 alpha, PGF2 alpha, and hydroxy-eicosatetraenoic acid), by nicotine, which showed an inverse dose dependence--with greatest inhibition in relation to the lowest dose. Nicotine, and possibly smoking, may affect colitis by an action on mucosal eicosanoids and on adherent surface mucus secretion in the rectum and large bowel. PMID:8307477

  6. Adherence of Entamoeba histolytica trophozoites to rat and human colonic mucosa.

    PubMed Central

    Ravdin, J I; John, J E; Johnston, L I; Innes, D J; Guerrant, R L

    1985-01-01

    We studied the adherence of [3H]thymidine-labeled axenic Entamoeba histolytica (strain HM1-IMSS) to in vitro preparations of rat and human colonic mucosa. Studies were performed with fixed or unfixed rat colonic mucosa, unfixed rat mucosa exposed to trypsin, unfixed rat submucosa, and fixed human colonic mucosa. Twenty percent of the amebae adhered to fixed rat colonic mucosa; adherence was specifically inhibited by N-acetyl-D-galactosamine (GalNAc), galactose, and asialofetuin. The adherence of amebae to fixed human colonic mucosa was also GalNAc inhibitable. Greater adherence was found with unfixed rat colonic mucosa (40.9%) and was not GalNAc inhibitable unless the tissue was first exposed to trypsin. However, GalNAc did inhibit the adherence of amebae to unfixed rat submucosa. Glutaraldehyde fixation of amebae inactivates known amebic adhesion proteins; there was a markedly decreased adherence of fixed amebae to trypsin-exposed mucosa or fixed rat colonic mucosa. However, fixed or viable amebae had equal levels of adherence to unfixed rat colonic mucosa, suggesting the presence of a host adhesion protein that binds to receptors on amebae. Human (10%) and rabbit (5%) immune sera reduced the adherence of viable amebae to fixed rat colonic mucosa. We concluded that the GalNAc-inhibitable adhesion protein on the surface of E. histolytica trophozoites mediated adherence to fixed rat mucosa, fixed human colonic mucosa, trypsin-exposed unfixed rat mucosa, and unfixed rat submucosa. The surface of unfixed rat colonic mucosa contained a glutaraldehyde- and trypsin-sensitive host adhesion protein, perhaps in the overlying mucus blanket, which bound viable or fixed E. histolytica trophozoites. Images PMID:2580787

  7. Effects of branched-chain amino acid granules on serum albumin level and prognosis are dependent on treatment adherence in patients with liver cirrhosis

    PubMed Central

    Takaguchi, Koichi; Moriwaki, Hisataka; Doyama, Hisashi; Iida, Masayuki; Yagura, Michiyasu; Shimada, Noritomo; Kang, Masahiro; Yamada, Haruki; Kumada, Hiromitsu

    2013-01-01

    Aim To test if the treatment adherence to branched-chain amino acid (BCAA) granules influences the serum albumin level and prognosis in prospective 2984 patients with decompensated liver cirrhosis who were prescribed BCAA granules containing 952 mg of L-isoleucine, 1904 mg of L-leucine and 1144 mg of L-valine at 4.15 g/sachet three times a day after meals. Methods The primary end-point was the time to the event defined as “hospital admission due to progression of hepatic failure”, and factors affecting this outcome were explored. Changes in serum albumin level were evaluated as the secondary end-point. Results Patients were divided into the good adherence group (those who reported to have taken “nearly all” prescribed doses) and the poor adherence group (those who reported to have taken “approximately half” or “less” doses), because such stratification was validated by treatment responses in plasma BCAA/tyrosine ratio. Factors related to the primary end-point were age, drug adherence during 6 months of study treatment, previous hepatic cancer, current clinical manifestations, previous clinical manifestations, baseline serum albumin level, platelet count and total bilirubin level. The cumulative event-free survival was significantly higher in the good adherence group. Increase in the serum albumin level was also greater in the good adherence group. Conclusion Higher BCAA treatment adherence better raised the serum albumin level, leading to improvement of event-free survival. These results indicate the importance of patient instruction for the adequate use of BCAA granules. PMID:23046471

  8. Structure and Function of the Mucus Clearance System of the Lung

    PubMed Central

    Button, Brenda M.; Button, Brian

    2013-01-01

    In cystic fibrosis (CF), a defect in ion transport results in thick and dehydrated airway mucus, which is difficult to clear, making such patients prone to chronic inflammation and bacterial infections. Physiotherapy using a variety of airway clearance techniques (ACTs) represents a key treatment regime by helping clear the airways of thickened, adhered, mucus and, thus, reducing the impact of lung infections and improving lung function. This article aims to bridge the gap between our understanding of the physiological effects of mechanical stresses elicited by ACTs on airway epithelia and the reported effectiveness of ACTs in CF patients. In the first part of this review, the effects of mechanical stress on airway epithelia are discussed in relation to changes in ion transport and stimulation in airway surface layer hydration. The second half is devoted to detailing the most commonly used ACTs to stimulate the removal of mucus from the airways of patients with CF. PMID:23751214

  9. The Relationship of Mucus Concentration (Hydration) to Mucus Osmotic Pressure and Transport in Chronic Bronchitis

    PubMed Central

    Coakley, Raymond D.; Button, Brian; Henderson, Ashley G.; Zeman, Kirby L.; Alexis, Neil E.; Peden, David B.; Lazarowski, Eduardo R.; Davis, C. William; Bailey, Summer; Fuller, Fred; Almond, Martha; Qaqish, Bahjat; Bordonali, Elena; Rubinstein, Michael; Bennett, William D.; Kesimer, Mehmet; Boucher, Richard C.

    2015-01-01

    Rationale: Chronic bronchitis (CB) is characterized by persistent cough and sputum production. Studies were performed to test whether mucus hyperconcentration and increased partial osmotic pressure, in part caused by abnormal purine nucleotide regulation of ion transport, contribute to the pathogenesis of CB. Objectives: We tested the hypothesis that CB is characterized by mucus hyperconcentration, increased mucus partial osmotic pressures, and reduced mucus clearance. Methods: We measured in subjects with CB as compared with normal and asymptomatic smoking control subjects indices of mucus concentration (hydration; i.e., percentage solids) and sputum adenine nucleotide/nucleoside concentrations. In addition, sputum partial osmotic pressures and mucus transport rates were measured in subjects with CB. Measurements and Results: CB secretions were hyperconcentrated as indexed by an increase in percentage solids and total mucins, in part reflecting decreased extracellular nucleotide/nucleoside concentrations. CB mucus generated concentration-dependent increases in partial osmotic pressures into ranges predicted to reduce mucus transport. Mucociliary clearance (MCC) in subjects with CB was negatively correlated with mucus concentration (percentage solids). As a test of relationships between mucus concentration and disease, mucus concentrations and MCC were compared with FEV1, and both were significantly correlated. Conclusions: Abnormal regulation of airway surface hydration may slow MCC in CB and contribute to disease pathogenesis. PMID:25909230

  10. High levels of brain-derived neurotrophic factor are associated with treatment adherence among crack-cocaine users.

    PubMed

    Scherer, Juliana N; Schuch, Silvia; Ornell, Felipe; Sordi, Anne O; Bristot, Giovana; Pfaffenseller, Bianca; Kapczinski, Flávio; Kessler, Felix H P; Fumagalli, Fabio; Pechansky, Flavio; von Diemen, Lisia

    2016-09-01

    Due to the complexity of crack -cocaine addiction treatment, the identification of biological markers that could help determining the impact or outcome of drug use has become a major subject of study. Therefore, we aim to evaluate the association of Brain-Derived Neurotrophic Factor (BDNF) and Thiobarbituric Acid Reactive Substances (TBARS) levels in crack -cocaine users with treatment adherence and with drug addiction severity. A sample of 47 male inpatient crack- cocaine users were recruited in a treatment unit, and blood samples were collected at admission and discharge in order to measure BDNF and TBARS serum levels. Subjects were split into 2 groups: treatment non-completers (n=23) and treatment completers (n=24). The completer group had a tendency of higher levels of BDNF than non-completers at admission (16.85±3.24 vs. 14.65±5.45, p=0.10), and significant higher levels at discharge (18.10±4.88 vs. 13.91±4.77, p=0.001). A negative correlation between BDNF levels at admission and years of crack use was observed. We did not find significant changes in TBARS levels during inpatient treatment, although the completer group tended to decrease these levels while non-completers tend to increase it. These findings suggest an association between higher levels of BDNF and better clinical outcomes in crack- cocaine users after detoxification. We believe that the variation in BDNF and TBARS found here add evidence to literature data that propose that such biomarkers could be used to better understand the physiopathology of crack- cocaine addiction. PMID:27473943

  11. Ulcerative colitis as a polymicrobial infection characterized by sustained broken mucus barrier

    PubMed Central

    Chen, Shui-Jiao; Liu, Xiao-Wei; Liu, Jian-Ping; Yang, Xi-Yan; Lu, Fang-Gen

    2014-01-01

    To reduce medication for patients with ulcerative colitis (UC), we need to establish the etiology of UC. The intestinal microbiota of patients with inflammatory bowel disease (IBD) has been shown to differ from that of healthy controls and abundant data indicate that it changes in both composition and localization. Small intestinal bacterial overgrowth is significantly higher in IBD patients compared with controls. Probiotics have been investigated for their capacity to reduce the severity of UC. The luminal surfaces of the gastrointestinal tract are covered by a mucus layer. This normally acts as a barrier that does not allow bacteria to reach the epithelial cells and thus limits the direct contact between the host and the bacteria. The mucus layer in the colon comprises an inner layer that is firmly adherent to the intestinal mucosa, and an outer layer that can be washed off with minimal rinsing. Some bacteria can dissolve the protective inner mucus layer. Defects in renewal and formation of the inner mucus layer allow bacteria to reach the epithelium and have implications for the causes of colitis. In this review, important elements of UC pathology are thought to be the intestinal bacteria, gut mucus, and the mucosa-associated immune system. PMID:25071341

  12. System-level factors as predictors of adherence to clinical appointment schedules in antiretroviral therapy in Cambodia.

    PubMed

    Daigle, Gary T; Jolly, Pauline E; Chamot, Eric A M; Ehiri, John; Zhang, Kui; Khan, Edward; Sou, Sanith

    2015-01-01

    Adherence to clinical appointment schedules by patients on antiretroviral therapy (ART) is necessary for the prevention of medication interruptions, viral rebound, and the development of drug resistance. An observational study conducted in 2010, Enablers and Adherence to Antiretroviral Therapy in Cambodia, sought to identify factors that predict on-time clinical appointment attendance by patients on ART. Clinical data, including appointment attendance across five consecutive visits, were collected from hospital records on a random sample of ART patients at government referral hospitals (RHs) in Battambang Province, Cambodia. Interviews were conducted to obtain quantitative information from patients on their experiences of support services provided by local NGOs and RHs. This information was used to identify ART patient care and support system factors that could potentially enable patients to adhere to clinical appointment schedules. These factors included adherence counseling, support groups, home-based care (HBC) services, and support provided for transportation to ART appointments. Bivariate and multivariable logistic regression analysis was done to assess relationships between system variables and the ART appointment adherence outcome. Of the 289 study participants, 20.4% had missed at least one of the five appointments in the study period. The hospital source of ART services, participation in a hospital-based support group, receiving a loan from a microfinance institution, and the frequency of adherence counseling were found to be associated with ART appointment adherence. No significant associations were found between other support system factors such as HBC, transportation support, food/monetary support, and appointment adherence. PMID:25803006

  13. Toward the modeling of mucus draining from the human lung: role of the geometry of the airway tree

    NASA Astrophysics Data System (ADS)

    Mauroy, Benjamin; Fausser, Christian; Pelca, Dominique; Merckx, Jacques; Flaud, Patrice

    2011-10-01

    Mucociliary clearance and cough are the two main natural mucus draining methods in the bronchial tree. If they are affected by a pathology, they can become insufficient or even ineffective, then therapeutic draining of mucus plays a critical role to keep mucus levels in the lungs acceptable. The manipulations of physical therapists are known to be very efficient clinically but they are mostly empirical since the biophysical mechanisms involved in these manipulations have never been studied. We develop in this work a model of mucus clearance in idealized rigid human bronchial trees and focus our study on the interaction between (1) tree geometry, (2) mucus physical properties and (3) amplitude of flow rate in the tree. The mucus is considered as a Bingham fluid (gel-like) which is moved upward in the tree thanks to its viscous interaction with air flow. Our studies point out the important roles played both by the geometry and by the physical properties of mucus (yield stress and viscosity). More particularly, the yield stress has to be overcome to make mucus flow. Air flow rate and yield stress determine the maximal possible mucus thickness in each branch of the tree at equilibrium. This forms a specific distribution of mucus in the tree whose characteristics are strongly related to the multi-scaled structure of the tree. The behavior of any mucus distribution is then dependent on this distribution. Finally, our results indicate that increasing air flow rates ought to be more efficient to drain mucus out of the bronchial tree while minimizing patient discomfort.

  14. Mucoactive agents for airway mucus hypersecretory diseases.

    PubMed

    Rogers, Duncan F

    2007-09-01

    Airway mucus hypersecretion is a feature of a number of severe respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). However, each disease has a different airway inflammatory response, with consequent, and presumably linked, mucus hypersecretory phenotype. Thus, it is possible that optimal treatment of the mucus hypersecretory element of each disease should be disease-specific. Nevertheless, mucoactive drugs are a longstanding and popular therapeutic option, and numerous compounds (eg, N-acetylcysteine, erdosteine, and ambroxol) are available for clinical use worldwide. However, rational recommendation of these drugs in guidelines for management of asthma, COPD, or CF has been hampered by lack of information from well-designed clinical trials. In addition, the mechanism of action of most of these drugs is unknown. Consequently, although it is possible to categorize them according to putative mechanisms of action, as expectorants (aid and/or induce cough), mucolytics (thin mucus), mucokinetics (facilitate cough transportability), and mucoregulators (suppress mechanisms underlying chronic mucus hypersecretion, such as glucocorticosteroids), it is likely that any beneficial effects are due to activities other than, or in addition to, effects on mucus. It is also noteworthy that the mucus factors that favor mucociliary transport (eg, thin mucus gel layer, "ideal" sol depth, and elasticity greater than viscosity) are opposite to those that favor cough effectiveness (thick mucus layer, excessive sol height, and viscosity greater than elasticity), which indicates that different mucoactive drugs would be required for treatment of mucus obstruction in proximal versus distal airways, or in patients with an impaired cough reflex. With the exception of mucoregulatory agents, whose primary action is unlikely to be directed against mucus, well-designed clinical trials are required to unequivocally determine the

  15. A comparison of adherence to correctly documented triage level of critically ill patients between emergency department and the ambulance service nurses.

    PubMed

    Jönsson, Kenneth; Fridlund, Bengt

    2013-07-01

    Priority or triage has always occurred in emergency care. Today it is performed by both nurses in emergency departments (EDs) and ambulance services (ASs) to ensure patient safety. Recent studies have shown that nurses are unlikely to change their first impressions and patients suffering from blunt trauma are undertriaged. Our study aimed to compare and evaluate the adherence to correct triage level documentation, between nurses in the ED and the AS, according to current regulations. Of 592 analysed triage records from a university, a central and a district hospital, the adherence was 64% by ED nurses and 43% by AS nurses (p<0.001), but individual percentages ranged from 27% to 88%. Patient safety is jeopardised when nurses do not adhere to the triage system and do not correctly document the triage level. Internal feedback and control are two approaches to improve the patient outcome, indicating that organisational actions must be taken. PMID:23830372

  16. Pretreatment of human cervicovaginal mucus with pluronic F127 enhances nanoparticle penetration without compromising mucus barrier properties to herpes simplex virus.

    PubMed

    Ensign, Laura M; Lai, Samuel K; Wang, Ying-Ying; Yang, Ming; Mert, Olcay; Hanes, Justin; Cone, Richard

    2014-12-01

    Mucosal drug delivery nanotechnologies are limited by the mucus barrier that protects nearly all epithelial surfaces not covered with skin. Most polymeric nanoparticles, including polystyrene nanoparticles (PS), strongly adhere to mucus, thereby limiting penetration and facilitating rapid clearance from the body. Here, we demonstrate that PS rapidly penetrate human cervicovaginal mucus (CVM), if the CVM has been pretreated with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large polyethylene glycol (PEG)-coated, nonmucoadhesive nanoparticles (PS-PEG) did not change in F127-pretreated CVM, implying that F127 did not significantly alter the native pore structure of CVM. Additionally, herpes simplex virus type 1 (HSV-1) remains adherent in F127-pretreated CVM, indicating that the presence of F127 did not reduce adhesive interactions between CVM and the virions. In contrast to treatment with a surfactant that has been approved for vaginal use as a spermicide (nonoxynol-9 or N9), there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for 1 week. Pluronic F127 pretreatment holds potential as a method to safely improve the distribution, retention, and efficacy of nanoparticle formulations without compromising CVM barrier properties to pathogens. PMID:25347518

  17. Pretreatment of Human Cervicovaginal Mucus with Pluronic F127 Enhances Nanoparticle Penetration without Compromising Mucus Barrier Properties to Herpes Simplex Virus

    PubMed Central

    2015-01-01

    Mucosal drug delivery nanotechnologies are limited by the mucus barrier that protects nearly all epithelial surfaces not covered with skin. Most polymeric nanoparticles, including polystyrene nanoparticles (PS), strongly adhere to mucus, thereby limiting penetration and facilitating rapid clearance from the body. Here, we demonstrate that PS rapidly penetrate human cervicovaginal mucus (CVM), if the CVM has been pretreated with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large polyethylene glycol (PEG)-coated, nonmucoadhesive nanoparticles (PS–PEG) did not change in F127-pretreated CVM, implying that F127 did not significantly alter the native pore structure of CVM. Additionally, herpes simplex virus type 1 (HSV-1) remains adherent in F127-pretreated CVM, indicating that the presence of F127 did not reduce adhesive interactions between CVM and the virions. In contrast to treatment with a surfactant that has been approved for vaginal use as a spermicide (nonoxynol-9 or N9), there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for 1 week. Pluronic F127 pretreatment holds potential as a method to safely improve the distribution, retention, and efficacy of nanoparticle formulations without compromising CVM barrier properties to pathogens. PMID:25347518

  18. Measuring Adherence to Medication in Schizophrenia: The Relationship between Attitudes toward Drug Therapy and Plasma Levels of New-Generation Antipsychotics

    PubMed Central

    Yalcin-Siedentopf, Nursen; Wartelsteiner, Fabienne; Kaufmann, Alexandra; Biedermann, Falko; Edlinger, Monika; Kemmler, Georg; Rettenbacher, Maria A.; Widschwendter, Christian G.; Zernig, Gerald; Fleischhacker, W. Wolfgang

    2015-01-01

    Background: Nonadherence to medication is still a major problem in the treatment of schizophrenia. The current longitudinal study investigated whether the patients’ attitudes toward treatment correlated with the ratio of observed vs expected plasma levels of antipsychotic drugs as an objective measurement of adherence. Methods: Data of patients starting monotherapy with a new-generation antipsychotic were collected 2, 4, and 12 weeks after the initiation of treatment. Next to the assessment of patients’ attitudes toward medication by means of the Drug Attitude Inventory, the ratio of the observed vs expected plasma level was calculated. Antipsychotic-induced side effects were evaluated by means of the Udvalg for Kliniske Undersogelser Side Effect Rating Scale. Results: A total of 93 patients were eligible for statistical analysis. About one-half of the ratios of observed vs expected plasma levels ranged from 0.5 to 2 and were considered normal, whereas the other ratios were considered either too low (<0.5) or too high (>2). No consistent correlation between patients’ attitude toward drug therapy and the individual ratios of observed vs expected plasma levels of medication was detected. This finding was not affected by side effects. Conclusions: Our results highlight the importance of recognizing the complex nature of adherence to medication in schizophrenia patients. Importantly, we found no consistent correlation between subjective and objective measures of medication adherence. Therefore, monitoring adherence to medication remains a challenge in clinical practice. PMID:25522423

  19. Influence of exercise adherence level on modifiable coronary heart disease risk factors and functional-fitness levels in middle-aged men.

    PubMed Central

    Wallace, E S; White, J A; Downie, A; Dalzell, G; Doran, D

    1993-01-01

    The study investigated the potential health benefits of two levels of short-term exercise intervention, compared with non-intervention, on selected modifiable coronary heart disease (CHD) risk factors and functional fitness states in middle-aged men. All subjects underwent medical screening and signed informed consent before carrying out a standardized graded treadmill walk which required exercise up to 85% of age-predicted maximal heart rate. The results of the test were used together with musculoskeletal fitness assessments, for the prescription of a personalized exercise programme lasting 14 weeks. In all, 55 subjects were classified by adherence into high (HA, n = 20), low (LA, n = 19), or non-adherence (NA, n = 16) groups according to the degree of documented participation in the programme based on standard criteria (American College of Sports Medicine 1978, 1990). In addition, the respective groups of subjects were classified according to other modifiable and non-modifiable CHD risk factors and compared by self-reported levels of activity and sport involvement as well as perceived body weight classification. The results indicated that there were more comprehensive improvements in functional fitness including significant gains in aerobic endurance capacity, muscular endurance and flexibility in the HA group compared with the LA and NA groups. However, there was little or no change in the modifiable CHD risk factors in any of the respective groups, although anthropometric indices of weight, body mass index (BMI), skinfolds and waist:hips ratio tended to decrease in the HA and LA groups but increased marginally in the NA group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8358578

  20. Strain-specific diversity of mucus-binding proteins in the adhesion and aggregation properties of Lactobacillus reuteri.

    PubMed

    Mackenzie, Donald A; Jeffers, Faye; Parker, Mary L; Vibert-Vallet, Amandine; Bongaerts, Roy J; Roos, Stefan; Walter, Jens; Juge, Nathalie

    2010-11-01

    Mucus-binding proteins (MUBs) have been revealed as one of the effector molecules involved in mechanisms of the adherence of lactobacilli to the host; mub, or mub-like, genes are found in all of the six genomes of Lactobacillus reuteri that are available. We recently reported the crystal structure of a Mub repeat from L. reuteri ATCC 53608 (also designated strain 1063), revealing an unexpected recognition of immunoglobulins. In the current study, we explored the diversity of the ATCC 53608 mub gene, and MUB expression levels in a large collection of L. reuteri strains isolated from a range of vertebrate hosts. This analysis revealed that the MUB was only detectable on the cell surface of two highly related isolates when using antibodies that were raised against the protein. There was considerable variation in quantitative mucus adhesion in vitro among L. reuteri strains, and mucus binding showed excellent correlation with the presence of cell-surface ATCC 53608 MUB. ATCC 53608 MUB presence was further highly associated with the autoaggregation of L. reuteri strains in washed cell suspensions, suggesting a novel role of this surface protein in cell aggregation. We also characterized MUB expression in representative L. reuteri strains. This analysis revealed that one derivative of strain 1063 was a spontaneous mutant that expressed a C-terminally truncated version of MUB. This frameshift mutation was caused by the insertion of a duplicated 13 nt sequence at position 4867 nt in the mub gene, producing a truncated MUB also lacking the C-terminal LPxTG region, and thus unable to anchor to the cell wall. This mutant, designated 1063N (mub-4867(i)), displayed low mucus-binding and aggregation capacities, further providing evidence for the contribution of cell-wall-anchored MUB to such phenotypes. In conclusion, this study provided novel information on the functional attributes of MUB in L. reuteri, and further demonstrated that MUB and MUB-like proteins

  1. Work of adhesion of respiratory tract mucus.

    PubMed

    Pillai, R S; Chandra, T; Miller, I F; Lloyd-Still, J; Yeates, D B

    1992-04-01

    A method was devised to measure the work of adhesion (WA) to a substrate of mucus, a viscoelastic gel, from the measured contact angle of glycerol on a mucus substrate and the known physical properties of a Teflon surface. Fifteen sputum samples from cystic fibrosis (CF) patients were compared with 25 mucus samples from canine tracheal pouches (CP), studied in the hydrated and partially dehydrated states. Apparent viscosity (eta A) and recoverable shear strain (SR) were measured by fluxgate magnetometry, and water content was inferred from vapor pressure osmometry. Na+, K+, and Ca2+ concentrations were measured with specific ion electrodes and Cl- with a chloridimeter. The Cl- concentration of the CP mucus was inversely proportional to its osmolality, and the Cl- concentration of the CP mucus was 102.5 +/- 1.6 meq/l compared with 55.6 +/- 2.5 meq/l for CF sputum. When CP mucus osmolality was increased from 316.0 +/- 5.5 to 430.0 +/- 7.5 mosmol/kg, WA increased from 25.1 +/- 1.8 to 31.1 +/- 1.2 ergs/cm2 and eta A increased from 391 +/- 55 to 622 +/- 121 P, respectively. CF sputum WA was 30.2 +/- 0.6 ergs/cm2, eta A was 1,110 +/- 316 P, and osmolality was 466.0 +/- 14.0 mosmol/kg. The increased WA and eta A of mucus in CF patients may thus be dependent on the hydration of mucus, which is related to the documented Cl- transport defect. PMID:1592754

  2. The modified mucus method in India.

    PubMed

    Dorairaj, K

    1991-12-01

    The modified mucus method-Prajanan Jagriti (fertility awakening) is intended to serve the cultural needs of illiterate and semilliterate women. Over 10 months, 3003 women in northern India were taught the modified mucus method. There were a total of 42 pregnancies in 24,702 cycles for a Pearl index of 2.04. High effectiveness is attributed to the support that was provided to clients by the instructor. PMID:1755473

  3. Long-term Effects of High and Low Glycemic Load Diets at Different Levels of Caloric Restriction on Dietary Adherence, Body Composition and Metabolism in CALERIE, a One Year Randomized Controlled Trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Context The effects of dietary macronutrient composition and level of energy intake on adherence to a calorically-restricted diet remain uncertain. Objective To examine the effects of dietary macronutrients, and level of caloric restriction (CR), for 12 months, on adherence to the prescribed regim...

  4. Oxidation increases mucin polymer cross-links to stiffen airway mucus gels

    PubMed Central

    Yuan, Shaopeng; Hollinger, Martin; Lachowicz-Scroggins, Marrah E.; Kerr, Sheena C.; Dunican, Eleanor M.; Daniel, Brian M.; Ghosh, Sudakshina; Erzurum, Serpel C.; Willard, Belinda; Hazen, Stanley L.; Huang, Xiaozhu; Carrington, Stephen D.; Oscarson, Stefan; Fahy, John V.

    2015-01-01

    Airway mucus in cystic fibrosis (CF) is highly elastic, but the mechanism behind this pathology is unclear. We hypothesized that the biophysical properties of CF mucus are altered because of neutrophilic oxidative stress. Using confocal imaging, rheology, and biochemical measures of inflammation and oxidation, we found that CF airway mucus gels have a molecular architecture characterized by a core of mucin covered by a web of DNA and a rheological profile characterized by high elasticity that can be normalized by chemical reduction. We also found that high levels of reactive oxygen species in CF mucus correlated positively and significantly with high concentrations of the oxidized products of cysteine (disulfide cross-links). To directly determine whether oxidation can cross-link mucins to increase mucus elasticity, we exposed induced sputum from healthy subjects to oxidizing stimuli and found a marked and thiol-dependent increase in sputum elasticity. Targeting mucin disulfide cross-links using current thiol-amino structures such as N-acetylcysteine (NAC) requires high drug concentrations to have mucolytic effects. We therefore synthesized a thiol-carbohydrate structure (methyl 6-thio-6-deoxy-α-D-galactopyranoside) and found that it had stronger reducing activity than NAC and more potent and fast-acting mucolytic activity in CF sputum. Thus, oxidation arising from airway inflammation or environmental exposure contributes to pathologic mucus gel formation in the lung, which suggests that it can be targeted by thiol-modified carbohydrates. PMID:25717100

  5. Oxidation increases mucin polymer cross-links to stiffen airway mucus gels.

    PubMed

    Yuan, Shaopeng; Hollinger, Martin; Lachowicz-Scroggins, Marrah E; Kerr, Sheena C; Dunican, Eleanor M; Daniel, Brian M; Ghosh, Sudakshina; Erzurum, Serpel C; Willard, Belinda; Hazen, Stanley L; Huang, Xiaozhu; Carrington, Stephen D; Oscarson, Stefan; Fahy, John V

    2015-02-25

    Airway mucus in cystic fibrosis (CF) is highly elastic, but the mechanism behind this pathology is unclear. We hypothesized that the biophysical properties of CF mucus are altered because of neutrophilic oxidative stress. Using confocal imaging, rheology, and biochemical measures of inflammation and oxidation, we found that CF airway mucus gels have a molecular architecture characterized by a core of mucin covered by a web of DNA and a rheological profile characterized by high elasticity that can be normalized by chemical reduction. We also found that high levels of reactive oxygen species in CF mucus correlated positively and significantly with high concentrations of the oxidized products of cysteine (disulfide cross-links). To directly determine whether oxidation can cross-link mucins to increase mucus elasticity, we exposed induced sputum from healthy subjects to oxidizing stimuli and found a marked and thiol-dependent increase in sputum elasticity. Targeting mucin disulfide cross-links using current thiol-amino structures such as N-acetylcysteine (NAC) requires high drug concentrations to have mucolytic effects. We therefore synthesized a thiol-carbohydrate structure (methyl 6-thio-6-deoxy-α-D-galactopyranoside) and found that it had stronger reducing activity than NAC and more potent and fast-acting mucolytic activity in CF sputum. Thus, oxidation arising from airway inflammation or environmental exposure contributes to pathologic mucus gel formation in the lung, which suggests that it can be targeted by thiol-modified carbohydrates. PMID:25717100

  6. Ionic bonding, the mechanism of viral uptake by shellfish mucus.

    PubMed Central

    Di Girolamo, R; Liston, J; Matches, J

    1977-01-01

    An investigation was conducted to determine the processes involved in the contamination of shellfish by viruses. Results of binding-release studies show that the process involves the attachment of viruses to mucus secreted, and then ingested, by shellfish during feeding. Analysis of the mucus-virus bond involved selective degradation of the mucus and use of chemical agents to block carboxyl and sulfate groups on the mucus. Results obtained indicate that the attachment of virus to mucus is primarily ionic and involves the binding of viral particles to sulfate radicals on the mucopolysaccharide moiety of shellfish mucus. PMID:13712

  7. Short communication: A low-cost method for analyzing nevirapine levels in hair as a marker of adherence in resource-limited settings.

    PubMed

    Gandhi, Monica; Yang, Qiyun; Bacchetti, Peter; Huang, Yong

    2014-01-01

    The measurement of antiretroviral concentrations in hair is emerging as an important technology to objectively quantify adherence to combination antiretroviral therapy. Hair levels of antiretrovirals are the strongest independent predictor of virologic success in large prospective cohorts of HIV-infected patients and surpass self-report in predicting outcomes. Hair is easy to collect and store, but validated methods to analyze antiretroviral levels in hair using liquid chromatography tandem mass spectrometry (LC-MS/MS) are expensive. We report here on the development of a thin-layer chromatography (TLC) assay for the semiquantitative analysis of nevirapine in hair. TLC assay results from 11 samples were consistent with results using LC-MS/MS [Spearman correlation coefficient 0.99 (95% CI 0.95-0.996)]. This simple, low-cost method of analyzing nevirapine concentrations in hair may provide a novel monitoring tool for antiretroviral adherence in resource-limited settings and merits further study in clinical settings. PMID:24164410

  8. Mechanosensitive ATP Release Maintains Proper Mucus Hydration of Airways

    PubMed Central

    Button, Brian; Okada, Seiko F.; Frederick, Charles Brandon; Thelin, William R.; Boucher, Richard C.

    2013-01-01

    The clearance of mucus from the airways protects the lungs from inhaled noxious and infectious materials. Proper hydration of the mucus layer enables efficient mucus clearance through beating of cilia on airway epithelial cells, and reduced clearance of excessively concentrated mucus occurs in patients with chronic obstructive pulmonary disease and cystic fibrosis. Key steps in the mucus transport process are airway epithelia sensing and responding to changes in mucus hydration. We reported that extracellular adenosine triphosphate (ATP) and adenosine were important luminal auto-crine and paracrine signals that regulated the hydration of the surface of human airway epithelial cultures through their action on apical membrane purinoceptors. Mucus hydration in human airway epithelial cultures was sensed by an interaction between cilia and the overlying mucus layer: Changes in mechanical strain, proportional to mucus hydration, regulated ATP release rates, adjusting fluid secretion to optimize mucus layer hydration. This system provided a feedback mechanism by which airways maintained mucus hydration in an optimum range for cilia propulsion. Understanding how airway epithelia can sense and respond to changes in mucus properties helps us to understand how the mucus clearance system protects the airways in health and how it fails in lung diseases such as cystic fibrosis. PMID:23757023

  9. Mechanosensitive ATP release maintains proper mucus hydration of airways.

    PubMed

    Button, Brian; Okada, Seiko F; Frederick, Charles Brandon; Thelin, William R; Boucher, Richard C

    2013-06-11

    The clearance of mucus from the airways protects the lungs from inhaled noxious and infectious materials. Proper hydration of the mucus layer enables efficient mucus clearance through beating of cilia on airway epithelial cells, and reduced clearance of excessively concentrated mucus occurs in patients with chronic obstructive pulmonary disease and cystic fibrosis. Key steps in the mucus transport process are airway epithelia sensing and responding to changes in mucus hydration. We reported that extracellular adenosine triphosphate (ATP) and adenosine were important luminal autocrine and paracrine signals that regulated the hydration of the surface of human airway epithelial cultures through their action on apical membrane purinoceptors. Mucus hydration in human airway epithelial cultures was sensed by an interaction between cilia and the overlying mucus layer: Changes in mechanical strain, proportional to mucus hydration, regulated ATP release rates, adjusting fluid secretion to optimize mucus layer hydration. This system provided a feedback mechanism by which airways maintained mucus hydration in an optimum range for cilia propulsion. Understanding how airway epithelia can sense and respond to changes in mucus properties helps us to understand how the mucus clearance system protects the airways in health and how it fails in lung diseases such as cystic fibrosis. PMID:23757023

  10. Impact of Helicobacter Pylori on Mucus Rheology

    NASA Astrophysics Data System (ADS)

    Celli, Jonathan; Keates, Sarah; Kelly, Ciaran; Turner, Bradley; Bansil, Rama; Erramilli, Shyamsunder

    2006-03-01

    It is well known that the viscoelastic properties of gastric mucin are crucial to the protection of the lining of the stomach against its own acidic secretions and other agents. Helicobacter Pylori, a rod shaped, gram-negative bacteria that dwells in the mucus layer of approximately 50% of the world's population is a class I carcinogen and is associated with gastric ulcers and severe gastritis. The structural damage to the mucus layer caused by H. Pylori is an important aspect of infection with this bacteria. We are examining the impact of H. Pylori on mucin and mucus rheology quantitatively using a combination of dynamic light scattering and multiple particle tracking experiments. Video microscopy data will also be presented on the motility of this bacteria in mucin at different pH and in other viscoelastic gels.

  11. Effect of grinding intensity and feed physical form on in vitro adhesion of Salmonella Typhimurium and mannose residues in intestinal mucus receptors for salmonellae.

    PubMed

    Callies, A; Sander, S J; Verspohl, J; Beineke, A; Kamphues, J

    2012-12-01

    The hypothesis of this study was that feeding a fine, pelleted diet (FP) compared to a coarse meal diet (CM) results in a higher mannose content in the intestinal mucus of pigs and therefore an increased in vitro adhesion of Salmonella Typhimurium DT104 L to the mucus. The 2 diets were fed to a total of 24 weaned pigs for 6 wk after which mannose content in the mucus was evaluated histochemically using the α1-3-d-mannose-specific lectin Galanthus nivalis agglutinin. The crypt width was determined as an indirect measure for the amount of secreted mucus. Ileal and cecal tissue samples were incubated with approximately 7.77 × 10(7) cfu Salmonella Typhimurium and numbers of salmonellae adhering to the mucus and/or mucosa were determined by culture techniques. There was no effect of feed physical form on the in vitro adhesion of S. Typhimurium either in the ileum (7.1 ± 0.19 log(10) cfu/g tissue) or in the cecum (6.8 ± 0.26 log(10) cfu/g). The mannose content of the mucus also did not differ between the treatment groups. The crypts of the duodenum, jejunum, and cecum were wider (P < 0.05) after feeding the CM diet. This might be an indication for a higher mucus production in these pigs. PMID:23365353

  12. OCCURRENCE OF AGGLUTININS IN THE PALLIAL CAVITY MUCUS OF OYSTERS

    EPA Science Inventory

    Lectins, carbohydrate-binding glycoproteins that cause agglutination of homologous particles, were found in the mucus and fluid from the mantel (pallial) cavity of eastern oysters Crassostrea virginica. ccurrence in mantle cavity fluid was probably due to dissociation from mucus ...

  13. Adhesion to brown trout skin mucus, antagonism against cyst adhesion and pathogenicity to rainbow trout of some inhibitory bacteria against Saprolegnia parasitica .

    PubMed

    Carbajal-González, M T; Fregeneda-Grandes, J M; González-Palacios, C; Aller-Gancedo, J M

    2013-04-29

    Biological control of saprolegniosis with bacteria might be an alternative to the use of chemical compounds. Among criteria for the selection of such bacteria are their absence of pathogenicity to fish and their ability to prevent adhesion of the pathogen to the skin mucus. The pathogenicity to rainbow trout of 21 bacterial isolates with in vitro inhibitory activity against Saprolegnia parasitica was studied. Fifteen of the isolates, identified as Aeromonas sobria, Pantoea agglomerans, Pseudomonas fluorescens, Serratia fonticola, Xanthomonas retroflexus and Yersinia kristensenii, were non-pathogenic when injected into rainbow trout. Their capacity to adhere to the skin mucus of male and female brown trout and to reduce the adhesion of S. parasitica cysts under exclusion, competition and displacement conditions was tested. The 15 bacterial isolates showed a low adhesion rate, ranging between 1.7% (for an A. sobria isolate) and 15.3% (a P. fluorescens isolate). This adhesion was greater in the case of mucus from male brown trout than from females. Similarities in the adhesion to male mucus and other substrates and correlation to that observed to polystyrene suggest that adhesion to skin mucus does not depend on the substrate. A high percentage (88.9%) of the S. parasitica cysts adhered to the skin mucus of male brown trout. Almost all of the bacteria reduced this adhesion ratio significantly under exclusion and competition conditions. However, only half of the isolates displaced cysts from skin mucus, and more bacterial cells were necessary for this effect. A novel method to study the adhesion of S. parasitica cysts to skin mucus of trout and their interactions with inhibitory bacteria is described. PMID:23670078

  14. Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pili containing a human- mucus binding protein

    PubMed Central

    Kankainen, Matti; Paulin, Lars; Tynkkynen, Soile; von Ossowski, Ingemar; Reunanen, Justus; Partanen, Pasi; Satokari, Reetta; Vesterlund, Satu; Hendrickx, Antoni P. A.; Lebeer, Sarah; De Keersmaecker, Sigrid C. J.; Vanderleyden, Jos; Hämäläinen, Tuula; Laukkanen, Suvi; Salovuori, Noora; Ritari, Jarmo; Alatalo, Edward; Korpela, Riitta; Mattila-Sandholm, Tiina; Lassig, Anna; Hatakka, Katja; Kinnunen, Katri T.; Karjalainen, Heli; Saxelin, Maija; Laakso, Kati; Surakka, Anu; Palva, Airi; Salusjärvi, Tuomas; Auvinen, Petri; de Vos, Willem M.

    2009-01-01

    To unravel the biological function of the widely used probiotic bacterium Lactobacillus rhamnosus GG, we compared its 3.0-Mbp genome sequence with the similarly sized genome of L. rhamnosus LC705, an adjunct starter culture exhibiting reduced binding to mucus. Both genomes demonstrated high sequence identity and synteny. However, for both strains, genomic islands, 5 in GG and 4 in LC705, punctuated the colinearity. A significant number of strain-specific genes were predicted in these islands (80 in GG and 72 in LC705). The GG-specific islands included genes coding for bacteriophage components, sugar metabolism and transport, and exopolysaccharide biosynthesis. One island only found in L. rhamnosus GG contained genes for 3 secreted LPXTG-like pilins (spaCBA) and a pilin-dedicated sortase. Using anti-SpaC antibodies, the physical presence of cell wall-bound pili was confirmed by immunoblotting. Immunogold electron microscopy showed that the SpaC pilin is located at the pilus tip but also sporadically throughout the structure. Moreover, the adherence of strain GG to human intestinal mucus was blocked by SpaC antiserum and abolished in a mutant carrying an inactivated spaC gene. Similarly, binding to mucus was demonstrated for the purified SpaC protein. We conclude that the presence of SpaC is essential for the mucus interaction of L. rhamnosus GG and likely explains its ability to persist in the human intestinal tract longer than LC705 during an intervention trial. The presence of mucus-binding pili on the surface of a nonpathogenic Gram-positive bacterial strain reveals a previously undescribed mechanism for the interaction of selected probiotic lactobacilli with host tissues. PMID:19805152

  15. Specialization of the sting venom and skin mucus of Cathorops spixii reveals functional diversification of the toxins.

    PubMed

    Ramos, Anderson Daniel; Conceição, Katia; Silva, Pedro Ismael; Richardson, Michael; Lima, Carla; Lopes-Ferreira, Mônica

    2012-05-01

    Cathorops spixii is the most common venomous fish on the Brazilian coast. Apart from the involvement with defense against pathogens, the possible contribution of skin mucus components to the development of injuries caused by venomous fish species has not been investigated. Thus, the present study was conducted to gain a better understanding of the peptide and protein components of fish skin mucus and the sting venom from the catfish C. spixii. Our results show that sting venom and skin mucus have distinct constituents that distinguished them like structural proteins, chaperones, ion transport, carbohydrate metabolism, oxidoreductase, cell cycle and protein binding present in sting venom and like tropomyosin 3 isoform 2 and energy metabolim proteins in skin mucus. But in a group of common 13 proteins we identified and isolated a WAP65 protein. The peptide fractions caused more harmful effects, such as venular stasis, hemorrhage and changes in the arteriolar wall diameter, and the protein fractions produced a typical inflammatory process in post-capillary venules. And finally we showed for the first time the presence WAP65 in sting venom and skin mucus of C. spixii using LC/MS/MS and also we purified this protein in the sting venom. Wap65 shows inflammatory action, working at different doses inducing an increase in the number of leukocytes rolling and adhering to the endothelium. PMID:22381657

  16. Vocal Fold Mucus Aggregation in Persons with Voice Disorders

    ERIC Educational Resources Information Center

    Bonilha, Heather Shaw; White, Lisa; Kuckhahn, Kelsey; Gerlach, Terri Treman; Deliyski, Dimitar D.

    2012-01-01

    Mucus aggregation on the vocal folds is a common finding from laryngeal endoscopy. Patients with voice disorders report the presence of mucus aggregation. Patients also report that mucus aggregation causes them to clear their throat, a behavior believed to be harmful to vocal fold mucosa. Even though clinicians and patients report and discuss…

  17. New research method looks at fish mucus

    EPA Science Inventory

    We have developed a new way to analyze fish tissues to understand fish ecology. Instead of killing the fish to collect the sample for analysis, we collect body mucus from the fish and analyze that. The fish can then be returned alive to the stream or lake.

  18. Automated detection of presence of mucus foci in airway diseases: preliminary results

    NASA Astrophysics Data System (ADS)

    Odry, Benjamin L.; Kiraly, Atilla P.; Novak, Carol L.; Naidich, David P.; Ko, Jane; Godoy, Myrna C. B.

    2009-02-01

    Chronic Obstructive Pulmonary Disease (COPD) is often characterized by partial or complete obstruction of airflow in the lungs. This can be due to airway wall thickening and retained secretions, resulting in foci of mucoid impactions. Although radiologists have proposed scoring systems to assess extent and severity of airway diseases from CT images, these scores are seldom used clinically due to impracticality. The high level of subjectivity from visual inspection and the sheer number of airways in the lungs mean that automation is critical in order to realize accurate scoring. In this work we assess the feasibility of including an automated mucus detection method in a clinical scoring system. Twenty high-resolution datasets of patients with mild to severe bronchiectasis were randomly selected, and used to test the ability of the computer to detect the presence or absence of mucus in each lobe (100 lobes in all). Two experienced radiologists independently scored the presence or absence of mucus in each lobe based on the visual assessment method recommended by Sheehan et al [1]. These results were compared with an automated method developed for mucus plug detection [2]. Results showed agreement between the two readers on 44% of the lobes for presence of mucus, 39% of lobes for absence of mucus, and discordant opinions on 17 lobes. For 61 lobes where 1 or both readers detected mucus, the computer sensitivity was 75.4%, the specificity was 69.2%, and the positive predictive value (PPV) was 79.3%. Six computer false positives were a-posteriori reviewed by the experts and reassessed as true positives, yielding results of 77.6% sensitivity, 81.8% for specificity, and 89.6% PPV.

  19. HIV Medication Adherence

    MedlinePlus

    HIV Treatment HIV Medication Adherence (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points Medication adherence means sticking ... exactly as prescribed. Why is adherence to an HIV regimen important? Adherence to an HIV regimen gives ...

  20. On the synthesis of mucus permeating nanocarriers.

    PubMed

    Bourganis, Vassilis; Karamanidou, Theodora; Samaridou, Eleni; Karidi, Konstantina; Kammona, Olga; Kiparissides, Costas

    2015-11-01

    The synthesis of nanocarriers with "slippery" surface (i.e., poly(lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) and polyelectrolyte complexes (PECs) of polyacrylic acid (PAA) with poly-L-lysine (PLL) and/or polyarginine (PArg)) and of nanocarriers (i.e., PLGA NPs, PLGA-PEG NPs, liposomes) containing a mucolytic agent (i.e., 4-mercaptobenzoic acid (4MBA)) is presented. Depending on the molecular weight (MW) of PEG (i.e., 2, 5 kDa), PLGA-PEG NPs with a "brush" or "dense brush" PEG configuration were prepared. The PLGA-PEG NPs exhibited increased mucus permeability in comparison with non-pegylated PLGA NPs when tested in fresh porcine intestinal mucus. The NPs that were prepared using PEG with a MW equal to 5 kDa and had a "dense brush" PEG configuration, were found to exhibit the highest mucus permeability. The average size and the surface charge of PECs could be effectively tuned by varying the PAA/polycation charge ratio, thus resulting in the synthesis of neutral as well as positively and negatively charged PECs. The PECs with negative surface charges were found to exhibit the highest mucus permeability followed by the neutral and finally the positively charged PECs. Depending on the initial concentration of the mucolytic agent, 4MBA loadings up to 13.65, 13.1 and 18.43 wt% were achieved for PLGA NPs, PLGA-PEG NPs and liposomes, respectively. PLGA and PLGA-PEG NPs were characterized by a rapid release of the mucolytic agent (i.e., >80 wt% of 4MBA was released in 20 min) whereas, its encapsulation in liposomes allowed a more controlled release (i.e., up to 30 wt% of 4MBA was released in 45 min). 4MBA loaded liposomes were found to exhibit increased mucus permeability depending on the composition of the phospholipid bilayer. PMID:25661586

  1. Coral mucus fuels the sponge loop in warm- and cold-water coral reef ecosystems

    PubMed Central

    Rix, Laura; de Goeij, Jasper M.; Mueller, Christina E.; Struck, Ulrich; Middelburg, Jack J.; van Duyl, Fleur C.; Al-Horani, Fuad A.; Wild, Christian; Naumann, Malik S.; van Oevelen, Dick

    2016-01-01

    Shallow warm-water and deep-sea cold-water corals engineer the coral reef framework and fertilize reef communities by releasing coral mucus, a source of reef dissolved organic matter (DOM). By transforming DOM into particulate detritus, sponges play a key role in transferring the energy and nutrients in DOM to higher trophic levels on Caribbean reefs via the so-called sponge loop. Coral mucus may be a major DOM source for the sponge loop, but mucus uptake by sponges has not been demonstrated. Here we used laboratory stable isotope tracer experiments to show the transfer of coral mucus into the bulk tissue and phospholipid fatty acids of the warm-water sponge Mycale fistulifera and cold-water sponge Hymedesmia coriacea, demonstrating a direct trophic link between corals and reef sponges. Furthermore, 21–40% of the mucus carbon and 32–39% of the nitrogen assimilated by the sponges was subsequently released as detritus, confirming a sponge loop on Red Sea warm-water and north Atlantic cold-water coral reefs. The presence of a sponge loop in two vastly different reef environments suggests it is a ubiquitous feature of reef ecosystems contributing to the high biogeochemical cycling that may enable coral reefs to thrive in nutrient-limited (warm-water) and energy-limited (cold-water) environments. PMID:26740019

  2. Coral mucus fuels the sponge loop in warm- and cold-water coral reef ecosystems.

    PubMed

    Rix, Laura; de Goeij, Jasper M; Mueller, Christina E; Struck, Ulrich; Middelburg, Jack J; van Duyl, Fleur C; Al-Horani, Fuad A; Wild, Christian; Naumann, Malik S; van Oevelen, Dick

    2016-01-01

    Shallow warm-water and deep-sea cold-water corals engineer the coral reef framework and fertilize reef communities by releasing coral mucus, a source of reef dissolved organic matter (DOM). By transforming DOM into particulate detritus, sponges play a key role in transferring the energy and nutrients in DOM to higher trophic levels on Caribbean reefs via the so-called sponge loop. Coral mucus may be a major DOM source for the sponge loop, but mucus uptake by sponges has not been demonstrated. Here we used laboratory stable isotope tracer experiments to show the transfer of coral mucus into the bulk tissue and phospholipid fatty acids of the warm-water sponge Mycale fistulifera and cold-water sponge Hymedesmia coriacea, demonstrating a direct trophic link between corals and reef sponges. Furthermore, 21-40% of the mucus carbon and 32-39% of the nitrogen assimilated by the sponges was subsequently released as detritus, confirming a sponge loop on Red Sea warm-water and north Atlantic cold-water coral reefs. The presence of a sponge loop in two vastly different reef environments suggests it is a ubiquitous feature of reef ecosystems contributing to the high biogeochemical cycling that may enable coral reefs to thrive in nutrient-limited (warm-water) and energy-limited (cold-water) environments. PMID:26740019

  3. Morphological selection of human spermatozoa in cervical mucus "in vivo".

    PubMed

    Ragni, G; Di Pietro, R; Bestetti, O; De Lauretis, L; Olivares, D; Guercilena, S

    1985-01-01

    Spermatozoa morphology at two levels in the cervical canal was compared, at the external and internal uterine orifices, in samples taken "in vivo" during 21 postcoital tests (P.C.T.s). P.C.T.s with cervical mucus, with Moghissi scores lower than 10 and exo- and endocervical pH less than 7 were excluded. At the upper level of the cervical canal, 12 of the 21 P.C.T. showed more than 5% more normal spermatozoa than at the lower level of the canal (in 5 of these P.C.T. the increase was greater than 10%). Selection for normal heads was seen in 2 and for normal tails in 4. The P.C.T. that selected for normal tails all had greater than 10% abnormal tails at the external orifice. These results confirm that there is some selection of spermatozoa during passage through the cervical canal. Above all, the selection appears to exclude those spermatozoa with defective locomotive mechanisms (abnormal tails), which indicates that the mucus acts as a "passive filter" with selection depending on the spermatozoa themselves in relation to motility. PMID:4061891

  4. Model for assessing bronchial mucus transport

    SciTech Connect

    Agnew, J.E.; Bateman, J.R.M.; Pavia, D.; Clarke, S.W.

    1984-02-01

    The authors propose a scheme for the assessment of regional mucus transport using inhaled Tc-99m aerosol particles and quantitative analysis of serial gamma-camera images. The model treats input to inner and intermediate lung regions as the total of initial deposition there plus subsequent transport into these regions from more peripheral airways. It allows for interregional differences in the proportion of particles deposited on the mucus-bearing conducting airways, and does not require a gamma image 24 hr after particle inhalation. Instead, distribution of particles reaching the respiratory bronchioles or alveoli is determined from a Kr-81m ventilation image, while the total amount of such deposition is obtained from 24-hr Tc-99m retention measured with a sensitive counter system. The model is applicable to transport by mucociliary action or by cough, and has been tested in ten normal and ten asthmatic subjects.

  5. Infection with the gastrointestinal nematode Ostertagia ostertagi in cattle affects mucus biosynthesis in the abomasum

    PubMed Central

    2011-01-01

    The mucus layer in the gastrointestinal (GI) tract is considered to be the first line of defense to the external environment. Alteration in mucus components has been reported to occur during intestinal nematode infection in ruminants, but the role of mucus in response to abomasal parasites remains largely unclear. The aim of the current study was to analyze the effects of an Ostertagia ostertagi infection on the abomasal mucus biosynthesis in cattle. Increased gene expression of MUC1, MUC6 and MUC20 was observed, while MUC5AC did not change during infection. Qualitative changes of mucins, related to sugar composition, were also observed. AB-PAS and HID-AB stainings highlighted a decrease in neutral and an increase in acidic mucins, throughout the infection. Several genes involved in mucin core structure synthesis, branching and oligomerization, such as GCNT3, GCNT4, A4GNT and protein disulphide isomerases were found to be upregulated. Increase in mucin fucosylation was observed using the lectin UEA-I and through the evaluation of fucosyltransferases gene expression levels. Finally, transcription levels of 2 trefoil factors, TFF1 and TFF3, which are co-expressed with mucins in the GI tract, were also found to be significantly upregulated in infected animals. Although the alterations in mucus biosynthesis started early during infection, the biggest effects were found when adult worms were present on the surface of the abomasal mucosa and are likely caused by the alterations in mucosal cell populations, characterized by hyperplasia of mucus secreting cells. PMID:21569362

  6. Lactobacillus reuteri Inhibition of Enteropathogenic Escherichia coli Adherence to Human Intestinal Epithelium

    PubMed Central

    Walsham, Alistair D. S.; MacKenzie, Donald A.; Cook, Vivienne; Wemyss-Holden, Simon; Hews, Claire L.; Juge, Nathalie; Schüller, Stephanie

    2016-01-01

    Enteropathogenic Escherichia coli (EPEC) is a major cause of diarrheal infant death in developing countries, and probiotic bacteria have been shown to provide health benefits in gastrointestinal infections. In this study, we have investigated the influence of the gut symbiont Lactobacillus reuteri on EPEC adherence to the human intestinal epithelium. Different host cell model systems including non-mucus-producing HT-29 and mucus-producing LS174T intestinal epithelial cell lines as well as human small intestinal biopsies were used. Adherence of L. reuteri to HT-29 cells was strain-specific, and the mucus-binding proteins CmbA and MUB increased binding to both HT-29 and LS174T cells. L. reuteri ATCC PTA 6475 and ATCC 53608 significantly inhibited EPEC binding to HT-29 but not LS174T cells. While pre-incubation of LS174T cells with ATCC PTA 6475 did not affect EPEC attaching/effacing (A/E) lesion formation, it increased the size of EPEC microcolonies. ATCC PTA 6475 and ATCC 53608 binding to the mucus layer resulted in decreased EPEC adherence to small intestinal biopsy epithelium. Our findings show that L. reuteri reduction of EPEC adhesion is strain-specific and has the potential to target either the epithelium or the mucus layer, providing further rationale for the selection of probiotic strains. PMID:26973622

  7. Lactobacillus reuteri Inhibition of Enteropathogenic Escherichia coli Adherence to Human Intestinal Epithelium.

    PubMed

    Walsham, Alistair D S; MacKenzie, Donald A; Cook, Vivienne; Wemyss-Holden, Simon; Hews, Claire L; Juge, Nathalie; Schüller, Stephanie

    2016-01-01

    Enteropathogenic Escherichia coli (EPEC) is a major cause of diarrheal infant death in developing countries, and probiotic bacteria have been shown to provide health benefits in gastrointestinal infections. In this study, we have investigated the influence of the gut symbiont Lactobacillus reuteri on EPEC adherence to the human intestinal epithelium. Different host cell model systems including non-mucus-producing HT-29 and mucus-producing LS174T intestinal epithelial cell lines as well as human small intestinal biopsies were used. Adherence of L. reuteri to HT-29 cells was strain-specific, and the mucus-binding proteins CmbA and MUB increased binding to both HT-29 and LS174T cells. L. reuteri ATCC PTA 6475 and ATCC 53608 significantly inhibited EPEC binding to HT-29 but not LS174T cells. While pre-incubation of LS174T cells with ATCC PTA 6475 did not affect EPEC attaching/effacing (A/E) lesion formation, it increased the size of EPEC microcolonies. ATCC PTA 6475 and ATCC 53608 binding to the mucus layer resulted in decreased EPEC adherence to small intestinal biopsy epithelium. Our findings show that L. reuteri reduction of EPEC adhesion is strain-specific and has the potential to target either the epithelium or the mucus layer, providing further rationale for the selection of probiotic strains. PMID:26973622

  8. Expression profiling analysis of immune-related genes in channel catfish (Ictalurus punctatus) skin mucus following Flavobacterium columnare challenge.

    PubMed

    Ren, Yichao; Zhao, Honggang; Su, Baofeng; Peatman, Eric; Li, Chao

    2015-10-01

    Fish are covered by a watery gel-mucus, mainly secreted by the goblet cells, serving as the physical and biochemical barrier between the external environment and the interior milieu, playing more important roles in fish that without scale. Despite the important roles of mucus in fish immunity, the knowledge of detailed molecular events happened during infection process is still limited. While most studies were focused on characterizing the protein and enzyme activities in the mucus following challenge, no studies have examined the gene expression profiles in fish mucus. In this regard, herein we carried out the first gene profiling analysis in catfish mucus using real-time PCR. Ten important immune-related genes were selected according to our previous studies. Their expression levels were examined in the early timepoints (namely, 1 h, 2 h, 4 h, 8 h, and 24 h) following Flavobacterium columnare challenge. Notably, expression levels of most of the selected genes were rapidly altered by the challenge. Seven genes were down-regulated, while only three genes were up-regulated. In addition, the gene expression patterns in mucus were very different from the mucosal surfaces (skin, gill and intestine) and the classical immune organs (liver, spleen and kidney). The unique expression patterns obtained here may be resulted from the great advantage of the large amount of attached bacteria in the mucus than the internal tissues, and resulted from the bacteria virulent actors to suppress the host immune response. Taken together, our results can expand our knowledge of fish mucosal immunity, and the un-lethal mucus sampling can provide early insight for developing the strategies for selection of disease resistant families and strains in catfish as well as other fish species. PMID:26220643

  9. Antidepressant adherence after psychiatric hospitalization

    PubMed Central

    Zivin, Kara; Ganoczy, Dara; Pfeiffer, Paul N.; Miller, Erin M.; Valenstein, Marcia

    2010-01-01

    Objective Depressed patients discharged from psychiatric hospitalizations face increased risks for adverse outcomes including suicide, yet antidepressant adherence rates during this high-risk period are unknown. Using Veterans Affairs (VA) data, we assessed antidepressant adherence and predictors of poor adherence among depressed veterans following psychiatric hospitalization. Method We identified VA patients nationwide with depressive disorders who had a psychiatric hospitalization between April 1, 1999 and September 30, 2003, received antidepressant medication, and had an outpatient appointment following discharge. We calculated medication possession ratios (MPRs), a measure of medication adherence, within three and six months following discharge. We assessed patient factors associated with having lower levels of adherence (MPRs <0.8) after discharge. Results 20,931 and 23,182 patients met criteria for three and six month MPRs. The mean three month MPR was 0.79 (s.d.=0.37). The mean six month MPR was 0.66 (s.d.=0.40). Patients with poorer adherence were male, younger, non-white, and had a substance abuse disorder, but were less likely to have PTSD or other anxiety disorders. Conclusion Poor antidepressant adherence is common among depressed patients after psychiatric hospitalization. Efforts to improve adherence at this time may be critical in improving the outcomes of these high-risk patients. PMID:19609666

  10. A simulated mucus layer protects Lactobacillus reuteri from the inhibitory effects of linoleic acid.

    PubMed

    De Weirdt, R; Coenen, E; Vlaeminck, B; Fievez, V; Van den Abbeele, P; Van de Wiele, T

    2013-12-01

    Lactobacillus reuteri is a commensal, beneficial gut microbe that colonises the intestinal mucus layer, where it makes close contact with the human host and may significantly affect human health. Here, we investigated the capacity of linoleic acid (LA), the most common polyunsaturated fatty acid (PUFA) in a Western-style diet, to affect L. reuteri ATCC PTA 6475 prevalence and survival in a simulated mucus layer. Short-term (1 h) survival and mucin-agar adhesion assays of a log-phase L. reuteri suspension in intestinal water demonstrated that the simulated mucus layer protected L. reuteri against the inhibitory effects of LA by lowering its contact with the bacterial cell membrane. The protective effect of the simulated mucus layer was further evaluated using a more complex and dynamic model of the colon microbiota (SHIME®), in which L. reuteri survival was monitored during 6 days of daily exposure to LA in the absence (L-SHIME) and presence (M-SHIME) of a simulated mucus layer. After 6 days, luminal L- and M-SHIME L. reuteri plate counts had decreased by 3.1±0.5 and 2.6±0.9 log cfu/ml, respectively. Upon supplementation of 1.0 g/l LA, the decline in the luminal L. reuteri population started earlier than was observed for the control. In contrast, mucin-agar levels of L. reuteri (in the M-SHIME) remained unaffected throughout the experiment even in the presence of high concentrations of LA. Overall, the results of this study indicate the importance of the mucus layer as a protective environment for beneficial gut microbes to escape from stress by high loads of the antimicrobial PUFA LA to the colon, i.e. due to a Western-style diet. PMID:24311313

  11. Ultraviolet-B wavelengths regulate changes in UV absorption of cleaner fish Labroides dimidiatus mucus.

    PubMed

    Zamzow, Jill P; Siebeck, Ulrike E; Eckes, Maxi J; Grutter, Alexandra S

    2013-01-01

    High-energy wavelengths in the ultraviolet-B (UVB, 280-315 nm) and the UVA (315-400-nm) portion of the spectrum are harmful to terrestrial and aquatic organisms. Interestingly, UVA is also involved in the repair of UV induced damage. Organisms living in shallow coral reef environments possess UV absorbing compounds, such as mycosporine-like amino acids, to protect them from UV radiation. While it has been demonstrated that exposure to UV (280-400 nm) affects the UV absorbance of fish mucus, whether the effects of UV exposure vary between UVB and UVA wavelengths is not known. Therefore, we investigated whether the UVB, UVA, or photosynthetically active radiation (PAR, 400-700 nm) portions of the spectrum affected the UV absorbance of epithelial mucus and Fulton's body condition index of the cleaner fish Labroides dimidiatus. We also compared field-measured UV absorbance with laboratory based high-performance liquid chromatography measurements of mycosporine-like amino acid concentrations. After 1 week, we found that the UV absorbance of epithelial mucus was higher in the UVB+UVA+PAR treatment compared with the UVA+PAR and PAR only treatments; after 2 and 3 weeks, however, differences between treatments were not detected. After 3 weeks, Fulton's body condition index was lower for fish in the UVB+UVA+PAR compared with PAR and UVA+PAR treatments; furthermore, all experimentally treated fish had a lower Fulton's body condition index than did freshly caught fish. Finally, we found a decrease with depth in the UV absorbance of mucus of wild-caught fish. This study suggests that the increase in UV absorbance of fish mucus in response to increased overall UV levels is a function of the UVB portion of the spectrum. This has important implications for the ability of cleaner fish and other fishes to adjust their mucus UV protection in response to variations in environmental UV exposure. PMID:24143264

  12. Structural and molecular insights into novel surface-exposed mucus adhesins from Lactobacillus reuteri human strains.

    PubMed

    Etzold, Sabrina; MacKenzie, Donald A; Jeffers, Faye; Walshaw, John; Roos, Stefan; Hemmings, Andrew M; Juge, Nathalie

    2014-05-01

    The mucus layer covering the gastrointestinal tract is the first point of contact of the intestinal microbiota with the host. Cell surface macromolecules are critical for adherence of commensal bacteria to mucus but structural information is scarce. Here we report the first molecular and structural characterization of a novel cell-surface protein, Lar_0958 from Lactobacillus reuteri JCM 1112(T) , mediating adhesion of L. reuteri human strains to mucus. Lar_0958 is a modular protein of 133 kDa containing six repeat domains, an N-terminal signal sequence and a C-terminal anchoring motif (LPXTG). Lar_0958 homologues are expressed on the cell-surface of L. reuteri human strains, as shown by flow-cytometry and immunogold microscopy. Adhesion of human L. reuteri strains to mucus in vitro was significantly reduced in the presence of an anti-Lar_0958 antibody and Lar_0958 contribution to adhesion was further confirmed using a L. reuteri ATCC PTA 6475 lar_0958 KO mutant (6475-KO). The X-ray crystal structure of a single Lar_0958 repeat, determined at 1.5 Å resolution, revealed a divergent immunoglobulin (Ig)-like β-sandwich fold, sharing structural homology with the Ig-like inter-repeat domain of internalins of the food borne pathogen Listeria monocytogenes. These findings provide unique structural insights into cell-surface protein repeats involved in adhesion of Gram-positive bacteria to the intestine. PMID:24593252

  13. Chemotaxis of Aeromonas hydrophila to the surface mucus of fish

    SciTech Connect

    Hazen, T.C.; Esch, G.W.; Dimock, R.V. Jr.; Mansfield, A.

    1982-01-01

    Isolates of Aeromonas hydrophila from various sources show different chemotactic responses to mucus from the surface of freshwater fish. Some isolates were nonchemotactic to fish surface mucus. Isolates of A. hydrophila from fish lesions had a significantly higher chemotactic index than isolates of A. hydrophila from water. Maximum chemotactic responses occurred more often to diluted fish mucus than to undiluted samples. Fish which were experimentally stressed did not produce mucus that was more or less chemotactic than that of unstressed fish. Fish with red-sore lesions produced surface mucus which was not chemotactic to A. hydrophila. Differences between fish, for any isolate, were also not significant. The chemotactic substance(s) in fish mucus has a molecular weight of approximately 100,000 and did not appear to be labile when heated to 56/sup 0/C.

  14. Coarse-Grained Modeling of Mucus Barrier Properties

    PubMed Central

    Gniewek, Pawel; Kolinski, Andrzej

    2012-01-01

    We designed a simple coarse-grained model of the glycocalyx layer, or adhesive mucus layer (AML), covered by mucus gel (luminal mucus layer) using a polymer lattice model and stochastic sampling (replica exchange Monte Carlo) for canonical ensemble simulations. We assumed that mucin MUC16 is responsible for the structural properties of the AML. Other mucins that are much smaller in size and less relevant for layer structure formation were not included. We further assumed that the system was in quasi-equilibrium. For systems with surface coverage and concentrations of model mucins mimicking physiological conditions, we determined the equilibrium distribution of inert nanoparticles within the mucus layers using an efficient replica exchange Monte Carlo sampling procedure. The results show that the two mucus layers penetrate each other only marginally, and the bilayer imposes a strong barrier for nanoparticles, with the AML layer playing a crucial role in the mucus barrier. PMID:22339855

  15. Imaging of mucus clearance in the airways of living spontaneously breathing mice by optical coherence microscopy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Pieper, Mario; Schulz-Hildebrandt, Hinnerk; Hüttmann, Gereon; König, Peter

    2016-03-01

    Mucus transport is essential to remove inhaled particles and pathogens from the lung. Impaired removal of mucus often results in worsening of lung diseases. To understand the mechanisms of mucus transport and to monitor the impact of therapeutic strategies, it is essential to visualize airways and mucus in living animals without disturbing transport processes by intubation or surgically opening the airways. We developed a custom-built optical coherence microscope (OCM) providing a lateral and axial resolution of approximately 1.5 µm with a field of view of 2 mm at up to 150 images/s. Images of the intact trachea and its mucus transport were recorded in anesthetized spontaneously breathing mice. NaCl solution (0.9% and 7%) or Lipopolysaccharide were applied intranasally. OCM resolved detailed structure of the trachea and enabled measuring the airway surface liquid (ASL) thickness through the tracheal wall. Without stimulation, the amount of ASL was only a few µm above the epithelium and remained constant. After intranasal application of 30 µl saline at different concentrations, an early fast cough-like fluid removal with velocities higher than 1 mm/s was observed that removed a high amount of liquid. The ASL thickness increased transiently and quickly returned to levels before stimulation. In contrast to saline, application of Lipopolysaccharide induced substantial mucus release and an additional slow mucus transport by ciliary beating (around 100 µm/s) towards the larynx was observed. In conclusion, OCM is appropriate unique tool to study mechanisms of mucus transport in the airways and effects of therapeutic interventions in living animals.

  16. Murine Cytomegalovirus Influences Foxj1 Expression, Ciliogenesis, and Mucus Plugging in Mice with Allergic Airway Disease

    PubMed Central

    Wu, Carol A.; Peluso, John J.; Shanley, John D.; Puddington, Lynn; Thrall, Roger S.

    2008-01-01

    We have followed throughout time the development of allergic airway disease (AAD) in both uninfected mice and mice infected intranasally with murine cytomegalovirus (MCMV). Histological evaluation of lung tissue from uninfected mice with AAD demonstrated mucus plugging after 14 and 21 days of ovalbumin-aerosol challenge, with resolution of mucus plugging occurring by 42 days. In MCMV/AAD mice, mucus plugging was observed after 7 days of ovalbumin-aerosol challenge and remained present at 42 days. The level of interleukin-13 in bronchoalveolar lavage fluid from MCMV/AAD mice was decreased compared with AAD mice and was accompanied by increased levels of interferon-γ. Levels of Muc5A/C, Muc5B, or Muc2 mucin mRNA in the lungs of MCMV/AAD mice were not elevated compared with AAD mice. MCMV was able to infect the airway epithelium, resulting in decreased expression of Foxj1, a transcription factor critical for ciliogenesis, and a loss of ciliated epithelial cells. In addition, an increase in the number of epithelial cells staining positive for periodic acid-Schiff was observed in MCMV/AAD airways. Together, these findings suggest that MCMV infection of the airway epithelium enhances goblet cell metaplasia and diminishes efficient mucociliary clearance in mice with AAD, resulting in increased mucus plugging. PMID:18258850

  17. The detection of gunshot residues in the nasal mucus of suspected shooters.

    PubMed

    Merli, Daniele; Brandone, Alberto; Amadasi, Alberto; Cattaneo, Cristina; Profumo, Antonella

    2016-07-01

    The identification and quantification of metallic residues produced by gunshots, called gunshot residues (GSR), provide crucial elements in forensic investigations. The research has been largely focused on their collection onto the hands of suspected shooters, but the method is often burdened by risks of contamination. This research was focused on the possibility of sampling GSR trapped inside the nasal mucus of consenting shooters. Samples of the nasal mucus of "blank" control subjects and shooters were chemically analysed by Instrumental Neutron Activation Analysis (INAA), for residues of antimony (Sb) and barium (Ba), while lead (Pb) was excluded as ubiquitously environmental contaminant and due to high instrumental quantification limit (IQL) of INAA for this element. Shots were fired using two types of weapons (pistols and revolvers) and different firing sequences. The mucus was sampled at different times: immediately after the shots, after 30-60-120 and 180 min. Different amounts of Sb and Ba were detected between controls and shooters, witnessing the ability of the nasal mucus to retain GSR at concentrations significantly different even from the highest basal levels. Moreover, in order to simulate actual cases, nasal mucus from five groups of shooters was sampled after different shots with the same weapon and cartridges, immediately and after 1, 3, 12, and 24 h. The highest values were always found in the first 3 h from firing, for both weapons. Interestingly, for all the weapons, significant Sb and Ba concentrations were also found up to 12 h after firing, contrary to what occurs on hands, even though a progressive decrease was detected, with values below the detection threshold only after 24 h, thus demonstrating that GSR are persistent in nasal mucus. These first results proving that both Sb and Ba were qualitatively detectable in the nasal mucus of shooters indicate that the chemical analysis of the nasal mucus of suspected shooters may represent a

  18. The Goblet Cell Protein Clca1 (Alias mClca3 or Gob-5) Is Not Required for Intestinal Mucus Synthesis, Structure and Barrier Function in Naive or DSS-Challenged Mice

    PubMed Central

    Mundhenk, Lars; Arike, Liisa; Glauben, Rainer; Heimesaat, Markus M.; Fischer, André; Bereswill, Stefan; Birchenough, George M. H.; Gruber, Achim D.; Johansson, Malin E. V.

    2015-01-01

    The secreted, goblet cell-derived protein Clca1 (chloride channel regulator, calcium-activated-1) has been linked to diseases with mucus overproduction, including asthma and cystic fibrosis. In the intestine Clca1 is found in the mucus with an abundance and expression pattern similar to Muc2, the major structural mucus component. We hypothesized that Clca1 is required for the synthesis, structure or barrier function of intestinal mucus and therefore compared wild type and Clca1-deficient mice under naive and at various time points of DSS (dextran sodium sulfate)-challenged conditions. The mucus phenotype in Clca1-deficient compared to wild type mice was systematically characterized by assessment of the mucus protein composition using proteomics, immunofluorescence and expression analysis of selected mucin genes on mRNA level. Mucus barrier integrity was assessed in-vivo by analysis of bacterial penetration into the mucus and translocation into sentinel organs combined analysis of the fecal microbiota and ex-vivo by assessment of mucus penetrability using beads. All of these assays revealed no relevant differences between wild type and Clca1-deficient mice under steady state or DSS-challenged conditions in mouse colon. Clca1 is not required for mucus synthesis, structure and barrier function in the murine colon. PMID:26162072

  19. Aerosol Medications for Treatment of Mucus Clearance Disorders.

    PubMed

    Rubin, Bruce K

    2015-06-01

    Airway mucus hypersecretion and secretion retention can result from inflammation, irritation, stimulation, or mucus-producing tumors. Secretion clearance can be furthered hampered by ciliary dysfunction and by weakness or restrictive lung disease, leading to an ineffective cough. There are a number of different mucoactive medications that have been used to reduce hypersecretion, make secretions easier to transport, or increase the efficiency of cough or mucus clearance. In this paper, I review the pathophysiology of secretory hyper-responsiveness and mucus hypersecretion and discuss the different aerosol medications that can be used to augment secretion clearance. PMID:26070577

  20. Food-associated Stimuli Enhance Barrier Properties of Gastrointestinal Mucus

    PubMed Central

    Yildiz, Hasan M.; Speciner, Lauren; Ozdemir, Cafer; Cohen, David E.; Carrier, Rebecca L.

    2015-01-01

    Orally delivered drugs and nutrients must diffuse through mucus to enter the circulatory system, but the barrier properties of mucus and their modulation by physiological factors are generally poorly characterized. The main objective of this study was to examine the impact of physicochemical changes occurring upon food ingestion on gastrointestinal (GI) mucus barrier properties. Lipids representative of postprandial intestinal contents enhanced mucus barriers, as indicated by a 10 – 142-fold reduction in the transport rate of 200 nm microspheres through mucus, depending on surface chemistry. Physiologically relevant increases in [Ca2+] resulted in a 2 - 4-fold reduction of transport rates, likely due to enhanced cross-linking of the mucus gel network. Reduction of pH from 6.5 to 3.5 also affected mucus viscoelasticity, reducing particle transport rates approximately 5 – 10-fold. Macroscopic visual observation and micro-scale lectin staining revealed mucus gel structural changes, including clumping into regions into which particles did not penetrate. Histological examination indicated food ingestion can prevent microsphere contact with and endocytosis by intestinal epithelium. Taken together, these results demonstrate that GI mucus barriers are significantly altered by stimuli associated with eating and potentially dosing of lipid-based delivery systems; these stimuli represent broadly relevant variables to consider upon designing oral therapies. PMID:25907034

  1. Food-associated stimuli enhance barrier properties of gastrointestinal mucus.

    PubMed

    Yildiz, Hasan M; Speciner, Lauren; Ozdemir, Cafer; Cohen, David E; Carrier, Rebecca L

    2015-06-01

    Orally delivered drugs and nutrients must diffuse through mucus to enter the circulatory system, but the barrier properties of mucus and their modulation by physiological factors are generally poorly characterized. The main objective of this study was to examine the impact of physicochemical changes occurring upon food ingestion on gastrointestinal (GI) mucus barrier properties. Lipids representative of postprandial intestinal contents enhanced mucus barriers, as indicated by a 10-142-fold reduction in the transport rate of 200 nm microspheres through mucus, depending on surface chemistry. Physiologically relevant increases in [Ca(2+)] resulted in a 2-4-fold reduction of transport rates, likely due to enhanced cross-linking of the mucus gel network. Reduction of pH from 6.5 to 3.5 also affected mucus viscoelasticity, reducing particle transport rates approximately 5-10-fold. Macroscopic visual observation and micro-scale lectin staining revealed mucus gel structural changes, including clumping into regions into which particles did not penetrate. Histological examination indicated food ingestion can prevent microsphere contact with and endocytosis by intestinal epithelium. Taken together, these results demonstrate that GI mucus barriers are significantly altered by stimuli associated with eating and potentially dosing of lipid-based delivery systems; these stimuli represent broadly relevant variables to consider upon designing oral therapies. PMID:25907034

  2. Radioisotope measurement of the velocity of tracheal mucus.

    PubMed

    Russo, K J; Palmer, D W; Beste, D J; Carl, G A; Belson, T P; Pelc, L R; Toohill, R J

    1985-04-01

    A radioisotope scanning technique for measuring the velocity of tracheal mucus has been developed utilizing a canine model. A solution of stannous phytate labeled with 99mTc is introduced percutaneously into the lower trachea and the upward movement of the leading edge of the radioactivity is followed by repeat scanning at 2-minute intervals using a modified rectilinear scanner, thus allowing calculation of the velocity of the mucus. It is believed that this technique may be of value in studying the effect of experimentally induced tracheal injuries on mucus velocity. Possible applications of the technique for the study of the velocity of mucus in the human trachea are discussed. PMID:3921912

  3. Transport of Particles in Intestinal Mucus under Simulated Infant and Adult Physiological Conditions: Impact of Mucus Structure and Extracellular DNA

    PubMed Central

    Macierzanka, Adam; Mackie, Alan R.; Bajka, Balazs H.; Rigby, Neil M.; Nau, Françoise; Dupont, Didier

    2014-01-01

    The final boundary between digested food and the cells that take up nutrients in the small intestine is a protective layer of mucus. In this work, the microstructural organization and permeability of the intestinal mucus have been determined under conditions simulating those of infant and adult human small intestines. As a model, we used the mucus from the proximal (jejunal) small intestines of piglets and adult pigs. Confocal microscopy of both unfixed and fixed mucosal tissue showed mucus lining the entire jejunal epithelium. The mucus contained DNA from shed epithelial cells at different stages of degradation, with higher amounts of DNA found in the adult pig. The pig mucus comprised a coherent network of mucin and DNA with higher viscosity than the more heterogeneous piglet mucus, which resulted in increased permeability of the latter to 500-nm and 1-µm latex beads. Multiple-particle tracking experiments revealed that diffusion of the probe particles was considerably enhanced after treating mucus with DNase. The fraction of diffusive 500-nm probe particles increased in the pig mucus from 0.6% to 64% and in the piglet mucus from ca. 30% to 77% after the treatment. This suggests that extracellular DNA can significantly contribute to the microrheology and barrier properties of the intestinal mucus layer. To our knowledge, this is the first time that the structure and permeability of the small intestinal mucus have been compared between different age groups and the contribution of extracellular DNA highlighted. The results help to define rules governing colloidal transport in the developing small intestine. These are required for engineering orally administered pharmaceutical preparations with improved delivery, as well as for fabricating novel foods with enhanced nutritional quality or for controlled calorie uptake. PMID:24755941

  4. Quantifying Isoniazid Levels in Small Hair Samples: A Novel Method for Assessing Adherence during the Treatment of Latent and Active Tuberculosis

    PubMed Central

    Gerona, Roy; Wen, Anita; Chin, Aaron T.; Koss, Catherine A.; Bacchetti, Peter; Metcalfe, John; Gandhi, Monica

    2016-01-01

    Background Tuberculosis (TB) is the leading cause of death from an infectious pathogen worldwide and the most prevalent opportunistic infection in people living with HIV. Isoniazid preventive therapy (IPT) reduces the incidence of active TB and reduces morbidity and mortality in HIV-infected patients independently of antiretroviral therapy. However, treatment of latent or active TB is lengthy and inter-patient variability in pharmacokinetics and adherence common. Current methods of assessing adherence to TB treatment using drug levels in plasma or urine assess short-term exposure and pose logistical challenges. Drug concentrations in hair assess long-term exposure and have demonstrated pharmacodynamic relevance in HIV. Methods A large hair sample from a patient with active TB was obtained for assay development. Methods to pulverize hair and extract isoniazid were optimized and then the drug detected by liquid chromatography/ tandem mass spectrometry (LC/MS-MS). The method was validated for specificity, accuracy, precision, recovery, linearity and stability to establish the assay’s suitability for therapeutic drug monitoring (TDM). Hair samples from patients on directly-observe isoniazid-based latent or active TB therapy from the San Francisco Department of Public Health TB clinic were then tested. Results Our LC/MS-MS-based assay detected isoniazid in quantities as low as 0.02ng/mg using 10–25 strands hair. Concentrations in spiked samples demonstrated linearity from 0.05–50ng/mg. Assay precision and accuracy for spiked quality-control samples were high, with an overall recovery rate of 79.5%. In 18 patients with latent or active TB on treatment, isoniazid was detected across a wide linear dynamic range. Conclusions An LC-MS/MS-based assay to quantify isoniazid levels in hair with performance characteristics suitable for TDM was developed and validated. Hair concentrations of isoniazid assess long-term exposure and may be useful for monitoring adherence to

  5. Pharmacologic agents for mucus clearance in bronchiectasis.

    PubMed

    Nair, Girish B; Ilowite, Jonathan S

    2012-06-01

    There are no approved pharmacologic agents to enhance mucus clearance in non-cystic fibrosis (CF) bronchiectasis. Evidence supports the use of hyperosmolar agents in CF, and studies with inhaled mannitol and hypertonic saline are ongoing in bronchiectasis. N-acetylcysteine may act more as an antioxidant than a mucolytic in other lung diseases. Dornase α is beneficial to patients with CF, but is not useful in patients with non-CF bronchiectasis. Mucokinetic agents such as β-agonists have the potential to improve mucociliary clearance in normals and many disease states, but have not been adequately studied in patients with bronchiectasis. PMID:22640851

  6. Unplugging Mucus in Cystic Fibrosis and Chronic Obstructive Pulmonary Disease.

    PubMed

    Mall, Marcus A

    2016-04-01

    Airway mucus obstruction is a key feature of cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). The thin layer of mucus that covers healthy airway surfaces has important protective functions in lung defense. However, excess mucus produces airflow obstruction and provides a nidus for bacterial infection and inflammation. Despite its importance in pathogenesis, understanding of the mechanisms underlying airway mucus obstruction, as well as therapeutic options, remain limited. Studies in the rare genetic disease CF identified airway surface dehydration due to cystic fibrosis transmembrane conductance regulator (CFTR) gene dysfunction as an important disease mechanism that may explain mucus stasis and plugging in a spectrum of muco-obstructive lung diseases, including COPD. This concept is supported by the phenotype of the β-epithelial Na(+) channel-transgenic mouse that exhibits airway surface dehydration and develops a spontaneous lung disease that shares key features with CF and COPD, such as airway mucus plugging, chronic neutrophilic inflammation, and structural lung damage. Furthermore, preclinical testing demonstrated that hydration strategies, including osmotically active hypertonic saline and preventive inhibition of the amiloride-sensitive epithelial Na(+) channel are effective in unplugging airways in this mouse model of chronic obstructive lung disease. On the other hand, genetic deletion of neutrophil elastase, a potent stimulus for mucus hypersecretion, reduced goblet cell metaplasia and mucin expression but had no effect on mucus obstruction in vivo. Collectively, these studies demonstrate that airway surface dehydration is sufficient to produce mucus obstruction even in the absence of mucus hypersecretion and support further clinical testing of hydrating agents as a promising therapeutic strategy to unplug mucus in CF and COPD. PMID:27115954

  7. Comparative analysis of the humoral immunity of skin mucus from several marine teleost fish.

    PubMed

    Guardiola, Francisco A; Cuesta, Alberto; Abellán, Emilia; Meseguer, José; Esteban, María A

    2014-09-01

    Fish skin mucus contains several immune substances that provide the first line of defence against a broad spectrum of pathogens although they are poorly studied to date. Terminal carbohydrate composition and levels of total IgM antibodies, several immune-related enzymes (lysozyme, peroxidase, alkaline phosphatase, esterases, proteases and antiproteases) as well as the bactericidal activity (against fish pathogenic Vibrio harveyi, Vibrio angillarum, Photobacterium damselae and non-pathogenic bacteria Escherichia coli, Bacillus subtilis, Shewanella putrefaciens) were identified and measured in the skin mucus of five marine teleosts: gilthead seabream (Sparus aurata), European sea bass (Dicentrarchus labrax), shi drum (Umbrina cirrosa), common dentex (Dentex dentex) and dusky grouper (Epinephelus marginatus). First, lectin binding results suggests that skin mucus contain, in order of abundance, N-acetylneuraminic acid, glucose, N-acetyl-glucosamine, N-acetyl-galactosamine, galactose and fucose residues. Second, results showed that while some immune activities were very similar in the studied fish (e.g. IgM and lysozyme activity) other such as protease, antiprotease, alkaline phosphatase, esterase and peroxidase activities varied depending on the fish species. High levels of peroxidase and protease activity were found in U. cirrosa respect to the values obtained in the other species while E. marginatus and S. aurata showed the highest levels of alkaline phosphatase and esterase activities, respectively. Moreover, skin mucus of S. aurata revealed higher bactericidal activity against pathogenic bacteria, contrarily, to what happened with non-pathogenic bacteria (E. coli, B. subtilis). Thus, study of the variations in the carbohydrate profile and immune-related components of the fish skin mucus could help to understand the fish resistance as well as the presence and distribution of pathogens and magnitude of infections, aspects that are of major importance for the

  8. Components of mucus of terrestrial slugs (Gastropoda).

    PubMed

    Deyrup-Olsen, I; Luchtel, D L; Martin, A W

    1983-09-01

    Mucous secretion by the body wall of the terrestrial slugs (Ariolimax columbianus, Arionidae; and other species) was found to involve at least three distinct stages--release of vesicles, formation of granules, and organization of strands. Mucus is stored intracellularly in membrane-bound vesicles, and these are shed intact from the mucous cells. Disruption of the vesicle membrane, with release of contents, can be effected by endogenous lytic agent(s), as well as by exogenous surfactants, lipid solvents, or hypotonic media. Thereupon 1-micron granules are released. These may be stable, or they may change to material that is finely granular or in the form of strands; the transition to strands is facilitated by shear stress exerted through the fluid containing the mucous components. Lectins organize, or are organized with, the strands, as evidenced by agglutination of erythrocytes on them. Mucous formation, as seen in the living slug, differs markedly from the one-step process of exocytosis of fluid mucus inferred from studies of mucous membranes fixed for ultrastructural investigation. PMID:6614215

  9. Mucus extravasation into the orbit during frontal sinus irrigation.

    PubMed

    Andrew, Nicholas; Pirbhai, Adnan; Moffat, David; Rajapaksa, Suresh; Wormald, Peter-John; Reid, Michael; Selva, Dinesh

    2013-01-01

    During minitrephination and irrigation of the frontal sinus, mucus extravasated into the orbit through a defect in the sinus floor. The mucus incited a foreign body reaction and became encapsulated within the orbit necessitating excision via an anterior orbitotomy. PMID:22955342

  10. Enhancement of the physicochemical qualities of gastric mucus by sofalcone.

    PubMed

    Piotrowski, J; Yamaki, K; Tamura, S; Slomiany, A; Slomiany, B L

    1991-09-01

    The effect of prolonged administration of an antiulcer drug, sofalcone, on the physicochemical properties of gastric mucus was investigated. The experiments were conducted with groups of rats receiving twice daily for three consecutive days a dose of 100 mg/kg sofalcone, while the control group received daily doses of vehicle. The rats were sacrificed 16 h after the last dose and gastric mucosa subjected to physicochemical measurements. The results revealed that sofalcone evoked a 23% increase in mucus gel dimension, while sulfo- and sialomucins content of the gel increased by 54 and 25%, respectively. These changes were accompanied by a 16% increase in mucus H+ retardation capacity, 2-fold increase in viscosity, and a 39% increase in the gel hydrophobicity. The mucus elaborated in the presence of sofalcone contained 67% more covalently bound fatty acids, exhibited 10% lower content of protein, 30% higher content of carbohydrate, and 18% higher content of lipids. The mucus of the sofalcone group also showed an increase in the proportion of the high molecular weight mucus glycoprotein form, which in the control group accounted for about 30% of gel mucin, while its content in mucus gel of animals receiving sofalcone reached the value of 50%. The results indicate that sofalcone enhances the protective qualities of mucus component of gastric mucosal barrier. PMID:1793890

  11. The role of airway mucus in pulmonary toxicology.

    PubMed Central

    Samet, J M; Cheng, P W

    1994-01-01

    Airway mucus is a complex airway secretion whose primary function as part of the mucociliary transport mechanism is to to serve as renewable and transportable barrier against inhaled particulates and toxic agents. The rheologic properties necessary for this function are imparted by glycoproteins, or mucins. Some respiratory disease states, e.g., asthma, cystic fibrosis, and bronchitis, are characterized by quantitative and qualitative changes in mucus biosynthesis that contribute to pulmonary pathology. Similar alterations in various aspects of mucin biochemistry and biophysics, leading to mucus hypersecretion and altered mucus rheology, result from inhalation of certain air pollutants, such as ozone, sulfur dioxide, nitrogen dioxide, and cigarette smoke. The consequences of these pollutant-induced alterations in mucus biology are discussed in the context of pulmonary pathophysiology and toxicology. PMID:7925190

  12. Faecal mucus degrading glycosidases in ulcerative colitis and Crohn's disease.

    PubMed

    Rhodes, J M; Gallimore, R; Elias, E; Allan, R N; Kennedy, J F

    1985-08-01

    Because the normal faecal flora includes bacteria which can produce mucus-digesting glycosidases, it follows that increased digestion of colonic mucus by these bacterial enzymes could be important in the pathogenesis of ulcerative colitis. Faecal activities of potential mucus-degrading glycosidases have therefore been assayed in samples from patients with inflammatory bowel disease and normal controls. The enzymes alpha-D-galactosidase, beta-D-galactosidase, beta-NAc-D-glucosaminidase alpha-L-fucosidase and neuraminidase were assayed. Considerable glycosidase activity was present in most faecal samples. Similar activities of all the enzymes assayed were found in faeces from patients with ulcerative colitis, Crohn's disease and normal controls and there was no significant correlation with disease activity. These results imply that relapse of ulcerative colitis is not initiated by increased degradation of colonic mucus by faecal glycosidases but do not exclude a role for bacterial mucus degradation in the pathogenesis of ulcerative colitis. PMID:2991089

  13. Pre-exposure Prophylaxis Adherence Measured by Plasma Drug Level in MTN-001: Comparison Between Vaginal Gel and Oral Tablets in Two Geographic Regions.

    PubMed

    Minnis, Alexandra M; van der Straten, Ariane; Salee, Parichat; Hendrix, Craig W

    2016-07-01

    Despite strong evidence that daily oral pre-exposure prophylaxis (PrEP) reduces HIV risk, effectiveness across studies has varied. Inconsistent adherence constitutes one explanation. Efforts to examine adherence are limited when they rely on self-reported measures. We examined recent adherence as measured by plasma tenofovir (TFV) concentration in participants of MTN-001, a phase 2 cross-over trial comparing oral tablet and vaginal gel formulations of TFV among 144 HIV-uninfected women at sites in the United States (U.S.) and sub-Saharan Africa (SSA). Adherence to daily product use was higher in the U.S. than in the SSA sites. Within region, however, adherence was similar between products. In the U.S., gel adherence was higher among married women, and lower among women using male condoms and injectable contraceptives. At the SSA sites, gel adherence was lower for younger women. Inconsistent adherence points to challenges in use of daily PrEP, even during a trial of short duration. PMID:25969178

  14. A new method of separation and quantitation of mucus glycoprotein in rat gastric mucus gel layer and its application to mucus secretion induced by 16,16-dimethyl PGE2.

    PubMed

    Komuro, Y; Ishihara, K; Ohara, S; Saigenji, K; Hotta, K

    1991-10-01

    A method was established for recovering the mucus gel layer of rat gastric mucosa without damage to underlying surface epithelium. The mucus gel was solubilized by stirring the gastric mucosa in a solution of N-acetylcysteine (NAC), a mucolytic agent. Optimal mucus gel solubilization was possible by treatment with 2% NAC for 5 minutes at room temperature. Mucus glycoprotein was quantitatively extracted and measured from the mucus gel sample obtained by the NAC treatment. This treatment caused no damage to surface epithelial cells, as observed by a light microscope. Besides NAC, pronase solution was also adequate for solubilizing the mucus gel layer without any damage to the surface epithelium. However, extraction and measurement of mucus glycoprotein from the pronase-treated mucus gel sample was not possible due to contamination by high molecular hexose-containing substances which were eluted along with the mucus glycoprotein from the column of Bio-Gel A-1.5m. This NAC method was used to examine changes in mucus glycoprotein content in the mucus gel at one hour following the oral administration of 16,16-dimethyl prostaglandin E2. A significant increase in mucus glycoprotein of the gel was brought about by the prostaglandin treatment. Thus, the present method was suitable for estimating the amount of mucus secreted in to the mucus gel layer. PMID:1752389

  15. N-acetyl-cysteine and prostaglandin. Comparable protection against experimental ethanol injury in the stomach independent of mucus thickness.

    PubMed

    Henagan, J M; Smith, G S; Schmidt, K L; Miller, T A

    1986-12-01

    The role of barrier mucus in mediating the protective effects of 16,16 dimethyl PGE2 (dm PGE2) against ethanol-induced gastric injury, with and without concomitant treatment with N-acetyl-cysteine (NAC), a potent mucolytic agent, was evaluated. Fasted rats were orally administered either saline, 10 micrograms/kg dm PGE2, 20% NAC, or 10 micrograms/kg dm PGE2 plus 20% NAC. In the first study, the rats were killed 15 minutes later and their stomachs were removed and assayed for barrier mucus adherent to the gastric wall using the Alcian blue technique. In the second study, the rats were orally given 2 mL of absolute ethanol (EtOH) after receiving one of these pretreatment regimens, and 5 minutes later they were killed and their stomachs were evaluated histologically by light microscopy for the magnitude of EtOH injury. Although NAC significantly reduced the thickness of barrier mucus by 76% when compared with control animals, it did not adversely affect the ability of dm PGE2 to spare the deep epithelium from injury by EtOH. In fact, NAC was as effective a protective agent as dm PGE2. Neither agent prevented damage to the surface epithelium by EtOH, verifying previous studies regarding the protective effects of prostaglandins. These results indicate that both dm PGE2 and NAC prevent EtOH-induced damage to the deeper layers of the gastric mucosa independent of mucus gel layer thickness, suggesting that other mechanisms than mucus are involved in mediating this protection. PMID:3789839

  16. KDN-containing glycoprotein from loach skin mucus.

    PubMed

    Nakagawa, H; Hama, Y; Sumi, T; Li, S C; Li, Y T

    2001-01-01

    It has been widely recognized that the mucus coat of fish plays a variety of important physical, chemical, and physiological functions. One of the major constituents of the mucus coat is mucus glycoprotein. We found that sialic acids in the skin mucus of the loach, Misgurnus anguillicaudatus, consisted predominantly of KDN. Subsequently, we isolated KDN-containing glycoprotein from loach skin mucus and characterized its chemical nature and structure. Loach mucus glycoprotein was purified from the Tris-HCl buffer extract of loach skin mucus by DEAE-cellulose chromatography, Nuclease P1 treatment, and Sepharose CL-6B gel filtration. The purified mucus glycoprotein was found to contain 38.5 KDN, 0.5% NeuAc, 25.0% GalNAc, 3.5% Gal, 0.5% GlcNAc and 28% amino acids. Exhaustive Actinase digestion of the glycoprotein yielded a glycopeptide with a higher sugar content and higher Thr and Ser contents. The molecular size of this glycopeptide was approximately 1/12 of the intact glycoprotein. These results suggest that approximately 11 highly glycosylated polypeptide units are linked in tandem through nonglycosylated peptides to form the glycoporotein molecule. The oligosaccharide alditols liberated from the loach mucus glycoprotein by alkaline borohydride treatment were separated by Sephadex G-25 gel filtration and HPLC. The purified sugar chains were analyzed b --> 6GalNAc-ol, KDNalpha2 --> 3(GalNAcbeta1 --> 14)GalNAc-ol, KDNalpha2 --> 6(GalNAcalpha1 --> 3)GalNAc-ol, KDNalpha2 --> 6(Gal3alpha1--> 3)GalNAc-ol, and NeuAcalpha2 --> 6Gal NAc-ol. It is estimated that one loach mucus glycoprotein molecule contains more than 500 KDN-containing sugar chains that are linked to Thr and Ser residues of the protein core through GalNAc. PMID:14533798

  17. Polymers in the gut compress the colonic mucus hydrogel

    PubMed Central

    Datta, Sujit S.; Preska Steinberg, Asher

    2016-01-01

    Colonic mucus is a key biological hydrogel that protects the gut from infection and physical damage and mediates host–microbe interactions and drug delivery. However, little is known about how its structure is influenced by materials it comes into contact with regularly. For example, the gut abounds in polymers such as dietary fibers or administered therapeutics, yet whether such polymers interact with the mucus hydrogel, and if so, how, remains unclear. Although several biological processes have been identified as potential regulators of mucus structure, the polymeric composition of the gut environment has been ignored. Here, we demonstrate that gut polymers do in fact regulate mucus hydrogel structure, and that polymer–mucus interactions can be described using a thermodynamic model based on Flory–Huggins solution theory. We found that both dietary and therapeutic polymers dramatically compressed murine colonic mucus ex vivo and in vivo. This behavior depended strongly on both polymer concentration and molecular weight, in agreement with the predictions of our thermodynamic model. Moreover, exposure to polymer-rich luminal fluid from germ-free mice strongly compressed the mucus hydrogel, whereas exposure to luminal fluid from specific-pathogen-free mice—whose microbiota degrade gut polymers—did not; this suggests that gut microbes modulate mucus structure by degrading polymers. These findings highlight the role of mucus as a responsive biomaterial, and reveal a mechanism of mucus restructuring that must be integrated into the design and interpretation of studies involving therapeutic polymers, dietary fibers, and fiber-degrading gut microbes. PMID:27303035

  18. Polymers in the gut compress the colonic mucus hydrogel.

    PubMed

    Datta, Sujit S; Preska Steinberg, Asher; Ismagilov, Rustem F

    2016-06-28

    Colonic mucus is a key biological hydrogel that protects the gut from infection and physical damage and mediates host-microbe interactions and drug delivery. However, little is known about how its structure is influenced by materials it comes into contact with regularly. For example, the gut abounds in polymers such as dietary fibers or administered therapeutics, yet whether such polymers interact with the mucus hydrogel, and if so, how, remains unclear. Although several biological processes have been identified as potential regulators of mucus structure, the polymeric composition of the gut environment has been ignored. Here, we demonstrate that gut polymers do in fact regulate mucus hydrogel structure, and that polymer-mucus interactions can be described using a thermodynamic model based on Flory-Huggins solution theory. We found that both dietary and therapeutic polymers dramatically compressed murine colonic mucus ex vivo and in vivo. This behavior depended strongly on both polymer concentration and molecular weight, in agreement with the predictions of our thermodynamic model. Moreover, exposure to polymer-rich luminal fluid from germ-free mice strongly compressed the mucus hydrogel, whereas exposure to luminal fluid from specific-pathogen-free mice-whose microbiota degrade gut polymers-did not; this suggests that gut microbes modulate mucus structure by degrading polymers. These findings highlight the role of mucus as a responsive biomaterial, and reveal a mechanism of mucus restructuring that must be integrated into the design and interpretation of studies involving therapeutic polymers, dietary fibers, and fiber-degrading gut microbes. PMID:27303035

  19. [Changes in the amino acid levels in hydrolysates of bacteria adhering to the rumen in sheep during feeding with high and low nitrogen diets].

    PubMed

    Legáth, J

    1992-01-01

    The effects of low and high nitrogen diets on amino acid levels were studied in hydrolyzates of ruminal bacteria adhered to four topographically different anatomic parts of the ruminal wall (dorsal, ventral and caudal parts as well as reticulum) in 18 sheep + of the Slovak Merino breed divided into three experimental groups. The epimural bacteria of the dorsal and ventral parts of the ovine rumen revealed the most sensitive reaction to the varying amounts of nitrogen ingested with the diet. In hydrolyzates of ruminal bacteria adhered to the dorsal and ventral epithelium, 15 and 14 amino acids were changing (Figs. 1, 2). In hydrolyzates of epimural bacteria, a sensitive reaction was observed in the following amino acids: alanine, histidine, thyroxin, arginine and proline (Tabs. I-IV). In all topographical and anatomical parts of the rumen, both alanine and histidine levels in hydrolyzates of epimural ruminal bacteria significantly increased with the diet with high-nitrogen content fed, but was falling in sheep fed with low-nitrogen diet. Changes in alanine concentrations may be explained by the fact that alanine forms a part of the mechanism for short-time storage of ammonia in bacterial cells (Bartos, 1987). The fact that alanine is in its lack deaminated to pyruvate (Havassy, 1976) is explained by significant fall in alanine contained in hydrolyzates of bacterial proteins when fed low nitrogen diets. Significant fall in alanine in shortage of amino acid bound nitrogen can be explained by the fact that under these conditions, the alanine skeleton is being incorporated in to 80% of amino acids synthetized de novo by ruminal bacteria (Syväoja and Kreula, 1980). When sheep flock was fed the high-nitrogen diet, thyroxin and proline levels were significantly reduced in hydrolyzates of epimural bacteria from all parts of the rumen, while low-nitrogen diet significantly increased the concentrations of both given amino acids in comparison with the control. Bartos (1987

  20. [Long term adherence to HAART in Senegal].

    PubMed

    Bastard, M; Fall, M Basty Koita

    2014-10-01

    Adherence is one of the main predictors of antiretroviral treatment success. A governmental initiative was launched in 1998 for HIV-infected patients in Senegal to provide access to highly active antiretroviral therapy (HAART). Adherence measurements, defined as pills taken/pills prescribed, were assessed between November 1999 and June 2010 using a pill count along with a questionnaire for 330 patients. Predictors of adherence and identification of adherence trajectories were explored through latent class mixed model. We also performed a survival analysis using Cox proportional hazard model. Three adherence behaviours were revealed as well as a better adherence for women. A third of patients had a high adherence trajectory over time and a third had an intermediate one. Male gender and low adherence behaviour over time were independently associated with a higher mortality rate. This study shows that an overall good adherence can be obtained in the long term in Senegal, suggests a better adherence for women and points out a large subsample of patients with intermediate level of adherence behaviour who are at risk for developing resistance to antiretroviral drugs. PMID:24615434

  1. Neonatal Pulmonary Macrophage Depletion Coupled to Defective Mucus Clearance Increases Susceptibility to Pneumonia and Alters Pulmonary Immune Responses.

    PubMed

    Saini, Yogesh; Wilkinson, Kristen J; Terrell, Kristy A; Burns, Kimberlie A; Livraghi-Butrico, Alessandra; Doerschuk, Claire M; O'Neal, Wanda K; Boucher, Richard C

    2016-02-01

    Resident immune cells (e.g., macrophages [MΦs]) and airway mucus clearance both contribute to a healthy lung environment. To investigate interactions between pulmonary MΦ function and defective mucus clearance, a genetic model of lysozyme M (LysM) promoter-mediated MΦ depletion was generated, characterized, and crossed with the sodium channel β subunit transgenic (Scnn1b-Tg) mouse model of defective mucus clearance. Diphtheria toxin A-mediated depletion of LysM(+) pulmonary MΦs in wild-type mice with normal mucus clearance resulted in lethal pneumonia in 24% of neonates. The pneumonias were dominated by Pasteurella pneumotropica and accompanied by emaciation, neutrophilic inflammation, and elevated Th1 cytokines. The incidence of emaciation and pneumonia reached 51% when LysM(+) MΦ depletion was superimposed on the airway mucus clearance defect of Scnn1b-Tg mice. In LysM(+) MΦ-depleted Scnn1b-Tg mice, pneumonias were associated with a broader spectrum of bacterial species and a significant reduction in airway mucus plugging. Bacterial burden (CFUs) was comparable between Scnn1b-Tg and nonpneumonic LysM(+) MΦ-depleted Scnn1b-Tg mice. However, the nonpneumonic LysM(+) MΦ-depleted Scnn1b-Tg mice exhibited increased airway inflammation, the presence of neutrophilic infiltration, and increased levels of inflammatory cytokines in bronchoalveolar lavage fluid compared with Scnn1b-Tg mice. Collectively, these data identify key MΦ-mucus clearance interactions with respect to both infectious and inflammatory components of muco-obstructive lung disease. PMID:26121027

  2. Medication adherence among adult patients on hemodialysis.

    PubMed

    Alkatheri, Abdulmalik M; Alyousif, Sarah M; Alshabanah, Najla; Albekairy, Abdulkareem M; Alharbi, Shemylan; Alhejaili, Fayze F; Alsayyari, Abdullah A; Qandil, Abeer Ma; Qandil, Amjad M

    2014-07-01

    Medication adherence was assessed in 89 patients on hemodialysis (HD) at the King Abdul Aziz Medical City using an Arabic version of the Morisky Medication Adherence Scale (MASS-8). The results of the study revealed that 31.46% and 40.45% of the participants showed low and medium adherence, respectively, while 28.09% showed high medication adherence. Accordingly, 71.91% of the patients visiting the dialysis unit were considered medication non-adherent. While being of older age (P = 0.012), being married (P = 0.012) increased the level of adherence, being of medium level of education (P = 0.024) decreased adherence levels. On the other hand, gender, presence of a care-giver, number of members in the household and employment status seems to have no effect on the level of medication adherence. These results call upon the practitioners in HD units to develop intervention programs that can increase the level of medication adherence. PMID:24969185

  3. Roles and regulation of the mucus barrier in the gut.

    PubMed

    Cornick, Steve; Tawiah, Adelaide; Chadee, Kris

    2015-01-01

    The gastrointestinal tract is coated by a thick layer of mucus that forms the front line of innate host defense. Mucus consists of high molecular weight glycoproteins called mucins that are synthesized and secreted by goblet cells and functions primarily to lubricate the epithelium and protect it from damage by noxious substances. Recent studies have also suggested the involvement of goblet cells and mucins in complex immune functions such as antigen presentation and tolerance. Under normal physiological conditions, goblet cells continually produce mucins to replenish and maintain the mucus barrier; however, goblet cell function can be disrupted by various factors that can affect the integrity of the mucus barrier. Some of these factors such as microbes, microbial toxins and cytokines can stimulate or inhibit mucin production and secretion, alter the chemical composition of mucins or degrade the mucus layer. This can lead to a compromised mucus barrier and subsequently to various pathological conditions like chronic inflammatory diseases. Insight into how these factors modulate the mucus barrier in the gut is necessary in order to develop strategies to combat these disorders. PMID:25838985

  4. Roles and regulation of the mucus barrier in the gut

    PubMed Central

    Cornick, Steve; Tawiah, Adelaide; Chadee, Kris

    2015-01-01

    The gastrointestinal tract is coated by a thick layer of mucus that forms the front line of innate host defense. Mucus consists of high molecular weight glycoproteins called mucins that are synthesized and secreted by goblet cells and functions primarily to lubricate the epithelium and protect it from damage by noxious substances. Recent studies have also suggested the involvement of goblet cells and mucins in complex immune functions such as antigen presentation and tolerance. Under normal physiological conditions, goblet cells continually produce mucins to replenish and maintain the mucus barrier; however, goblet cell function can be disrupted by various factors that can affect the integrity of the mucus barrier. Some of these factors such as microbes, microbial toxins and cytokines can stimulate or inhibit mucin production and secretion, alter the chemical composition of mucins or degrade the mucus layer. This can lead to a compromised mucus barrier and subsequently to various pathological conditions like chronic inflammatory diseases. Insight into how these factors modulate the mucus barrier in the gut is necessary in order to develop strategies to combat these disorders. PMID:25838985

  5. Breakdown of gastric mucus in presence of Helicobacter pylori.

    PubMed Central

    Sidebotham, R L; Batten, J J; Karim, Q N; Spencer, J; Baron, J H

    1991-01-01

    The potential of Helicobacter pylori to degrade gastric mucus was examined. Colonies of H pylori cultured from antral mucosal biopsy specimens of patients with non-autoimmune gastritis were washed with sterile saline, passed through a sterilisation filter, and the filtrate examined for urease, protease, and mucolytic activity. The filtrate failed to hydrolyse bovine serum albumin, or to degrade stable mucus glycoprotein structures of high particle weight that had been separated from human gastric mucus on Sepharose 2B. The high particle weight mucus glycoprotein was, however, extensively degraded when incubated with H pylori filtrate (which possessed urease activity) in the presence of 2 M urea, to release fragments of Mr approximately 2 X 10(6). The high particle weight mucus glycoprotein was also broken down to a comparable extent when incubated with Jack bean urease in the presence of 2 M urea, or 1 M ammonium carbonate, or 40 mM carbonate-bicarbonate buffer (pH 8.7), but not when treated with 4 M urea alone, or Jack bean urease alone. These results indicate that the loss of high particle weight mucus glycoprotein in gastric mucus from patients with gastritis and gastric ulcers is unlikely to be due to the mucolytic action of an extra-cellular protease produced by H pylori, but it may result from the destabilising effects of a carbonate-bicarbonate buffer, generated at the mucosal surface when H pylori urease hydrolyses transuded plasma urea. Images PMID:1997534

  6. In vivo colonization of the mouse large intestine and in vitro penetration of intestinal mucus by an avirulent smooth strain of Salmonella typhimurium and its lipopolysaccharide-deficient mutant.

    PubMed Central

    Nevola, J J; Laux, D C; Cohen, P S

    1987-01-01

    The relative abilities of an avirulent Salmonella typhimurium strain with wild-type lipopolysaccharide (LPS) character, SL5319, and a nearly isogenic LPS-deficient mutant, SL5325, to colonize the large intestines of streptomycin-treated CD-1 mice in vivo and to penetrate colonic mucus in vitro were studied. Previously it had been shown that, when fed simultaneously to streptomycin-treated mice (approximately 10(10) CFU each), the S. typhimurium strain with wild-type LPS colonized at 10(8) CFU/g of feces indefinitely, whereas the LPS-deficient mutant dropped within 3 days to a level of only 10(4) CFU/g of feces. In the present investigation, when SL5325 was allowed to colonize for 8 days before feeding mice SL5319 or when it was fed to mice simultaneously with an Escherichia coli strain of human fecal origin (10(10) CFU each), both strains colonized indefinitely at 10(7) CFU/g of feces. Moreover, when the wild-type and LPS-deficient mutant strains were fed to mice simultaneously in low numbers (approximately 10(5) CFU each) the strains survived equally well in the large intestines for 8 days, after which the LPS-deficient mutant was eliminated (less than 10(2) CFU/g of feces), whereas the wild-type colonized at a level of 10(7) CFU/g of feces. In addition although both strains were able to adhere to mucus and epithelial cell preparations in vitro, the wild-type strain was shown to have greater motility and chemotactic activity on CD-1 mouse colonic mucus in vitro and to more rapidly penetrate and form a stable association with immobilized colonic mucosal components in vitro. Based on these data, we suggest that the ability of an S. typhimurium strain to colonize the streptomycin-treated mouse large intestine may, in part, depend on its ability to penetrate deeply into the mucus layer on the intestinal wall and subsequently, through growth, colonize the mucosa. PMID:3316026

  7. Adhesion properties of Lactobacillus rhamnosus mucus-binding factor to mucin and extracellular matrix proteins.

    PubMed

    Nishiyama, Keita; Nakamata, Koichi; Ueno, Shintaro; Terao, Akari; Aryantini, Ni Putu Desy; Sujaya, I Nengah; Fukuda, Kenji; Urashima, Tadasu; Yamamoto, Yuji; Mukai, Takao

    2015-01-01

    We previously described potential probiotic Lactobacillus rhamnosus strains, isolated from fermented mare milk produced in Sumbawa Island, Indonesia, which showed high adhesion to porcine colonic mucin (PCM) and extracellular matrix (ECM) proteins. Recently, mucus-binding factor (MBF) was found in the GG strain of L. rhamnosus as a mucin-binding protein. In this study, we assessed the ability of recombinant MBF protein from the FSMM22 strain, one of the isolates of L. rhamnosus from fermented Sumbawa mare milk, to adhere to PCM and ECM proteins by overlay dot blot and Biacore assays. MBF bound to PCM, laminin, collagen IV, and fibronectin with submicromolar dissociation constants. Adhesion of the FSMM22 mbf mutant strain to PCM and ECM proteins was significantly less than that of the wild-type strain. Collectively, these results suggested that MBF contribute to L. rhamnosus host colonization via mucin and ECM protein binding. PMID:25351253

  8. 21 CFR 884.1040 - Viscometer for cervical mucus.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... evaluation of a female with chronic infertility, to determine the time of ovulation and the penetrability of... device that is intended to measure the relative viscoelasticity of cervical mucus collected from a...

  9. The outer mucus layer hosts a distinct intestinal microbial niche

    PubMed Central

    Li, Hai; Limenitakis, Julien P.; Fuhrer, Tobias; Geuking, Markus B.; Lawson, Melissa A.; Wyss, Madeleine; Brugiroux, Sandrine; Keller, Irene; Macpherson, Jamie A.; Rupp, Sandra; Stolp, Bettina; Stein, Jens V.; Stecher, Bärbel; Sauer, Uwe; McCoy, Kathy D.; Macpherson, Andrew J.

    2015-01-01

    The overall composition of the mammalian intestinal microbiota varies between individuals: within each individual there are differences along the length of the intestinal tract related to host nutrition, intestinal motility and secretions. Mucus is a highly regenerative protective lubricant glycoprotein sheet secreted by host intestinal goblet cells; the inner mucus layer is nearly sterile. Here we show that the outer mucus of the large intestine forms a unique microbial niche with distinct communities, including bacteria without specialized mucolytic capability. Bacterial species present in the mucus show differential proliferation and resource utilization compared with the same species in the intestinal lumen, with high recovery of bioavailable iron and consumption of epithelial-derived carbon sources according to their genome-encoded metabolic repertoire. Functional competition for existence in this intimate layer is likely to be a major determinant of microbiota composition and microbial molecular exchange with the host. PMID:26392213

  10. CFTR, Mucins, and Mucus Obstruction in Cystic Fibrosis

    PubMed Central

    Kreda, Silvia M.; Davis, C. William; Rose, Mary Callaghan

    2012-01-01

    Mucus pathology in cystic fibrosis (CF) has been known for as long as the disease has been recognized and is sometimes called mucoviscidosis. The disease is marked by mucus hyperproduction and plugging in many organs, which are usually most fatal in the airways of CF patients, once the problem of meconium ileus at birth is resolved. After the CF gene, CFTR, was cloned and its protein product identified as a cAMP-regulated Cl− channel, causal mechanisms underlying the strong mucus phenotype of the disease became obscure. Here we focus on mucin genes and polymeric mucin glycoproteins, examining their regulation and potential relationships to a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR). Detailed examination of CFTR expression in organs and different cell types indicates that changes in CFTR expression do not always correlate with the severity of CF disease or mucus accumulation. Thus, the mucus hyperproduction that typifies CF does not appear to be a direct cause of a defective CFTR but, rather, to be a downstream consequence. In organs like the lung, up-regulation of mucin gene expression by inflammation results from chronic infection; however, in other instances and organs, the inflammation may have a non-infectious origin. The mucus plugging phenotype of the β-subunit of the epithelial Na+ channel (βENaC)-overexpressing mouse is proving to be an archetypal example of this kind of inflammation, with a dehydrated airway surface/concentrated mucus gel apparently providing the inflammatory stimulus. Data indicate that the luminal HCO3 − deficiency recently described for CF epithelia may also provide such a stimulus, perhaps by causing a mal-maturation of mucins as they are released onto luminal surfaces. In any event, the path between CFTR dysfunction and mucus hyperproduction has proven tortuous, and its unraveling continues to offer its own twists and turns, along with fascinating glimpses into biology. PMID:22951447

  11. Tracheal Mucus Flow Rates in Experimental Bronchitis in Rats

    PubMed Central

    Lightowler, Norah M.; Williams, J. R. B.

    1969-01-01

    The flow of mucus in the trachea of rats previously exposed to an atmosphere of SO2 in air was measured and correlated with the histological changes in the trachea, bronchi and lungs. Reduction in the speed of mucus flow in the exposed trachea was found with increasing severity of bronchopulmonary changes. ImagesFigs. 9-12Figs. 6-7Figs. 2-5 PMID:5772066

  12. Could gastropods crawl using Newtonian mucus?

    NASA Astrophysics Data System (ADS)

    Lai, Janice; Vazquez-Torres, Maria; Del Alamo, Juan C.; Rodriguez-Rodriguez, Javier; Lasheras, Juan C.

    2010-11-01

    The locomotion of terrestrial gastropods is driven by a train of periodic muscle contractions (pedal waves) and relaxations (interwaves) that propagate from their tail to their head (direct waves). We study the locomotion of these animals on smooth flat surfaces by measuring the three-dimensional displacements of the ventral foot surface induced by the passage of the waves. A simple model based on lubrication theory is proposed in accordance with the experimental observations. This model uncovers a new mode of locomotion that works even when the lubricant between the foot and the animal is Newtonian. The model can also be adapted to situations where the animal's foot is in contact with the ground only at discrete points, as is the case when it crawls on a wire mesh or on rough soil surfaces. Furthermore, comparison between the stress exerted by the animal on the substrate and the model predictions allows us to clarify the role of the complex rheology observed in the mucus of terrestrial gastropods.

  13. A crucial role of Flagellin in the induction of airway mucus production by Pseudomonas aeruginosa.

    PubMed

    Ben Mohamed, Fatima; Mohamed, Fatima Ben; Garcia-Verdugo, Ignacio; Medina, Mathieu; Balloy, Viviane; Chignard, Michel; Ramphal, Reuben; Touqui, Lhousseine

    2012-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen involved in nosocomial infections. Flagellin is a P. aeruginosa virulence factor involved in host response to this pathogen. We examined the role of flagellin in P. aeruginosa-induced mucus secretion. Using a mouse model of pulmonary infection we showed that PAK, a wild type strain of P. aeruginosa, induced airway mucus secretion and mucin muc5ac expression at higher levels than its flagellin-deficient mutant (ΔFliC). PAK induced expression of MUC5AC and MUC2 in both human airway epithelial NCI-H292 cell line and in primary epithelial cells. In contrast, ΔFliC infection had lower to no effect on MUC5AC and MUC2 expressions. A purified P. aeruginosa flagellin induced MUC5AC expression in parallel to IL-8 secretion in NCI-H292 cells. Accordingly, ΔFliC mutant stimulated IL-8 secretion at significantly lower levels compared to PAK. Incubation of NCI-H292 cells with exogenous IL-8 induced MUC5AC expression and pre-incubation of these cells with an anti-IL-8 antibody abrogated flagellin-mediated MUC5AC expression. Silencing of TLR5 and Naip, siRNA inhibited both flagellin-induced MUC5AC expression and IL-8 secretion. Finally, inhibition of ERK abolished the expression of both PAK- and flagellin-induced MUC5AC. We conclude that: (i) flagellin is crucial in P. aeruginosa-induced mucus hyper-secretion through TLR5 and Naip pathways; (ii) this process is mediated by ERK and amplified by IL-8. Our findings help understand the mechanisms involved in mucus secretion during pulmonary infectious disease induced by P. aeruginosa, such as in cystic fibrosis. PMID:22768318

  14. Characterization of shed medicinal leech mucus reveals a diverse microbiota

    PubMed Central

    Ott, Brittany M.; Rickards, Allen; Gehrke, Lauren; Rio, Rita V. M.

    2015-01-01

    Microbial transmission through mucosal-mediated mechanisms is widespread throughout the animal kingdom. One example of this occurs with Hirudo verbana, the medicinal leech, where host attraction to shed conspecific mucus facilitates horizontal transmission of a predominant gut symbiont, the Gammaproteobacterium Aeromonas veronii. However, whether this mucus may harbor other bacteria has not been examined. Here, we characterize the microbiota of shed leech mucus through Illumina deep sequencing of the V3-V4 hypervariable region of the 16S rRNA gene. Additionally, Restriction Fragment Length Polymorphism (RFLP) typing with subsequent Sanger Sequencing of a 16S rRNA gene clone library provided qualitative confirmation of the microbial composition. Phylogenetic analyses of full-length 16S rRNA sequences were performed to examine microbial taxonomic distribution. Analyses using both technologies indicate the dominance of the Bacteroidetes and Proteobacteria phyla within the mucus microbiota. We determined the presence of other previously described leech symbionts, in addition to a number of putative novel leech-associated bacteria. A second predominant gut symbiont, the Rikenella-like bacteria, was also identified within mucus and exhibited similar population dynamics to A. veronii, suggesting persistence in syntrophy beyond the gut. Interestingly, the most abundant bacterial genus belonged to Pedobacter, which includes members capable of producing heparinase, an enzyme that degrades the anticoagulant, heparin. Additionally, bacteria associated with denitrification and sulfate cycling were observed, indicating an abundance of these anions within mucus, likely originating from the leech excretory system. A diverse microbiota harbored within shed mucus has significant potential implications for the evolution of microbiomes, including opportunities for gene transfer and utility in host capture of a diverse group of symbionts. PMID:25620963

  15. Low Social Support Level Is Associated with Non-Adherence to Diet at 1 Year in the Family Intervention Trial for Heart Health (FIT Heart)

    ERIC Educational Resources Information Center

    Aggarwal, Brooke; Liao, Ming; Allegrante, John P.; Mosca, Lori

    2010-01-01

    Objective: Evaluate the relationship between low social support (SS) and adherence to diet in a cardiovascular disease (CVD) lifestyle intervention trial. Design: Prospective substudy. Setting and Participants: Blood relatives/cohabitants of hospitalized cardiac patients in a randomized controlled trial (n = 458; 66% female, 35% nonwhite, mean age…

  16. The pathophysiological mechanisms underlying mucus hypersecretion induced by cold temperatures in cigarette smoke-exposed rats.

    PubMed

    Li, Min-Chao; Yang, Gang; Zhou, Xiang-Dong; Tselluyko, Sergey; Perelman, Juliy M

    2014-01-01

    In a recent study, we demonstrated that transient receptor potential melastatin 8 (TRPM8), a calcium-permeable cation channel that is activated by cold temperatures, is localized in the bronchial epithelium and is upregulated in subjects with chronic obstructive pulmonary disease, which causes them to be more sensitive to cold air. In the present study, we found that exposure to cold temperatures induced ciliary ultrastructural anomalies and mucus accumulation on the epithelial surface. Male Sprague-Dawley rats were exposed to cold temperatures to determine the effects of cold air on ultrastructural changes in cilia and the airway epithelial surface. The rats were also exposed to cigarette smoke and/or cold temperatures to determine the effects of smoke and cold air on TRPM8 expression and the role of cold air in cigarette smoke-induced mucus hypersecretion. Following real-time RT-PCR and western blot analysis, we observed a high expression of TRPM8 mRNA and protein in the bronchial tissue following cigarette smoke inhalation. As shown by ELISA, concurrent cold air enhanced the levels of mucin 5AC (MUC5AC) protein, as well as those of inflammatory factors [tumor necrosis factor (TNF)-α and interleukin (IL)-8] that were induced by cigarette smoke inhalation to a greater extent than stimulation with separate stimuli (cold air and cigarette smoke separately). The results suggest that cold air stimuli are responsible for the ultrastructural abnormalities of bronchial cilia, which contribute to abnormal mucus clearance. In addition, cold air synergistically amplifies cigarette smoke-induced mucus hypersecretion and the production of inflammatory factors through the elevated expression of the TRPM8 channel that is initiated by cigarette smoke inhalation. PMID:24154796

  17. A Tale of Transmission: Aeromonas veronii Activity within Leech-Exuded Mucus.

    PubMed

    Ott, Brittany M; Dacks, Andrew M; Ryan, Kenneth J; Rio, Rita V M

    2016-05-01

    Transmission, critical to the establishment and persistence of host-associated microbiotas, also exposes symbionts to new environmental conditions. With horizontal transmission, these different conditions represent major lifestyle shifts. Yet genome-wide analyses of how microbes adjust their transcriptomes toward these dramatic shifts remain understudied. Here, we provide a comprehensive and comparative analysis of the global transcriptional profiles of a symbiont as it shifts between lifestyles during transmission. The gammaproteobacteriumAeromonas veroniiis transmitted from the gut of the medicinal leech to other hosts via host mucosal castings, yetA. veroniican also transition from mucosal habitancy to a free-living lifestyle. These three lifestyles are characterized by distinct physiological constraints and consequently lifestyle-specific changes in the expression of stress-response genes. Mucus-boundA. veroniihad the greatest expression in terms of both the number of loci and levels of transcription of stress-response mechanisms. However, these bacteria are still capable of proliferating within the mucus, suggesting the availability of nutrients within this environment. We found thatA. veroniialters transcription of loci in a synthetic pathway that obtains and incorporatesN-acetylglucosamine (NAG; a major component of mucus) into the bacterial cell wall, enabling proliferation. Our results demonstrate that symbionts undergo dramatic local adaptation, demonstrated by widespread transcriptional changes, throughout the process of transmission that allows them to thrive while they encounter new environments which further shape their ecology and evolution. PMID:26896136

  18. Complex rheological behaviors of loach (Misgurnus anguillicaudatus) skin mucus

    SciTech Connect

    Wang, Xiang Su, Heng Lv, Weiyang Du, Miao Song, Yihu Zheng, Qiang

    2015-01-15

    The functions and structures of biological mucus are closely linked to rheology. In this article, the skin mucus of loach (Misgurnus anguillicaudatus) was proved to be a weak hydrogel susceptible to shear rate, time, and history, exhibiting: (i) Two-region breakdown of its gel structure during oscillatory strain sweep; (ii) rate-dependent thickening followed by three-region thinning with increased shear rate, and straight thinning with decreased shear rate; and (iii) time-dependent rheopexy at low shear rates, and thixotropy at high shear rates. An interesting correlation between the shear rate- and time-dependent rheological behaviors was also revealed, i.e., the rheopexy-thixotropy transition coincided with the first-second shear thinning region transition. Apart from rheology, a structure of colloidal network was observed in loach skin mucus using transmission electron microscopy. The complex rheology was speculated to result from inter- and intracolloid structural alterations. The unique rheology associated with the colloidal network structure, which has never been previously reported in vertebrate mucus, may play a key role in the functions (e.g., flow, reannealing, lubrication, and barrier) of the mucus.

  19. Protein-mediated adhesion of Lactobacillus acidophilus BG2FO4 on human enterocyte and mucus-secreting cell lines in culture.

    PubMed Central

    Coconnier, M H; Klaenhammer, T R; Kernéis, S; Bernet, M F; Servin, A L

    1992-01-01

    The adhesion of Lactobacillus acidophilus BG2FO4, a human stool isolate, to two human enterocytelike cell lines (Caco-2 and HT-29) and to the mucus secreted by a subpopulation of mucus-secreting HT29-MTX cells was investigated. Scanning electron microscopy revealed that the bacteria interacted with the well-defined apical microvilli of Caco-2 cells without cell damage and with the mucus secreted by the subpopulation of HT29-MTX cells. The adhesion to Caco-2 cells did not require calcium and involved an adhesion-promoting factor that was present in the spent supernatant of L. acidophilus cultures. This factor promoted adhesion of poorly adhering human Lactobacillus casei GG but did not promote adhesion of L. casei CNRZ 387, a strain of dairy origin. The adherence components on the bacterial cells and in the spent supernatant were partially characterized. Carbohydrates on the bacterial cell wall appeared to be partly responsible for the interaction between the bacteria and the extracellular adhesion-promoting factor. The adhesion-promoting factor was proteinaceous, since trypsin treatment dramatically decreased the adhesion of the L. acidophilus strain. The adhesion-promoting factor may be an important component of Lactobacillus species that colonize the gastrointestinal tract. Images PMID:1622282

  20. Analyzing Adherence to Prenatal Supplement: Does Pill Count Measure Up?

    PubMed Central

    Appelgren, Kristie E.; Nietert, Paul J.; Hulsey, Thomas C.; Hollis, Bruce W.; Wagner, Carol L.

    2010-01-01

    Objective. To determine if adherence as measured by pill count would show a significant association with serum-based measures of adherence. Methods. Data were obtained from a prenatal vitamin D supplementation trial where subjects were stratified by race and randomized into three dosing groups: 400 (control), 2000, or 4000 IU vitamin D3/day. One measurement of adherence was obtained via pill counts remaining compared to a novel definition for adherence using serum 25-hydroxy-vitamin D (25-OH-D) levels (absolute change in 25(OH)D over the study period and the subject's steady-state variation in their 25(OH)D levels). A multivariate logistic regression model examined whether mean percent adherence by pill count was significantly associated with the adherence measure by serum metabolite levels. Results. Subjects' mean percentage of adherence by pill count was not a significant predictor of adherence by serum metabolite levels. This finding was robust across a series of sensitivity analyses. Conclusions. Based on our novel definition of adherence, pill count was not a reliable predictor of adherence to protocol, and calls into question how adherence is measured in clinical research. Our findings have implications regarding the determination of efficacy of medications under study and offer an alternative approach to measuring adherence of long half-life supplements/medications. PMID:20169132

  1. [Mucoceles of the minor salivary glands. Extravasation mucoceles (mucus granulomas) and retention mucoceles (mucus retention cysts) (author's transl)].

    PubMed

    Seifert, G; Donath, K; von Gumberz, C

    1981-06-01

    360 cases of salivary glands cysts (= 6%) were collected in the Salivary Glands Register (Institute of Pathology, University of Hamburg) from 1965 until 1979 among a total of 5739 register cases. 273 cases of the cystic lesions (= 76%) were mucoceles of the minor salivary glands. The analysis of these 273 cases revealed the following results: 1. Two types of mucoceles can be morphologically distinguished: extravasation mucoceles and retention mucoceles. 2. The extravasation mucocele is in our material (240 cases = 88.7%) the most frequent type of mucocele. The term "extravasation mucocele" of the anglo-american literature is identical with the term "mucus granuloma" ("Schleimgranulom") introduced by Hamperl (1932). 3. The main signs of the mucus granulomas are: predominant location (79%) at the lower lip, age peak in the 2nd decade and more frequent occurrence (in 60%) in the male sex. 4. Three stages of development can be distinguished in the pathogenesis of the mucus granulomas: an initial stage (interstitial mucus lakes), a resorption stage (mucus granulomas with macrophages, foam cells and foreign bodies giant cells) and a terminal stage with the development of a pseudocyst (capsule of collagen tissue, no epithelial demarcation). 5. The retention mucocele (synonym: mucus retention cyst) is a rare type of mucocele (33 cases = 11.3%). The main signs are: nearly equal occurrence in all oral regions, age peak in the 8th decade, moderate predominance of the female sex. 6. The retention mucoceles contain viscous mucous material, possess always an epithelial demarcation of the cysts differentiated analogous to the different segments of the salivary duct system and show as a rule no inflammatory reaction compared with the extravasation mucoceles. 7. Microtraumas and mucus congestions play the important role in the development of the extravasation mucocele. The final formation depends on the amount of the overflowed mucus and the intensity of the mucus phagocytosis. 8

  2. Familial non-cystic fibrosis mucus inspissation of respiratory tract.

    PubMed Central

    Perlman, M; Williams, J; Hirsch, M; Bar-Ziv, J

    1975-01-01

    Perlman, M., Williams, J., Hirsch, M., and Bar-Ziv, J. (1975). Archives of Disease in Childhood, 50, 727. Familial non-cystic fibrosis mucus inspissation of respiratory tract. Two sibs, whose parents are first cousins, have had chronic obstructive airways disease from birth with recurrent otitis media, sinusitis, and mastoiditis. The disease, associated with clinically abnormal mucus, differs from other familial obstructive airways diseases and probably constitutes a new entity. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 PMID:1190822

  3. Culture independent characterization of bacteria associated with the mucus of the coral Acropora digitifera from the Gulf of Mannar.

    PubMed

    Nithyanand, Paramasivam; Indhumathi, Thiruvalluvan; Ravi, Arumugam Veera; Pandian, Shunmugiah Karutha

    2011-06-01

    Corals are sessile eukaryotic hosts which provide a unique surface for microbial colonization. Culture independent studies show that the coral mucus and tissue harbour diverse and abundant prokaryotic communities. However, little is known about the diversity of bacteria associated with the corals of Gulf of Mannar. The present study characterised the bacterial diversity associated with the mucus of the coral Acropora digitifera from the Gulf of Mannar by 16S rRNA gene clone library construction. The bacterial communities of the mucus of A. digitifera were diverse, with representatives within the Alphaproteobacteria, Gammaproteobacteria, Actinobacteria, Firmicutes and several unclassified bacteria. The culture independent bacterial population was totally different from our previous culture dependent study of the mucus and tissue of the same coral. 36% of the bacteria in the clone library of A. digitifera were found to be novel after full length sequencing of the 16S rRNA gene wherein several clones were found to be novel at the Genus and species level. The current study further supports the findings that Actinobacteria amount to a certain proportion among bacterial communities associated with corals. PMID:25187139

  4. Medication Adherence in Patients with Bipolar Disorder: A Comprehensive Review.

    PubMed

    Levin, Jennifer B; Krivenko, Anna; Howland, Molly; Schlachet, Rebecca; Sajatovic, Martha

    2016-09-01

    Poor medication adherence is a pervasive problem that causes disability and suffering as well as extensive financial costs among individuals with bipolar disorder (BD). Barriers to adherence are numerous and cross multiple levels, including factors related to bipolar pathology and those unique to an individual's circumstances. External factors, including treatment setting, healthcare system, and broader health policies, can also affect medication adherence in people with BD. Fortunately, advances in research have suggested avenues for improving adherence. A comprehensive review of adherence-enhancement interventions for the years 2005-2015 is included. Specific bipolar adherence-enhancement approaches that target knowledge gaps, cognitive patterns, specific barriers, and motivation may be helpful, as may approaches that capitalize on technology or novel drug-delivery systems. However, much work remains to optimally facilitate long-term medication adherence in people with BD. For adherence-enhancement approaches to be widely adapted, they need to be easily accessible, affordable, and practical. PMID:27435356

  5. Adherence to Antiretroviral Therapy and Virologic Failure

    PubMed Central

    Bezabhe, Woldesellassie M.; Chalmers, Leanne; Bereznicki, Luke R.; Peterson, Gregory M.

    2016-01-01

    Abstract The often cited need to achieve ≥95% (nearly perfect) adherence to antiretroviral therapy (ART) for successful virologic outcomes in HIV may present a barrier to initiation of therapy in the early stages of HIV. This meta-analysis synthesized 43 studies (27,905 participants) performed across >26 countries, to determine the relationship between cut-off point for optimal adherence to ART and virologic outcomes. Meta-analysis was performed using a random-effect model to calculate pooled odds ratios with corresponding 95% confidence intervals. The mean rate of patients reporting optimal adherence was 63.4%. Compared with suboptimal adherence, optimal adherence was associated with a lower risk of virologic failure (0.34; 95% CI: 0.26–0.44). There were no significant differences in the pooled odds ratios among different optimal adherence thresholds (≥98–100%, ≥95%, ≥80–90%). Study design (randomized controlled trial vs observational study) (regression coefficient 0.74, 95% CI: 0.04–1.43, P < 0.05) and study region (developing vs developed countries; regression coefficient 0.56, 95% CI: 0.01–1.12, P < 0.05) remained as independent predictors of between-study heterogeneity, with more patients with optimal adherence from developing countries or randomized controlled trials experiencing virologic failure. The threshold for optimal adherence to achieve better virologic outcomes appears to be wider than the commonly used cut-off point (≥95% adherence). The cut-off point for optimal adherence could be redefined to a slightly lower level to encourage the prescribing ART at an early stage of HIV infection. PMID:27082595

  6. Treatment Adherence in Adolescents With Inflammatory Bowel Disease: The Collective Impact of Barriers to Adherence and Anxiety/Depressive Symptoms

    PubMed Central

    Gray, Wendy N.; Denson, Lee A.; Baldassano, Robert N.

    2012-01-01

    Objective Knowledge of factors impacting adolescents’ ability to adhere to their inflammatory bowel disease (IBD) regimen is limited. The current study examines the collective impact of barriers to adherence and anxiety/depressive symptoms on adolescent adherence to the IBD regimen. Methods Adolescents (n = 79) completed measures of barriers to adherence, adherence, and anxiety/depressive symptoms at one of two specialty pediatric IBD clinics. Results Most adolescents reported barriers to adherence and 1 in 8 reported borderline or clinically elevated levels of anxiety/depressive symptoms. Anxiety/depressive symptoms moderated the relationship between barriers to adherence and adherence. Post hoc probing revealed a significant, additive effect of higher anxiety/depressive symptoms in the barriers–adherence relationship, with adherence significantly lower among adolescents with higher barriers and higher anxiety/depressive symptoms. Conclusions In order to optimize adherence in adolescents, interventions should target not only barriers to adherence but also any anxiety/depressive symptoms that may negatively impact efforts to adhere to recommended treatment. PMID:22080456

  7. Evaluation of medication adherence in Lebanese hypertensive patients.

    PubMed

    Yassine, Mohammad; Al-Hajje, Amal; Awada, Sanaa; Rachidi, Samar; Zein, Salam; Bawab, Wafa; Bou Zeid, Mayssam; El Hajj, Maya; Salameh, Pascale

    2016-09-01

    Controlling hypertension is essential in cardiovascular diseases. Poor medication adherence is associated with poor disease outcomes, waste of healthcare resources, and contributes to reduced blood pressure control. This study evaluates treatment adherence to antihypertensive therapy in Lebanese hypertensive patients by estimating the proportion of adherent hypertensive patients using a validated tool and investigates what factors predict this behavior. A questionnaire-based cross-sectional study was conducted on a random sample of 210 hypertensive outpatients selected from clinics located in tertiary-care hospitals and from private cardiology clinics located in Beirut. Adherence level was measured using a validated 8-item Modified Morisky Medication Adherence Scale (MMMAS). Among 210 patients, 50.5% showed high adherence, 27.1% medium adherence, and 22.4% low adherence to medication. Mean MMMAS score was 6.59±2.0. In bivariate analyses, having controlled blood pressure (p=0.003) and taking a combination drug (p=0.023) were predictors of high adherence. Forgetfulness (p<0.01), complicated drug regimen (p=0.001), and side effects (p=0.006) were predictors of low adherence after multiple liner regression. Logistic regression results showed that calcium channel blockers (p=0.030) were associated with increased adherence levels. In conclusion, developing multidisciplinary intervention programs to address the factors identified, in addition to educational strategies targeting healthcare providers, are necessary to enhance patient adherence. PMID:26232704

  8. Infection with the gastrointestinal nematode Ostertagia ostertagi affects mucus biosynthesis in the abomasum of cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mucus layer in the gastrointestinal (GI) tract is considered to be the first line of defense to the external environment. Alteration in mucus components has been reported to occur during intestinal nematode infection in ruminants, but the role of mucus in the response to abomasal parasites remai...

  9. Oestrus synchronisation and superovulation alter the production and biochemical constituents of ovine cervicovaginal mucus.

    PubMed

    Maddison, Jessie W; Rickard, Jessica P; Mooney, Ethan; Bernecic, Naomi C; Soleilhavoup, Clement; Tsikis, Guillaume; Druart, Xavier; Leahy, Tamara; de Graaf, Simon P

    2016-09-01

    Controlled breeding programmes utilising exogenous hormones are common in the Australian sheep industry, however the effects of such programmes on cervicovaginal mucus properties are lacking. As such, the aim of this study was to investigate cervicovaginal (CV) mucus from naturally cycling (NAT), progesterone synchronised (P4), prostaglandin synchronised (PGF2α), and superovulated (SOV) Merino ewes. Experiment 1; volume, colour, spinnbarkeit, chemical profile and protein concentration of mucus (NAT, P4, PGF2α and SOV; n=5 ewes/treatment) during the follicular (5 d) and luteal phases (8 d) was investigated. Experiment 2; in vivo mucus pH and in vitro mucus penetration by frozen-thawed spermatozoa (NAT, P4 and SOV; n=11 ewes/treatment) was investigated over oestrus (2 d) and the mid-luteal phase (pH only, 2 d). Oestrus mucus was more abundant, clearer in colour and less proteinaceous than luteal phase mucus (p<0.05). SOV increased mucus production and protein concentration (p<0.05) while PGF2α reduced mucus volume (p<0.05). Mucus pH (oestrus 6.2-6.5), chemical profile and mucus penetration by sperm were unchanged (p>0.05). Results indicate that exogenous hormones used for controlled breeding affect cervicovaginal mucus production, but few other tested characteristics. Further research is required to explain fertility differences between synchronised and naturally cycling animals following cervical AI. PMID:27496692

  10. EFFECTIVENESS OF COUGH FOR ENHANCING MUCUS CLEARANCE IN ASYMPTOMATIC SMOKERS

    EPA Science Inventory

    Using monodisperse aerosols radiolabeled with 99mTc, we studied the effectiveness of ough and rapid inhalations for clearing mucus in en asymptomatic smokers. On three eparate study days, each subject breathed 5 um (MMAD) 99mTc-iron oxide particles under ontrolled breathing condi...

  11. Chemotaxis of Flavobacterium columnare: To Channel Catfish Mucus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare is the etiological agent of columnaris disease in fresh water fish. The disease is characterized by chronic skin lesions and severe mortality. The skin mucus constitutes a large portion of body and many infectious organisms including F. columnare, is believed to invade throu...

  12. MUCUS GLYCOPROTEIN SECRETION BY TRACHEAL EXPLANTS: EFFECTS OF POLLUTANTS

    EPA Science Inventory

    Tracheal slices incubated with radioactive precursors in tissue culture medium. The authors have used anin vitro approach, a combined method utilizing exposure to pneumotoxins in vivo coupled with quantitation of mucus secretion rates in vitro, to study the effects of inhaled pol...

  13. Enzymatic sulfation of mucus glycoprotein in gastric mucosa

    SciTech Connect

    Liau, Y.H.; Carter, S.R.; Gwozdzinski, K.; Nadziejko, C.; Slomiany, A.; Slomiany, B.L.

    1986-05-01

    Among the posttranslational modifications that mucus glycoprotein undergo prior to secretion into the gastric lumen is the process of sulfation of the carbohydrate chains. These sulfate groups impart strongly negative charge to nucus glycoprotein and are thought to play a major role in the maintenance of gastric mucosal integrity. The authors report here the presence and some properties of an enzyme involved in the sulfation of gastric mucus glycoprotein. The sulfotransferase activity which catalyzes the transfer of sulfate ester group from PAPS to mucus glycoprotein was located in the detergent extracts of the microsomal fraction of rat gastric mucosa. Optimum enzymatic activity for sulfation of gastric mucin was obtained using 0.5% Triton X-100 and 25mM NaF at a pH of 6.8. ATP, ADP, MgCl/sub 2/ and MnCl/sub 2/ at concentrations examined were inhibitory. Under optimal conditions, the rate of sulfate incorporation was proportional to the microsomal enzyme protein concentration up to 50..mu..g and remained constant with time of incubation for at least 1h. The apparent Km value of the enzyme for gastric mucus glycoprotein was 8.3 x 10/sup -6/M. The /sup 35/S-labeled product of the enzyme reaction cochromatographed on Bio-Gel A-50 with gastric mucin, and gave on CsCl equilibrium density gradient centrifugation a band at the density of 1.48 in which the /sup 35/S label coincided with the glycoprotein.

  14. Sodium alginate decreases the permeability of intestinal mucus

    PubMed Central

    Mackie, Alan R.; Macierzanka, Adam; Aarak, Kristi; Rigby, Neil M.; Parker, Roger; Channell, Guy A.; Harding, Stephen E.; Bajka, Balazs H.

    2016-01-01

    In the small intestine the nature of the environment leads to a highly heterogeneous mucus layer primarily composed of the MUC2 mucin. We set out to investigate whether the soluble dietary fibre sodium alginate could alter the permeability of the mucus layer. The alginate was shown to freely diffuse into the mucus and to have minimal effect on the bulk rheology when added at concentrations below 0.1%. Despite this lack of interaction between the mucin and alginate, the addition of alginate had a marked effect on the diffusion of 500 nm probe particles, which decreased as a function of increasing alginate concentration. Finally, we passed a protein stabilised emulsion through a simulation of oral, gastric and small intestinal digestion. We subsequently showed that the addition of 0.1% alginate to porcine intestinal mucus decreased the diffusion of fluorescently labelled lipid present in the emulsion digesta. This reduction may be sufficient to reduce problems associated with high rates of lipid absorption such as hyperlipidaemia. PMID:26726279

  15. Transient motion of mucus plugs in respiratory airways

    NASA Astrophysics Data System (ADS)

    Zamankhan, Parsa; Hu, Yingying; Helenbrook, Brian; Takayama, Shuichi; Grotberg, James B.

    2011-11-01

    Airway closure occurs in lung diseases such as asthma, cystic fibrosis, or emphysema which have an excess of mucus that forms plugs. The reopening process involves displacement of mucus plugs in the airways by the airflow of respiration. Mucus is a non-Newtonian fluid with a yield stress; therefore its behavior can be approximated by a Bingham fluid constitutive equation. In this work the reopening process is approximated by simulation of a transient Bingham fluid plug in a 2D channel. The governing equations are solved by an Arbitrary Lagrangian Eulerian (ALE) finite element method through an in-house code. The constitutive equation for the Bingham fluid is implemented through a regularization method. The effects of the yield stress on the flow features and wall stresses are discussed with applications to potential injuries to the airway epithelial cells which form the wall. The minimum driving pressure for the initiation of the motion is computed and its value is related to the mucus properties and the plug shape. Supported by HL84370 and HL85156.

  16. In vitro screening of mucus and solvent extracts of Eisenia foetida against human bacterial and fungal pathogens.

    PubMed

    Andleeb, Saiqa; Ejaz, Mubashir; Awan, Uzma Azeem; Ali, Shaukat; Kiyani, Ayesha; Shafique, Irsa; Zafar, Atiya

    2016-05-01

    Earthworms are macro invertebrate and have been widely used as therapeutic drugs for thousands of years. In the current research, experiments viz., the antibacterial, antifungal and antioxidant activity of mucus and solvent extracts of Eisenia foetida were conducted to investigate for the first time in Pakistan against human infectious pathogens. Antimicrobial activity of E. foetida against human pathogens underwent investigation through an agar disc diffusion method while an ABTS(•+) free radical scavenging method assessed the antioxidant activity. The percentage of bacterial and fungal growth was analyzed statistically with One-Way Analysis of Variance (ANOVA). Results showed that the mucus IV of E. foetida produced a strong potent antibacterial and antifungal activity. Pseudomonas aeruginosa exhibited the highest inhibition zone (33.67±1.53 mm), followed by Klebsiella pneumonia (30.33±1.53mm), Penicillium notatum (30±0.051), Escherichia coli (29±1 mm), Candida albicans (28.33±0.54 mm), Staphylococcus aureus (27±1mm), Serratia marcescens (25.33±0.58 mm), Aspergillus flavus (25.33±0.58 mm), Staphylococcus epidermidis (24.33±0.58 mm), Streptococcus pyogenes (21.67±1.53 mm), and Aspergillus niger (20.67±0.53 mm). Mucus IV of E. foetida also showed the highest antioxidant activity (99%). The results clearly indicate that the mucus and solvent extracts contain effective antimicrobial properties and bioactive compounds to inhibit the growth of infectious pathogens. We conclude that mucus extracts of earthworm have significant level of antimicrobial and antioxidant activities and in future could be potentially used against various infectious pathogens. PMID:27166541

  17. Enhancing adherence through education.

    PubMed

    Smrtka, Jennifer; Caon, Christina; Saunders, Carol; Becker, Brenda L; Baxter, Nancy

    2010-10-01

    The treatment of multiple sclerosis (MS) has advanced greatly since the introduction of disease-modifying therapies (DMTs) in the early 1990s. Although the DMTs have exhibited significant efficacy in relapsing-remitting MS and other forms of the disease, the degree of benefit depends heavily on patient adherence to recommended regimens. This article addresses some of the most pressing areas of unmet need in educating advanced-practice nurses, neurologists, patients, and support care partners regarding strategies that can overcome obstacles to adherence. The observations presented here are based on clinical experience with real-life cognitive, psychosocial, and cultural impediments to adherence. The article also explores the ways in which adherence may be affected by emerging therapies for MS (such as oral agents) as well as the educational needs that will arise with the further evolution of MS care. PMID:21049830

  18. Adherence to Insulin Therapy.

    PubMed

    Sarbacker, G Blair; Urteaga, Elizabeth M

    2016-08-01

    IN BRIEF Six million people with diabetes use insulin either alone or in combination with an oral medication. Many barriers exist that lead to poor adherence with insulin. However, there is an underwhelming amount of data on interventions to address these barriers and improve insulin adherence. Until pharmacological advancements create easier, more acceptable insulin regimens, it is imperative to involve patients in shared decision-making. PMID:27574371

  19. Effect of epithelium ATP release on cyclic pressure-induced airway mucus secretion

    PubMed Central

    Tong, Jin; Zhou, Xiang-dong; Perelman, Juliy M.; Kolosov, Victor P.

    2013-01-01

    The cyclic mechanical effect of airflow during breathing creates the optimal airway hydration state. MUC (mucin) 5AC is an important component of the airway mucus. The formation of MUC5AC is related to ATP and intracellular calcium in the epithelial cells. In this study, we evaluated the effect of ATP release from intracellular calcium in epithelial cells on cyclic pressure-induced mucus secretion in the airway. 16HBE (human bronchial epithelial cells) were cultured in vitro on cyclically tilted cultured plates and divided into five groups: control, tilt, tilt and BAPTA–AM (1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid–acetoxymethyl ester), tilt and EGTA and tilt and RB-2 (reactive blue-2). The shear stress and compressive stress were induced by the surface tension of the liquid, atmospheric pressure and liquid gravity. Cell activity, MUC5AC mRNA expression level, MUC5AC protein expression level and ATP release and intracellular calcium changes were measured with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay, RT–PCR (reverse transcription–PCR), HPLC and inverted fluorescence microscope, respectively. We detected that cyclic pressure significantly increased MUC5AC secretion and ATP release. The enhanced ATP release could be inhibited by both BAPTA–AM and RB-2, while EGTA did not have a suppressive effect. BAPTA–AM, EGTA and RB-2 did not obviously inhibit MUC5AC mRNA expression. Cyclic pressure did not induce MUC5AC secretion in the airway mucus epithelium via Ca2+-dependent ATP release, and nearly all Ca2+ was provided by stored intracellular Ca2+. PMID:24329423

  20. Effect of epithelium ATP release on cyclic pressure-induced airway mucus secretion.

    PubMed

    Tong, Jin; Zhou, Xiang-Dong; Perelman, Juliy M; Kolosov, Victor P

    2013-12-16

    The cyclic mechanical effect of airflow during breathing creates the optimal airway hydration state. Mucin (MUC) 5AC is an impotent component of the airway mucus. The formation of MUC5AC is related to adenosine triphosphate (ATP) and intracellular calciumin the epithelial cells. In this study, we evaluated the effect of ATP release from and intracellular calcium in epithelial cells on cyclic pressure-induced mucus secretion in the airway. Human bronchial epithelial cells (16HBE) were cultured in vitro on cyclically tilted cultured plates and divided into 5 groups: control, tilt, tilt and BAPTA-AM, tilt and EGTA, and tilt and RB-2. The shear stress and compressive stress were induced by the surface tension of the liquid, atmospheric pressure and liquid gravity. Cell activity, MUC5AC mRNA expression level, MUC5AC protein expression level and ATP release, and intracellular calcium changes were measured with the MTT assay, RT-PCR, high performance liquid chromatography (HPLC) and inverted fluorescence microscope, respectively. We detected that cyclic pressure significantly increased MUC5AC secretion and ATP release. The enhanced ATP release could be inhibited by both BAPTA-AM and RB-2, while EGTA did not have a suppressive effect. BAPTA-AM, EGTA, and RB-2 did not obviously inhibit MUC5AC mRNA expression.Cyclic pressure did not induce MUC5AC secretion in the airway mucus epithelium via Ca2+-dependent ATP release, and nearly all Ca2+ was provided by stored intracellular Ca2+. PMID:24329423

  1. Measuring Single Particle Microrheology of Human Mucus Using the 3D Force Microscope

    NASA Astrophysics Data System (ADS)

    Cribb, Jeremy; Hill, D. B.; Taylor, R.; O'Brien, E. T.; Davis, C. W.; Matsui, H.; Vicci, L.; Matthews, G.; Fisher, J.; Desai, K. V.; Wilde, B.; Superfine, R.

    2003-11-01

    In many patients with Cystic Fibrosis, the viscosity of mucus is higher than that found in normal patients, contributing to the failure of cilia to sweep mucus away from the lungs effectively. Microrheological measurements of biologically relevant fluids, such as mucus, are important to understand the physical environment in which cilia operate. The complex viscoelastic moduli and apparent viscosity of several mucus concentrations were determined by tracking 1 micron beads undergoing Brownian motion. Further, the apparent viscosity of each mucus solution was determined from the Stokes' drag on a superparamagnetic bead driven by the 3-dimensional force microscope (3DFM).

  2. The Vat-AIEC protease promotes crossing of the intestinal mucus layer by Crohn's disease-associated Escherichia coli.

    PubMed

    Gibold, Lucie; Garenaux, Estelle; Dalmasso, Guillaume; Gallucci, Camille; Cia, David; Mottet-Auselo, Benoit; Faïs, Tiphanie; Darfeuille-Michaud, Arlette; Nguyen, Hang Thi Thu; Barnich, Nicolas; Bonnet, Richard; Delmas, Julien

    2016-05-01

    The aetiology of Crohn's disease (CD) involves disorders in host genetic factors and intestinal microbiota. Adherent-invasive Escherichia coli (AIEC) are receiving increased attention because in studies of mucosa-associated microbiota, they are more prevalent in CD patients than in healthy subjects. AIEC are associated both with ileal and colonic disease phenotypes. In this study, we reported a protease called Vat-AIEC from AIEC that favours the mucosa colonization. The deletion of the Vat-AIEC-encoding gene resulted in an adhesion-impaired phenotype in vitro and affected the colonization of bacteria in contact with intestinal epithelial cells in a murine intestinal loop model, and also their gut colonization in vivo. Furthermore, unlike LF82Δvat-AIEC, wild-type AIEC reference strain LF82 was able to penetrate a mucus column extensively and promoted the degradation of mucins and a decrease in mucus viscosity. Vat-AIEC transcription was stimulated by several chemical conditions found in the ileum environment. Finally, the screening of E. coli strains isolated from CD patients revealed a preferential vat-AIEC association with AIEC strains belonging to the B2 phylogroup. Overall, this study revealed a new component of AIEC virulence that might favour their implantation in the gut of CD patients. PMID:26499863

  3. How can we improve adherence?

    PubMed

    Price, Patricia

    2016-01-01

    Many patients with wound healing difficulties are also coping with the management of a chronic disease or chronic condition that requires them to make lifestyle behaviour changes, for example, managing glucose levels through diet and exercise and regular foot inspection. Many find it difficult to make such changes and often experience feelings of powerlessness when faced with a lifetime of behavioural and psychological change. This article will explore the importance of understanding the patient difficulties associated with adherence to a regime and how life changes can be difficult to maintain over sustained periods of time. However, the article will also discuss the importance of this topic in trying to understand the clinical evidence base for treatment--as many clinical trials investigating treatments for the diabetic foot do not include information on the extent to which patients in the trial conformed to the trial protocol. The article gives an overview of recent developments--including lessons we can learn from other chronic conditions where permanent life changes are required--in particular the need to keep health messages simple, tailored to the individual and repeated frequently. The evidence to date suggests that no one single form of adherence intervention will work with all patients; this is not surprising given complex and multifactorial nature of adherence and the myriad of barriers that exist that patients and health care professionals need to overcome. PMID:26453542

  4. Adherence to Sublingual Immunotherapy.

    PubMed

    Incorvaia, Cristoforo; Mauro, Marina; Leo, Gualtiero; Ridolo, Erminia

    2016-02-01

    Adherence is a major issue in any medical treatment. Allergen immunotherapy (AIT) is particularly affected by a poor adherence because a flawed application prevents the immunological effects that underlie the clinical outcome of the treatment. Sublingual immunotherapy (SLIT) was introduced in the 1990s, and the early studies suggested that adherence and compliance to such a route of administration was better than the traditional subcutaneous route. However, the recent data from manufacturers revealed that only 13% of patients treated with SLIT reach the recommended 3-year duration. Therefore, improved adherence to SLIT is an unmet need that may be achieved by various approaches. The utility of patient education and accurate monitoring during the treatment was demonstrated by specific studies, while the success of technology-based tools, including online platforms, social media, e-mail, and a short message service by phone, is currently considered to improve the adherence. This goal is of pivotal importance to fulfill the object of SLIT that is to modify the natural history of allergy, ensuring a long-lasting clinical benefit, and a consequent pharmaco-economic advantage, when patients complete at least a 3-year course of treatment. PMID:26758865

  5. Akkermansia muciniphila Adheres to Enterocytes and Strengthens the Integrity of the Epithelial Cell Layer.

    PubMed

    Reunanen, Justus; Kainulainen, Veera; Huuskonen, Laura; Ottman, Noora; Belzer, Clara; Huhtinen, Heikki; de Vos, Willem M; Satokari, Reetta

    2015-06-01

    Akkermansia muciniphila is a Gram-negative mucin-degrading bacterium that resides in the gastrointestinal tracts of humans and animals. A. muciniphila has been linked with intestinal health and improved metabolic status in obese and type 2 diabetic subjects. Specifically, A. muciniphila has been shown to reduce high-fat-diet-induced endotoxemia, which develops as a result of an impaired gut barrier. Despite the accumulating evidence of the health-promoting effects of A. muciniphila, the mechanisms of interaction of the bacterium with the host have received little attention. In this study, we used several in vitro models to investigate the adhesion of A. muciniphila to the intestinal epithelium and its interaction with the host mucosa. We found that A. muciniphila adheres strongly to the Caco-2 and HT-29 human colonic cell lines but not to human colonic mucus. In addition, A. muciniphila showed binding to the extracellular matrix protein laminin but not to collagen I or IV, fibronectin, or fetuin. Importantly, A. muciniphila improved enterocyte monolayer integrity, as shown by a significant increase in the transepithelial electrical resistance (TER) of cocultures of Caco-2 cells with the bacterium. Further, A. muciniphila induced interleukin 8 (IL-8) production by enterocytes at cell concentrations 100-fold higher than those for Escherichia coli, suggesting a very low level of proinflammatory activity in the epithelium. In conclusion, our results demonstrate that A. muciniphila adheres to the intestinal epithelium and strengthens enterocyte monolayer integrity in vitro, suggesting an ability to fortify an impaired gut barrier. These results support earlier associative in vivo studies and provide insights into the interaction of A. muciniphila with the host. PMID:25795669

  6. Akkermansia muciniphila Adheres to Enterocytes and Strengthens the Integrity of the Epithelial Cell Layer

    PubMed Central

    Reunanen, Justus; Kainulainen, Veera; Huuskonen, Laura; Ottman, Noora; Belzer, Clara; Huhtinen, Heikki; de Vos, Willem M.

    2015-01-01

    Akkermansia muciniphila is a Gram-negative mucin-degrading bacterium that resides in the gastrointestinal tracts of humans and animals. A. muciniphila has been linked with intestinal health and improved metabolic status in obese and type 2 diabetic subjects. Specifically, A. muciniphila has been shown to reduce high-fat-diet-induced endotoxemia, which develops as a result of an impaired gut barrier. Despite the accumulating evidence of the health-promoting effects of A. muciniphila, the mechanisms of interaction of the bacterium with the host have received little attention. In this study, we used several in vitro models to investigate the adhesion of A. muciniphila to the intestinal epithelium and its interaction with the host mucosa. We found that A. muciniphila adheres strongly to the Caco-2 and HT-29 human colonic cell lines but not to human colonic mucus. In addition, A. muciniphila showed binding to the extracellular matrix protein laminin but not to collagen I or IV, fibronectin, or fetuin. Importantly, A. muciniphila improved enterocyte monolayer integrity, as shown by a significant increase in the transepithelial electrical resistance (TER) of cocultures of Caco-2 cells with the bacterium. Further, A. muciniphila induced interleukin 8 (IL-8) production by enterocytes at cell concentrations 100-fold higher than those for Escherichia coli, suggesting a very low level of proinflammatory activity in the epithelium. In conclusion, our results demonstrate that A. muciniphila adheres to the intestinal epithelium and strengthens enterocyte monolayer integrity in vitro, suggesting an ability to fortify an impaired gut barrier. These results support earlier associative in vivo studies and provide insights into the interaction of A. muciniphila with the host. PMID:25795669

  7. The Influence of Wireless Self-Monitoring Program on the Relationship Between Patient Activation and Health Behaviors, Medication Adherence, and Blood Pressure Levels in Hypertensive Patients: A Substudy of a Randomized Controlled Trial

    PubMed Central

    Kim, Ju Young; Wineinger, Nathan. E

    2016-01-01

    Background Active engagement in the management of hypertension is important in improving self-management behaviors and clinical outcomes. Mobile phone technology using wireless monitoring tools are now widely available to help individuals monitor their blood pressure, but little is known about the conditions under which such technology can effect positive behavior changes or clinical outcomes. Objective To study the influence of wireless self-monitoring program and patient activation measures on health behaviors, medication adherence, and blood pressure levels as well as control of blood pressure in hypertensive patients. Methods We examined a subset of 95 hypertensive participants from a 6-month randomized controlled trial designed to determine the utility of a wireless self-monitoring program (n=52 monitoring program, n=43 control), which consisted of a blood pressure monitoring device connected with a mobile phone, reminders for self-monitoring, a Web-based disease management program, and a mobile app for monitoring and education, compared with the control group receiving a standard disease management program. Study participants provided measures of patient activation, health behaviors including smoking, drinking, and exercise, medication adherence, and blood pressure levels. We assessed the influence of wireless self-monitoring as a moderator of the relationship between patient activation and health behaviors, medication adherence, and control of blood pressure. Results Improvements in patient activation were associated with improvements in cigarette smoking (beta=−0.46, P<.001) and blood pressure control (beta=0.04, P=.02). This relationship was further strengthened in reducing cigarettes (beta=−0.60, P<.001), alcohol drinking (beta=−0.26, P=.01), and systolic (beta=−0.27, P=.02) and diastolic blood pressure (beta=−0.34, P=.007) at 6 months among individuals participating in the wireless self-monitoring program. No differences were observed with

  8. Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy.

    PubMed

    Mastorakos, Panagiotis; da Silva, Adriana L; Chisholm, Jane; Song, Eric; Choi, Won Kyu; Boyle, Michael P; Morales, Marcelo M; Hanes, Justin; Suk, Jung Soo

    2015-07-14

    Gene therapy has emerged as an alternative for the treatment of diseases refractory to conventional therapeutics. Synthetic nanoparticle-based gene delivery systems offer highly tunable platforms for the delivery of therapeutic genes. However, the inability to achieve sustained, high-level transgene expression in vivo presents a significant hurdle. The respiratory system, although readily accessible, remains a challenging target, as effective gene therapy mandates colloidal stability in physiological fluids and the ability to overcome biological barriers found in the lung. We formulated highly stable DNA nanoparticles based on state-of-the-art biodegradable polymers, poly(β-amino esters) (PBAEs), possessing a dense corona of polyethylene glycol. We found that these nanoparticles efficiently penetrated the nanoporous and highly adhesive human mucus gel layer that constitutes a primary barrier to reaching the underlying epithelium. We also discovered that these PBAE-based mucus-penetrating DNA nanoparticles (PBAE-MPPs) provided uniform and high-level transgene expression throughout the mouse lungs, superior to several gold standard gene delivery systems. PBAE-MPPs achieved robust transgene expression over at least 4 mo following a single administration, and their transfection efficiency was not attenuated by repeated administrations, underscoring their clinical relevance. Importantly, PBAE-MPPs demonstrated a favorable safety profile with no signs of toxicity following intratracheal administration. PMID:26124127

  9. Mucus barrier-triggered disassembly of siRNA nanocarriers

    NASA Astrophysics Data System (ADS)

    Thomsen, Troels B.; Li, Leon; Howard, Kenneth A.

    2014-10-01

    The mucus overlying mucosal epithelial surfaces presents not only a biological barrier to the penetration of potential pathogens, but also therapeutic modalities including RNAi-based nanocarriers. Movement of nanomedicines across the mucus barriers of the gastrointestinal mucosa is modulated by interactions of the nanomedicine carriers with mucin glycoproteins inside the mucus, potentiated by the large surface area of the nanocarrier. We have developed a fluorescence activation-based reporter system showing that the interaction between polyanionic mucins and the cationic chitosan/small interfering RNA (siRNA) nanocarriers (polyplexes) results in the disassembly and consequent triggered release of fluorescent siRNA. The quantity of release was found to be dependent on the molar ratio between chitosan amino groups and siRNA phosphate groups (NP ratio) of the polyplexes with a maximal estimated 48.6% release of siRNA over 30 min at NP 60. Furthermore, a microfluidic in vitro model of the gastrointestinal mucus barrier was used to visualize the dynamic interaction between chitosan/siRNA nanocarriers and native purified porcine stomach mucins. We observed strong interactions and aggregations at the mucin-liquid interface, followed by an NP ratio dependent release and consequent diffusion of siRNA across the mucin barrier. This work describes a new model of interaction at the nanocarrier-mucin interface and has important implications for the design and development of nucleic acid-based nanocarrier therapeutics for mucosal disease treatments and also provides insights into nanoscale pathogenic processes.The mucus overlying mucosal epithelial surfaces presents not only a biological barrier to the penetration of potential pathogens, but also therapeutic modalities including RNAi-based nanocarriers. Movement of nanomedicines across the mucus barriers of the gastrointestinal mucosa is modulated by interactions of the nanomedicine carriers with mucin glycoproteins inside the

  10. Persisting with prevention: The importance of adherence for HIV prevention

    PubMed Central

    Weiss, Helen A; Wasserheit, Judith N; Barnabas, Ruanne V; Hayes, Richard J; Abu-Raddad, Laith J

    2008-01-01

    Background Only four out of 31 completed randomized controlled trials (RCTs) of HIV prevention strategies against sexual transmission have shown significant efficacy. Poor adherence may have contributed to the lack of effect in some of these trials. In this paper we explore the impact of various levels of adherence on measured efficacy within an RCT. Analysis We used simple quantitative methods to illustrate the impact of various levels of adherence on measured efficacy by assuming a uniform population in terms of sexual behavior and the binomial model for the transmission probability per partnership. At 100% adherence the measured efficacy within an RCT is a reasonable approximation of the true biological efficacy. However, as adherence levels fall, the efficacy measured within a trial substantially under-estimates the true biological efficacy. For example, at 60% adherence, the measured efficacy can be less than half of the true biological efficacy. Conclusion Poor adherence during a trial can substantially reduce the power to detect an effect, and improved methods of achieving and maintaining high adherence within trials are needed. There are currently 12 ongoing HIV prevention trials, all but one of which require ongoing user-adherence. Attention must be given to methods of maximizing adherence when piloting and designing RCTs and HIV prevention programmes. PMID:18620578

  11. Adherence to treatment in adolescents

    PubMed Central

    Taddeo, Danielle; Egedy, Maud; Frappier, Jean-Yves

    2008-01-01

    Health care professionals must be alert to the high prevalence of low adherence to treatment during adolescence. Low adherence increases morbidity and medical complications, contributes to poorer quality of life and an overuse of the health care system. Many different factors have an impact on adherence. However, critical factors to consider in teens are their developmental stage and challenges, emotional issues and family dysfunction. Direct and indirect methods have been described to assess adherence. Eliciting an adherence history is the most useful way for clinicians to evaluate adherence, and could be the beginning of a constructive dialogue with the adolescent. Interventions to improve adherence are multiple – managing mental health issues appropriately, building a strong relationship, customizing the treatment regimen if possible, empowering the adolescent to deal with adherence issues, providing information, ensuring family and peer support, and motivational enhancement therapy. Evaluation of adherence at regular intervals should be an important aspect of health care for adolescents. PMID:19119348

  12. New developments in goblet cell mucus secretion and function

    PubMed Central

    Birchenough, George M.H.; Johansson, Malin E.V.; Gustafsson, Jenny K.; Bergström, Joakim H.; Hansson, Gunnar C.

    2015-01-01

    Goblet cells and their main secretory product, mucus, have long been poorly appreciated; however, recent discoveries have changed this and placed these cells at the center stage of our understanding of mucosal biology and the immunology of the intestinal tract. The mucus system differs substantially between the small and large intestine, although it is built around MUC2 mucin polymers in both cases. Furthermore, that goblet cells and the regulation of their secretion also differ between these two parts of the intestine is of fundamental importance for a better understanding of mucosal immunology. There are several types of goblet cell which can be delineated based on their location and function. The surface colonic goblet cells secrete continuously to maintain the inner mucus layer, whereas goblet cells of the colonic and small intestinal crypts secrete upon stimulation, for example after endocytosis or in response to acetyl choline. However, despite much progress in recent years our understanding of goblet cell function and regulation is still in its infancy. PMID:25872481

  13. Coral Mucus Is a Hot Spot for Viral Infections.

    PubMed

    Nguyen-Kim, Hanh; Bettarel, Yvan; Bouvier, Thierry; Bouvier, Corinne; Doan-Nhu, Hai; Nguyen-Ngoc, Lam; Nguyen-Thanh, Thuy; Tran-Quang, Huy; Brune, Justine

    2015-09-01

    There is increasing suspicion that viral communities play a pivotal role in maintaining coral health, yet their main ecological traits still remain poorly characterized. In this study, we examined the seasonal distribution and reproduction pathways of viruses inhabiting the mucus of the scleractinians Fungia repanda and Acropora formosa collected in Nha Trang Bay (Vietnam) during an 11-month survey. The strong coupling between epibiotic viral and bacterial abundance suggested that phages are dominant among coral-associated viral communities. Mucosal viruses also exhibited significant differences in their main features between the two coral species and were also remarkably contrasted with their planktonic counterparts. For example, their abundance (inferred from epifluorescence counts), lytic production rates (KCN incubations), and the proportion of lysogenic cells (mitomycin C inductions) were, respectively, 2.6-, 9.5-, and 2.2-fold higher in mucus than in the surrounding water. Both lytic and lysogenic indicators were tightly coupled with temperature and salinity, suggesting that the life strategy of viral epibionts is strongly dependent upon environmental circumstances. Finally, our results suggest that coral mucus may represent a highly favorable habitat for viral proliferation, promoting the development of both temperate and virulent phages. Here, we discuss how such an optimized viral arsenal could be crucial for coral viability by presumably forging complex links with both symbiotic and adjacent nonsymbiotic microorganisms. PMID:26092456

  14. Coral Mucus Is a Hot Spot for Viral Infections

    PubMed Central

    Nguyen-Kim, Hanh; Bouvier, Thierry; Bouvier, Corinne; Doan-Nhu, Hai; Nguyen-Ngoc, Lam; Nguyen-Thanh, Thuy; Tran-Quang, Huy; Brune, Justine

    2015-01-01

    There is increasing suspicion that viral communities play a pivotal role in maintaining coral health, yet their main ecological traits still remain poorly characterized. In this study, we examined the seasonal distribution and reproduction pathways of viruses inhabiting the mucus of the scleractinians Fungia repanda and Acropora formosa collected in Nha Trang Bay (Vietnam) during an 11-month survey. The strong coupling between epibiotic viral and bacterial abundance suggested that phages are dominant among coral-associated viral communities. Mucosal viruses also exhibited significant differences in their main features between the two coral species and were also remarkably contrasted with their planktonic counterparts. For example, their abundance (inferred from epifluorescence counts), lytic production rates (KCN incubations), and the proportion of lysogenic cells (mitomycin C inductions) were, respectively, 2.6-, 9.5-, and 2.2-fold higher in mucus than in the surrounding water. Both lytic and lysogenic indicators were tightly coupled with temperature and salinity, suggesting that the life strategy of viral epibionts is strongly dependent upon environmental circumstances. Finally, our results suggest that coral mucus may represent a highly favorable habitat for viral proliferation, promoting the development of both temperate and virulent phages. Here, we discuss how such an optimized viral arsenal could be crucial for coral viability by presumably forging complex links with both symbiotic and adjacent nonsymbiotic microorganisms. PMID:26092456

  15. The effect of nanoparticle permeation on the bulk rheological properties of mucus from the small intestine.

    PubMed

    Wilcox, M D; Van Rooij, L K; Chater, P I; Pereira de Sousa, I; Pearson, J P

    2015-10-01

    The effectiveness of delivering oral therapeutic peptides, proteins and nucleotides is often hindered by the protective mucus barrier that covers mucosal surfaces of the gastrointestinal (GI) tract. Encapsulation of active pharmaceutical ingredients (API) in nanocarriers is a potential strategy to protect the cargo but they still have to pass the mucus barrier. Decorating nanoparticles with proteolytic enzymes has been shown to increase the permeation through mucus. Here we investigate the effect of poly(acrylic acid) (PAA) nanoparticles decorated with bromelain (BRO), a proteolytic enzyme from pineapple stem, on the bulk rheology of mucus as well as non-decorated poly(lactic-co-glycolic acid) (PLGA) nanoparticles. Porcine intestinal mucus from the small intestine was incubated for 30min in the presence of PLGA nanoparticles or polyacrylic nanoparticles decorated with bromelain (PAA-BRO). The effect of nanoparticles on the rheological properties, weight of gel, released glycoprotein content from mucus as well as the viscosity of liquid removed was assessed. Treatment with nanoparticles decreased mucus gel strength with PAA-BRO reducing it the most. PAA-BRO nanoparticles resulted in the release of increased glycoprotein from the gel network whereas mucus remained a gel and exhibited a similar breakdown stress to control mucus. Therefore it would be possible to use bromelain to increase the permeability of nanoparticles through mucus without destroying the gel and leaving the underlying mucosa unprotected. PMID:25758122

  16. Adherence to Continuous Positive Airway Pressure Treatment for Obstructive Sleep Apnea: Implications for Future Interventions

    PubMed Central

    Weaver, Terri E.; Sawyer, Amy M.

    2010-01-01

    Adherence to continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea (OSA) is a critical problem with adherence rates ranging from 30–60%. Poor adherence to CPAP is widely recognized as a significant limiting factor in treating OSA, reducing the overall effectiveness of the treatment and leaving many OSA patients at heightened risk for comorbid conditions, impaired function and quality of life. The extant literature examining adherence to CPAP provides critical insight to measuring adherence outcomes, defining optimal adherence levels, and predicting CPAP adherence. This research has revealed salient factors that are associated with or predict CPAP adherence and may guide the development of interventions to promote CPAP adherence. Over the past 10 years, intervention studies to promote CPAP adherence have incorporated a multitude of strategies including education, support, cognitive behavioral approaches, and mixed strategies. This review of the current state of science of CPAP adherence will (1) synthesize the extant literature with regard to measuring, defining, and predicting CPAP adherence, (2) review published intervention studies aimed at promoting CPAP adherence, and (3) suggest directions for future empiric study of adherence to CPAP that will have implications for translational science. Our current understanding of CPAP adherence suggests that adherence is a multi-factorial, complex clinical problem that requires similarly designed approaches to effectively address poor CPAP adherence in the OSA population. PMID:20308750

  17. Mucus Hyperconcentration as a Unifying Aspect of the Chronic Bronchitic Phenotype.

    PubMed

    Button, Brian; Anderson, Wayne H; Boucher, Richard C

    2016-04-01

    Abnormalities in mucus production and qualitative properties such as mucus hydration are central to the pathophysiology of airway disease including cystic fibrosis, asthma, and chronic bronchitis. In vitro air-liquid interface epithelial cell cultures demonstrate direct relationships between mucociliary transport, periciliary liquid (PCL) height, and mucus concentration (expressed as percent solids or partial osmotic pressure). In health, the osmotic modulus/pressure of the PCL exceeds that of the mucus layer, resulting in efficient, low-friction movement of mucus. In disease, through multiple mechanisms, the osmotic pressure of the mucus begins to exceed basal PCL values, resulting in compression of the cilia and slowing of mucus transport. The in vivo data in both cystic fibrosis and chronic bronchitis parallel in vitro data demonstrating that when mucus osmotic pressure is increased, mucociliary clearance is decreased. In chronic bronchitis, there is a direct correlation between FEV1 and percent solids of mucus, demonstrating a strong relationship between disease progression and mucus abnormalities. Animal models, based mechanistically on raised sodium absorption (and therefore water absorption) from airway surfaces, mimic the pathophysiology of chronic obstructive pulmonary disease. Collectively, these data suggest the importance of mucus concentration in the pathogenesis of airway disease. It is important to understand the precise mechanisms that result in mucus hyperconcentration, for example, mucin overproduction versus abnormal regulation of ion/water transport, which may be unique to and characteristic of each disease phenotype. The measurement of mucus concentration may be a simple method to diagnose chronic bronchitis, monitor its progression, and serve as a biomarker for development of new therapies. PMID:27115951

  18. Dissolution of lipids from mucus: A possible mechanism for prompt disruption of gut barrier function by alcohol

    PubMed Central

    Qin, Xiaofa; Deitch, Edwin A.

    2014-01-01

    Acute and/or chronic alcohol ingestion has been shown to exacerbate the morbidity and mortality rate associated with acute mechanical and/or thermal trauma. While alcohol ingestion can affect many organs and systems, clinical and preclinical studies indicate that alcohol ingestion can cause a ‘leaky gut’ syndrome which in turn contributes to infection and systemic organ dysfunction. This study investigated the acute effect of alcohol on gut barrier function. Using an in vivo isolated gut sac model of naïve male rats, each individual gut sac was injected with different concentrations (0, 5, 10, 20, and 40%, v/v) of alcohol. After different times of alcohol exposure, each isolated gut segment was harvested and intestinal permeability and mucosal surface hydrophobicity (a physiologic marker of mucus barrier function) were measured as well as luminal DNA, mucus, protein and free fatty acids. The results showed that alcohol caused dose-dependent and time-dependent increases in gut permeability and decreases in mucosal surface hydrophobicity, with significant changes to be observed 5 min after treatment with 10% alcohol. In addition, it is further found that these changes in permeability and hydrophobicity are more closely associated with increased intestinal luminal free fatty acids levels but not protein or DNA levels. These results suggest that alcohol may cause loss of gut barrier function by extracting and dissolving lipids from the mucus with a resultant decrease in mucosal surface hydrophobicity, which is a critical component of gut barrier function. PMID:25445722

  19. 1,8-Cineol Reduces Mucus-Production in a Novel Human Ex Vivo Model of Late Rhinosinusitis

    PubMed Central

    Greiner, Johannes F. W.; Müller, Janine; Brotzmann, Viktoria; Ebmeyer, Jörg

    2015-01-01

    Inflammatory diseases of the respiratory system such as rhinosinusitis, chronic obstructive pulmonary disease, or bronchial asthma are strongly associated with overproduction and hypersecretion of mucus lining the epithelial airway surface. 1,8-cineol, the active ingredient of the pharmaceutical drug Soledum, is commonly applied for treating such inflammatory airway diseases. However, its potential effects on mucus overproduction still remain unclear.In the present study, we successfully established ex vivo cultures of human nasal turbinate slices to investigate the effects of 1,8-cineol on mucus hypersecretion in experimentally induced rhinosinusitis. The presence of acetyl-α-tubulin-positive cilia confirmed the integrity of the ex vivo cultured epithelium. Mucin-filled goblet cells were also detectable in nasal slice cultures, as revealed by Alcian Blue and Periodic acid-Schiff stainings. Treatment of nasal slice cultures with lipopolysaccharides mimicking bacterial infection as observed during late rhinosinusitis led to a significantly increased number of mucin-filled goblet cells. Notably, the number of mucin-filled goblet cells was found to be significantly decreased after co-treatment with 1,8-cineol. On a molecular level, real time PCR-analysis further showed 1,8-cineol to significantly reduce the expression levels of the mucin genes MUC2 and MUC19 in close association with significantly attenuated NF-κB-activity. In conclusion, we demonstrate for the first time a 1,8-cineol-dependent reduction of mucin-filled goblet cells and MUC2-gene expression associated with an attenuated NF-κB-activity in human nasal slice cultures. Our findings suggest that these effects partially account for the clinical benefits of 1,8-cineol-based therapy during rhinosinusitis. Therefore, topical application of 1,8-cineol may offer a novel therapeutic approach to reduce bacteria-induced mucus hypersecretion. PMID:26207629

  20. [Development of ultrastructural changes in human cervix mucus during the ovarian cycle. Scanning electron microscope study].

    PubMed

    Chrétien, F C; Cohen, J; Psychoyos, A

    1976-01-01

    The use of the Scanning Electron Microscope has made it possible through observation to study the human cervical mucus through the various stages of the ovarian cycle, as well as to describe the significant variations of the meshed woof making up the ultrastructure during the ovarian cycle. While the slackening of the woof and the dimension of the meshes are minimal at both the beginning and end of the cycle, they reach a maximum on forteenth day. In the ovulatory period, lateral expansions from the filaments are numerous. On the other hand, median and terminal thicknesses are almost inexistant during the same period : their frequency decreases during the first part of the cycle, then increases during the luteal phase. During both the preceding and following days of ovulation, one can observe numerous twistings at the level of the filaments which probably express the relaxation and then contraction of the latter. The preparatory technique as well as the method of observation used appear reliable enough to allow a comparison of the cervical mucus ultrastructure in varied physiological, pathological and experimental situations. PMID:956619

  1. Acceptability of the modified mucus method: study of the psychosocial factors affecting acceptance.

    PubMed

    Dorairaj, K

    1988-01-01

    A three-phase study designed to study the acceptability and use-effectiveness of the modified mucus method covered a sample of 2,601 poor rural migrant women living in eight low-income areas--villages and resettlement slum colonies. In phase I, the women were exposed to NFP awareness, i.e., the modified mucus method, and 61.6% of the women accepted the method, and agreed to learn and use it. The learning phase is three cycles. Of these acceptors, 83.7% were fertile. A large percentage of the acceptors are Hindus. The low acceptance by the Sikhs was who were non pregnant, menstruating cohabiting. 15.3% were nonmenstruating owing to pregnancy or breast feeding; 0.9% were menstruating, but not cohabitating; 35.4% of the women were not interested in learning or using the method. A comparative study of the acceptance and nonacceptance for the selected sociodemographic and family planning variables is analysed. The acceptors of NFP differed significantly from the acceptors of sterilization and IUD in their occupation, educational levels, duration of marriage, number of living children, number of living sons, knowledge of family planning, and previous use of family planning. PMID:2902034

  2. Proteomic analysis of epidermal mucus from sea lice-infected Atlantic salmon, Salmo salar L.

    PubMed

    Provan, F; Jensen, L B; Uleberg, K E; Larssen, E; Rajalahti, T; Mullins, J; Obach, A

    2013-03-01

    Health diets that contain immunostimulants and other functional ingredients can strengthen the immune response in Atlantic salmon, Salmo salar, and thereby reduce sea lice, Lepeophtheirus salmonis, infection levels. Such diets can be used to supplement other treatments and will potentially reduce the need for delousing and medication. A sea lice infection trial was conducted on fish with an average weight of 215 g. One control diet and four experimental diets containing functional ingredients were produced. The diets were fed to salmon for 4 weeks before infection with sea lice copepodids. When lice had developed to chalimus III/IV, 88 fish per diet were examined for lice loads. Mucus samples from fish fed the different diets were taken before and after lice infection. Mass spectrometry-based proteomics was used to characterize the protein composition in the epidermal mucus of Atlantic salmon and to identify quantitative alterations in protein expression. Multivariate analysis of the generated data sets was performed to identify protein biomarkers. Putative biomarkers associated with functional feed intake and with sea lice infection have been identified and can form the basis for strategic validation experiments with selected functional feeds. PMID:23305410

  3. Size-Limited Penetration of Nanoparticles into Porcine Respiratory Mucus after Aerosol Deposition.

    PubMed

    Murgia, Xabier; Pawelzyk, Paul; Schaefer, Ulrich F; Wagner, Christian; Willenbacher, Norbert; Lehr, Claus-Michael

    2016-04-11

    We investigated the rheological properties and the penetration of differently sized carboxylated nanoparticles in pig pulmonary mucus, on different distance and time scales. Nanoparticles were either mechanically mixed into the mucus samples or deposited as an aerosol, the latter resembling a more physiologically relevant delivery scenario. After mechanical dispersion, 500 nm particles were locally trapped; a fraction of carboxylated tracer particles of 100 or 200 nm in diameter could however freely diffuse in these networks over distances of approximately 20 μm. In contrast, after aerosol deposition on top of the mucus layer only particles with a size of 100 nm were able to penetrate into mucus, suggesting the presence of smaller pores at the air-mucus interface compared to within mucus. These findings are relevant to an understanding of the fate of potentially harmful aerosol particles, such as pathogens, pollutants, and other nanomaterials after incidental inhalation, as well as for the design of pulmonary drug delivery systems. PMID:26957140

  4. Skin mucus of Cyprinus carpio inhibits cyprinid herpesvirus 3 binding to epidermal cells

    PubMed Central

    2011-01-01

    Cyprinid herpesvirus 3 (CyHV-3) is the aetiological agent of a mortal and highly contagious disease in common and koi carp. The skin is the major portal of entry of CyHV-3 in carp after immersion in water containing the virus. In the present study, we used in vivo bioluminescence imaging to investigate the effect of skin mucus removal and skin epidermis lesion on CyHV-3 entry. Physical treatments inducing removal of the mucus up to complete erosion of the epidermis were applied on a defined area of carp skin just before inoculation by immersion in infectious water. CyHV-3 entry in carp was drastically enhanced on the area of the skin where the mucus was removed with or without associated epidermal lesion. To investigate whether skin mucus inhibits CyHV-3 binding to epidermal cells, tail fins with an intact mucus layer or without mucus were inoculated ex vivo. While electron microscopy examination revealed numerous viral particles bound on the fins inoculated after mucus removal, no particle could be detected after infection of mucus-covered fins. Finally, anti-CyHV-3 neutralising activity of mucus extract was tested in vitro. Incubation of CyHV-3 with mucus extract reduced its infectivity in a dose dependent manner. The present study demonstrates that skin mucus removal and epidermal lesions enhance CyHV-3 entry in carp. It highlights the role of fish skin mucus as an innate immune protection against viral epidermal entry. PMID:21816061

  5. Different macro- and micro-rheological properties of native porcine respiratory and intestinal mucus.

    PubMed

    Bokkasam, Harish; Ernst, Matthias; Guenther, Marco; Wagner, Christian; Schaefer, Ulrich F; Lehr, Claus-Michael

    2016-08-20

    Aim of this study was to investigate the similarities and differences at macro- and microscale in the viscoelastic properties of mucus that covers the epithelia of the intestinal and respiratory tract. Natural mucus was collected from pulmonary and intestinal regions of healthy pigs. Macro-rheological investigations were carried out through conventional plate-plate rheometry. Microrheology was investigated using optical tweezers. Our data revealed significant differences both in macro- and micro-rheological properties between respiratory and intestinal mucus. PMID:27311353

  6. A Biophysical Basis for Mucus Solids Concentration as a Candidate Biomarker for Airways Disease

    PubMed Central

    Hill, David B.; Vasquez, Paula A.; Mellnik, John; McKinley, Scott A.; Vose, Aaron; Mu, Frank; Henderson, Ashley G.; Donaldson, Scott H.; Alexis, Neil E.; Boucher, Richard C.; Forest, M. Gregory

    2014-01-01

    In human airways diseases, including cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), host defense is compromised and airways inflammation and infection often result. Mucus clearance and trapping of inhaled pathogens constitute key elements of host defense. Clearance rates are governed by mucus viscous and elastic moduli at physiological driving frequencies, whereas transport of trapped pathogens in mucus layers is governed by diffusivity. There is a clear need for simple and effective clinical biomarkers of airways disease that correlate with these properties. We tested the hypothesis that mucus solids concentration, indexed as weight percent solids (wt%), is such a biomarker. Passive microbead rheology was employed to determine both diffusive and viscoelastic properties of mucus harvested from human bronchial epithelial (HBE) cultures. Guided by sputum from healthy (1.5–2.5 wt%) and diseased (COPD, CF; 5 wt%) subjects, mucus samples were generated in vitro to mimic in vivo physiology, including intermediate range wt% to represent disease progression. Analyses of microbead datasets showed mucus diffusive properties and viscoelastic moduli scale robustly with wt%. Importantly, prominent changes in both biophysical properties arose at ∼4 wt%, consistent with a gel transition (from a more viscous-dominated solution to a more elastic-dominated gel). These findings have significant implications for: (1) penetration of cilia into the mucus layer and effectiveness of mucus transport; and (2) diffusion vs. immobilization of micro-scale particles relevant to mucus barrier properties. These data provide compelling evidence for mucus solids concentration as a baseline clinical biomarker of mucus barrier and clearance functions. PMID:24558372

  7. Improving adherence to antiretroviral therapy in sub-Saharan African HIV-positive populations: an enhanced adherence package.

    PubMed

    Kunutsor, S; Walley, J; Muchuro, S; Katabira, E; Balidawa, H; Namagala, E; Ikoona, E

    2012-01-01

    With the increasing access to antiretroviral therapy in sub-Saharan African HIV-positive populations, it is important to find additional simple, effective, and feasible methods of improving and maintaining adequately high levels of adherence. In this study, we undertook the development, testing, implementation, and evaluation of various adherence support interventions at four sites in Uganda. A one-group pre- and post-intervention design was employed under routine operational conditions. Various adherence support strategies were identified, adapted, and developed. These strategies which included a combination of elements such as counseling, group education, leaflets, late attendee tracing, and adherence diaries was implemented for an antiretroviral treatment cohort which had baseline levels of adherence measured preintervention. Follow-up was from August 2009 through August 2010. Mean adherence and proportions of clients achieving adherence levels of 95% and above were determined at end of follow-up. Of the 967 participants enrolled, 856 (88.5%) completed follow-up. A before-and-after comparison of outcomes demonstrated that mean adherence (95% confidence interval [CI]) improved statistically significant from baseline following implementation of the interventions (97.4% [96.9-97.9%] to 99.1% [99.0-99.3%], P=0.001). There was also a significant difference between proportions with optimal (≥ 95%) and suboptimal adherence (<95%) pre- and post-intervention (7.0% difference, 95% CI: 4.6-9.4%, P<0.001). We conclude that additional adherence strategies (including counseling, group education, leaflets, late attendee tracing, and adherence diaries) can substantially improve and maintain high levels of treatment adherence in the long term. Health systems in sub-Saharan African countries should consider integrating these elements into their treatment programs for HIV/AIDS. PMID:22621288

  8. Imaging endocervical mucus anatomy and dynamics in macaque female reproductive track using optical coherence tomography

    PubMed Central

    Chen, Siyu; Yi, Ji; Dong, Biqin; Sun, Cheng; Kiser, Patrick F.; Hope, Thomas J.

    2015-01-01

    Background Endocervical mucus acts as an important barrier to block human immunodeficiency virus (HIV) infection and other sexually transmitted diseases (STDs). Disruption of the mucus layer increases the risk of infection for females. An effective method to image the mucus properties can serve as a pre-screening step to risk-stratify the susceptible population. Methods We proposed to use optical coherence tomography (OCT) to quantitatively measure the thickness of endocervical mucus. We used a home-built bench-top OCT system to monitor the dynamic change in mucus thickness of a cultivated sample. We also fabricated a prototype endoscopic OCT probe to demonstrate potential in situ applications. Results We observed a 200% increase in the endocervical mucus thickness after cultivating in 37 °C phosphate buffered saline solution for 30 minutes. During mucus hydrolysis, we found that mucus layer thickness decreased to about 60% of its original value after applying neuraminidase. Three dimensional volumetric image of intact macaque inner vaginal wall was also acquired. Conclusions We demonstrated that OCT can quantitatively measure the endocervical mucus thickness and its dynamics in ex vivo experiments. Endoscopic OCT has the potential to resolve fine structures inside macaque female reproductive track (FRT) for in vivo applications. PMID:25694952

  9. Nano-carrier systems: Strategies to overcome the mucus gel barrier.

    PubMed

    Dünnhaupt, S; Kammona, O; Waldner, C; Kiparissides, C; Bernkop-Schnürch, A

    2015-10-01

    The present review provides an overview of nanotechnology-based strategies to overcome various mucus gel barriers including the intestinal, nasal, ocular, vaginal, buccal and pulmonary mucus layer without destroying them. It focuses on the one hand on strategies to improve the mucus permeation behavior of particles and on the other hand on systems avoiding the back-diffusion of particles out of the mucus gel layer. Nanocarriers with improved mucus permeation behavior either exhibit a high density of positive and negative charges, bearing mucolytic enzymes such as papain and bromelain on their surface or display a slippery surface due to PEG-ylation. Furthermore, self-nanoemulsifying-drug-delivery-systems (SNEDDS) turned out to exhibit comparatively high mucus permeating properties. Strategies in order to avoid back-diffusion are based on thiolated polymers reacting to a higher extent with cysteine subunits of the mucus at pH 7 in deeper mucus regions than at pH 5 being prevalent in luminal mucus regions of the intestinal and vaginal mucosa. Furthermore, particles changing their zeta potential from negative to positive once they have reached the epithelium seem to be promising carriers. The summarized knowledge should provide a good starting point for further developments in this field. PMID:25712487

  10. Luteolin Attenuates Airway Mucus Overproduction via Inhibition of the GABAergic System.

    PubMed

    Shen, Mei-Lin; Wang, Chen-Hung; Lin, Ching-Huei; Zhou, Ning; Kao, Shung-Te; Wu, Dong Chuan

    2016-01-01

    Airway mucus overproduction is one of the most common symptoms of asthma that causes severe clinical outcomes in patients. Despite the effectiveness of general asthma therapies, specific treatments that prevent mucus overproduction in asthma patients remain lacking. Recent studies have found that activation of GABAA receptors (GABAAR) is important for promoting mucus oversecretion in lung airway epithelia. Here, we report that luteolin, a natural flavonoid compound, suppresses mucus overproduction by functionally inhibiting the GABAergic system. This hypothesis was investigated by testing the effects of luteolin on goblet cell hyperplasia, excessive mucus secretion, and GABAergic transmission using histological and electrophysiological approaches. Our results showed that 10 mg/kg luteolin significantly decreased the number of goblet cells in the lung tissue and inhibited mucus overproduction in an in vivo asthma model induced by ovalbumin (OVA) in mice. Patch-clamp recordings showed that luteolin inhibited GABAAR-mediated currents in A549 cells. Furthermore, the inhibitory effects of luteolin on OVA-induced goblet cell hyperplasia and mucus overproduction were occluded by the GABAAR antagonist picrotoxin. In conclusion, our observations indicate that luteolin effectively attenuates mucus overproduction at least partially by inhibiting GABAARs, suggesting the potential for therapeutic administration of luteolin in the treatment of mucus overproduction in asthma patients. PMID:27595800

  11. Lubiprostone Decreases Mouse Colonic Inner Mucus Layer Thickness and Alters Intestinal Microbiota

    PubMed Central

    Musch, Mark W.; Wang, Yunwei; Claud, Erika C.

    2013-01-01

    Background Lubiprostone has been used to treat constipation through its effects to stimulate Cl− secretion, resulting in water and electrolyte secretion. Aim Potential associated changes in intestinal mucus and the colonizing bacteria (microbiome) have not been studied. As mucus obstructions may play a role in cystic fibrosis, the hypothesis that lubiprostone alters intestinal mucus and the microbiome was investigated. Methods Ion transport studies were performed ex vivo. For mucus and microbiome studies, mice were gavaged daily with lubiprostone or vehicle. Mucin from intestinal sections was analyzed in Carnoy’s fixed tissues stained with Alcian blue. Microbiome composition was analyzed by 16S rRNA gene-based sequencing. Results Lubiprostone stimulated short circuit current in all mouse intestinal segments after both serosal and mucosal additions, albeit at lower concentrations in the latter. Current was Cl-dependent and blocked by mucosal diphenylcarboxylic acid, serosal bumetanide, and serosal Ba++. The CFTR inhibitor CFTRinh172 had a marginal effect. Mucus near epithelial cells (inner layer mucus) was not present in the small intestine of any mice. Proximal colon inner mucus layer was thicker in ΔF/ΔF compared with +/ΔF and +/+ mice. Lubiprostone decreased inner mucus layer thickness in both proximal and distal colon of all mice. Furthermore, lubiprostone altered the intestinal microbiome by increasing abundance of Lactobacillus and Alistipes. Conclusions Lubiprostone activates non-CFTR Cl− secretion and alters the colonic inner mucus layer, which is associated with changes in the composition of the enteric microbiome. PMID:23329012

  12. Antibacterial properties of fish mucus from Channa punctatus and Cirrhinus mrigala.

    PubMed

    Kuppulakshmi, C; Prakash, M; Gunasekaran, G; Manimegalai, G; Sarojini, S

    2008-01-01

    Extracts and preparations made from the animal origin were used extensively in folk and modern medicine for treating many human diseases. In the present study efforts have been made to find the antimicrobial effect of the mucus of two bottom dwelling fresh water fishes namely, Channa punctatus and Cirrhinus mrigala. Fish mucus were tested against ten pathogenic bacteria such as Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Lactobacillus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella paratyphi, Salmonella typhi, Staphylococcus aureus and Vibrio cholera. The activity was measured in terms of zone of inhibition in mm. The mucus collected from Cirrhinus mrigala shows a strong inhibiting activity than the mucus of Channa punctatus. PMID:18700685

  13. Luteolin Attenuates Airway Mucus Overproduction via Inhibition of the GABAergic System

    PubMed Central

    Shen, Mei-Lin; Wang, Chen-Hung; Lin, Ching-Huei; Zhou, Ning; Kao, Shung-Te; Wu, Dong Chuan

    2016-01-01

    Airway mucus overproduction is one of the most common symptoms of asthma that causes severe clinical outcomes in patients. Despite the effectiveness of general asthma therapies, specific treatments that prevent mucus overproduction in asthma patients remain lacking. Recent studies have found that activation of GABAA receptors (GABAAR) is important for promoting mucus oversecretion in lung airway epithelia. Here, we report that luteolin, a natural flavonoid compound, suppresses mucus overproduction by functionally inhibiting the GABAergic system. This hypothesis was investigated by testing the effects of luteolin on goblet cell hyperplasia, excessive mucus secretion, and GABAergic transmission using histological and electrophysiological approaches. Our results showed that 10 mg/kg luteolin significantly decreased the number of goblet cells in the lung tissue and inhibited mucus overproduction in an in vivo asthma model induced by ovalbumin (OVA) in mice. Patch-clamp recordings showed that luteolin inhibited GABAAR-mediated currents in A549 cells. Furthermore, the inhibitory effects of luteolin on OVA-induced goblet cell hyperplasia and mucus overproduction were occluded by the GABAAR antagonist picrotoxin. In conclusion, our observations indicate that luteolin effectively attenuates mucus overproduction at least partially by inhibiting GABAARs, suggesting the potential for therapeutic administration of luteolin in the treatment of mucus overproduction in asthma patients. PMID:27595800

  14. Determinants of Medication Adherence to Topical Glaucoma Therapy

    PubMed Central

    Dreer, Laura E.; Girkin, Christopher; Mansberger, Steven L.

    2011-01-01

    Introduction/Purpose To determine the associations between medical, demographic, socioeconomic, and ocular factors and adherence to topical glaucoma ocular hypotensive therapy. Methods One-hundred and sixteen patients with ocular hypertension or open angle glaucoma from two tertiary glaucoma services participated in this prospective study. Adherence to ocular hypotensive therapy was measured using an electronic dose monitor (Travatan Dosing Aid, Alcon Laboratories Inc., Fort Worth, TX) and collected data at 3-months after enrollment. We used 3 different definitions of adherence: 1) Definition 1: the proportion of days taking the prescribed number of drops within 3 hours of the prescribed dosing time; 2) Definition 2: the proportion of days taking any drops within 3 hours of the prescribed dosing time; and 3) Definition 3: the proportion of days taking any drops within 6 hours of the prescribed dosing time. Univariate and multivariate models were used to determine the association between the three adherence definitions, medical, demographic, socioeconomic, and ocular factors at 3-month follow-up. The main outcome measures for this study were risk factors for poor objective medication adherence. Results Adherence, using Definition 1, Definition 2, and Definition 3, was 64%, 75%, and 80%, respectively. Age, total number of other eye diseases, and race were significantly associated with full treatment adherence (Definition 1), with race alone significantly predicting 11% of full treatment adherence. For Definition 2, age, income, level of education, and total number of eye diseases were significantly associated with partial adherence (3 hours), again race alone significantly predicted 15% of partial adherence (any drops within 3 hours). For Definition 3, race, income, level of education, and total number of other eye diseases significantly predicted partial adherence (any drops within 6 hours), both race and income predicted 19% of partial treatment adherence

  15. Fate of paclitaxel lipid nanocapsules in intestinal mucus in view of their oral delivery.

    PubMed

    Groo, Anne-Claire; Saulnier, Patrick; Gimel, Jean-Christophe; Gravier, Julien; Ailhas, Caroline; Benoit, Jean-Pierre; Lagarce, Frederic

    2013-01-01

    The bioavailability of paclitaxel (Ptx) has previously been improved via its encapsulation in lipid nanocapsules (LNCs). In this work, the interactions between LNCs and intestinal mucus are studied because they are viewed as an important barrier to successful oral delivery. The rheological properties of different batches of pig intestinal mucus were studied under different conditions (the effect of hydration and the presence of LNCs). Fluorescence resonance energy transfer (FRET) was used to study the stability of LNCs in mucus at 37°C for at least 3 hours. Diffusion through 223, 446, and 893 μm mucus layers of 8.4, 16.8, and 42 μg/mL Ptx formulated as Taxol® (Bristol-Myers Squibb, Rueil-Malmaison, France) or encapsulated in LNCs (Ptx-LNCs) were investigated. The effect of the size of the LNCs on their diffusion was also investigated (range, 25-110 nm in diameter). Mucus behaves as a non-Newtonian gel with rheofluidifying properties and a flow threshold. The viscous (G″) and elastic (G') moduli and flow threshold of the two mucus batches varied with water content, but G' remained below G″. LNCs had no effect on mucus viscosity and flow threshold. The FRET efficiency remained at 78% after 3 hours. Because the destruction of the LNCs would lead to a FRET efficiency below 25%, these results suggest only a slight modification of LNCs after their contact with mucus. The diffusion of Taxol® and Ptx-LNCs in mucus decreases if the mucus layer is thicker. Interestingly, the apparent permeability across mucus is higher for Ptx-LNCs than for Taxol® for drug concentrations of 16.8 and 42 μg/mL Ptx (P<0.05). The diffusion of Ptx-LNCs through mucus is not size-dependent. This study shows that LNCs are stable in mucus, do not change mucus rheological properties, and improve Ptx diffusion at low concentrations, thus making these systems good candidates for Ptx oral delivery. The study of the physicochemical interaction between the LNC surface and its diffusion in mucus

  16. Mucus Sugar Content Shapes the Bacterial Community Structure in Thermally Stressed Acropora muricata

    PubMed Central

    Lee, Sonny T. M.; Davy, Simon K.; Tang, Sen-Lin; Kench, Paul S.

    2016-01-01

    It has been proposed that the chemical composition of a coral’s mucus can influence the associated bacterial community. However, information on this topic is rare, and non-existent for corals that are under thermal stress. This study therefore compared the carbohydrate composition of mucus in the coral Acropora muricata when subjected to increasing thermal stress from 26 to 31°C, and determined whether this composition correlated with any changes in the bacterial community. Results showed that, at lower temperatures, the main components of mucus were N-acetyl glucosamine and C6 sugars, but these constituted a significantly lower proportion of the mucus in thermally stressed corals. The change in the mucus composition coincided with a shift from a γ-Proteobacteria- to a Verrucomicrobiae- and α-Proteobacteria-dominated community in the coral mucus. Bacteria in the class Cyanobacteria also started to become prominent in the mucus when the coral was thermally stressed. The increase in the relative abundance of the Verrucomicrobiae at higher temperature was strongly associated with a change in the proportion of fucose, glucose, and mannose in the mucus. Increase in the relative abundance of α-Proteobacteria were associated with GalNAc and glucose, while the drop in relative abundance of γ-Proteobacteria at high temperature coincided with changes in fucose and mannose. Cyanobacteria were highly associated with arabinose and xylose. Changes in mucus composition and the bacterial community in the mucus layer occurred at 29°C, which were prior to visual signs of coral bleaching at 31°C. A compositional change in the coral mucus, induced by thermal stress could therefore be a key factor leading to a shift in the associated bacterial community. This, in turn, has the potential to impact the physiological function of the coral holobiont. PMID:27047481

  17. Mucus Sugar Content Shapes the Bacterial Community Structure in Thermally Stressed Acropora muricata.

    PubMed

    Lee, Sonny T M; Davy, Simon K; Tang, Sen-Lin; Kench, Paul S

    2016-01-01

    It has been proposed that the chemical composition of a coral's mucus can influence the associated bacterial community. However, information on this topic is rare, and non-existent for corals that are under thermal stress. This study therefore compared the carbohydrate composition of mucus in the coral Acropora muricata when subjected to increasing thermal stress from 26 to 31°C, and determined whether this composition correlated with any changes in the bacterial community. Results showed that, at lower temperatures, the main components of mucus were N-acetyl glucosamine and C6 sugars, but these constituted a significantly lower proportion of the mucus in thermally stressed corals. The change in the mucus composition coincided with a shift from a γ-Proteobacteria- to a Verrucomicrobiae- and α-Proteobacteria-dominated community in the coral mucus. Bacteria in the class Cyanobacteria also started to become prominent in the mucus when the coral was thermally stressed. The increase in the relative abundance of the Verrucomicrobiae at higher temperature was strongly associated with a change in the proportion of fucose, glucose, and mannose in the mucus. Increase in the relative abundance of α-Proteobacteria were associated with GalNAc and glucose, while the drop in relative abundance of γ-Proteobacteria at high temperature coincided with changes in fucose and mannose. Cyanobacteria were highly associated with arabinose and xylose. Changes in mucus composition and the bacterial community in the mucus layer occurred at 29°C, which were prior to visual signs of coral bleaching at 31°C. A compositional change in the coral mucus, induced by thermal stress could therefore be a key factor leading to a shift in the associated bacterial community. This, in turn, has the potential to impact the physiological function of the coral holobiont. PMID:27047481

  18. Adherence to Glycemic Monitoring in Diabetes

    PubMed Central

    Patton, Susana R.

    2015-01-01

    Glucose monitoring either by self-monitoring of blood glucose (SMBG) or continuous glucose monitoring (CGM) plays an important role in diabetes management and in reducing risk for diabetes-related complications. However, despite evidence supporting the role of glucose monitoring in better patient health outcomes, studies also reveal relatively poor adherence rates to SMBG and CGM use and numerous patient-reported barriers. Fortunately, some promising intervention strategies have been identified that promote at least short-term improvements in patients’ adherence to SMBG. These include education, problem solving, contingency management, goal setting, cognitive behavioral therapy, and motivational interviewing. Specific to CGM, interventions to promote greater use among patients are currently under way, yet one pilot study provides data suggesting better maintenance of CGM use in patients showing greater readiness for behavior change. The purpose of this review is to summarize the literature specific to glucose monitoring in patients with diabetes focusing specifically on current adherence rates, barriers to monitoring, and promising intervention strategies that may be ready to deploy now in the clinic setting to promote greater patient adherence to glucose monitoring. Yet, to continue to help patients with diabetes adhere to glucose monitoring, future research is needed to identify the treatment strategies and the intervention schedules that most likely lead to long-term maintenance of optimal glycemic monitoring levels. PMID:25591853

  19. Development of adherence metrics for caloric restriction interventions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective measures are needed to quantify dietary adherence during caloric restriction (CR) while participants are freeliving. One method to monitor adherence is to compare observed weight loss to the expected weight loss during a prescribed level of CR. Normograms (graphs) of expected weight loss c...

  20. Development of adherence metrics for caloric restriction interventions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective measures are needed to quantify dietary adherence during caloric restriction (CR) while participants are freeliving. One method to monitor adherence is to compare observed weight loss to the expected weight loss during a prescribed level of CR. Normograms (graphs)of expected weight loss ca...

  1. Understanding how adherence goals promote adherence behaviours: a repeated measure observational study with HIV seropositive patients

    PubMed Central

    2012-01-01

    Background The extent to which patients follow treatments as prescribed is pivotal to treatment success. An exceptionally high level (> 95%) of HIV medication adherence is required to suppress viral replication and protect the immune system and a similarly high level (> 80%) of adherence has also been suggested in order to benefit from prescribed exercise programmes. However, in clinical practice, adherence to both often falls below the desirable level. This project aims to investigate a wide range of psychological and personality factors that may lead to adherence/non-adherence to medical treatment and exercise programmes. Methods HIV positive patients who are referred to the physiotherapist-led 10-week exercise programme as part of the standard care are continuously recruited. Data on social cognitive variables (attitude, intention, subjective norms, self-efficacy, and outcome beliefs) about the goal and specific behaviours, selected personality factors, perceived quality of life, physical activity, self-reported adherence and physical assessment are collected at baseline, at the end of the exercise programme and again 3 months later. The project incorporates objective measures of both exercise (attendance log and improvement in physical measures such as improved fitness level, weight loss, improved circumferential anthropometric measures) and medication adherence (verified by non-invasive hair analysis). Discussion The novelty of this project comes from two key aspects, complemented with objective information on exercise and medication adherence. The project assesses beliefs about both the underlying goal such as following prescribed treatment; and about the specific behaviours such as undertaking the exercise or taking the medication, using both implicit and explicit assessments of patients’ beliefs and attitudes. We predict that i) the way people think about the underlying goal of their treatments explains medication and exercise behaviours over and above

  2. Smoking produced mucus and clearance of particulates in the lung

    SciTech Connect

    Sterling, T.D.; Poland, T.M.

    1992-12-31

    Some studies of miners have shown a lesser relative lung-cancer risk for smokers than for nonsmokers. For example, experiments by Cross and associates with dogs have shown an apparent protective effect of cigarette smoke against radon-daughter and dust exposure. One reason for these changes may be the thickened mucus layer in the tracheobronchial region of smokers. Physiological changes in the lung due to smoking may decrease the effects of radioactive particles in cancers in the bronchial region by apparently promoting faster clearance, in that region, of radioactive particles and by decreasing the radiation dose through reduced penetration to the sensitive basal epithelial cells. Because of the short half-life of radon daughters, even if there is possible tobacco-related delay of particle clearance from the alveolar region it cannot affect radon clearance. Therefore, the possible mitigating effect of tobacco on radon-produced cancer appears to be limited to the tracheobronchial region. It would be of value to a number of occupations if the same changes in the lungs due to smoking could be produced in exposed workers in the absence of cigarette-smoking. Beta-carotene and vitamin A, which affect maintenance and secretion of the mucosal lining, appear to thicken mucus, thereby providing protection against radon-induced lung cancers that is similar to smoking-related changes in the lung.

  3. Stimulation of proteolytic digestion by intestinal goblet cell mucus.

    PubMed

    Shora, W; Forstner, G G; Forstner, J F

    1975-03-01

    Intestinal goblet cell mucus (GCM) was added to incubations of casein and trypsin (or chymotrypsin) to discover whether mucus could inhibit proteolysis. Contrary to expectation, GCM stimulated casein hydrolysis, reaching a maximum effect at a GCM to casein ratio (w/w) of 0.083. GCM did not contain proteolytic enzymes or proenzymes as contaminants, nor did GCM serve as a substrate for trypsin. Stimulation was not reduced by removing 85% of the sialic acid from GCM. Harsh physical treatment (boiling and freezing) of casein decreased (50%) the GCM effect, as did partial predigestion of casein by trypsin, and elevation of trypsin concentration beyond 3 mug per ml. Thus the undegraded structure of casein appeared to be important for the stimulation of proteolysis by GCM. GCM also enhanced the hydrolysis by trypsin of intestinal brush border membrane protein, but had no effect on the hydrolysis of hemoglobin, albumin, or benzoyl arginine ethyl ester. These results suggest that GCM reacts with specific substrates, in a fashion which promotes their digestion by trypsin or chymotrypsin. PMID:1112451

  4. Reconceptualizing medication adherence: six phases of dynamic adherence.

    PubMed

    Gearing, Robin E; Townsend, Lisa; MacKenzie, Michael; Charach, Alice

    2011-01-01

    Nonadherence is the Achilles' heel of effective psychiatric treatment. It affects the resolution of mental health symptoms and interferes with the assessment of treatment response. The meaning of the term adherence has evolved over time and is now associated with a variety of definitions and measurement methods. The result has been a poorly operationalized and nonstandardized term that is often interpreted differently by providers and patients. Drawing extensively from the literature, this article aims to (1) describe changes in the concept of adherence, drawing from the mental health treatment literature, (2) present a more comprehensive definition of adherence that recognizes the role of patient-provider transactions, (3) introduce dynamic adherence, a six-phase model, which incorporates the role of transactional processes and other factors that influence patients' adherence decisions, and (4) provide recommendations for providers to improve adherence as well as their relationships with patients. PMID:21790266

  5. Spatial organization of cilia tufts governs airways mucus transport: Application to severe asthma

    NASA Astrophysics Data System (ADS)

    Khelloufi, Mustapha Kamel; Gras, Delphine; Chanez, Pascal; Viallat, Annie

    2014-11-01

    We study the coupling between both density and spatial repartition of beating cilia tufts, and the coordinated transport of mucus in an in-vitro epithelial model. We use a fully differentiated model epithelium in air liquid interface (ALI) obtained from endo-bronchial biopsies from healthy subjects and patients with asthma. The asthma phenotype is known to persist in the model. Mucus transport is characterized by the trajectories and velocities of microscopic beads incorporated in the mucus layer. When the beating cilia tufts density is higher than dc = 11/100 × 100 μm2 a spherical spiral coordinated mucus transport is observed over the whole ALI chamber (radius = 6 mm). Below dc, local mucus coordinated transport is observed on small circular domains on the epithelium surface. We reveal that the radii of these domains scale with the beating cilia tufts density with a power 3.7. Surprisingly, this power law is independent on cilia beat frequency, concentration and rheological properties of mucus for healthy subject and patient with asthma. The rotating or linear mucus transport is related to dispersion of the cilia tufts on the epithelium surface. We show that impaired mucus transport observed in severe asthma model epithelia is due to a drastic lack and dysfunction of cilia tufts. The author acknowledges the support of the French Agence Nationale de la Recherche (ANR) under reference ANR-13-BSV5-0015-01.

  6. 76 FR 36557 - Prospective Grant of Exclusive License; Devices for Clearing Mucus From Endotracheal Tubes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-22

    ...-074-2005/0 ``Mucus Slurping Endotracheal Tube''; U.S. Patent 7,503,328 to Oculus Innovative Sciences... to remove mucus before it reaches the tip of the endotracheal tube (ETT). A continuous aspiration endotracheal tube for subglottic secretions is fitted at its distal-most tip with a molded, hollow,...

  7. On the effect of mucus rheology on the muco-ciliary transport.

    PubMed

    Sedaghat, M H; Shahmardan, M M; Norouzi, M; Nazari, M; Jayathilake, P G

    2016-02-01

    A two dimensional numerical model is used to study the muco-ciliary transport process in human respiratory tract. Here, hybrid finite difference-lattice Boltzmann method is used to model the flow physics of the transport of mucus and periciliary liquid (PCL) layer in the airway surface liquid. The immersed boundary method is also used to implement the propulsive effect of the cilia and also the effects of the interface between the mucus and PCL layers. The main contribution of this study is on elucidating the role of the viscoelastic behavior of mucus on the muco-ciliary transport and for this purpose an Oldroyd-B model is used as the constitutive equation of mucus for the first time. Results show that the viscosity and viscosity ratio of mucus have an enormous effect on the muco-ciliary transport process. It is also seen that the mucus velocity is affected by mucus relaxation time when its value is less than 0.002 s. Results also indicate that the variation of these properties on the mucus velocity at lower values of viscosity ratio is more significant. PMID:26656465

  8. Bacterial decomposition of coral mucus as evaluated by long-term and quantitative observation

    NASA Astrophysics Data System (ADS)

    Tanaka, Y.; Ogawa, H.; Miyajima, T.

    2011-06-01

    Coral mucus released from Acropora formosa and Montipora digitata was incubated with bacteria under dark conditions for 1 year to evaluate the quantitative degradability. All the mucus samples showed a similar decomposition pattern: about 80% of total organic carbon (TOC) in the mucus was mineralized within 1 month, while some mucus was slowly decomposed over the 1 year. Regression analysis using an exponential curve considering three degradability pools (labile, semilabile, and refractory) fitted the changes of the TOC concentrations very well ( r 2 > 0.99). Compiling the data on the two coral species, the labile organic C in the coral mucus had mineralization rates of 10-18% d-1 and accounted for 79-87% of the initial TOC in the mucus. Semilabile organic C had mineralization rates of 0.3-1.6% d-1 and accounted for 11-18% of the initial TOC. Refractory organic C accounted for 6% at most. These results suggest that not all coral mucus is rapidly decomposed by bacteria but some mucus remains as semilabile and refractory organic matter for several months.

  9. An Autoregulatory Mechanism Governing Mucociliary Transport Is Sensitive to Mucus Load

    PubMed Central

    Liu, Linbo; Shastry, Suresh; Byan-Parker, Suzanne; Houser, Grace; K. Chu, Kengyeh; Birket, Susan E.; Fernandez, Courtney M.; Gardecki, Joseph A.; Grizzle, William E.; Wilsterman, Eric J.; Sorscher, Eric J.; Rowe, Steven M.

    2014-01-01

    Mucociliary clearance, characterized by mucus secretion and its conveyance by ciliary action, is a fundamental physiological process that plays an important role in host defense. Although it is known that ciliary activity changes with chemical and mechanical stimuli, the autoregulatory mechanisms that govern ciliary activity and mucus transport in response to normal and pathophysiological variations in mucus are not clear. We have developed a high-speed, 1-μm-resolution, cross-sectional imaging modality, termed micro-optical coherence tomography (μOCT), which provides the first integrated view of the functional microanatomy of the epithelial surface. We monitored invasion of the periciliary liquid (PCL) layer by mucus in fully differentiated human bronchial epithelial cultures and full thickness swine trachea using μOCT. We further monitored mucociliary transport (MCT) and intracellular calcium concentration simultaneously during invasion of the PCL layer by mucus using colocalized μOCT and confocal fluorescence microscopy in cell cultures. Ciliary beating and mucus transport are up-regulated via a calcium-dependent pathway when mucus causes a reduction in the PCL layer and cilia height. When the load exceeds a physiological limit of approximately 2 μm, this gravity-independent autoregulatory mechanism can no longer compensate, resulting in diminished ciliary motion and abrogation of stimulated MCT. A fundamental integrated mechanism with specific operating limits governs MCT in the lung and fails when periciliary layer compression and mucus viscosity exceeds normal physiologic limits. PMID:24937762

  10. Preliminary Results on the Influence of Engineered Artificial Mucus Layer on Phonation

    ERIC Educational Resources Information Center

    Döllinger, Michael; Gröhn, Franziska; Berry, David A.; Eysholdt, Ulrich; Luegmair, Georg

    2014-01-01

    Purpose: Previous studies have confirmed the influence of dehydration and an altered mucus (e.g., due to pathologies) on phonation. However, the underlying reasons for these influences are not fully understood. This study was a preliminary inquiry into the influences of mucus architecture and concentration on vocal fold oscillation. Method: Two…

  11. Investigation of mucus transport in an idealized lung airway model using multiphase CFD analysis

    NASA Astrophysics Data System (ADS)

    Rajendran, Rahul; Banerjee, Arindam

    2015-11-01

    Mucus, a Bingham fluid is transported in the pulmonary airways by consistent beating of the cilia and exhibits a wide range of physical properties in response to the core air flow and various pathological conditions. A better understanding of the interfacial instability is required as it plays a crucial role in gas transport, mixing, mucus clearance and drug delivery. In the current study, mucus is modelled as a Newtonian fluid and the two phase gas-liquid flow in the airways is investigated using an inhomogeneous Eulerian-Eulerian approach. The complex interface between the phases is tracked using the conventional VOF (Volume of Fluid) method. Results from our CFD simulations which are performed in idealized single and double bifurcation geometries will be presented and the influence of airflow rate, mucus layer thickness, mucus viscosity, airway geometry (branching & diameter) and surface tension on mucus flow behavior will be discussed. Mean mucus layer thickness, pressure drop due to momentum transfer & increased airway resistance, mucus transport speed and the flow morphology will be compared to existing experimental and theoretical data.

  12. Materials Adherence Experiment: Technology

    SciTech Connect

    Jenkins, P.P.; Landis, G.A.; Oberle, L.G.

    1997-12-31

    NASA`s Mars Pathfinder mission, launched December 4, 1996, reflects a new philosophy of exploiting new technologies to reduce mission cost and accelerate the pace of space exploration. Pathfinder will demonstrate a variety of new technologies aimed at reducing the cost of Mars exploration. Chief among these will be the demonstration of a solar-powered spacecraft on the surface of Mars. The Materials Adherence Experiment on Pathfinder was designed to measure the degradation of solar arrays due to dust settling out of the atmosphere and blocking light to the solar array, lowering the array power output.

  13. Efficient mucus permeation and tight junction opening by dissociable "mucus-inert" agent coated trimethyl chitosan nanoparticles for oral insulin delivery.

    PubMed

    Liu, Min; Zhang, Jian; Zhu, Xi; Shan, Wei; Li, Lian; Zhong, Jiaju; Zhang, Zhirong; Huang, Yuan

    2016-01-28

    Oral administration of protein drugs is greatly impeded by the lack of drug carriers that can efficiently overcome the absorption barriers of mucosa tissue, which consists of not only epithelium but also a blanket of mucus gel. We herein report a novel self-assembled nanoparticle (NP) platform for oral delivery of insulin by facilitating the efficient permeation through both of these two barriers. The NP possesses a core composed of insulin and trimethyl chitosan (TMC), and a dissociable "mucus-inert" hydrophilic coating of N-(2-hydroxypropyl) methacrylamide copolymer (pHPMA) derivative. The NPs exhibited free Brownian motion and excellent permeability in mucus, which enabled the access of the NP core to the epithelial cell surface underneath the mucus. Moreover, investigation of NP behavior showed that the pHPMA molecules started to dissociate as the NP permeates through mucus, and the TMC NP core was then exposed to facilitate transepithelial transport via paracellular pathway. The pHPMA coating significantly improved transepithelial transport of TMC-based NP and their ability to open tight junctions between the mucus-secreting epithelial cells. Moreover, in diabetic rats, pHPMA coated NPs generated a prominent hypoglycemic response following oral administration, and exhibited a relative bioavailability 2.8-fold higher than that of uncoated TMC-based NPs. Our study provided the evidence of using pHPMA as "mucus-inert" agent to enhance mucus permeation of TMC-based NPs, and validated a novel strategy to overcome the multiple absorption barriers using NP platform with dissociable hydrophilic coating and TMC-based core possessing tight junction-opening ability. PMID:26686663

  14. Adherence in the CAPRISA 004 Tenofovir Gel Microbicide Trial

    PubMed Central

    Mansoor, Leila E

    2014-01-01

    High adherence is key to microbicide effectiveness. Here we provide a description of adherence interventions and the adherence rates achieved in the CAPRISA 004 Tenofovir Gel Trial. Adherence support for the before-and-after dosing strategy (BAT 24) was provided at enrolment and at each monthly study visit. This initially comprised individual counselling and was replaced midway by a structured theory-based adherence support program (ASP) based on motivational interviewing. The 889 women were followed for an average of 18 months and attended a total of 17031 monthly visits. On average women reported 5 sex acts and returned 5.9 empty applicators per month. The adherence rate based on applicator count in relation to all reported sex acts was 72.2% compared to the 82.0% self-reported adherence during the last sex act. Adherence support activities, which achieve levels of adherence similar to or better than those achieved by the CAPRISA 004 ASP, will be critical to the success of future microbicide trials. PMID:24643315

  15. Assessing adherence in Thai patients taking combination antiretroviral therapy.

    PubMed

    Kerr, S J; Avihingsanon, A; Putcharoen, O; Chetchotisakd, P; Layton, M; Ubolyam, S; Ruxrungtham, K; Cooper, D A; Phanuphak, P; Duncombe, C

    2012-03-01

    In settings where medications and viral load (VL) monitoring are limited by cost, clinicians need reliable ways to assess patient adherence to therapy. We assessed sensitivity and specificity of two self-reported adherence tools (a visual analogue scale [VAS] and the CASE [Center for Adherence Support Evaluation] adherence index), against a standard of detectable VL, with 288 patients from three sites in Thailand. We also assessed predictors of non-adherence. The sensitivity and specificity of the VAS <95% and CASE adherence index ≤11 against a VL >50 copies/mL were 26% and 90%, 19% and 95%, respectively. Against a VL ≥1000 copies/mL sensitivities increased to 55% and 36%, respectively, and specificities were unchanged. Attending a clinic not staffed by HIV specialists (odds ratio [OR] 3.14; 95% confidence interval [CI] 1.19-8.34) and being educated to primary school level or less (OR 2.24; 95% CI 1.01-4.94) were associated with self-reported adherence <95% on the VAS in multivariate analysis. Adherence assessed by the VAS was a more accurate predictor of detectable VL. Policy-makers in resource-limited settings should ensure that treatment centres are staffed with well-trained personnel aware of the importance of good patient adherence. PMID:22581867

  16. A microfluidic in vitro system for the quantitative study of the stomach mucus barrier function.

    PubMed

    Li, Leon; Lieleg, Oliver; Jang, Sae; Ribbeck, Katharina; Han, Jongyoon

    2012-10-21

    In the stomach, a layer of gastric mucus protects the epithelial cells of the stomach wall against damage by the acidic digestive juices in the gastric lumen. Despite considerable research, the biophysical mechanisms for this acid barrier are not understood. We present an in vitro microfluidic tool to characterize the stomach acid barrier, in which purified mucin polymers are "secreted" against an acidic zone on chip, mimicking the in vivo secretion of gastric mucus into an acidic stomach lumen. This device reconstitutes both the H(+) concentration gradient and outward flow environment of the mucus layer in vivo. Our experiments demonstrate that a continuously secreted mucin layer hinders acid diffusion, suggesting novel insights into the barrier role of mucins. More broadly, our system may serve as a platform tool for studying the barrier functions provided by mucus layers in the body and for studying mucus drug interactions. PMID:22878692

  17. Mucus Barriers to Microparticles and Microbes are Altered in Hirschsprung's Disease.

    PubMed

    Yildiz, Hasan M; Carlson, Taylor L; Goldstein, Allan M; Carrier, Rebecca L

    2015-05-01

    Mucus forms a protective hydrogel layer over the intestinal epithelium, presenting a selective and robust barrier to the uptake of particulates and microbe invasion. Disease can alter mucus production and composition, thus potentially modifying mucosal barrier properties. Hirschsprung's disease (HD) is a developmental abnormality of the nervous system often complicated by intestinal infection. An investigation of colonic mucus barrier properties in an HD animal model, endothelin receptor B mutant mice, revealed significantly reduced microsphere (passive) and microbe (active) transport rates (7-fold and 3.6-fold, respectively, in proximal colonic mucus) relative to wild-type. Transport differences were evident in both the ganglionic and aganglionic colon segments, in agreement with the risk of HD-associated enterocolitis after surgery to remove aganglionic colon segments. The development of therapies aimed at altering colonic mucus barrier properties could be explored towards preventing the onset of enterocolitis in HD. PMID:25644515

  18. Mucus Barriers to Microparticles and Microbes are Altered in Hirschprung’s Disease

    PubMed Central

    Yildiz, Hasan M.; Carlson, Taylor L.; Goldstein, Allan M.; Carrier, Rebecca L.

    2015-01-01

    Mucus forms a protective hydrogel layer over the intestinal epithelium, presenting a selective and robust barrier to the uptake of particulates and microbe invasion. Disease can alter mucus production and composition, thus potentially modifying mucosal barrier properties. Hirschsprung’s disease (HD) is a developmental abnormality of the nervous system often complicated by intestinal infection. An investigation of colonic mucus barrier properties in an HD animal model, endothelin receptor B mutant mice, revealed significantly reduced microsphere (passive) and microbe (active) transport rates (7-fold and 3.6-fold, respectively, in proximal colonic mucus) relative to wild-type. Transport differences were evident in both the ganglionic and aganglionic colon segments, in agreement with the risk of Hirschsprung’s disease-associated enterocolitis after surgery to remove aganglionic colon segments. The development of therapies aimed at altering colonic mucus barrier properties could be explored towards preventing the onset of enterocolitis in Hirschsprung’s disease. PMID:25644515

  19. Activation of immune responses in mice by an oral administration of bunching onion (Allium fistulosum) mucus.

    PubMed

    Ueda, Hiroshi; Takeuchi, Atsuko; Wako, Tadayuki

    2013-01-01

    Bunching onion [Allium fistulosum L. (Liliaceae)] secretes mucus in the cavities of its green leaves. The effects of the mucus, which is consumed as food, were examined. The mucus augmented the production of tumor necrosis factor (TNF)-α and monocyte chemotactic protein (MCP)-1 from RAW 264 cells and of interleukin (IL)-12 from J774.1 cells; however, extracts from green leaves and white sheaths did not. An oral administration of this mucus to mice augmented the immune functions of peritoneal cells by increasing TNF-α and IL-12 production and phagocytosis. It also augmented interferon (IFN)-γ production from spleen cells and natural killer (NK) activity. These results suggest that an oral administration of the A. fistulosum mucus can enhance natural immunity. PMID:24018671

  20. Screening of an E. coli O157:H7 Bacterial Artificial Chromosome Library by Comparative Genomic Hybridization to Identify Genomic Regions Contributing to Growth in Bovine Gastrointestinal Mucus and Epithelial Cell Colonization

    PubMed Central

    Bai, Jianing; McAteer, Sean P.; Paxton, Edith; Mahajan, Arvind; Gally, David L.; Tree, Jai J.

    2011-01-01

    Enterohemorrhagic E. coli (EHEC) O157:H7 can cause serious gastrointestinal and systemic disease in humans following direct or indirect exposure to ruminant feces containing the bacterium. The main colonization site of EHEC O157:H7 in cattle is the terminal rectum where the bacteria intimately attach to the epithelium and multiply in the intestinal mucus. This study aimed to identify genomic regions of EHEC O157:H7 that contribute to colonization and multiplication at this site. A bacterial artificial chromosome (BAC) library was generated from a derivative of the sequenced E. coli O157:H7 Sakai strain. The library contains 1152 clones averaging 150 kbp. To verify the library, clones containing a complete locus of enterocyte effacement (LEE) were identified by DNA hybridization. In line with a previous report, these did not confer a type III secretion (T3S) capacity to the K-12 host strain. However, conjugation of one of the BAC clones into a strain containing a partial LEE deletion restored T3S. Three hundred eighty-four clones from the library were subjected to two different selective screens; one involved three rounds of adherence assays to bovine primary rectal epithelial cells while the other competed the clones over three rounds of growth in bovine rectal mucus. The input strain DNA was then compared with the selected strains using comparative genomic hybridization (CGH) on an E. coli microarray. The adherence assay enriched for pO157 DNA indicating the importance of this plasmid for colonization of rectal epithelial cells. The mucus assay enriched for multiple regions involved in carbohydrate utilization, including hexuronate uptake, indicating that these regions provide a competitive growth advantage in bovine mucus. This BAC-CGH approach provides a positive selection screen that complements negative selection transposon-based screens. As demonstrated, this may be of particular use for identifying genes with redundant functions such as adhesion and carbon

  1. Mechanisms of cilia-driven transport in the airways in the absence of mucus.

    PubMed

    Bermbach, Saskia; Weinhold, Karina; Roeder, Thomas; Petersen, Frank; Kugler, Christian; Goldmann, Torsten; Rupp, Jan; König, Peter

    2014-07-01

    Airway mucus is thought to be required for the clearance of inhaled particles by mucociliary transport, but this view has recently been challenged. To test if mucus is necessary for cilia-driven particle transport, we removed mucus from murine and human ex vivo airway preparations by thorough rinsing with buffer with or without additional dithiothreitol washing. The transport of particles with diameters of 4.5 μm, 200 nm, and 40 nm and of bacteria was analyzed by video microscopy. Complete removal of mucus was verified by wheat germ agglutinin staining and by scanning electron microscopy. In the absence of mucus, we observed efficient transport of particles and bacteria by direct cilia-mediated propulsion or via fluid flow generated by ciliary beating. Virus-sized particles had the tendency to attach to cilia. Because direct contact of particles with ciliated cells occurs in the absence of mucus, we examined if this direct interaction changes epithelial function. Neither bacteria- nor LPS-induced nuclear translocation of NF-κB p65 in ciliated cells occurred, indicating that mere contact between ciliated cells and bacteria during transport does not activate the epithelium. Attachment of virus-sized particles to cilia could induce mucus release and/or increase the ciliary beat frequency. Our results indicate that cilia-driven transport of particles with various sizes is possible in murine and human airways without the presence of mucus. If mucus-free transport fails, the epithelium can react by releasing mucus or increasing the ciliary beat frequency to maintain particle transport. PMID:24467665

  2. Adherence of Clostridium thermocellum to cellulose.

    PubMed Central

    Bayer, E A; Kenig, R; Lamed, R

    1983-01-01

    The adherence of Clostridium thermocellum, a cellulolytic, thermophilic anaerobe, to its insoluble substrate (cellulose) was studied. The adherence phenomenon was determined to be selective for cellulose. The observed adherence was not significantly affected by various parameters, including salts, pH, temperature, detergents, or soluble sugars. A spontaneous adherence-defective mutant strain (AD2) was isolated from the wild-type strain YS. Antibodies were prepared against the bacterial cell surface and rendered specific to the cellulose-binding factor (CBF) by adsorption to mutant AD2 cells. By using these CBF-specific antibodies, crossed immunoelectrophoresis of cell extracts revealed a single discrete precipitation peak in the parent strain which was absent in the mutant. This difference was accompanied by an alteration in the polypeptide profile whereby sonicates of strain YS contained a 210,000-molecular-weight band which was missing in strain AD2. The CBF antigen could be removed from cell extracts by adsorption to cellulose. A combined gel-overlay--immunoelectrophoretic technique demonstrated that the cellulose-binding properties of the CBF were accompanied by carboxymethylcellulase activity. During the exponential phase of growth, a large part of the CBF antigen and related carboxymethylcellulase activity was associated with the cells of wild-type strain YS. However, the amounts decreased in stationary-phase cells. Cellobiose-grown mutant AD2 cells lacked the cell-associated CBF, but the latter was detected in the extracellular fluid. Increased levels of CBF were observed when cells were grown on cellulose. In addition, mutant AD2 regained cell-associated CBF together with the property of cellulose adherence. The presence of the CBF antigen and related adherence characteristics appeared to be a phenomenon common to other naturally occurring strains of this species. Images PMID:6630152

  3. Adhering heat-killed human Lactobacillus acidophilus, strain LB, inhibits the process of pathogenicity of diarrhoeagenic bacteria in cultured human intestinal cells.

    PubMed

    Coconnier, M H; Bernet, M F; Chauvière, G; Servin, A L

    1993-12-01

    Heat-killed L. acidophilus, strain LB, was tested for its ability to adhere in vitro onto human enterocyte-like Caco-2 and muco-secreting HT29-MTX cells in culture. The heat-killed LB bacteria exhibited a high adhesive property. A diffuse pattern of adhesion was observed to the undifferentiated cells, the apical brush border of the enterocytic cells, and to the mucus layer that covered the surface of the mucus-secreting cells. The inhibitory effect of heat-killed LB organisms against the human intestinal Caco-2 cell-adhesion and cell-invasion by a large variety of diarrhoeagenic bacteria was investigated. The following dose-dependent inhibitions were obtained: (i) against the cell-association of enterotoxigenic, diffusely-adhering and enteropathogenic Escherichia coli, Listeria monocytogenes, Yersinia pseudotuberculosis, and Salmonella typhimurium; (ii) against the cell-invasion by enteropathogenic Escherichia coli, Yersinia pseudotuberculosis, Listeria monocytogenes and Salmonella typhimurium. PMID:8188996

  4. Adherence to highly active antiretroviral therapy in HIV-infected inmates.

    PubMed

    Inés, Sandra M; Moralejo, Leticia; Marcos, Miguel; Fuertes, Aurelio; Luna, Guillermo

    2008-03-01

    Adherence to highly active antiretroviral therapy (HAART) has been scarcely studied in correctional settings. Our study aims to evaluate the relationship between adherence and virological outcome and to determine factors related to adherence in correctional settings. A cross-sectional retrospective study was performed in Topas prison (Salamanca, Spain). 50 inmates starting HAART were studied. Adherence was estimated through a self-report questionnaire and variables related to adherence (covering individual factors, the illness itself and the therapeutic regimen) were recorded. HIV-RNA levels and CD4 lymphocyte count were measured before starting therapy and six months after. Statistical analysis was performed using univariate and multivariate methods. 21 inmates (42%) were considered adherent and 29 (58%) were non-adherent. Adherence to treatment, as measured by our questionnaire, was the only significant and independent factor associated with an undetectable viral load at six months of therapy. Five variables were significantly associated with adherence to treatment, four of them as predictor factors for good adherence: an active occupation inside prison, the absence of HIV-related symptoms, a good or average acceptance of treatment, and a higher academic background; previous injection drug use as a risk factor for HIV transmission was associated with non-adherence. A simple self-report questionnaire may be useful for assessing adherence in prison inmates. Recognizing variables associated with adherence is essential to identify prisoners at high risk of being non-adherents in order to develop strategies for improving compliance. PMID:18336264

  5. Heterogeneity of airways mucus: variations in the amounts and glycoforms of the major oligomeric mucins MUC5AC and MUC5B.

    PubMed Central

    Kirkham, Sara; Sheehan, John K; Knight, David; Richardson, Paul S; Thornton, David J

    2002-01-01

    Respiratory mucus contains a mixture of gel-forming mucins but the functional significance of these different mucin species is unknown. To help gain a better understanding of mucus in airways we therefore need to ascertain the concentration of each of the gel-forming mucins within respiratory secretions. Thus the aim of this study was to determine the amounts of specific gel-forming mucins directly from solubilized secretions of the airways and purified mucin preparations. We investigated the feasibility of using direct-binding ELISA employing mucin-specific antisera but were unable to obtain reliable data owing to interference with the immobilization of the mucins on the assay surface by 6 M urea and high levels of non-mucin proteins. We therefore developed an alternative approach based on quantitative Western blotting after agarose-gel electrophoresis, which was not subject to these problems. Here we demonstrate that this procedure provides reliable and reproducible data and have employed it to determine the amounts of the MUC2, MUC5AC and MUC5B mucins in saline-induced sputa from healthy airways and spontaneous sputa from asthmatic airways. Additionally we have used this procedure to analyse these glycoproteins in mucin preparations purified from cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) mucus. Our findings indicate that MUC5AC and MUC5B are the major oligomeric mucins and that airways mucus contains variable amounts of these glycoproteins. By contrast, the MUC2 mucin comprised, at most, only 2.5% of the weight of the gel-forming mucins, indicating that MUC2 is a minor component in sputum. Finally, we show that the amounts and glycosylated variants of the MUC5AC and MUC5B mucins can be altered significantly in diseased airways with, for instance, an increase in the low-charge form of the MUC5B mucin in CF and COPD mucus. PMID:11802783

  6. Rationale and design of the Primary pREvention strategies at the community level to Promote Adherence of treatments to pREvent cardiovascular diseases trial number (CTRI/2012/09/002981)

    PubMed Central

    Fathima, Farah N.; Joshi, Rajnish; Agrawal, Twinkle; Hegde, Shailendra; Xavier, Denis; Misquith, Dominic; Chidambaram, N.; Kalantri, S. P.; Chow, Clara; Islam, Shofiqul; Devereaux, P. J.; Gupta, Rajeev; Pais, Prem; Yusuf, Salim

    2013-01-01

    Introduction Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality in low-income countries including India. There is a need for effective, low-cost methods to prevent CVDs in rural India. One strategy is to identify and implement interventions at high-risk individuals using community health workers (CHWs). There is a paucity of CHW-based CVD intervention trials from low-income countries. Methods We designed a multicenter, household-level, cluster-randomized trial with 1:1 allocation to intervention and control arms. The CHWs undertook a door-to-door survey and screened 5,699 households in 28 villages from 3 rural regions in India to identify at-risk households. The households were defined as those with ≥1 individual aged ≥35 years and at moderate or high risk for CVD based on the non–laboratory-based National Health and Nutrition Examination Survey score. All at-risk individuals were invited to attend a physician-led village clinic that provided a CVD risk reduction prescription and education about target risk factor levels for CVD control. All households in which at least 1 member at moderate to high risk for CVD had received a risk reduction prescription were eligible for randomization. Households randomized to the CHW-based intervention will receive 1 household visit by a CHW every 2 months, for 12 months. During these visits, CHWs will measure blood pressure, ascertain and reinforce adherence to prescribed therapies, and modify therapy to meet targets. Households randomized to the control arm do not receive CHW visits. At 12 months after randomization, we will evaluate 2 primary outcomes of systolic blood pressure and adherence to antihypertensive drugs and secondary outcomes of INTERHEART risk score, body mass index, and waist-to-hip ratios. At 18 to 24 months after randomization and 6 to 12 months after the last intervention, we will record these outcomes to evaluate sustainability of intervention. Results Community health

  7. Rat and human colonic mucins bind to and inhibit adherence lectin of Entamoeba histolytica.

    PubMed Central

    Chadee, K; Petri, W A; Innes, D J; Ravdin, J I

    1987-01-01

    Establishment of adherence by Entamoeba histolytica is mediated by a 170-kD Gal/GalNAc inhibitable lectin and is required for cytolysis and phagocytosis of mammalian target cells. We studied the biochemical mechanisms of the in vitro interaction between rat and human colonic mucins and axenic E. histolytica trophozoites. Crude mucus prevented amebic adherence to Chinese hamster ovary (CHO) cells by up to 70%. Purification of the colonic mucins by Sepharose 4B chromatography, nuclease digestion, and cesium chloride gradient centrifugation resulted in a 1,000-fold enrichment of the inhibitory mucins. Purified rat mucin inhibited amebic adherence to and cytolysis of homologous rat colonic epithelial cells. Oxidation and enzymatic cleavage of rat mucin Gal and GalNAc residues completely abrogated mucin inhibition of amebic adherence. The binding of rat 125I-mucin to amebae was galactose specific, saturable, reversible, and pH dependent. A monoclonal antibody specific for the 170-kD amebic Gal/GalNAc lectin completely inhibited the binding of rat 125I-mucin. Rat mucin bound to Affigel affinity purified the amebic lectin from conditioned medium. Colonic mucin glycoproteins act as an important host defense by binding to the parasite's adherence lectin, thus preventing amebic attachment to and cytolysis of host epithelial cells. Images PMID:2890655

  8. Occurrence of organo-arsenicals in jellyfishes and their mucus.

    PubMed

    Hanaoka, K; Ohno, H; Wada, N; Ueno, S; Goessler, W; Kuehnelt, D; Schlagenhaufen, C; Kaise, T; Irgolic, K J

    2001-08-01

    Water-soluble arsenic compound fractions were extracted from seven species of jellyfishes and subjected to analysis by high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) for arsenicals. A low content of arsenic was found to be the characteristic of jellyfish. Arsenobetaine (AB) was the major arsenic compound without exception in the tissues of the jellyfish species and mucus-blobs collected from some of them. Although the arsenic content in Beroe cucumis, which preys on Bolinopsis mikado, was more than 13 times that in B. mikado, the chromatograms of these two species were similar in the distribution pattern of arsenicals. The nine species of jellyfishes including two species treated in the previous paper can be classified into arsenocholine (AC)-rich and AC-poor species. Jellyfishes belonging to Semaostamae were classified as AC-rich species. PMID:11482664

  9. [Adherence to psychopharmacological treatment: Psychotherapeutic strategies to enhance adherence].

    PubMed

    Lencer, R; Korn, D

    2015-05-01

    Effective psychopharmacological medication with good tolerability represents the cornerstone of treatment for severe mental illness; however, the 1-year adherence rates are only approximately 50%. The term adherence emphasizes the collaborative responsibility of the clinician and the patient for a positive treatment outcome. Reasons for non-adherence are manifold and include patient-specific factors, such as self-stigmatization, lack of social and familial support, cognitive impairment and substance use besides insufficient effectiveness and the occurrence of side effects of the psychotropic drugs. To enhance adherence, both clinician and patient have to fully understand all the reasons for and against adherence to medication before a collaborative decision is made on future long-term treatment. A positive attitude towards medication critically depends on whether patients feel that the medication supports the attainment of the individual goals. PMID:25903501

  10. Pseudomonas aeruginosa outer membrane adhesins for human respiratory mucus glycoproteins.

    PubMed Central

    Carnoy, C; Scharfman, A; Van Brussel, E; Lamblin, G; Ramphal, R; Roussel, P

    1994-01-01

    The attachment of Pseudomonas aeruginosa to human respiratory mucus represents an important step in the development of lung infection, especially in cases of cystic fibrosis. For this purpose, microtiter plate adhesion assays have been developed and have suggested that nonpilus adhesins of P. aeruginosa are the most important ones for binding to human respiratory mucins. In order to characterize these mucin-binding adhesins, outer membrane proteins (OMP) from two adhesive strains, 1244-NP and PAK-NP, and their poorly adhesive rpoN mutants, 1244-N3 and PAK-N1, were prepared by a mild extraction with Zwittergent 3-14. Mucin-binding adhesins were detected after polyacrylamide gel electrophoresis and blotting of the OMP on nitrocellulose replicas, using human bronchial mucins labeled with 125I. The binding properties of these OMP with lactotransferrin, another glycoprotein abundant in respiratory mucus, were also studied. Radiolabeled mucins detected four bands at 48, 46, 28, and 25 kDa with strain PAK-NP. With the nonmucoid strain 1244-NP, five bands were observed at 48, 46, 42, 28, and 25 kDa. The bands at 48 and 25 kDa were also visualized by radiolabeled lactotransferrin. These bands were partially or completely displaced by nonradiolabeled respiratory mucin glycopeptides but not by tetramethylurea, suggesting that they recognized carbohydrate sites. In contrast, the poorly adhesive strains showed weakly binding bands. These results demonstrate that outer membranes from two different nonpiliated P. aeruginosa strains express multiple adhesins with an affinity for human respiratory mucins and/or lactotransferrin. Images PMID:8168955

  11. Effect of viscosity on metachrony in mucus propelling cilia.

    PubMed

    Gheber, L; Korngreen, A; Priel, Z

    1998-01-01

    In the present work we report that increasing the viscosity of the medium caused not only a decrease in the ciliary beat frequency but also changes in the metachrony and correlation between cilia. The study was performed using double and triple simultaneous photoelectric measurements on cultured ciliary cells from the frog esophagus in the viscosity range of 1-2,000 cp. We observed that increasing the viscosity intensified the fluctuations in all the measured parameters. Ciliary beat frequency decreased moderately. Even at quite high viscosities (circa 2000 cp.), cilia were still active with beating frequencies of 3-5 Hz. In addition, the degree of correlation between cilia parallel to the effective stroke direction (ESD) decreased, while that perpendicular to the ESD at a low range of viscosities remained unchanged and even increased at high viscosities. Medium viscosities in the range of 30-1,500 cp. altered the metachronal wave properties of cultured frog esophagus. The metachronal wavelength increased by up to 50%, and the wave direction changed towards more orthoplectic type of coordination. According to our recently suggested model [Gheber and Priel, 1990: Cell Motil. Cytoskeleton 16:167-181], these effects can be explained by a decrease in the temporal asymmetry of the ciliary beat. Since similar results were observed in water propelling cilia of Paramecium subjected to medium viscosity ranges of up to 40 cp. [Machemer, 1972: J. Exp. Biol. 57:239-259], we conclude that hydrodynamic interactions govern the metachronal wave properties of both mucus and water propelling cilia, though mucus propelling cilia, with their better adaptation to increased load, are affected at much higher viscosities than water propelling cilia. PMID:9453710

  12. Investigation of mucus obtained from different fish species on the acute pain induced with scalpel incision in paw of rats

    PubMed Central

    Cetin, Nihal; Suleyman, Bahtiyar; Kuyrukluyildiz, Ufuk; Nalkiran, Hatice Sevim; Kiran, Altan; Gencoglu, Songul; Duzgun, Ahmet; Kurtoglu, Ilker Zeki; Yarali, Oguzhan; Gul, Mehmet Ali; Suleyman, Halis

    2015-01-01

    No comparative study could be found for the analgesic activity of mucuses from the Oncorhynchus mykiss (OM), Salvelinus fontinalis (SF), Salmo coruhensis (SC), Acipenser gueldenstaedtii (AG), and Acipenser baerii (AB) fish species in the literature. We aimed to investigate the effects of mucuses obtained from the abovementioned fish species on scalpel incision-induced pain in the rat paw and to examine the role of oxidant/antioxidant parameters and COX-2 gene expression in the analgesic activities. Animals were divided into groups: SIC (scalpel incision; SI), SIDS (SI+25 mg/kg diclofenac sodium), SOM (SI+25 mg/kg OM mucus), SFM (SI+25 mg/kg SF mucus), SCM (SI+25 mg/kg SC mucus), SAgM (SI+25 mg/kg AG mucus), SAbM (SI+25 mg/kg AB mucus), and HG (healthy). The paw pain thresholds were measured with a Basile algesimeter before and after diclofenac sodium (DS) or mucus administration, and then the rats were euthanized with thiopental sodium. Oxidant/antioxidant and COX-2 gene expression parameters were measured in paw tissues. OM, SC, AG, and AB fish mucuses could not decrease the SI-induced pain. However, SF fish mucus prevented this pain by 69% after the first hour and by 58.3% after the third hour. DS was shown to suppress pain more weakly than SF, preventing the pain by 62.1% and 50.0% after the first and third hours, respectively. SF mucus and DS significantly inhibited increase of COX-2 gene expression, while other fish mucuses could not. None of the fish mucuses except SF mucus in conjunction with DS could significantly inhibit the increase in oxidant parameters and decrease in antioxidants. SF fish mucus should be comparatively assessed in clinical practice for treatment of postoperative pain. PMID:26490740

  13. Evaluating therapist adherence in motivational interviewing by comparing performance with standardized and real patients

    PubMed Central

    Imel, Zac E.; Baldwin, Scott A.; Baer, John; Hartzler, Bryan; Dunn, Christopher; Rosengren, David; Atkins, David C.

    2014-01-01

    Objective The goal of measuring therapist adherence is to determine if a therapist can perform a given treatment. Yet the evaluation of therapist behaviors in most clinical trials is limited. Typically, randomized trials have few therapists and minimize therapist variability through training and supervision. Furthermore, therapist adherence is confounded with uncontrolled differences in patients across therapists. Consequently, the extent to which adherence measures capture differences in actual therapist adherence versus other sources of variance is unclear. Method We estimated intra-class correlations (ICCs) for therapist adherence in sessions with real and standardized patients (RPs and SPs), using ratings from a motivational interviewing (MI) dissemination trial (Baer et al., 2009) in which 189 therapists recorded 826 sessions with both patient types. We also examined the correlations of therapist adherence between SP and RP sessions, and the reliability of therapist level adherence scores with generalizability coefficients (GCs). Results ICC’s for therapist adherence were generally large (average ICC for SPs = 0.44, RPs = 0.40), meaning that a given therapist’s adherence scores were quite similar across their sessions. Both ICCs and GCs were larger for SP sessions as compared to RPs on global measures of MI adherence, such as Empathy and MI Spirit. Correlations between therapist adherence with real and standardized patients were moderate to large on three of five adherence measures. Conclusion Differences in therapist-level adherence ratings were substantial, and standardized patients have promise as tools to evaluate therapist behavior. PMID:24588405

  14. Interventional tools to improve medication adherence: review of literature

    PubMed Central

    Costa, Elísio; Giardini, Anna; Savin, Magda; Menditto, Enrica; Lehane, Elaine; Laosa, Olga; Pecorelli, Sergio; Monaco, Alessandro; Marengoni, Alessandra

    2015-01-01

    Medication adherence and persistence is recognized as a worldwide public health problem, particularly important in the management of chronic diseases. Nonadherence to medical plans affects every level of the population, but particularly older adults due to the high number of coexisting diseases they are affected by and the consequent polypharmacy. Chronic disease management requires a continuous psychological adaptation and behavioral reorganization. In literature, many interventions to improve medication adherence have been described for different clinical conditions, however, most interventions seem to fail in their aims. Moreover, most interventions associated with adherence improvements are not associated with improvements in other outcomes. Indeed, in the last decades, the degree of nonadherence remained unchanged. In this work, we review the most frequent interventions employed to increase the degree of medication adherence, the measured outcomes, and the improvements achieved, as well as the main limitations of the available studies on adherence, with a particular focus on older persons. PMID:26396502

  15. Mucus permeating carriers: formulation and characterization of highly densely charged nanoparticles.

    PubMed

    Pereira de Sousa, Irene; Steiner, Corinna; Schmutzler, Matthias; Wilcox, Matthew D; Veldhuis, Gert J; Pearson, Jeffrey P; Huck, Christian W; Salvenmoser, Willi; Bernkop-Schnürch, Andreas

    2015-11-01

    The GI mucus layer represents a significant block to drug carriers absorption. Taking an example from nature, virus-mimicking nanoparticles (NPs) with highly densely charged surface were designed with the aim to improve their mucus permeation ability. NPs were formulated by combining chitosan with chondroitin sulfate and were characterized by particle size, ζ-potential and hydrophobicity. The interaction occurring between NPs and diluted porcine intestinal mucus was investigated by a new method. Furthermore, the rotating tube technique was exploited to evaluate the NPs permeation ability in fresh undiluted porcine intestinal mucus. NPs (400-500 nm) presenting a slightly positive (4.02 mV) and slightly negative (-3.55 mV) ζ-potential resulted to be hydrophobic and hydrophilic, respectively. On the one hand the hydrophobic NPs undergo physico-chemical changes when incubated with mucus, namely the size increased and the ζ-potential decreased. On the other hand, the hydrophilic NPs did not significantly change size and net charge during incubation with mucus. Both types of NPs showed a 3-fold higher diffusion ability compared to the reference 50/50 DL-lactide/glycolide copolymer NPs (136 nm, -23 mV, hydrophilic). Based on these results, this work gives valuable information for the further design of mucus-penetrating NPs. PMID:25576256

  16. Therapeutic Potential to Modify the Mucus Barrier in Inflammatory Bowel Disease

    PubMed Central

    Sun, Jing; Shen, Xiao; Li, Yi; Guo, Zhen; Zhu, Weiming; Zuo, Lugen; Zhao, Jie; Gu, Lili; Gong, Jianfeng; Li, Jieshou

    2016-01-01

    Recently, numerous studies have shown that disruption of the mucus barrier plays an important role in the exacerbation of inflammatory bowel disease, particularly in ulcerative colitis. Alterations in the mucus barrier are well supported by published data and are widely accepted. The use of fluorescence in situ hybridization and Carnoy’s fixation has revealed the importance of the mucus barrier in maintaining a mutualistic relationship between host and bacteria. Studies have raised the possibility that modulation of the mucus barrier may provide therapies for the disease, using agents such as short-chain fatty acids, prebiotics and probiotics. This review describes changes in the mucus barrier of patients with inflammatory bowel disease and in animal models of the disease. We also review the involvement of the mucus barrier in the exacerbation of the disease and explore the therapeutic potential of modifying the mucus barrier with short-chain fatty acids, prebiotics, probiotics, fatty acid synthase, H2S, neutrophil elastase inhibitor and phophatidyl choline. PMID:26784223

  17. Recurrent respiratory infections in a child with fucosidosis: is the mucus too thin for effective transport?

    PubMed

    Rubin, B K; MacLeod, P M; Sturgess, J; King, M

    1991-01-01

    Fucosidosis is caused by a deficiency of the lysosomal enzyme alpha-L-fucosidase (ALF) leading to an accumulation of glycoproteins in a variety of cells. Infants and young children with this disorder are prone to recurrent sinus and pulmonary infections and often die of pneumonia. We studied the mucociliary and systemic immune function in a 6 year old girl with fucosidosis and recurrent respiratory infections. All measurements of systemic immune function were normal. Sweat chloride was normal when measured on angiokeratotic skin but was greater than 65 mg/L on uninvolved areas. During the placement of tympanic ventilation tubes, tracheal mucus was gently aspirated and a mucosal biopsy was taken. Tracheal mucus transport was not measured. The biopsy material was examined under phase contrast microscopy and revealed ciliated cells with apparently normal beating. TEM of these cells showed a characteristic pattern of vacuoles in the cytoplasm as described in other tissues from patients with fucosidosis. Ciliary ultrastructure was normal. Mucus viscoelasticity was measured in a magnetic microrheometer. The loss tangent was 2 SD above the mean for normal mucus and mechanical impedance was about 2 SD below the mean. These changes are similar in direction but double in magnitude to what has been described with methacholine administration in dogs. The high compliance of the mucus may be due to incomplete assembly of mucus glycoprotein or to decreased secretion of glycoproteins in respiratory secretions. This leads to mucus that is abnormally watery and thus difficult to clear from the airway. PMID:1896242

  18. Pegylated Polyaspartamide-Polylactide-Based Nanoparticles Penetrating Cystic Fibrosis Artificial Mucus.

    PubMed

    Craparo, Emanuela Fabiola; Porsio, Barbara; Sardo, Carla; Giammona, Gaetano; Cavallaro, Gennara

    2016-03-14

    Here, the preparation of mucus-penetrating nanoparticles for pulmonary administration of ibuprofen in patients with cystic fibrosis is described. A fluorescent derivative of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide is synthesized by derivatization with rhodamine, polylactide, and poly(ethylene glycol), to obtain polyaspartamide-polylactide derivatives with different degrees of pegylation. Starting from these copolymers, fluorescent nanoparticles with different poly(ethylene glycol) content, empty and loaded with ibuprofen, showed spherical shape, colloidal size, slightly negative ζ potential, and biocompatibility toward human bronchial epithelial cells. The high surface poly(ethylene glycol) density of fluorescent nanoparticles and poly(ethylene glycol) brush-like conformation assumed on their surface, conferred to pegylated nanoparticles the mucus-penetrating properties, properly demonstrated by assessing their ability to avoid interactions with mucus components and to penetrate cystic fibrosis artificial mucus. Finally, ibuprofen release profile and uptake capacity within human bronchial epithelial cells in the presence of cystic fibrosis artificial mucus showed how these mucus-penetrating nanoparticles could rapidly diffuse through the mucus barrier reaching the mucosal surface, where they could offer a sustained delivery of ibuprofen at the site of disease. PMID:26866983

  19. Alteration in Pimephales promelas mucus production after exposure to nanosilver or silver nitrate.

    PubMed

    Hawkins, Adam D; Thornton, Cammi; Steevens, Jeffery A; Willett, Kristine L

    2014-12-01

    The fish gill's ability to produce mucus effectively is a critical part of the stress response and protection against xenobiotic toxicity. Adult fathead minnows were exposed to silver nitrate (0.82 µg/L or 13.2 µg/L), polyvinylpyrrolidone-coated silver nanoparticles (11.1 µg/L or 208 µg/L), and citrate-coated silver nanoparticles (10.1 µg/L or 175 µg/L) for 96 h. Mucus concentrations based on glucose as a surrogate were determined at 0 h, 1 h, 2 h, 3 h, 4 h and 24 h after re-dosing each day. Higher mucus production rates following silver treatment were observed at the beginning as compared to controls and compared to after 3 d of exposure. Control fish produced consistent mucus concentrations throughout the exposure (0.62 mg/L and 0.40 mg/L at 24 h and 96 h, respectively). Following 24 h of exposure, all silver treatment groups produced significantly more mucus than controls. Following 96 h of exposure, mucus concentrations in treatment groups were significantly reduced compared with each respective treatment at 24 h. Reduced mucus production following long-term silver exposure could prevent the gills from removing silver, and thus increase toxicity. PMID:25262928

  20. Scalable Method to Produce Biodegradable Nanoparticles that Rapidly Penetrate Human Mucus

    PubMed Central

    Xu, Qingguo; Boylan, Nicholas J.; Cai, Shutian; Miao, Bolong; Patel, Himatkumar; Hanes, Justin

    2013-01-01

    Mucus typically traps and rapidly removes foreign particles from the airways, gastrointestinal tract, nasopharynx, female reproductive tract and the surface of the eye. Nanoparticles capable of rapid penetration through mucus can potentially avoid rapid clearance, and open significant opportunities for controlled drug delivery at mucosal surfaces. Here, we report an industrially scalable emulsification method to produce biodegradable mucus-penetrating particles (MPP). The emulsification of diblock copolymers of poly(lactic-co-glycolic acid) and polyethylene glycol (PLGA-PEG) using low molecular weight (MW) emulsifiers forms dense brush PEG coatings on nanoparticles that allow rapid nanoparticle penetration through fresh undiluted human mucus. In comparison, conventional high MW emulsifiers, such as polyvinyl alcohol (PVA), interrupts the PEG coating on nanoparticles, resulting in their immobilization in mucus owing to adhesive interactions with mucus mesh elements. PLGA-PEG nanoparticles with a wide range of PEG MW (1, 2, 5, and 10 kDa), prepared by the emulsification method using low MW emulsifiers, all rapidly penetrated mucus. A range of drugs, from hydrophobic small molecules to hydrohilic large biologics, can be efficiently loaded into biodegradable MPP using the method described. This readily scalable method should facilitate the production of MPP products for mucosal drug delivery, as well as potentially longer-circulating particles following intravenous administration. PMID:23751567

  1. Towards a versatile technique for tracking nanoparticle-mucus interaction: a step on the road

    NASA Astrophysics Data System (ADS)

    Nafee, N.; Schneider, M.

    2014-02-01

    Respiratory mucus is one of the main barriers for nanoparticle-based pulmonary delivery systems. This holds true especially for lung diseases like cystic fibrosis, where a very tenacious thick mucus layer hinders particle diffusion to the lung epithelium or the target area. Typically, mean square displacement of particles is used for mobility evaluation. In contrast, our objective is to develop a feasible technique to track directed particle penetration as a prerequisite for efficient pulmonary nanotherapy. Therefore, particle diffusion in artificial mucus was monitored based on confocal laser scanning microscopy (CLSM) and particle-mucus interaction was observed. As pharmaceutical relevant and benign materials, solid lipid nanoparticles (SLNs) were prepared by hot-melt emulsification using glyceryl behenate and different stabilizing agents such as poloxamer-407, tween-80, and polyvinyl alcohol (PVA). The diffusion of labeled SLNs in stained artificial sputum representing CF-patient sputum was verified by 3D time laps imaging. Thus, the effect of coating, particle size and mucus viscosity on nanoparticle diffusion was studied. Using image analysis software "Image J", the total fluorescent signal after 30 min in case of poloxamer-coated SLNs was 5 and 100 folds higher than tween- and PVA-coated SLNs, respectively. Nevertheless, increasing mucus viscosity reduced the diffusion of tweencoated SLNs by a factor of 10. Studying particle-mucus interaction by CLSM can be considered a promising and versatile technique.

  2. Prenatal secondhand cigarette smoke promotes Th2 polarization and impairs goblet cell differentiation and airway mucus formation.

    PubMed

    Singh, Shashi P; Gundavarapu, Sravanthi; Peña-Philippides, Juan C; Rir-Sima-ah, Jules; Mishra, Neerad C; Wilder, Julie A; Langley, Raymond J; Smith, Kevin R; Sopori, Mohan L

    2011-11-01

    Parental, particularly maternal, smoking increases the risk for childhood allergic asthma and infection. Similarly, in a murine allergic asthma model, prenatal plus early postnatal exposure to secondhand cigarette smoke (SS) exacerbates airways hyperreactivity and Th2 responses in the lung. However, the mechanism and contribution of prenatal versus early postnatal SS exposure on allergic asthma remain unresolved. To identify the effects of prenatal and/or early postnatal SS on allergic asthma, BALB/c dams and their offspring were exposed gestationally and/or 8-10 wk postbirth to filtered air or SS. Prenatal, but not postnatal, SS strongly increased methacholine and allergen (Aspergillus)-induced airway resistance, Th2 cytokine levels, and atopy and activated the Th2-polarizing pathway GATA3/Lck/ERK1/2/STAT6. Either prenatal and/or early postnatal SS downregulated the Th1-specific transcription factor T-bet and, surprisingly, despite high levels of IL-4/IL-13, dramatically blocked the allergen-induced mucous cell metaplasia, airway mucus formation, and the expression of mucus-related genes/proteins: Muc5ac, γ-aminobutyric acid A receptors, and SAM pointed domain-containing Ets-like factor. Given that SS/nicotine exposure of normal adult mice promotes mucus formation, the results suggested that fetal and neonatal lung are highly sensitive to cigarette smoke. Thus, although the gestational SS promotes Th2 polarization/allergic asthma, it may also impair and/or delay the development of fetal and neonatal lung, affecting mucociliary clearance and Th1 responses. Together, this may explain the increased susceptibility of children from smoking parents to allergic asthma and childhood respiratory infections. PMID:21930963

  3. Improved adherence with contingency management.

    PubMed

    Rosen, Marc I; Dieckhaus, Kevin; McMahon, Thomas J; Valdes, Barbara; Petry, Nancy M; Cramer, Joyce; Rounsaville, Bruce

    2007-01-01

    Contingency management (CM) based interventions that reinforce adherence to prescribed medications have shown promise in a variety of disadvantaged populations. Fifty-six participants with histories of illicit substance use who were prescribed antiretroviral medication but evidenced suboptimal adherence during a baseline assessment were randomly assigned to 16 weeks of weekly CM-based counseling or supportive counseling, followed by 16 additional weeks of data collection and adherence feedback to providers. The CM intervention involved review of data generated by electronic pill-bottle caps that record bottle opening (MEMS) and brief substance abuse counseling. CM participants were reinforced for MEMS-measured adherence with drawings from a bowl for prizes and bonus drawings for consecutive weeks of perfect adherence. Potential total earnings averaged $800. Mean MEMS-measured adherence to the reinforced medication increased from 61% at baseline to 76% during the 16-week treatment phase and was significantly increased relative to the supportive counseling group (p = 0.01). Furthermore, mean log-transformed viral load was significantly lower in the CM group. However, by the end of the 16-week follow-up phase, differences between groups in adherence and viral load were no longer significantly different. Proportions of positive urine toxicology tests did not differ significantly between the two groups at any phase. A brief CM-based intervention was associated with significantly higher adherence and lower viral loads. Future studies should evaluate methods to extend effects for longer term benefits. PMID:17263651

  4. Optimizing adherence to antiretroviral therapy

    PubMed Central

    Sahay, Seema; Reddy, K. Srikanth; Dhayarkar, Sampada

    2011-01-01

    HIV has now become a manageable chronic disease. However, the treatment outcomes may get hampered by suboptimal adherence to ART. Adherence optimization is a concrete reality in the wake of ‘universal access’ and it is imperative to learn lessons from various studies and programmes. This review examines current literature on ART scale up, treatment outcomes of the large scale programmes and the role of adherence therein. Social, behavioural, biological and programme related factors arise in the context of ART adherence optimization. While emphasis is laid on adherence, retention of patients under the care umbrella emerges as a major challenge. An in-depth understanding of patients’ health seeking behaviour and health care delivery system may be useful in improving adherence and retention of patients in care continuum and programme. A theoretical framework to address the barriers and facilitators has been articulated to identify problematic areas in order to intervene with specific strategies. Empirically tested objective adherence measurement tools and approaches to assess adherence in clinical/ programme settings are required. Strengthening of ART programmes would include appropriate policies for manpower and task sharing, integrating traditional health sector, innovations in counselling and community support. Implications for the use of theoretical model to guide research, clinical practice, community involvement and policy as part of a human rights approach to HIV disease is suggested. PMID:22310817

  5. [Treatment adherence: a key element].

    PubMed

    Bastida, Guillermo; Sánchez Montes, Cristina; Aguas, Mariam

    2011-12-01

    A substantial percentage of patients fail to follow health professionals' recommendations, which affects the management of chronic diseases, reducing the effectiveness of therapeutic interventions and increasing the costs of the disease. Lack of adherence is a multidimensional phenomenon and is influenced by numerous factors that should be identified. A multiplicity of measures is available to improve adherence, such as simplifying treatment administration, but none of these measures is effective when used alone. One way of tackling lack of adherence is by identifying patients' barriers to medication and involving them in decision making. Ulcerative colitis (UC) poses a risk for lack of treatment adherence. In this disease, poor adherence correlates with poor disease control (drug effectiveness) and with higher costs. As in other chronic diseases, the causes associated with poor adherence are multiple, including psychosocial factors, the physician-patient relationship and patients' prejudices toward medication. A single dose of aminosalycylates (5-ASA) should be recommended, as this dose is as safe and effective as other regimens. However, by itself, this recommendation does not seem to improve adherence. Identifying the scale of the problem and developing strategies to involve the patient in decision making is crucial to improve treatment adherence. PMID:25443221

  6. Biologic Influences on Exercise Adherence.

    ERIC Educational Resources Information Center

    Dishman, Rod K.

    1981-01-01

    Diagnostic profiles of 362 male participants in an exercise program were analyzed to determine the biological variables between exercise adherence and symptoms of coronary disease. Findings indicated that individuals with lower metabolic capacity tended to adhere longer, to be less fit, were leaner, and began with more symptoms related to coronary…

  7. Diffusion-sensitive optical coherence tomography for real-time monitoring of mucus thinning treatments

    NASA Astrophysics Data System (ADS)

    Blackmon, Richard L.; Kreda, Silvia M.; Sears, Patrick R.; Ostrowski, Lawrence E.; Hill, David B.; Chapman, Brian S.; Tracy, Joseph B.; Oldenburg, Amy L.

    2016-03-01

    Mucus hydration (wt%) has become an increasingly useful metric in real-time assessment of respiratory health in diseases like cystic fibrosis and COPD, with higher wt% indicative of diseased states. However, available in vivo rheological techniques are lacking. Gold nanorods (GNRs) are attractive biological probes whose diffusion through tissue is sensitive to the correlation length of comprising biopolymers. Through employment of dynamic light scattering theory on OCT signals from GNRs, we find that weakly-constrained GNR diffusion predictably decreases with increasing wt% (more disease-like) mucus. Previously, we determined this method is robust against mucus transport on human bronchial epithelial (hBE) air-liquid interface cultures (R2=0.976). Here we introduce diffusion-sensitive OCT (DS-OCT), where we collect M-mode image ensembles, from which we derive depth- and temporally-resolved GNR diffusion rates. DS-OCT allows for real-time monitoring of changing GNR diffusion as a result of topically applied mucus-thinning agents, enabling monitoring of the dynamics of mucus hydration never before seen. Cultured human airway epithelial cells (Calu-3 cell) with a layer of endogenous mucus were doped with topically deposited GNRs (80x22nm), and subsequently treated with hypertonic saline (HS) or isotonic saline (IS). DS-OCT provided imaging of the mucus thinning response up to a depth of 600μm with 4.65μm resolution, over a total of 8 minutes in increments of >=3 seconds. For both IS and HS conditions, DS-OCT captured changes in the pattern of mucus hydration over time. DS-OCT opens a new window into understanding mechanisms of mucus thinning during treatment, enabling real-time efficacy feedback needed to optimize and tailor treatments for individual patients.

  8. Differences in Adherence and Non-Adherence Behaviour Patterns to Inhaler Devices Between COPD and Asthma Patients.

    PubMed

    Plaza, Vicente; López-Viña, Antolín; Entrenas, Luis Manuel; Fernández-Rodríguez, Concepción; Melero, Carlos; Pérez-Llano, Luis; Gutiérrez-Pereyra, Fernando; Tarragona, Eduard; Palomino, Rosa; Cosio, Borja G

    2016-10-01

    Differences between COPD and asthma may also differentially affect adherence to inhaled drugs in each disease. We aimed to determine differences in behaviour patterns of adherence and non-adherence to inhaled therapy between patients with COPD and patients with asthma using the Test of Adherence to Inhalers (TAI) questionnaire. A total of 910 patients (55% with asthma, 45% with COPD) participated in a cross-sectional multicentre study. Data recorded included sociodemographics, education level, asthma or COPD history, TAI score, the Asthma Control Test (ACT), the COPD Assessment Test (CAT) and spirometry. Asthma patients were statistically significant less adherents, 140 (28%) vs. 201 (49%), and the pattern of non-adherence was more frequently erratic (66.8% vs. 47.8%) and deliberate (47.2% vs. 34.1%) than COPD patients; however unwitting non-adherence was more frequently observed in COPD group (31.2% vs. 22.8%). Moreover, taking together all sample studied, only being younger than 50 years of age (OR 1.88 [95% CI: 1.26-2.81]) and active working status (OR 1.45 [95% CI: 1.00-2.09]) were risk factors for non-adherence in the multivariate analysis, while having asthma remained in the limits of the significance (OR 1.44 [95%CI: 0.97-2.14]). Even though non-adherence to inhalers is more frequently observed in asthma than in COPD patients and exhibited a different non-adherence patterns, these differences are more likely to be related to sociodemographic characteristics. However, differences in non-adherence patterns should be considered when designing specific education programmes tailored to each disease. PMID:26788620

  9. Symptom severity, self-reported adherence, and electronic pill monitoring in poorly adherent patients with bipolar disorder

    PubMed Central

    Sajatovic, Martha; Levin, Jennifer; Sams, Johnny; Cassidy, Kristin A; Akagi, Kouri; Aebi, Michelle E; Ramirez, Luis F; Safren, Steven A; Tatsuoka, Curtis

    2015-01-01

    Objectives This analysis of screening and baseline data from an ongoing trial examined self-report versus automated adherence monitoring and assessed the relationship between bipolar disorder (BD) symptoms and adherence in 104 poorly adherent individuals. Methods Adherence was measured with the Tablets Routine Questionnaire (TRQ) and the Medication Event Monitoring System (MEMS). Symptoms were measured with the Montgomery–Åsberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), and the Brief Psychiatric Rating Scale (BPRS). Results Mean age of the sample was 46.3 years [standard deviation (SD) = 9.41], with 72% (n = 75) women and 71% (n = 74) African American subjects. Adherence improved from screening to baseline with a mean missed drug proportion measured by TRQ of 61.43% (SD = 26.48) versus baseline mean of 46.61% (SD = 30.55). Mean proportion of missed medication using MEMS at baseline was 66.43% (SD = 30.40). Correlation between TRQ and MEMS was 0.47. Correlation between a single index drug and all BD medications was 0.95. Symptoms were generally positively correlated with TRQ (worse adherence = more severe symptoms), but in most instances was only at a trend level (p > 0.05) with the exception of correlation between baseline TRQ and MADRS and BPRS, which were positive (r = 0.20 and r = 0.21, respectively) and significant (p ≤ 0.05). Conclusions In patients with BD, monitoring increased adherence by 15%. MEMS identified 20% more non-adherence than self-report. Using a standard procedure to identify a single index drug for adherence monitoring may be one way to assess global adherence in patients with BD receiving polypharmacy treatment. Greater BD symptom severity may be a clinical indicator to assess for adherence problems. PMID:26529124

  10. Adherence with drug therapy in the rheumatic diseases Part one: a review of adherence rates.

    PubMed

    Hill, Jackie

    2005-01-01

    Drug therapy plays a major role in the management of many rheumatic diseases and is particularly important in rheumatoid arthritis (RA) because of the significant rates of morbidity and mortality (Pincus, 1995). Understanding of the pathogenesis of RA has led to the development of new and more effective drugs (Emery et al., 1999), but the ultimate efficacy of any drug therapy depends upon the patient's decision to take it. There is widespread agreement that many people with rheumatic disease do not adhere to their medication regimens (Deyo et al., 1981; Belcon et al., 1984; Pullar et al., 1988; Hill et al., 2001). Research has demonstrated that 50% of women taking hormone replacement therapy for the prevention of osteoporosis discontinue treatment after a year (Fordham, 2000) and similar rates of discontinuation are found in other chronic diseases (Haynes et al., 1996, 2000). This is bewildering as, in asymptomatic illnesses such as hypertension and diabetes, the expectation is that levels of adherence would be lower than in diseases where pain and stiffness are present. The picture becomes even more confusing when we consider the findings from a recent multi-country study of RA, which found no association between adherence and disease severity, nor with the treatment prescribed (Viller et al., 1999). In chronic disease poor adherence is commonplace. The World Health Organization (WHO) recognizes this and has recently stated that 'poor adherence to treatment of chronic diseases is a worldwide problem of striking magnitude' and cites adherence to long-term therapy for chronic illnesses in developed countries averaging just 50% (WHO, 2003). The first part of this two part review focuses on adherence with drug therapy, and the second part discusses different methods of measuring it. PMID:17041995

  11. Adherence to health regimens among frequent attenders of Finnish healthcare

    PubMed Central

    Hirsikangas, Sari; Kanste, Outi; Korpelainen, Juha; Kyngäs, Helvi

    2016-01-01

    Objectives The aim of the study was to describe adherence to health regimens and the factors associated with it among adult frequent attenders (FAs). Design This was a cross-sectional study. The study sample consisted of 462 healthcare FAs in 7 municipal health centres in northern Finland. An FA is a person who has had 8 or more outpatient visits to a GP (in a health centre) or 4 or more outpatient visits to a university hospital during 1 year. The main outcome was self-reported adherence to health regimens. Results Of the FAs, 82% adhered well to their health regimens. Carrying out self-care, medical care and feeling responsible for self-care were the most significant predictors to good adherence in all models. No significant differences in adherence were found in male and female subjects, age groups or educational levels. Support from healthcare providers and support from relatives were not significant predictors of good adherence. Conclusion FAs in Finland adhere well to health regimens and exceptionally well to medication. Variables that predict the best adherence of FAs to health regimens are carrying out self-care, receiving medical care and feeling responsible for self-care. PMID:26996780

  12. Associations between patient factors and medication adherence: A Jordanian experience

    PubMed Central

    Basheti, Iman A.; Hait, Sami Saqf El; Qunaibi, Eyad A.; Aburuz, Salah; Bulatova, Nailya

    2015-01-01

    Objective: To explore the effect of patient characteristics and health beliefs on their medication adherence. Methods: Patients (n=167) with chronic conditions (mean age 58.9; SD=13.54, 53% males) were recruited from March 2009- to March 2010 using a cross sectional study design. Data collected included patients’ demographics, medical conditions, medications therapeutic regimen, frequency of physician visits and health beliefs. Patient self-reported adherence to medications was assessed by the researcher using a validated and published scale. Treatment related problems (TRPs) were evaluated for each patient by competent clinical pharmacists. Associations between patient characteristics/health beliefs with adherence were explored. Results: About half of the patients (46.1%) were non-adherent. A significant association was found between lower adherence and higher number of disease states (p<0.001), higher number of medications (p=0.001), and higher number of identified TRPs (p = 0.003). Patient adherence was positively affected by older age, higher educational level, and higher number of physician visits per month, while it was negatively affected by reporting difficulties with getting prescription refills on time. Conclusion: This study identified different factors that may negatively affect adherence, including higher number of medications and disease states, higher number of identified TRPs and inability to getting prescription refills on time. Hence, more care needs to be provided to patients with complex therapeutic regimens in order to enhance adherence. PMID:27011772

  13. Mucus extravasation phenomenon on the alveolar ridge in neonate: a case report.

    PubMed

    Kalra, N; Chaudhary, S; Singh, B

    2004-03-01

    Pediatric dentists often come across lesions in neonates, the most common ones being Bohn's nodules and Epstein Pearls. Other common lesions seen in the oral cavity of neonates are congenital epulis, hemangiomas and mucus extravasation cysts. Mucus extravasation phenomenon is generally encountered over the lip but rarely seen over the alveolar ridge. Presented here is a case of a 1-month-old baby with a mucus extravasation cyst measuring 0.7 x 1 cm in size over the alveolar ridge. PMID:15255445

  14. Cognitive function and adherence to anticoagulation treatment in patients with atrial fibrillation

    PubMed Central

    Jankowska-Polańska, Beata; Katarzyna, Lomper; Lidia, Alberska; Joanna, Jaroch; Dudek, Krzysztof; Izabella, Uchmanowicz

    2016-01-01

    Background Medication adherence is an integral part of the comprehensive care of patients with atrial fibrillation (AF) receiving oral anticoagulations (OACs) therapy. Many patients with AF are elderly and may suffer from some form of cognitive impairment. This study was conducted to investigate whether cognitive impairment affects the level of adherence to anticoagulation treatment in AF patients. Methods The study involved 111 AF patients (mean age, 73.5 ± 8.3 years) treated with OACs. Cognitive function was assessed using the Mini Mental State Examination (MMSE). The level of adherence was assessed by the 8-item Morisky Medication Adherence Scale (MMAS-8). Scores on the MMAS-8 range from 0 to 8, with scores < 6 reflecting low adherence, 6 to < 8 medium adherence, and 8 high adherence. Results 46.9% of AF patients had low adherence, 18.8% had moderate adherence, and 33.3% had high adherence to OACs. Patients with lower adherence were older than those with moderate or high adherence (76.6 ± 8.7 vs. 71.3 ± 6.4 vs. 71.1 ± 6.7 years) and obtained low MMSE scores, indicating cognitive disorders or dementia (MMSE = 22.3 ± 4.2). Patients with moderate or high adherence obtained high MMSE test results (27.5 ± 1.7 and 27.5 ± 3.6). According to Spearman's rank correlation, worse adherence to treatment with OACs was determined by older age (rS = −0.372) and lower MMSE scores (rS = 0.717). According to multivariate regression analysis, the level of cognitive function was a significant independent predictor of adherence (b = 1.139). Conclusions Cognitive impairment is an independent determinant of compliance with pharmacological therapy in elderly patients with AF. Lower adherence, beyond the assessment of cognitive function, is related to the age of patients. PMID:27605935

  15. EBM84 attenuates airway inflammation and mucus hypersecretion in an ovalbumin-induced murine model of asthma.

    PubMed

    Shin, In Sik; Lee, Mee Young; Jeon, Woo Young; Shin, Na Ra; Seo, Chang Seob; Ha, Hyekyung

    2013-04-01

    EBM84 is a traditional herbal medicine and a combination of extracts obtained from Pinellia ternata and Zingiber officinale. It is traditionally used to treat vomiting, nausea, sputum and gastrointestinal disorders, and functions is an effective expectorant. In this study, we evaluated the protective effects of EBM84 on asthmatic responses, particularly mucus hypersecretion in an ovalbumin (OVA)-induced murine model of asthma. We also analyzed EBM84 composition using high performance liquid chromatography. Animals were sensitized on days 0 and 14 via intraperitoneal injection using 20 µg OVA. On days 21, 22 and 23 after initial sensitization, the mice received an airway challenge with OVA (1% w/v in PBS) for 1 h using an ultrasonic nebulizer (NE-U12). EBM84 was administered by gavage to the mice at doses of 16.9, 33.8 and 67.5 mg/kg once daily from days 18 to 23. EBM84 administration significantly lowered elevated levels of interleukin (IL)-4, IL-13, eotaxin and immunoglobulin (Ig)E in the bronchoalveolar lavage fluid or plasma. Airway inflammation and mucus hypersecretion were attenuated following EBM84 administration. EBM84 also inhibited the overexpression of mucin 5AC (MUC5AC) induced by OVA challenge in lung tissue. This result was consistent with the immunohistochemistry results. Our results indicate that EBM84 effectively inhibited airway inflammation and mucus hypersecretion via the downregulation of T helper 2 (Th2) cytokines, which reduced MUC5AC expression. Therefore, EBM84 has potential as a useful medicine for the treatment of allergic asthma. PMID:23403738

  16. SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production

    PubMed Central

    Chen, Gang; Korfhagen, Thomas R.; Xu, Yan; Kitzmiller, Joseph; Wert, Susan E.; Maeda, Yutaka; Gregorieff, Alexander; Clevers, Hans; Whitsett, Jeffrey A.

    2009-01-01

    Various acute and chronic inflammatory stimuli increase the number and activity of pulmonary mucus-producing goblet cells, and goblet cell hyperplasia and excess mucus production are central to the pathogenesis of chronic pulmonary diseases. However, little is known about the transcriptional programs that regulate goblet cell differentiation. Here, we show that SAM-pointed domain–containing Ets-like factor (SPDEF) controls a transcriptional program critical for pulmonary goblet cell differentiation in mice. Initial cell-lineage–tracing analysis identified nonciliated secretory epithelial cells, known as Clara cells, as the progenitors of goblet cells induced by pulmonary allergen exposure in vivo. Furthermore, in vivo expression of SPDEF in Clara cells caused rapid and reversible goblet cell differentiation in the absence of cell proliferation. This was associated with enhanced expression of genes regulating goblet cell differentiation and protein glycosylation, including forkhead box A3 (Foxa3), anterior gradient 2 (Agr2), and glucosaminyl (N-acetyl) transferase 3, mucin type (Gcnt3). Consistent with these findings, levels of SPDEF and FOXA3 were increased in mouse goblet cells after sensitization with pulmonary allergen, and the proteins were colocalized in goblet cells lining the airways of patients with chronic lung diseases. Deletion of the mouse Spdef gene resulted in the absence of goblet cells in tracheal/laryngeal submucosal glands and in the conducting airway epithelium after pulmonary allergen exposure in vivo. These data show that SPDEF plays a critical role in regulating a transcriptional network mediating the goblet cell differentiation and mucus hyperproduction associated with chronic pulmonary disorders. PMID:19759516

  17. In vitro mucus transportability, cytogenotoxicity, and hematological changes as non-destructive physiological biomarkers in fish chronically exposed to metals.

    PubMed

    Seriani, Robson; Abessa, Denis M S; Moreira, Lucas B; Cabrera, Joana P G; Sanches, Juliana Q; Silva, Carolina L S; Amorim, Francisca A; Rivero, Dolores H R F; Silva, Flavia L; Fitorra, Lilian S; Carvalho-Oliveira, Regiani; Macchione, Mariangela; Ranzani-Paiva, Maria J T

    2015-02-01

    The biomonitoring of fish using biomarkers represents a useful tool for the assessment of aquatic pollution. This study evaluated the sublethal toxic effects of aquatic pollution on fish collected from a site contaminated by metals. Water and fish (Oreochromis niloticus) samples were collected from a pond in the Parque Ecológico do Tietê (PET) that lies along the Tietê River (São Paulo, Brazil), and from a control site (an experimental fish farm). The metal content of the water was evaluated, and fish were used to examine the properties of gill mucus and blood. The PET fish were evaluated for alterations in the in vitro transportability of mucus and changes in blood properties (e.g., cell volume, hemoglobin concentration, red blood cells, and white blood cell count). The results of the water analyzes indicated metal levels above the legal standards for Fe (0.71 mg/L), Ni (0.06 mg/L), Mn (0.11 mg/L), and Pb (0.48 mg/L). Compared to the controls, the hematologic parameter analyzes of PET fish revealed significantly higher numbers of erythrocytes (RBC), leukocytes (WBC), lymphocytes, erythroblasts, and Mean Corpuscular Volume (MCV); however, the hemoglobin content and Mean Corpuscular Hemoglobin Concentration (MCHC) values were significantly lower. The frequencies of nuclear abnormalities and micronuclei were significantly higher and the mucociliary transport was significantly lower in PET fish than in the controls. These results suggest that fish from the contaminated site exhibit a series of physiological responses, which probably indicate health disturbances. Furthermore, the results suggest that blood and mucus are promising, non-destructive targets for use in the monitoring of pollution. PMID:25463867

  18. Adherence to Antiretroviral Medications among Persons who Inject Drugs in Transitional, Low and Middle Income Countries: An International Systematic Review

    PubMed Central

    Feelemyer, Jonathan; Jarlais, Don Des; Arasteh, Kamyar; Uuskula, Anneli

    2014-01-01

    Adherence to antiretroviral (ART) medication is vital to reducing morbidity and mortality among HIV positive persons. People who inject drugs (PWID) are at high risk for HIV infection in transitional/low/middle income countries (TLMIC). We conducted a systematic review of studies reporting adherence to ARTs among persons with active injection drug use and/or histories of injection drug use in TLMIC. Meta-regression was performed to examine relationships between location, adherence measurements, and follow-up period. Fifteen studies were included from seven countries. Adherence levels ranged from 33% to 97%; mean weighted adherence was 72%. ART adherence was associated with different methods of measuring adherence and studies conducted in Eastern Europe and East Asia. The great heterogeneity observed precludes generalization to TLMIC as a whole. Given the critical importance of ART adherence more research is needed on ART adherence among PWID in TLMIC, including the use of standardized methods for reporting adherence to ARTs. PMID:25331268

  19. Sexual relationships outside primary partnerships and abstinence are associated with lower adherence and adherence gaps: data from the Partners PrEP Ancillary Adherence Study

    PubMed Central

    Kintu, Alexander; Hankinson, Susan E.; Balasubramanian, Raji; Ertel, Karen; Tumwesigye, Elioda; Bangsberg, David R.; Haberer, Jessica E.

    2015-01-01

    Objective To assess the role of sexual relationships on levels and patterns of adherence to medication for pre-exposure prophylaxis (PrEP) against HIV. Methods We enrolled 1,147 HIV-negative individuals in long-term serodiscordant relationships at three sites in Uganda from the Partners PrEP Study- a randomized placebo-controlled trial of daily oral tenofovir and emtricitabine/tenofovir. We used generalized estimation equations to assess the effects of sexual relationships on low adherence (<80%) and on gaps in adherence. Results Fifty-three percent were male, 51% were 18-34 years and 24% were polygamous. Participants who reported sex in the past month with someone other than their primary partner and with <100% condom use were more than twice as likely to have low adherence (aOR 2.48, 95% CI: 1.70-3.62) compared to those who had sex with only their primary partners and 100% condom use. Using the same reference group, those who abstained from sex in the previous month had 30% increased odds of low adherence (aOR 1.30, 95% CI: 1.05-1.62), and participants in non-polygamous marriages who reported sex with both their primary and other partners and <100% condom use were almost twice as likely to be low adherers (aOR 1.76, 95% CI: 1.01-3.08). At least one 72-hour gap in adherence was seen in 598 participants (54.7%); 23.2% had at least one one-week gap. Conclusions Risk of low overall adherence was higher in participants who reported sex outside primary partnerships and suboptimal condom use, as well as in those who abstained from sex. Adherence gaps were common, potentially creating risk for HIV acquisition. PMID:25942457

  20. Clustering based on adherence data

    PubMed Central

    2011-01-01

    Adherence to a medical treatment means the extent to which a patient follows the instructions or recommendations by health professionals. There are direct and indirect ways to measure adherence which have been used for clinical management and research. Typically adherence measures are monitored over a long follow-up or treatment period, and some measurements may be missing due to death or other reasons. A natural question then is how to describe adherence behavior over the whole period in a simple way. In the literature, measurements over a period are usually combined just by using averages like percentages of compliant days or percentages of doses taken. In the paper we adapt an approach where patient adherence measures are seen as a stochastic process. Repeated measures are then analyzed as a Markov chain with finite number of states rather than as independent and identically distributed observations, and the transition probabilities between the states are assumed to fully describe the behavior of a patient. The patients can then be clustered or classified using their estimated transition probabilities. These natural clusters can be used to describe the adherence of the patients, to find predictors for adherence, and to predict the future events. The new approach is illustrated and shown to be useful with a simple analysis of a data set from the DART (Development of AntiRetroviral Therapy in Africa) trial in Uganda and Zimbabwe. PMID:21385451

  1. Race and Residential Socioeconomics as Predictors of CPAP Adherence

    PubMed Central

    Billings, Martha E.; Auckley, Dennis; Benca, Ruth; Foldvary-Schaefer, Nancy; Iber, Conrad; Redline, Susan; Rosen, Carol L.; Zee, Phyllis; Kapur, Vishesh K.

    2011-01-01

    Study Objectives: There are few established predictors of CPAP adherence; poor adherence limits its effectiveness. We investigated whether race, education level, and residential economic status predict CPAP adherence in participants enrolled in a trial with standard access to treatment. Design: A multi-center randomized trial of home vs. lab-based evaluation and treatment of OSA assessing adherence to CPAP at 1 and 3 months. Setting: Seven AASM-accredited sleep centers in 5 U.S. cities. Participants: Subjects with moderate to severe OSA (AHI ≥ 15 and Epworth Sleepiness Scale score > 12) who completed follow-up at 1 and/or 3 months (n = 135). Measurements and Results: Subjects' demographic data were collected upon enrollment; CPAP use at 1 and 3 months was assessed at clinic follow-up. In unadjusted analyses, CPAP adherence (average minutes per night of CPAP use) at 3 months was lower in black subjects and in subjects from lower socioeconomic status ZIP codes. In adjusted analyses using multivariate linear regression, black race was predictive of CPAP adherence at one month (P = 0.03). At 3 months, black race was predictive in analyses only when ZIP code SES was not adjusted for. Conclusion: Black race and lower socioeconomic residential areas are associated with poorer adherence to CPAP in subjects with standardized access to care and treatment. Disparities remain despite provision of standardized care in a clinical trial setting. Future research is needed to identify barriers to adherence and to develop interventions tailored to improve CPAP adherence in at risk populations. Portable Monitoring for Diagnosis and Management of Sleep Apnea (HomePAP) Clinical Trial Information: NIH clinical trials registry number: NCT00642486. URL: http://clinicaltrials.gov/show/NCT00642486. Citation: Billings ME; Auckley D; Benca R; Foldvary-Schaefer N; Iber C; Redline S; Rosen CL; Zee P; Kapur VK. Race and residential socioeconomics as predictors of CPAP adherence. SLEEP 2011

  2. Smartphone medication adherence apps: Potential benefits to patients and providers

    PubMed Central

    Dayer, Lindsey; Heldenbrand, Seth; Anderson, Paul; Gubbins, Paul O.; Martin, Bradley C.

    2014-01-01

    Objectives To provide an overview of medication adherence, discuss the potential for smartphone medication adherence applications (adherence apps) to improve medication nonadherence, evaluate features of adherence apps across operating systems (OSs), and identify future opportunities and barriers facing adherence apps. Practice description Medication nonadherence is a common, complex, and costly problem that contributes to poor treatment outcomes and consumes health care resources. Nonadherence is difficult to measure precisely, and interventions to mitigate it have been largely unsuccessful. Practice innovation Using smartphone adherence apps represents a novel approach to improving adherence. This readily available technology offers many features that can be designed to help patients and health care providers improve medication-taking behavior. Main outcome measures Currently available apps were identified from the three main smartphone OSs (Apple, Android, and Blackberry). In addition, desirable features for adherence apps were identified and ranked by perceived importance to user desirability using a three-point rating system: 1, modest; 2, moderate; or 3, high. The 10 highest-rated apps were installed and subjected to user testing to assess app attributes using a standard medication regimen. Results 160 adherence apps were identified and ranked. These apps were most prevalent for the Android OS. Adherence apps with advanced functionality were more prevalent on the Apple iPhone OS. Among all apps, MyMedSchedule, MyMeds, and RxmindMe rated the highest because of their basic medication reminder features coupled with their enhanced levels of functionality. Conclusion Despite being untested, medication apps represent a possible strategy that pharmacists can recommend to nonadherent patients and incorporate into their practice. PMID:23571625

  3. The properties of the mucus barrier, a unique gel - how can nanoparticles cross it?

    PubMed

    Pearson, Jeffrey P; Chater, Peter I; Wilcox, Matthew D

    2016-04-01

    The key criterion for a nanoparticle drug-delivery system is the ability to produce substantial bioavailability without damaging the physiological protective mechanisms. The main area for drug delivery is the aerodigestive tract. All epithelial surfaces have a membrane-bound layer and in the lung this layer is surmounted by a gel layer. In the gastrointestinal tract the membrane-bound mucin layer is covered by a mucus bilayer. The pore sizes of mucus gels are around 100 to 200 nm. Consequently, only nanoparticles in this size range could potentially penetrate without modification of these layers. To study nanoparticle permeation with results that pertain to in vivo conditions, native mucus mucin preparations must be used. Strategies to increase pores in mucus gels are discussed herein. PMID:27010985

  4. Effects of nasal allergen challenge on dynamic viscoelasticity of nasal mucus.

    PubMed

    Hattori, M; Majima, Y; Ukai, K; Sakakura, Y

    1993-04-01

    The effects of nasal provocation on the rheologic properties of nasal mucus were investigated in patients with allergic rhinitis provoked by house dust. The elastic modulus (G') and the dynamic viscosity (eta') of nasal mucus were determined by an oscillating sphere magnetic rheometer. Before and after the allergen challenge, G' increased, whereas eta' decreased with increasing oscillatory frequency; these findings indicate that the nasal mucus under these conditions is a non-newtonian fluid and has the cross-linked gel-like nature typical of mucus. Both G' and eta' values after nasal provocation were significantly lower than before. The values of G' and eta' after allergen challenge were in the optimal viscoelasticity range for mucociliary transport. PMID:8476173

  5. Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients

    PubMed Central

    Worlitzsch, Dieter; Tarran, Robert; Ulrich, Martina; Schwab, Ute; Cekici, Aynur; Meyer, Keith C.; Birrer, Peter; Bellon, Gabriel; Berger, Jürgen; Weiss, Tilo; Botzenhart, Konrad; Yankaskas, James R.; Randell, Scott; Boucher, Richard C.; Döring, Gerd

    2002-01-01

    Current theories of CF pathogenesis predict different predisposing “local environmental” conditions and sites of bacterial infection within CF airways. Here we show that, in CF patients with established lung disease, Psuedomonas aeruginosa was located within hypoxic mucopurulent masses in airway lumens. In vitro studies revealed that CF-specific increases in epithelial O2 consumption, linked to increased airway surface liquid (ASL) volume absorption and mucus stasis, generated steep hypoxic gradients within thickened mucus on CF epithelial surfaces prior to infection. Motile P. aeruginosa deposited on CF airway surfaces penetrated into hypoxic mucus zones and responded to this environment with increased alginate production. With P. aeruginosa growth in oxygen restricted environments, local hypoxia was exacerbated and frank anaerobiosis, as detected in vivo, resulted. These studies indicate that novel therapies for CF include removal of hypoxic mucus plaques and antibiotics effective against P. aeruginosa adapted to anaerobic environments. PMID:11827991

  6. Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals.

    PubMed

    Shan, Meimei; Gentile, Maurizio; Yeiser, John R; Walland, A Cooper; Bornstein, Victor U; Chen, Kang; He, Bing; Cassis, Linda; Bigas, Anna; Cols, Montserrat; Comerma, Laura; Huang, Bihui; Blander, J Magarian; Xiong, Huabao; Mayer, Lloyd; Berin, Cecilia; Augenlicht, Leonard H; Velcich, Anna; Cerutti, Andrea

    2013-10-25

    A dense mucus layer in the large intestine prevents inflammation by shielding the underlying epithelium from luminal bacteria and food antigens. This mucus barrier is organized around the hyperglycosylated mucin MUC2. Here we show that the small intestine has a porous mucus layer, which permitted the uptake of MUC2 by antigen-sampling dendritic cells (DCs). Glycans associated with MUC2 imprinted DCs with anti-inflammatory properties by assembling a galectin-3-Dectin-1-FcγRIIB receptor complex that activated β-catenin. This transcription factor interfered with DC expression of inflammatory but not tolerogenic cytokines by inhibiting gene transcription through nuclear factor κB. MUC2 induced additional conditioning signals in intestinal epithelial cells. Thus, mucus does not merely form a nonspecific physical barrier, but also constrains the immunogenicity of gut antigens by delivering tolerogenic signals. PMID:24072822

  7. Impaired Mucus Detachment Disrupts Mucociliary Transport in a Piglet Model of Cystic Fibrosis

    PubMed Central

    Hoegger, Mark J.; Fischer, Anthony J.; McMenimen, James D.; Ostedgaard, Lynda S.; Tucker, Alex J.; Awadalla, Maged A.; Moninger, Thomas O.; Michalski, Andrew S.; Hoffman, Eric A.; Zabner, Joseph; Stoltz, David A.; Welsh, Michael J.

    2015-01-01

    Lung disease in people with cystic fibrosis (CF) is initiated by defective host defense that predisposes airways to bacterial infection. People with advanced CF exhibit deficits in mucociliary transport (MCT), a process that traps and propels bacteria out of lungs, but whether this occurs first or is secondary to airway remodeling has been unclear. To assess MCT, we tracked movement of radiodense microdisks in airways of newborn CF piglets. Cholinergic stimulation, which elicits mucus secretion, caused microdisks to become stuck. Impaired MCT was not due to periciliary liquid depletion; rather, CF submucosal glands secreted mucus strands that remained tethered to gland ducts and hindered MCT. Inhibiting anion secretion in non-CF airways replicated CF abnormalities. These findings identify impaired MCT as a primary defect, link CFTR loss in submucosal glands to failure of mucus detachment from glands, and suggest that submucosal glands and tethered mucus may be targets for early CF treatment. PMID:25124441

  8. Effects of irradiated Ergosan on the growth performance and mucus biological components of rainbow trout Oncorhynchus mykiss

    NASA Astrophysics Data System (ADS)

    Sheikhzadeh, Najmeh; Chehrara, Fatemeh; Heidarieh, Marzieh; Nofouzi, Katayoon; Baradaran, Behzad

    2016-01-01

    Effects of irradiated and non-irradiated Ergosan extract (alginic acid) on rainbow trout growth performance and skin mucosal immunity were compared. Ergosan was irradiated at 30 kGy in a cobalt-60 irradiator. A total of 252 fish (128.03±9.4 g) were randomly divided into four equal groups, given the basal diet either unsupplemented with Ergosan (control group) or supplemented with crude Ergosan (5 g/kg), ethanol-extracted Ergosan (0.33 g/kg) or irradiated Ergosan (0.33 g/kg) according to this protocol: basal diet for 15 days, treatment diet for 15 days, basal diet for 10 days and treatment diet for 15 days. Highest growth performance was observed in fish fed irradiated Ergosan ( P <0.05). Dietary administration of different Ergosan types did not cause any changes in mucus protein level, but improved alkaline phosphatase level and hemagglutination titer compared with the control (basal diet without Ergosan) on day 55 of feeding trial ( P <0.05). Furthermore, the highest value of lysozyme activity was observed in gamma-irradiated Ergosan on day 55. In conclusion, gamma-irradiated Ergosan at 0.33 g/kg was found to improve growth performance and mucus biological components significantly in comparison with the control group (basal diet without Ergosan).

  9. β2-Adrenoceptor involved in smoking-induced airway mucus hypersecretion through β-arrestin-dependent signaling.

    PubMed

    Zhou, Yujiao; Zhang, Yuan; Guo, Yang; Zhang, Youyi; Xu, Ming; He, Bei

    2014-01-01

    Progression of chronic obstructive pulmonary disease is associated with small airway obstruction by accumulation of inflammatory mucous exudates. However, the mechanism of mucin hypersecretion after exposure to cigarette smoke (CS) is still not clear. In this study, we explored the contribution of β2-adrenoceptor (β2-AR) signaling to CS extract (CSE)-induced mucus hypersecretion in vitro and examined the effect of a β-blocker on airway mucin hypersecretion in vivo. NCI-H292 epithelial cell line was used to determine the contribution of β2-AR signaling to CSE-induced MUC5AC production by treatment with β2-AR antagonists propranolol and ICI118551 and β2-AR-targeted small interfering RNA. The effect of propranolol on airway mucus hypersecretion was examined in a rat model exposed to CS. MUC5AC expression was assayed by real-time PCR, immunohistochemistry and ELISA. β2-AR and its downstream signaling were detected by western blot analysis. We found that pretreating NCI-H292 cells with propranolol, ICI118551 for 30 min or β2AR-targeted siRNA for 48 h reduced MUC5AC mRNA and protein levels stimulated by CSE. However,inhibiting the classical β2AR-cAMP-PKA pathway didn't attenuate CSE-induced MUC5AC production, while silencing β-arretin2 expression significantly decreased ERK and p38MAPK phosphorylation, thus reduced the CSE-stimulated MUC5AC production. In vivo, we found that administration of propranolol (25 mg kg(-1) d(-1)) for 28 days significantly attenuated the airway goblet cell metaplasia, mucus hypersecretion and MUC5AC expression of rats exposed to CS. From the study, β2-AR-β-arrestin2-ERK1/2 signaling was required for CS-induced airway MUC5AC expression. Chronic propranolol administration ameliorated airway mucus hypersecretion and MUC5AC expression in smoking rats. The exploration of these mechanisms may contribute to the optimization of β2-AR target therapy in chronic obstructive pulmonary disease. PMID:24905583

  10. Influenza A penetrates host mucus by cleaving sialic acids with neuraminidase

    PubMed Central

    2013-01-01

    Background Influenza A virus (IAV) neuraminidase (NA) cleaves sialic acids (Sias) from glycans. Inhibiting NA with oseltamivir suppresses both viral infection, and viral release from cultured human airway epithelial cells. The role of NA in viral exit is well established: it releases budding virions by cleaving Sias from glycoconjugates on infected cells and progeny virions. The role of NA in viral entry remains unclear. Host respiratory epithelia secrete a mucus layer rich in heavily sialylated glycoproteins; these could inhibit viral entry by mimicking sialylated receptors on the cell surface. It has been suggested that NA allows influenza to penetrate the mucus by cleaving these sialylated decoys, but the exact mechanism is not yet established. Methods We tested IAV interaction with secreted mucus using frozen human trachea/bronchus tissue sections, and bead-bound purified human salivary mucins (HSM) and purified porcine submaxillary mucins (PSM). The protective effect of mucus was analyzed using MDCK cells coated with purified HSM and PSM with known Sia content. Oseltamivir was used to inhibit NA activity, and the fluorescent reporter substrate, 4MU-Neu5Ac, was used to quantify NA activity. Results IAV binds to the secreted mucus layer of frozen human trachea/bronchus tissues in a Sia dependent manner. HSM inhibition of IAV infection is Sia dose-dependent, but PSM cannot inhibit infection of underlying cells. HSM competitively inhibits NA cleavage of 4MU-Neu5Ac, reporter substrate. Human IAV effectively cleaves Sias from HSM but not from PSM, and binds to HSM but not to PSM. Conclusion IAV interacts with human mucus on frozen tissue sections and mucus-coated beads. Inhibition of IAV infection by sialylated human mucus is dose-dependent, and enhanced when NA is inhibited with oseltamivir. Thus NA cleaves sialylated decoys during initial stages of infection. Understanding IAV interactions with host mucins is a promising new avenue for drug development. PMID

  11. Draft genome sequence of Kocuria sp. SM24M-10 isolated from coral mucus

    PubMed Central

    Palermo, Bruna Rafaella Z.; Castro, Daniel B.A.; Pereira, Letícia Bianca; Cauz, Ana Carolina G.; Magalhães, Beatriz L.; Carlos, Camila; da Costa, Fernanda L.P.; Scagion, Guilherme P.; Higa, Juliana S.; Almeida, Ludimila D.; das Neves, Meiriele da S.; Cordeiro, Melina Aparecida; do Prado, Paula F.V.; da Silva, Thiago M.; Balsalobre, Thiago Willian A.; Paulino, Luciana C.; Vicentini, Renato; Ferraz, Lúcio F.C.; Ottoboni, Laura M.M.

    2015-01-01

    Here, we describe the genomic features of the Actinobacteria Kocuria sp. SM24M-10 isolated from mucus of the Brazilian endemic coral Mussismilia hispida. The sequences are available under accession number LDNX01000000 (http://www.ncbi.nlm.nih.gov/nuccore/LDNX00000000). The genomic analysis revealed interesting information about the adaptation of bacteria to the marine environment (such as genes involved in osmotic and oxidative stress) and to the nutrient-rich environment provided by the coral mucus. PMID:26981384

  12. [Inhibitory effect of nasal mucus on the absorption of drugs through respiratory epithelium].

    PubMed

    Hayashi, H

    1990-01-01

    The absorption of Dibekacin (DKB) through rabbit's tracheal mucosa with and without nasal mucus were examined in vitro. The modified double chamber method was used for the purpose of this study. DKB solution (20 mg/ml) and Hanks' balanced salt solution were put into the donor compartment (DC) and the receiver compartment (RC), respectively. A plate with a hole and the tracheal mucosa were inserted between the compartments in the order of DC, dialytic membrane, the plate, the rabbit tracheal mucosa and RC. The hole of the plate was filled with nasal mucus or Hanks' solution. The latter was used as the control. The chamber was incubated in a humidified atmosphere of 5% CO2 in air for 3 hours at 37 degrees C. The absorption rate (AR) was obtained by dividing the concentration of DKB in RC by that in DC. The nasal mucus from patients with chronic sinusitis significantly decreased the AR of DKB compared with that in the control (P less than 0.05). The AR significantly decreased with increments in the thickness of nasal mucus by chronic sinusitis. This decreased AR was improved by the addition of N-Acetyl-L-cysteine (NAC) to DKB solution in DC. NAC can cleave disulfied bonds of mucus glycoprotein and this results in the decrease of viscoelasticity of nasal mucus. The results indicate that nasal mucus by chronic sinusitis intercept the absorption of drugs through respiratory epithelium in vitro. One of the mechanisms of the intercepter may be due to the high molecular-reticular structure of nasal mucus. PMID:2319385

  13. Effects of chelating agents on the rheological property of cervical mucus.

    PubMed

    Lee, Chi H; Wang, Yicheng; Shin, Sang-Chul; Chien, Yie W

    2002-06-01

    As an ongoing effort to elucidate the mechanisms involved in the calcium-dependent fertility regulation process, the viscoelastic properties of the mucus obtained from lamb cervix and human semen, as well as their water and total protein contents after exposure to EDTA, a chelating agent, or Nonoxynol-9 (N-9), a spermicidal agent, were examined. The viscosity was measured using a Cone Plate Digital Viscometer, while the water and total protein contents were determined by the lyophilization process and the Lowry method, respectively. The significant changes in the rheological properties of mucus, such as its viscosity and the water content, upon exposure to EDTA were demonstrated. The viscosity of cervical mucus and human semen were significantly increased by EDTA treatment (as compared to the controls): lamb cervical mucus (2.9 +/- 0.3 vs. 2.2 +/- 0.3 cps) and human semen (5.0 +/- 0.3 vs. 4.3 +/- 0.3 cps), respectively. The hydration rate was decreased by EDTA treatment as compared with the control (93.6 +/- 0.7 vs. 96.8 +/- 0.8%). Among tested samples, the reduction in the percentage of sperm penetration through the cervical mucus was the highest in the mucus containing EDTA, which had the lowest water content (93.6 +/- 0.7%), indicating that there is a positive relationship between the hydration rate of the cervical mucus and its ability to permit the penetration of spermatozoa. This result indicates that spermicidal activity exerted by high concentrations of EDTA is in part due to its effect on the rheological properties of cervical mucus or semen. PMID:12127644

  14. Draft genome sequence of Kocuria sp. SM24M-10 isolated from coral mucus.

    PubMed

    Palermo, Bruna Rafaella Z; Castro, Daniel B A; Pereira, Letícia Bianca; Cauz, Ana Carolina G; Magalhães, Beatriz L; Carlos, Camila; da Costa, Fernanda L P; Scagion, Guilherme P; Higa, Juliana S; Almeida, Ludimila D; das Neves, Meiriele da S; Cordeiro, Melina Aparecida; do Prado, Paula F V; da Silva, Thiago M; Balsalobre, Thiago Willian A; Paulino, Luciana C; Vicentini, Renato; Ferraz, Lúcio F C; Ottoboni, Laura M M

    2016-03-01

    Here, we describe the genomic features of the Actinobacteria Kocuria sp. SM24M-10 isolated from mucus of the Brazilian endemic coral Mussismilia hispida. The sequences are available under accession number LDNX01000000 (http://www.ncbi.nlm.nih.gov/nuccore/LDNX00000000). The genomic analysis revealed interesting information about the adaptation of bacteria to the marine environment (such as genes involved in osmotic and oxidative stress) and to the nutrient-rich environment provided by the coral mucus. PMID:26981384

  15. Design of a Specific Colonic Mucus Marker Using a Human Commensal Bacterium Cell Surface Domain*

    PubMed Central

    Coïc, Yves-Marie; Baleux, Francoise; Poyraz, Ömer; Thibeaux, Roman; Labruyere, Elisabeth; Chretien, Fabrice; Sobhani, Iradj; Lazure, Thierry; Wyplosz, Benjamin; Schneider, Gunter; Mulard, Laurence; Sansonetti, Philippe J.; Marteyn, Benoit S.

    2012-01-01

    Imaging living cells and organs requires innovative, specific, efficient, and well tolerated fluorescent markers targeting cellular components. Such tools will allow proceeding to the dynamic analysis of cells and the adaptation of tissues to environmental cues. In this study, we have identified and synthesized a novel non-toxic fluorescent marker allowing a specific fluorescent staining of the human colonic mucus. Our strategy to identify a molecule able to specifically bind to the human colonic mucus was on the basis of the mucus adhesion properties of commensal bacteria. We identified and characterized the mucus-binding property of a 70-amino acid domain (MUB70) expressed on the surface of Lactobacillus strains. The chemical synthesis of MUB70 was achieved using the human commensal bacterium Lactobacillus reuteri AF120104 protein as a template. The synthesized Cy5-conjugated MUB70 marker specifically stained the colonic mucus on fixed human, rabbit, and guinea pig tissues. Interestingly, murine tissue was not stained, suggesting significant differences in the composition of the murine colonic mucus. In addition, this marker stained the mucus of living cultured human colonic cells (HT29-MTX) and human colonic tissue explants. Using a biotinylated derivative of MUB70, we demonstrated that this peptide binds specifically to Muc2, the most abundant secreted mucin, through its glycosylated moieties. Hence, Cy5-MUB70 is a novel and specific fluorescent marker for mammalian colonic mucus. It may be used for live imaging analysis but also, as demonstrated in this study, as a marker for the diagnosis and the prognosis of colonic mucinous carcinomas. PMID:22427651

  16. Design of a specific colonic mucus marker using a human commensal bacterium cell surface domain.

    PubMed

    Coïc, Yves-Marie; Baleux, Francoise; Poyraz, Ömer; Thibeaux, Roman; Labruyere, Elisabeth; Chretien, Fabrice; Sobhani, Iradj; Lazure, Thierry; Wyplosz, Benjamin; Schneider, Gunter; Mulard, Laurence; Sansonetti, Philippe J; Marteyn, Benoit S

    2012-05-01

    Imaging living cells and organs requires innovative, specific, efficient, and well tolerated fluorescent markers targeting cellular components. Such tools will allow proceeding to the dynamic analysis of cells and the adaptation of tissues to environmental cues. In this study, we have identified and synthesized a novel non-toxic fluorescent marker allowing a specific fluorescent staining of the human colonic mucus. Our strategy to identify a molecule able to specifically bind to the human colonic mucus was on the basis of the mucus adhesion properties of commensal bacteria. We identified and characterized the mucus-binding property of a 70-amino acid domain (MUB(70)) expressed on the surface of Lactobacillus strains. The chemical synthesis of MUB(70) was achieved using the human commensal bacterium Lactobacillus reuteri AF120104 protein as a template. The synthesized Cy5-conjugated MUB(70) marker specifically stained the colonic mucus on fixed human, rabbit, and guinea pig tissues. Interestingly, murine tissue was not stained, suggesting significant differences in the composition of the murine colonic mucus. In addition, this marker stained the mucus of living cultured human colonic cells (HT29-MTX) and human colonic tissue explants. Using a biotinylated derivative of MUB(70), we demonstrated that this peptide binds specifically to Muc2, the most abundant secreted mucin, through its glycosylated moieties. Hence, Cy5-MUB(70) is a novel and specific fluorescent marker for mammalian colonic mucus. It may be used for live imaging analysis but also, as demonstrated in this study, as a marker for the diagnosis and the prognosis of colonic mucinous carcinomas. PMID:22427651

  17. Hyper-osmolarity and calcium chelation: Effects on cystic fibrosis mucus.

    PubMed

    Ermund, Anna; Meiss, Lauren N; Gustafsson, Jenny K; Hansson, Gunnar C

    2015-10-01

    A non-functional Cystic Fibrosis Transmembrane conductance Regulator (CFTR) leads to the disease cystic fibrosis (CF). Although the CFTR is expressed in multiple organs, pulmonary disease is the major cause of illness and death in patients with CF. Stagnant mucus, causing airway obstruction, bacterial overgrowth, persistent inflammation and tissue destruction characterizes the disease, but how the defect in CFTR function is coupled to the mucus phenotype is still controversial. We have recently shown that bicarbonate ions passing through CFTR are necessary for proper unfolding of the MUC2 mucin, thus highlighting the importance of bicarbonate ion transport via the CFTR and the ability of these ions to raise the pH and chelate calcium bound to the mucin as the important steps in forming normal mucus. In order to find potential CF treatments and expand our knowledge about the usefulness of bicarbonate as an active ingredient in formulations to alleviate mucus plugging, we used an Ussing-type chamber and explants from the F508del-CFTR mutant mouse ileum to test the effect of calcium chelators on mucus attachment, either in isolation or in combination with osmolytes such as mannitol or hypertonic saline. We found that increasing the concentration of bicarbonate, both alone or in combination with increased osmolarity of the solution, detached the otherwise attached CF mucus. PMID:26134505

  18. Role of mucus in gastric mucosal injury induced by local ischemia/reperfusion.

    PubMed

    Seno, K; Joh, T; Yokoyama, Y; Itoh, M

    1995-09-01

    The role of gastric mucus was evaluated in a rat model of gastric epithelial damage induced by local ischemia/reperfusion (I/R) stress. In this model, blood-to-lumen chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) clearance served as an index of injury. Tetraprenyl acetone (TPA; 100 mg, 200 mg/kg IP) was used to stimulate mucus production. Administration of TPA increased both the hexosamine content in gastric tissue and the amount of alcian blue-periodic acid Schiff (AB-PAS) stained mucus in the mucosa in a dose-dependent manner. Increases in 51Cr-EDTA clearance induced by I/R were significantly attenuated by TPA in a dose-dependent manner. N-acetyl-L-cysteine (NAC; 0.6%, 0.8%) was perfused into the gastric lumen to assess the effect of reduction in mucus on the injury induced by I/R. Although mean values of hexosamine content were increased by perfusion with NAC, AB-PAS-stained mucus in the mucosa was significantly decreased in a dose-dependent manner. Perfusion of NAC did not change basal 51Cr-EDTA clearance but significantly exacerbated the increase in clearance induced by I/R in a dose-dependent manner. These results indicate that gastric mucus protects the gastric mucosa against I/R stress in vivo. PMID:7665977

  19. The effects of smoking and smoking cessation on nasal mucociliary clearance, mucus properties and inflammation

    PubMed Central

    Utiyama, Daniela Mitiyo Odagiri; Yoshida, Carolina Tieko; Goto, Danielle Miyuki; de Santana Carvalho, Tômas; de Paula Santos, Ubiratan; Koczulla, Andreas Rembert; Saldiva, Paulo Hilário Nascimento; Nakagawa, Naomi Kondo

    2016-01-01

    OBJECTIVE: The aim of the present study was to assess nasal mucociliary clearance, mucus properties and inflammation in smokers and subjects enrolled in a Smoking Cessation Program (referred to as quitters). METHOD: A total of 33 subjects with a median (IQR) smoking history of 34 (20-58) pack years were examined for nasal mucociliary clearance using a saccharine transit test, mucus properties using contact angle and sneeze clearability tests, and quantification of inflammatory and epithelial cells, IL-6 and IL-8 concentrations in nasal lavage fluid. Twenty quitters (mean age: 51 years, 9 male) were assessed at baseline, 1 month, 3 months and 12 months after smoking cessation, and 13 smokers (mean age: 52 years, 6 male) were assessed at baseline and after 12 months. Clinicaltrials.gov: NCT02136550. RESULTS: Smokers and quitters showed similar demographic characteristics and morbidities. At baseline, all subjects showed impaired nasal mucociliary clearance (mean 17.6 min), although 63% and 85% of the quitters demonstrated significant nasal mucociliary clearance improvement at 1 month and 12 months, respectively. At 12 months, quitters also showed mucus sneeze clearability improvement (∼26%), an increased number of macrophages (2-fold) and no changes in mucus contact angle or cytokine concentrations. CONCLUSION: This study showed that smoking cessation induced early improvements in nasal mucociliary clearance independent of mucus properties and inflammation. Changes in mucus properties were observed after only 12 months of smoking cessation. PMID:27438569

  20. Lung Gene Therapy with Highly Compacted DNA Nanoparticles that Overcome the Mucus Barrier

    PubMed Central

    Suk, Jung Soo; Kim, Anthony J.; Trehan, Kanika; Schneider, Craig S.; Cebotaru, Liudmila; Woodward, Owen M.; Boylan, Nicholas J.; Boyle, Michael P.; Lai, Samuel K.; Guggino, William B.; Hanes, Justin

    2014-01-01

    Inhaled gene carriers must penetrate the highly viscoelastic and adhesive mucus barrier in the airway in order to overcome rapid mucociliary clearance and reach the underlying epithelium; however, even the most widely used viral gene carriers are unable to efficiently do so. We developed two polymeric gene carriers that compact plasmid DNA into small and highly stable nanoparticles with dense polyethylene glycol (PEG) surface coatings. These highly compacted, densely PEG-coated DNA nanoparticles rapidly penetrate human cystic fibrosis (CF) mucus ex vivo and mouse airway mucus ex situ. Intranasal administration of the mucus penetrating DNA nanoparticles greatly enhanced particle distribution, retention and gene transfer in the mouse lung airways compared to conventional gene carriers. Successful delivery of a full-length plasmid encoding the cystic fibrosis transmembrane conductance regulator protein was achieved in mouse lungs and airway cells, including a primary culture of mucus-covered human airway epithelium grown at air-liquid interface, without causing acute inflammation or toxicity. Highly compacted mucus penetrating DNA nanoparticles hold promise for lung gene therapy. PMID:24440664

  1. Predicting first traversal times for virions and nanoparticles in mucus with slowed diffusion.

    PubMed

    Erickson, Austen M; Henry, Bruce I; Murray, John M; Klasse, Per Johan; Angstmann, Christopher N

    2015-07-01

    Particle-tracking experiments focusing on virions or nanoparticles in mucus have measured mean-square displacements and reported diffusion coefficients that are orders of magnitude smaller than the diffusion coefficients of such particles in water. Accurate description of this subdiffusion is important to properly estimate the likelihood of virions traversing the mucus boundary layer and infecting cells in the epithelium. However, there are several candidate models for diffusion that can fit experimental measurements of mean-square displacements. We show that these models yield very different estimates for the time taken for subdiffusive virions to traverse through a mucus layer. We explain why fits of subdiffusive mean-square displacements to standard diffusion models may be misleading. Relevant to human immunodeficiency virus infection, using computational methods for fractional subdiffusion, we show that subdiffusion in normal acidic mucus provides a more effective barrier against infection than previously thought. By contrast, the neutralization of the mucus by alkaline semen, after sexual intercourse, allows virions to cross the mucus layer and reach the epithelium in a short timeframe. The computed barrier protection from fractional subdiffusion is some orders of magnitude greater than that derived by fitting standard models of diffusion to subdiffusive data. PMID:26153713

  2. Analysis of gunshot residues as trace in nasal mucus by GFAAS.

    PubMed

    Aliste, Marina; Chávez, Luis Guillermo

    2016-04-01

    When a gun is fired, the majority of gunshot residues are deposited on the shooter's hands. But these residues disappear through contact with surfaces or washing. Therefore, the maximum time frame to find GSR on a suspect's hands is 8h. The mucus, inside of a nostril, forms a surface layer where they are trapped foreign particles. In this way, mucus inside of a gunshot suspect's nostrils could act like an adhesive medium to stick on it gaseous particles from a gunshot. In this study, the presence of GSR in nasal mucus and its residence time is examined. A new procedure for the sampling of possible gunshot residue accumulated in the nasal mucus is designed. Samples are taken with cotton swabs moistened with a solution of EDTA and, after an acid digestion, are analysed by graphite furnace atomic absorption spectrometry. In addition, samples of hands are taken for comparison purposes. GSR recovery has been successful. The concentration of GSR in nasal mucus is found to be lower than on the hands, but with a longer residence time. Thus, it is possible to expand the sampling time of a suspect also, as nasal mucus cannot be contaminated by handling weapons. PMID:26874050

  3. The protease-activated receptor-2 agonist induces gastric mucus secretion and mucosal cytoprotection

    PubMed Central

    Kawabata, Atsufumi; Kinoshita, Mitsuhiro; Nishikawa, Hiroyuki; Kuroda, Ryotaro; Nishida, Minoru; Araki, Hiromasa; Arizono, Naoki; Oda, Yasuo; Kakehi, Kazuaki

    2001-01-01

    Protease-activated receptor-2 (PAR-2), a receptor activated by trypsin/tryptase, modulates smooth muscle tone and exocrine secretion in the salivary glands and pancreas. Given that PAR-2 is expressed throughout the gastrointestinal tract, we investigated effects of PAR-2 agonists on mucus secretion and gastric mucosal injury in the rat. PAR-2–activating peptides triggered secretion of mucus in the stomach, but not in the duodenum. This mucus secretion was abolished by pretreatment with capsaicin, which stimulates and ablates specific sensory neurons, but it was resistant to cyclo-oxygenase inhibition. In contrast, capsaicin treatment failed to block PAR-2–mediated secretion from the salivary glands. Intravenous calcitonin gene–related peptide (CGRP) and neurokinin A markedly elicited gastric mucus secretion, as did substance P to a lesser extent. Specific antagonists of the CGRP1 and NK2, but not the NK1, receptors inhibited PAR-2–mediated mucus secretion. Pretreatment with the PAR-2 agonist strongly prevented gastric injury caused by HCl-ethanol or indomethacin. Thus, PAR-2 activation triggers the cytoprotective secretion of gastric mucus by stimulating the release of CGRP and tachykinins from sensory neurons. In contrast, the PAR-2–mediated salivary exocrine secretion appears to be independent of capsaicin-sensitive sensory neurons. PMID:11390426

  4. Predicting First Traversal Times for Virions and Nanoparticles in Mucus with Slowed Diffusion

    PubMed Central

    Erickson, Austen M.; Henry, Bruce I.; Murray, John M.; Klasse, Per Johan; Angstmann, Christopher N.

    2015-01-01

    Particle-tracking experiments focusing on virions or nanoparticles in mucus have measured mean-square displacements and reported diffusion coefficients that are orders of magnitude smaller than the diffusion coefficients of such particles in water. Accurate description of this subdiffusion is important to properly estimate the likelihood of virions traversing the mucus boundary layer and infecting cells in the epithelium. However, there are several candidate models for diffusion that can fit experimental measurements of mean-square displacements. We show that these models yield very different estimates for the time taken for subdiffusive virions to traverse through a mucus layer. We explain why fits of subdiffusive mean-square displacements to standard diffusion models may be misleading. Relevant to human immunodeficiency virus infection, using computational methods for fractional subdiffusion, we show that subdiffusion in normal acidic mucus provides a more effective barrier against infection than previously thought. By contrast, the neutralization of the mucus by alkaline semen, after sexual intercourse, allows virions to cross the mucus layer and reach the epithelium in a short timeframe. The computed barrier protection from fractional subdiffusion is some orders of magnitude greater than that derived by fitting standard models of diffusion to subdiffusive data. PMID:26153713

  5. The Mucus of Actinia equina (Anthozoa, Cnidaria): An Unexplored Resource for Potential Applicative Purposes.

    PubMed

    Stabili, Loredana; Schirosi, Roberto; Parisi, Maria Giovanna; Piraino, Stefano; Cammarata, Matteo

    2015-08-01

    The mucus produced by many marine organisms is a complex mixture of proteins and polysaccharides forming a weak watery gel. It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens. In the present study we focused on mucus produced by a benthic cnidarian, the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection. We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. Some biological activities such as hemolytic, cytotoxic, and antibacterial lysozyme-like activities were also studied. The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones' mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. PMID:26295400

  6. High occurrence of viruses in the mucus layer of scleractinian corals.

    PubMed

    Nguyen-Kim, Hanh; Bouvier, Thierry; Bouvier, Corinne; Doan-Nhu, Hai; Nguyen-Ngoc, Lam; Rochelle-Newall, Emma; Baudoux, Anne-Claire; Desnues, Christelle; Reynaud, Stéphanie; Ferrier-Pages, Christine; Bettarel, Yvan

    2014-12-01

    Viruses attract increasing interest from environmental microbiologists seeking to understand their function and role in coral health. However, little is known about their main ecological traits within the coral holobiont. In this study, a quantitative and qualitative characterization of viral and bacterial communities was conducted on the mucus of seven different coral species of the Van Phong Bay (Vietnam). On average, the concentrations of viruses and bacteria were, respectively, 17- and twofold higher in the mucus than in the surrounding water. The examination of bacterial community composition also showed remarkable differences between mucus and water samples. The percentage of active respiring cells was nearly threefold higher in mucus (m = 24.8%) than in water (m = 8.6%). Interestingly, a positive and highly significant correlation was observed between the proportion of active cells and viral abundance in the mucus, suggesting that the metabolism of the bacterial associates is probably a strong determinant of the distribution of viruses within the coral holobiont. Overall, coral mucus, given its unique physicochemical characteristics and sticking properties, can be regarded as a highly selective biotope for abundant, diversified and specialized symbiotic microbial and viral organisms. PMID:25756121

  7. The Mucus of Actinia equina (Anthozoa, Cnidaria): An Unexplored Resource for Potential Applicative Purposes

    PubMed Central

    Stabili, Loredana; Schirosi, Roberto; Parisi, Maria Giovanna; Piraino, Stefano; Cammarata, Matteo

    2015-01-01

    The mucus produced by many marine organisms is a complex mixture of proteins and polysaccharides forming a weak watery gel. It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens. In the present study we focused on mucus produced by a benthic cnidarian, the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection. We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. Some biological activities such as hemolytic, cytotoxic, and antibacterial lysozyme-like activities were also studied. The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones’ mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. PMID:26295400

  8. Lung gene therapy with highly compacted DNA nanoparticles that overcome the mucus barrier.

    PubMed

    Suk, Jung Soo; Kim, Anthony J; Trehan, Kanika; Schneider, Craig S; Cebotaru, Liudmila; Woodward, Owen M; Boylan, Nicholas J; Boyle, Michael P; Lai, Samuel K; Guggino, William B; Hanes, Justin

    2014-03-28

    Inhaled gene carriers must penetrate the highly viscoelastic and adhesive mucus barrier in the airway in order to overcome rapid mucociliary clearance and reach the underlying epithelium; however, even the most widely used viral gene carriers are unable to efficiently do so. We developed two polymeric gene carriers that compact plasmid DNA into small and highly stable nanoparticles with dense polyethylene glycol (PEG) surface coatings. These highly compacted, densely PEG-coated DNA nanoparticles rapidly penetrate human cystic fibrosis (CF) mucus ex vivo and mouse airway mucus ex situ. Intranasal administration of the mucus penetrating DNA nanoparticles greatly enhanced particle distribution, retention and gene transfer in the mouse lung airways compared to conventional gene carriers. Successful delivery of a full-length plasmid encoding the cystic fibrosis transmembrane conductance regulator protein was achieved in the mouse lungs and airway cells, including a primary culture of mucus-covered human airway epithelium grown at air-liquid interface, without causing acute inflammation or toxicity. Highly compacted mucus penetrating DNA nanoparticles hold promise for lung gene therapy. PMID:24440664

  9. An in vitro study of mucoadhesion and biocompatibility of polymer coated liposomes on HT29-MTX mucus-producing cells.

    PubMed

    Adamczak, Małgorzata I; Hagesaether, Ellen; Smistad, Gro; Hiorth, Marianne

    2016-02-10

    Drug delivery to the oral cavity poses a significant challenge due to the short residence time of the formulations at the site of action. From this point of view, nanoparticulate drug delivery systems with ability to adhere to the oral mucosa are advantageous as they could increase the effectiveness of the therapy. Positively, negatively and neutrally charged liposomes were coated with four different types of polymers: alginate, low-ester pectin, chitosan and hydrophobically modified ethyl hydroxyethyl cellulose. The mucoadhesion was studied using a novel in vitro method allowing the liposomes to interact with a mucus-producing confluent HT29-MTX cell-line without applying any external force. MTT viability and paracellular permeability tests were conducted on the same cell-line. The alginate-coated liposomes achieved a high specific (genuine) mucin interaction, with a low potential of cell-irritation. The positively charged uncoated liposomes achieved the highest initial mucoadhesion, but also displayed a higher probability of cell-irritation. The chitosan-coated liposomes displayed the highest potential for long lasting mucoadhesion, but with the drawback of a higher general adhesion (tack) and a higher potential for irritating the cells. PMID:26706437

  10. Direct Visualization of Mucus Production by the Cold-Water Coral Lophelia pertusa with Digital Holographic Microscopy.

    PubMed

    Zetsche, Eva-Maria; Baussant, Thierry; Meysman, Filip J R; van Oevelen, Dick

    2016-01-01

    Lophelia pertusa is the dominant reef-building organism of cold-water coral reefs, and is known to produce significant amounts of mucus, which could involve an important metabolic cost. Mucus is involved in particle removal and feeding processes, yet the triggers and dynamics of mucus production are currently still poorly described because the existing tools to study these processes are not appropriate. Using a novel microscopic technique-digital holographic microscopy (DHM)-we studied the mucus release of L. pertusa under various experimental conditions. DHM technology permits μm-scale observations and allows the visualization of transparent mucoid substances in real time without staining. Fragments of L. pertusa were first maintained in flow-through chambers without stressors and imaged with DHM, then exposed to various stressors (suspended particles, particulate food and air exposure) and re-imaged. Under non-stressed conditions no release of mucus was observed, whilst mucus strings and sheaths were produced in response to suspended particles (activated charcoal and drill cuttings sediment) i.e. in a stressed condition. Mucus strings and so-called 'string balls' were also observed in response to exposure to particulate food (brine shrimp Artemia salina). Upon air-exposure, mucus production was clearly visible once the fragments were returned to the flow chamber. Distinct optical properties such as optical path length difference (OPD) were measured with DHM in response to the various stimuli suggesting that different mucus types are produced by L. pertusa. Mucus produced to reject particles is similar in refractive index to the surrounding seawater, suggesting that the energy content of this mucus is low. In contrast, mucus produced in response to either food particle addition or air exposure had a higher refractive index, suggesting a higher metabolic investment in the production of these mucoid substances. This paper shows for the first time the potential of

  11. Penetrability of the inner mucus layer: who is out there?

    PubMed Central

    Li, Hai; Limenitakis, Julien P; Ganal, Stephanie C; Macpherson, Andrew J

    2015-01-01

    Large numbers of microorganisms colonise the skin and mucous membranes of animals, with their highest density in the lower gastrointestinal tract. The impact of these microbes on the host can be demonstrated by comparing animals (usually mice) housed under germ-free conditions, or colonised with different compositions of microbes. Inbreeding and embryo manipulation programs have generated a wide variety of mouse strains with a fixed germ-line (isogenic) and hygiene comparisons robustly show remarkably strong interactions between the microbiota and the host, which can be summarised in three axioms. (I) Live microbes are largely confined to their spaces at body surfaces, provided the animal is not suffering from an infection. (II) There is promiscuous molecular exchange throughout the host and its microbiota in both directions 1. (III) Every host organ system is profoundly shaped by the presence of body surface microbes. It follows that one must draw a line between live microbial and host “spaces” (I) to understand the crosstalk (II and III) at this interesting interface of the host-microbial superorganism. Of course, since microbes can adapt to very different niches, there has to be more than one line. In this issue of EMBO Reports, Johansson and colleagues have studied mucus, which is the main physical frontier for most microbes in the intestinal tract: they report how different non-pathogenic microbiota compositions affect its permeability and the functional protection of the epithelial surface 2. PMID:25572842

  12. Medication Adherence Measures: An Overview

    PubMed Central

    Lam, Wai Yin; Fresco, Paula

    2015-01-01

    WHO reported that adherence among patients with chronic diseases averages only 50% in developed countries. This is recognized as a significant public health issue, since medication nonadherence leads to poor health outcomes and increased healthcare costs. Improving medication adherence is, therefore, crucial and revealed on many studies, suggesting interventions can improve medication adherence. One significant aspect of the strategies to improve medication adherence is to understand its magnitude. However, there is a lack of general guidance for researchers and healthcare professionals to choose the appropriate tools that can explore the extent of medication adherence and the reasons behind this problem in order to orchestrate subsequent interventions. This paper reviews both subjective and objective medication adherence measures, including direct measures, those involving secondary database analysis, electronic medication packaging (EMP) devices, pill count, and clinician assessments and self-report. Subjective measures generally provide explanations for patient's nonadherence whereas objective measures contribute to a more precise record of patient's medication-taking behavior. While choosing a suitable approach, researchers and healthcare professionals should balance the reliability and practicality, especially cost effectiveness, for their purpose. Meanwhile, because a perfect measure does not exist, a multimeasure approach seems to be the best solution currently. PMID:26539470

  13. Medication Adherence Measures: An Overview.

    PubMed

    Lam, Wai Yin; Fresco, Paula

    2015-01-01

    WHO reported that adherence among patients with chronic diseases averages only 50% in developed countries. This is recognized as a significant public health issue, since medication nonadherence leads to poor health outcomes and increased healthcare costs. Improving medication adherence is, therefore, crucial and revealed on many studies, suggesting interventions can improve medication adherence. One significant aspect of the strategies to improve medication adherence is to understand its magnitude. However, there is a lack of general guidance for researchers and healthcare professionals to choose the appropriate tools that can explore the extent of medication adherence and the reasons behind this problem in order to orchestrate subsequent interventions. This paper reviews both subjective and objective medication adherence measures, including direct measures, those involving secondary database analysis, electronic medication packaging (EMP) devices, pill count, and clinician assessments and self-report. Subjective measures generally provide explanations for patient's nonadherence whereas objective measures contribute to a more precise record of patient's medication-taking behavior. While choosing a suitable approach, researchers and healthcare professionals should balance the reliability and practicality, especially cost effectiveness, for their purpose. Meanwhile, because a perfect measure does not exist, a multimeasure approach seems to be the best solution currently. PMID:26539470

  14. Induction of Apoptosis and Antitumor Activity of Eel Skin Mucus, Containing Lactose-Binding Molecules, on Human Leukemic K562 Cells

    PubMed Central

    Kwak, Choong-Hwan; Lee, Sook-Hyun; Lee, Sung-Kyun; Ha, Sun-Hyung; Suh, Seok-Jong; Kwon, Kyung-Min; Chung, Tae-Wook; Ha, Ki-Tae; Chang, Young-Chae; Lee, Young-Choon; Kim, Dong-Soo; Chang, Hyeun-Wook; Kim, Cheorl-Ho

    2015-01-01

    For innate immune defense, lower animals such as fish and amphibian are covered with skin mucus, which acts as both a mechanical and biochemical barrier. Although several mucus sources have been isolated and studied for their biochemical and immunological functions, the precise mechanism(s) of action remains unknown. In the present study, we additionally found the eel skin mucus (ESM) to be a promising candidate for use in anti-tumor therapy. Our results showed that the viability of K562 cells was decreased in a dose-dependent manner by treatment with the isolated ESM. The cleaved forms of caspase-9, caspase-3 and poly adenosine diphosphate-ribose polymerase were increased by ESM. The levels of Bax expression and released cytochrome C were also increased after treatment with ESM. Furthermore, during the ESM mediated-apoptosis, phosphorylation levels of ERK1/2 and p38 but not JNK were increased and cell viabilities of the co-treated cells with ESM and inhibitors of ERK 1/2 or p38 were also increased. In addition, treatment with lactose rescued the ESM-mediated decrease in cell viability, indicating lactose-containing glycans in the leukemia cells acted as a counterpart of the ESM for interaction. Taken together, these results suggest that ESM could induce mitochondria-mediated apoptosis through membrane interaction of the K562 human leukemia cells. To the best of our knowledge, this is the first observation that ESM has anti-tumor activity in human cells. PMID:26090845

  15. [Concept analysis of medication adherence in patients with chronic disease].

    PubMed

    Huang, Jen-Ying; Chen, Hsing-Mei

    2014-06-01

    Pharmacotherapy plays an important role in the management of chronic diseases. However, many patients with chronic disease do not adhere to their medication regimen. This results in worsening symptoms and frequent re-hospitalizations. As a result, healthcare providers may view these patients as bad. Medication adherence is a complex concept. Analyzing this concept may assist nurses to improve patient-centered care. This paper uses Walker & Avant's method to conduct a concept analysis of medication adherence. Results show the defining attributes of medication adherence as: (1) knowing and agreeing to the medication; (2) communicating and negotiating the regimen; and (3) active, continuous involvement in and appraisal of the treatment effect. Identified antecedents of medication adherence included the patient having: (1) a prescribed medication regimen; (2) cognitive and action abilities in her / his role as a patient; and (3) level of preparation for medication treatment. Identified consequences of medication adherence include: (1) improving symptom control; (2) decreasing re-hospitalizations and mortality; (3) reducing medical care costs; (4) restoring self-esteem; and (5) diminishing depression. It is hoped that this concept analysis provides a reference for nurses to achieve a better understanding of medication adherence and further improve nursing practice. PMID:24899565

  16. Adherence to inhaled corticosteroids: An ancillary study of the Childhood Asthma Management Program clinical trial

    PubMed Central

    Krishnan, Jerry A.; Bender, Bruce G.; Wamboldt, Frederick S.; Szefler, Stanley J.; Adkinson, N. Franklin; Zeiger, Robert S.; Wise, Robert A.; Bilderback, Andrew L.; Rand, Cynthia S.

    2011-01-01

    Background Information comparing subjective and objective measurements of adherence to study medications and the effects of adherence on treatment-related differences in asthma clinical trials are limited. Objective We sought to compare subjective and objective measurements of children’s adherence to inhaled corticosteroids or placebo and to determine whether adherence to study medications modified treatment-related differences in outcomes. Methods In an ancillary study conducted in 3 of 8 Childhood Asthma Management Program Clinical Centers, adherence was assessed by using self-reported and objective data in 5- to 12-year-old children with mild or moderate asthma who were randomly assigned to 200 μg of inhaled budesonide twice per day (n = 84) or placebo (n = 56) for 4 years. The κ statistic was used to evaluate agreement between self-reported adherence (daily diary cards) and objectively measured adherence (number of doses left in study inhalers). Multivariable analyses were used to determine whether adherence to study treatment modified treatment-related differences in outcomes. Results Adherence of less than 80% was seen in 75% of 140 children when adherence was measured objectively but only in 6% of children when measured by means of self-report. There was poor agreement between objective and subjective measurements of adherence of at least 80% (κ = 0.00; 95% CI, −0.05 to 0.04); self-reported adherence over the 4-year period generally overestimated objectively measured adherence (93.6% vs 60.8%, P < .0001). There was little evidence to indicate that adherence modified treatment-related differences in outcomes. Conclusion Researchers should use objective rather than self-reported adherence data to identify clinical trial participants with low levels of adherence to study treatment. PMID:22104610

  17. Differential expression of skin mucus C-type lectin in two freshwater eel species, Anguilla marmorata and Anguilla japonica.

    PubMed

    Tsutsui, Shigeyuki; Yoshinaga, Tatsuki; Komiya, Kaoru; Yamashita, Hiroka; Nakamura, Osamu

    2016-08-01

    Two types of lactose-specific lectins, galectin (AJL-1) and C-type lectin (AJL-2), were previously identified in the mucus of adult Anguilla japonica. Here, we compared the expression profiles of these two homologous lectins at the adult and juvenile stages between the tropical eel Anguilla marmorata and the temperate eel A. japonica. Only one lectin, predicted to be an orthologue of AJL-1 by LC-MS/MS, was detected in the mucus of adult A. marmorata. We also found that an orthologous gene to AJL-2 was expressed at very low levels, or not at all, in the skin of adult A. marmorata. However, we detected the gene expression of an AJL-2-orthologue in the skin of juvenile A. marmorata, and a specific antibody also detected the lectin in the juvenile fish epidermis. These findings suggest that expression profiles of mucosal lectins vary during development as well as between species in the Anguilla genus. PMID:27026508

  18. TMEM16A mediates the hypersecretion of mucus induced by Interleukin-13

    SciTech Connect

    Lin, Jiachen; Jiang, Youfan; Li, Li; Liu, Yanan; Tang, Hui; Jiang, Depeng

    2015-06-10

    Previous studies showed that the Ca{sup 2+}-activated Cl{sup −} channel (CaCC) was involved in the pathogenesis of mucus hypersecretion induced by Interleukin-13 (IL-13). However, the mechanisms underlying the process were unknown. Recently, transmembrane protein 16A (TMEM16A) was identified as the channel underlying the CaCC current. The aim of the current study was to investigate whether the TMEM16A channel is part of the mechanism underlying IL-13-induced mucus hypersecretion. We observed that both TMEM16A mRNA and protein expression were significantly up-regulated after treatment with IL-13 in human bronchial epithelial 16 (HBE 16) cells, which correlated with an increase in mucus production. Additionally, mucus hypersecretion in rat airways was induced by intratracheal instillation of IL-13 and similar increases were observed in the expression of TMEM16A mRNA and protein in the bronchial epithelium. Niflumic acid (NA), a selective antagonist of CaCC, markedly blocked IL-13-induced mucin (MUC) 5AC mRNA and protein production in vivo and in vitro. Further investigation with HBE16 cells revealed that TMEM16A overexpression clearly promoted mucus production, IκBα phosphorylation, and p65 accumulation in the nucleus. The loss of TMEM16A resulted in inhibition of mucus production, and the TMEM16A-mediated production of MUC5AC was significantly blocked by a nuclear factor-kappa B (NF-κB) inhibitor. Therefore, the TMEM16A channel acts upstream of NF-κB in the regulation of mucus production. This is the first demonstration that the TMEM16A-NF-κB pathway is positively involved in IL-13-induced mucus production, which provides novel insight into the molecular mechanism of mucin overproduction. - Highlights: • TMEM16A acts as downstream events of IL-13 signaling pathway. • Established the link between TMEM16A and mucus hypersecretion. • NF-κB activation might be responsible for TMEM16A mediated mucus secretion.

  19. How Patients Take Malaria Treatment: A Systematic Review of the Literature on Adherence to Antimalarial Drugs

    PubMed Central

    Bruxvoort, Katia; Goodman, Catherine; Kachur, S. Patrick; Schellenberg, David

    2014-01-01

    Background High levels of patient adherence to antimalarial treatment are important in ensuring drug effectiveness. To achieve this goal, it is important to understand levels of patient adherence, and the range of study designs and methodological challenges involved in measuring adherence and interpreting results. Since antimalarial adherence was reviewed in 2004, there has been a major expansion in the use of artemisinin-based combination therapies (ACTs) in the public sector, as well as initiatives to make them more widely accessible through community health workers and private retailers. These changes and the large number of recent adherence studies raise the need for an updated review on this topic. Objective We conducted a systematic review of studies reporting quantitative results on patient adherence to antimalarials obtained for treatment. Results The 55 studies identified reported extensive variation in patient adherence to antimalarials, with many studies reporting very high adherence (90–100%) and others finding adherence of less than 50%. We identified five overarching approaches to assessing adherence based on the definition of adherence and the methods used to measure it. Overall, there was no clear pattern in adherence results by approach. However, adherence tended to be higher among studies where informed consent was collected at the time of obtaining the drug, where patient consultations were directly observed by research staff, and where a diagnostic test was obtained. Conclusion Variations in reported adherence may reflect factors related to patient characteristics and the nature of their consultation with the provider, as well as methodological variations such as interaction between the research team and patients before and during the treatment. Future studies can benefit from an awareness of the impact of study procedures on adherence outcomes, and the identification of improved measurement methods less dependent on self-report. PMID:24465418

  20. Investigating Reasons for CPAP Adherence in Adolescents: A Qualitative Approach

    PubMed Central

    Prashad, Priya S.; Marcus, Carole L.; Maggs, Jill; Stettler, Nicolas; Cornaglia, Mary A.; Costa, Priscilla; Puzino, Kristina; Xanthopoulos, Melissa; Bradford, Ruth; Barg, Frances K.

    2013-01-01

    Study Objectives: Adolescents with obstructive sleep apnea syndrome (OSAS) represent an important but understudied subgroup of long-term continuous positive airway pressure (CPAP) users. The purpose of this qualitative study was to identify factors related to adherence from the perspective of adolescents and their caregivers. Methods: Individual open-ended, semi-structured interviews were conducted with adolescents (n = 21) and caregivers (n = 20). Objective adherence data from the adolescents' CPAP machines during the previous month was obtained. Adolescents with different adherence levels and their caregivers were asked their views on CPAP. Using a modified grounded theory approach, we identified themes and developed theories that explained the adolescents' adherence patterns. Results: Adolescent participants (n = 21) were aged 12-18 years, predominantly male (n = 15), African American (n = 16), users of CPAP for at least one month. Caregivers were mainly mothers (n = 17). Seven adolescents had high use (mean use 381 ± 80 min per night), 7 had low use (mean use 30 ± 24 min per night), and 7 had no use during the month prior to being interviewed. Degree of structure in the home, social reactions, mode of communication among family members, and perception of benefits were issues that played a role in CPAP adherence. Conclusions: Understanding the adolescent and family experience of using CPAP may be key to increasing adolescent CPAP adherence. As a result of our findings, we speculate that health education, peer support groups, and developmentally appropriate individualized support strategies may be important in promoting adherence. Future studies should examine these theories of CPAP adherence. Citation: Prashad PS; Marcus CL; Maggs J; Stettler N; Cornaglia MA; Costa P; Puzino K; Xanthopoulos M; Bradford R; Barg FK. Investigating reasons for CPAP adherence in adolescents: a qualitative approach. J Clin Sleep Med 2013;9(12):1303-1313. PMID:24340293

  1. Pharmacists’ perspectives on promoting medication adherence among patients with HIV

    PubMed Central

    Kibicho, Jennifer W.; Owczarzak, Jill

    2015-01-01

    Objectives To provide pharmacists’ perspectives on medication adherence barriers for patients with human immunodeficiency virus (HIV) and to describe pharmacists’ strategies for promoting adherence to antiretroviral medications. Design Multisite, qualitative, descriptive study. Setting Four midwestern U.S. states, from August through October 2009. Participants 19 pharmacists at 10 pharmacies providing services to patients with HIV. Intervention Pharmacists were interviewed using a semistructured interview guide. Main outcome measures Barriers to medication adherence, pharmacist interventions, challenges to promoting adherence. Results Pharmacists reported a range of adherence barriers that were patient specific (e.g., cognitive factors, lack of social support), therapy related (e.g., adverse effects, intolerable medications), and structural level (e.g., strained provider relationships). They used a combination of individually tailored, patient-specific interventions that identified and resolved adherence barriers and actively anticipated and addressed potential adherence barriers. Pharmacist interventions included medication-specific education to enhance patient self-efficacy, follow-up calls to monitor adherence, practical and social support to motivate adherence, and patient referrals to other health care providers. However, the pharmacists faced internal (e.g., lack of time, lack of trained personnel) and external (e.g., insurance policies that disallowed patient enrollment in automatic prescription refill program) challenges. Conclusion Pharmacists in community settings went beyond prescription drug counseling mandated by law to provide additional pharmacy services that were tailored to the needs of patients with HIV. Given that many individuals with HIV are living longer, more research is needed on the effectiveness and cost effectiveness of pharmacists’ interventions in clinical practice, in order to inform insurance reimbursement policies. PMID

  2. Modeling and Simulation of Mucus Flow in Human Bronchial Epithelial Cell Cultures - Part I: Idealized Axisymmetric Swirling Flow.

    PubMed

    Vasquez, Paula A; Jin, Yuan; Palmer, Erik; Hill, David; Forest, M Gregory

    2016-08-01

    A multi-mode nonlinear constitutive model for mucus is constructed directly from micro- and macro-rheology experimental data on cell culture mucus, and a numerical algorithm is developed for the culture geometry and idealized cilia driving conditions. This study investigates the roles that mucus rheology, wall effects, and HBE culture geometry play in the development of flow profiles and the shape of the air-mucus interface. Simulations show that viscoelasticity captures normal stress generation in shear leading to a peak in the air-mucus interface at the middle of the culture and a depression at the walls. Linear and nonlinear viscoelastic regimes can be observed in cultures by varying the hurricane radius and mean rotational velocity. The advection-diffusion of a drug concentration dropped at the surface of the mucus flow is simulated as a function of Peclet number. PMID:27494700

  3. Modeling and Simulation of Mucus Flow in Human Bronchial Epithelial Cell Cultures – Part I: Idealized Axisymmetric Swirling Flow

    PubMed Central

    Vasquez, Paula A.; Jin, Yuan; Palmer, Erik; Hill, David; Forest, M. Gregory

    2016-01-01

    A multi-mode nonlinear constitutive model for mucus is constructed directly from micro- and macro-rheology experimental data on cell culture mucus, and a numerical algorithm is developed for the culture geometry and idealized cilia driving conditions. This study investigates the roles that mucus rheology, wall effects, and HBE culture geometry play in the development of flow profiles and the shape of the air-mucus interface. Simulations show that viscoelasticity captures normal stress generation in shear leading to a peak in the air-mucus interface at the middle of the culture and a depression at the walls. Linear and nonlinear viscoelastic regimes can be observed in cultures by varying the hurricane radius and mean rotational velocity. The advection-diffusion of a drug concentration dropped at the surface of the mucus flow is simulated as a function of Peclet number. PMID:27494700

  4. Treatment adherence to an antiretroviral regime: the lived experience of Native Hawaiians and kokua.

    PubMed

    Ka'opua, L

    2001-09-01

    Treatment adherence to Highly Active Antiretroviral Therapy (HAART) is a critical issue in human immunodeficiency virus (HIV) care. HAART can extend the longevity of people living with HIV, but treatment efficacy relies on strict adherence that is difficult for many consumers to manage. Results presented in this article are based on semi-structured in-depth interviews with Native Hawaiian consumers (n = 6) who reported moderate to low levels of overall HAART adherence, and based on their kokua, or primary support. All interviews were recorded on audiotape, transcribed verbatim, and analyzed using Grounded Theory methods. Research questions that guided the inquiry, included: What are the challenges of Hawaiians who report moderate to low levels of HAART adherence? How does non-adherence occur? What is the role of the kokua (primary caregiver) and/or family members in treatment adherence? What types of support enhance adherence? The unpredictability of living with HIV was a major challenge to adherence. Symptom distress and active use of alcohol and other drugs interfered with the capacity to appropriately adhere. Two patterns of non-adherence were identified: interrupted regime and intermittent use. Tangible and emotional types of support, sometimes delivered in culture-specific ways, were viewed as helpful in maintaining compliance and in resuming the regime when difficulties arose. The findings complement extant research on HAART by providing an understanding of adherence as a lived experience among Native Hawaiians and their kokua. PMID:12180508

  5. A microfluidic model to study fluid dynamics of mucus plug rupture in small lung airways

    PubMed Central

    Hu, Yingying; Bian, Shiyao; Grotberg, John; Filoche, Marcel; White, Joshua; Takayama, Shuichi; Grotberg, James B.

    2015-01-01

    Fluid dynamics of mucus plug rupture is important to understand mucus clearance in lung airways and potential effects of mucus plug rupture on epithelial cells at lung airway walls. We established a microfluidic model to study mucus plug rupture in a collapsed airway of the 12th generation. Mucus plugs were simulated using Carbopol 940 (C940) gels at concentrations of 0.15%, 0.2%, 0.25%, and 0.3%, which have non-Newtonian properties close to healthy and diseased lung mucus. The airway was modeled with a polydimethylsiloxane microfluidic channel. Plug motion was driven by pressurized air. Global strain rates and shear stress were defined to quantitatively describe plug deformation and rupture. Results show that a plug needs to overcome yield stress before deformation and rupture. The plug takes relatively long time to yield at the high Bingham number. Plug length shortening is the more significant deformation than shearing at gel concentration higher than 0.15%. Although strain rates increase dramatically at rupture, the transient shear stress drops due to the shear-thinning effect of the C940 gels. Dimensionless time-averaged shear stress, Txy, linearly increases from 3.7 to 5.6 times the Bingham number as the Bingham number varies from 0.018 to 0.1. The dimensionless time-averaged shear rate simply equals to Txy/2. In dimension, shear stress magnitude is about one order lower than the pressure drop, and one order higher than yield stress. Mucus with high yield stress leads to high shear stress, and therefore would be more likely to cause epithelial cell damage. Crackling sounds produced with plug rupture might be more detectable for gels with higher concentration. PMID:26392827

  6. Measuring beliefs about gluten free diet adherence in adult coeliac disease using the theory of planned behaviour.

    PubMed

    Sainsbury, Kirby; Mullan, Barbara

    2011-04-01

    The theory of planned behaviour (TPB) was used to elicit the salient beliefs about gluten free diet (GFD) adherence in adults with coeliac disease (CD) and to design a TPB questionnaire to predict adherence levels. This questionnaire was administered to 265 CD participants with adherence and quality of life (QOL) measures, a GFD knowledge test, and self-reported psychiatric history. Regression analyses were used to test the fit of the TPB in predicting adherence, and to determine the nature of the relationships between adherence, QOL, knowledge, and psychiatric history. The TPB combined with self-reported depression and anxiety, and QOL explained significant variance in intention (41.0%) and adherence (33.7%). Poorer dietary adherence and psychiatric history were also associated with lower QOL. Findings suggest that the TPB provides an adequate model for predicting GFD adherence in CD, and the presence of psychiatric conditions represents a potential intervention target to improve adherence and QOL. PMID:21277925

  7. Adaptive cytoprotection in the small intestine: role of mucus.

    PubMed

    Cepinskas, G; Specian, R D; Kvietys, P R

    1993-05-01

    Gastric mucosal injury induced by strong irritants can be dramatically reduced by pretreating the mucosa with mild forms of the same irritant. This phenomenon has been termed "adaptive cytoprotection." The aim of the present study was to use in vivo and in vitro approaches to study adaptive cytoprotection in the small intestine using physiologically relevant concentrations of oleic acid. Anesthetized rats were instrumented for perfusion of the proximal jejunum with 10 or 40 mM oleic acid (in 20 mM sodium taurocholate). Mucosal epithelial integrity was continuously monitored by measuring the blood-to-lumen clearance of 51Cr-labeled EDTA. Perfusion of the lumen with 40 mM oleic acid produced a 10-fold increase in 51Cr-EDTA clearance, which was not affected by a previous perfusion with 10 mM oleic acid, i.e., no adaptive cytoprotection. In another series of experiments, oleic acid was placed in the lumen rather than perfused, and mucosal epithelial integrity was assessed histologically. Intraluminal placement of 10 mM oleic acid resulted in the generation of a mucus layer over the epithelium. Subsequent placement of 40 mM oleic acid did not produce significant epithelial cell injury, i.e., adaptive cytoprotection. In in vitro studies, mucin (1, 5, and 10 mg/ml) was layered over confluent monolayers of Caco-2 cells prior to addition of 2 mM oleic acid in 4 mM sodium taurocholate. The epithelial cell injury induced by oleic acid was inhibited by mucin in a dose-dependent manner. Further studies indicate that mucin does not prevent, but simply delays, the onset of cell injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8498518

  8. Oxidized mucus proteinase inhibitor: a fairly potent neutrophil elastase inhibitor.

    PubMed Central

    Boudier, C; Bieth, J G

    1994-01-01

    N-chlorosuccinimide oxidizes one of the methionine residues of mucus proteinase inhibitor with a second-order rate constant of 1.5 M-1.s-1. Cyanogen bromide cleavage and NH2-terminal sequencing show that the modified residue is methionine-73, the P'1 component of the inhibitor's active centre. Oxidation of the inhibitor decreases its neutrophil elastase inhibitory capacity but does not fully abolish it. The kinetic parameters describing the elastase-oxidized inhibitor interaction are: association rate constant kass. = 2.6 x 10(5) M-1.s-1, dissociation rate constant kdiss. = 2.9 x 10(-3) s-1 and equilibrium dissociation constant Ki = 1.1 x 10(-8) M. Comparison with the native inhibitor indicates that oxidation decreases kass. by a factor of 18.8 and increases kdiss. by a factor of 6.4, and therefore leads to a 120-fold increase in Ki. Yet, the oxidized inhibitor may still act as a potent elastase inhibitor in the upper respiratory tract where its concentration is 500-fold higher than Ki, i.e. where the elastase inhibition is pseudo-irreversible. Experiments in vitro with fibrous human lung elastin, the most important natural substrate of elastase, support this view: 1.35 microM elastase is fully inhibited by 5-6 microM oxidized inhibitor whether the enzyme-inhibitor complex is formed in the presence or absence of elastin and whether elastase is pre-adsorbed on elastin or not. PMID:7945266

  9. Older Adults' Uptake and Adherence to Exercise Classes: Instructors' Perspectives.

    PubMed

    Hawley-Hague, Helen; Horne, Maria; Skelton, Dawn A; Todd, Chris

    2016-01-01

    Exercise classes provide a range of benefits for older adults, but adherence levels are poor. We know little of instructors' experiences of delivering exercise classes to older adults. Semistructured interviews, informed by the Theory of Planned Behavior (TPB), were conducted with instructors (n = 19) delivering multicomponent exercise classes to establish their perspectives on older adults' uptake and adherence to exercise classes. Analysis revealed 'barriers' to uptake related to identity, choice/control, cost, and venue, and 'solutions' included providing choice/control, relating exercise to identity, a personal touch, and social support. Barriers to adherence included unrealistic expectations and social influences, and solutions identified were encouraging commitment, creating social cohesion, and an emphasis on achieving outcomes. Older adults' attitudes were an underlying theme, which related to all barriers and solutions. The instructor plays an important, but not isolated, role in older adults' uptake and adherence to classes. Instructors' perspectives help us to further understand how we can design successful exercise classes. PMID:26214265

  10. The challenge of patient adherence.

    PubMed

    Martin, Leslie R; Williams, Summer L; Haskard, Kelly B; Dimatteo, M Robin

    2005-09-01

    Quality healthcare outcomes depend upon patients' adherence to recommended treatment regimens. Patient nonadherence can be a pervasive threat to health and wellbeing and carry an appreciable economic burden as well. In some disease conditions, more than 40% of patients sustain significant risks by misunderstanding, forgetting, or ignoring healthcare advice. While no single intervention strategy can improve the adherence of all patients, decades of research studies agree that successful attempts to improve patient adherence depend upon a set of key factors. These include realistic assessment of patients' knowledge and understanding of the regimen, clear and effective communication between health professionals and their patients, and the nurturance of trust in the therapeutic relationship. Patients must be given the opportunity to tell the story of their unique illness experiences. Knowing the patient as a person allows the health professional to understand elements that are crucial to the patient's adherence: beliefs, attitudes, subjective norms, cultural context, social supports, and emotional health challenges, particularly depression. Physician-patient partnerships are essential when choosing amongst various therapeutic options to maximize adherence. Mutual collaboration fosters greater patient satisfaction, reduces the risks of nonadherence, and improves patients' healthcare outcomes. PMID:18360559

  11. The microbiome of coral surface mucus has a key role in mediating holobiont health and survival upon disturbance

    PubMed Central

    Glasl, Bettina; Herndl, Gerhard J; Frade, Pedro R

    2016-01-01

    Microbes are well-recognized members of the coral holobiont. However, little is known about the short-term dynamics of mucus-associated microbial communities under natural conditions and after disturbances, and how these dynamics relate to the host's health. Here we examined the natural variability of prokaryotic communities (based on 16S ribosomal RNA gene amplicon sequencing) associating with the surface mucus layer (SML) of Porites astreoides, a species exhibiting cyclical mucus aging and shedding. Shifts in the prokaryotic community composition during mucus aging led to the prevalence of opportunistic and potentially pathogenic bacteria (Verrucomicrobiaceae and Vibrionaceae) in aged mucus and to a twofold increase in prokaryotic abundance. After the release of aged mucus sheets, the community reverted to its original state, dominated by Endozoicimonaceae and Oxalobacteraceae. Furthermore, we followed the fate of the coral holobiont upon depletion of its natural mucus microbiome through antibiotics treatment. After re-introduction to the reef, healthy-looking microbe-depleted corals started exhibiting clear signs of bleaching and necrosis. Recovery versus mortality of the P. astreoides holobiont was related to the degree of change in abundance distribution of the mucus microbiome. We conclude that the natural prokaryotic community inhabiting the coral SML contributes to coral health and that cyclical mucus shedding has a key role in coral microbiome dynamics. PMID:26953605

  12. The microbiome of coral surface mucus has a key role in mediating holobiont health and survival upon disturbance.

    PubMed

    Glasl, Bettina; Herndl, Gerhard J; Frade, Pedro R

    2016-09-01

    Microbes are well-recognized members of the coral holobiont. However, little is known about the short-term dynamics of mucus-associated microbial communities under natural conditions and after disturbances, and how these dynamics relate to the host's health. Here we examined the natural variability of prokaryotic communities (based on 16S ribosomal RNA gene amplicon sequencing) associating with the surface mucus layer (SML) of Porites astreoides, a species exhibiting cyclical mucus aging and shedding. Shifts in the prokaryotic community composition during mucus aging led to the prevalence of opportunistic and potentially pathogenic bacteria (Verrucomicrobiaceae and Vibrionaceae) in aged mucus and to a twofold increase in prokaryotic abundance. After the release of aged mucus sheets, the community reverted to its original state, dominated by Endozoicimonaceae and Oxalobacteraceae. Furthermore, we followed the fate of the coral holobiont upon depletion of its natural mucus microbiome through antibiotics treatment. After re-introduction to the reef, healthy-looking microbe-depleted corals started exhibiting clear signs of bleaching and necrosis. Recovery versus mortality of the P. astreoides holobiont was related to the degree of change in abundance distribution of the mucus microbiome. We conclude that the natural prokaryotic community inhabiting the coral SML contributes to coral health and that cyclical mucus shedding has a key role in coral microbiome dynamics. PMID:26953605

  13. Early host-pathogen interactions in a marine bivalve: Crassostrea virginica pallial mucus modulates Perkinsus marinus growth and virulence.

    PubMed

    Pales Espinosa, Emmanuelle; Winnicki, Sarah; Allam, Bassem

    2013-06-13

    Perkinsus marinus is an important protistan parasite of the eastern oyster Crassostrea virginica. Recent findings showed that oyster pallial organs (mantle, gills) are a major portal of entry for the parasite. Therefore, mucus covering these organs represents the first host effectors encountered by P. marinus. This study consisted of several experiments designed to investigate the effect of oyster pallial mucus on the growth, protease production and infectivity of P. marinus. In each experiment, P. marinus performance in cultures supplemented with pallial mucus (mantle, gill, or both) was compared to that of parasite cells grown in unsupplemented media or in cultures supplemented with oyster plasma or digestive extracts. P. marinus grown in media supplemented with C. virginica mantle mucus showed a significantly higher growth rate than cultures enriched with the other supplemental extracts, while cultures grown in gill mucus promoted higher protease production. Conversely, P. marinus grown in cultures supplemented with pallial mucus of the non-compatible host Crassostrea gigas (Pacific oyster) were dramatically inhibited. Challenge experiments showed a significant increase in P. marinus virulence in cultures supplemented with C. virginica pallial mucus as compared to unsupplemented cultures or to those supplemented with digestive extract or plasma. These results suggest that C. virginica mucus plays a significant role in the pathogenesis of P. marinus by enhancing the proliferation and the infectivity of this devastating parasite. The contrasting results obtained with both oyster species indicate that P. marinus host specificity may begin in the mucus. PMID:23759561

  14. Changes in Adherence to Non-Pharmacological Guidelines for Hypertension.

    PubMed

    Park, Kyong; Cho, Sukyung; Bower, Julie K

    2016-01-01

    This study aimed to compare levels of adherence to non-pharmacological guidelines between patients with and without hypertension diagnoses, and examined temporal changes in adherence during recent decades. We used data from the Korean National Health and Nutrition Examination Survey (1998-2012), including 13,768 Korean hypertensive patients aged ≥ 30 years who were categorized according to the presence or absence of a hypertension diagnosis, based on blood pressure and self-reported information. Adherence to the guidelines was calculated for 6 components, including dietary and lifestyle habits. A multivariable generalized linear regression model was used. The proportion of hypertensive patients aware of their condition increased from 33.4% in 1998 to 74.8% in 2012 (p < 0.001), although these increments plateaued during recent survey years. Patients with hypertension diagnoses were older, and more likely to be female,and have lower education levels than those without hypertension diagnoses, for most survey years. Overall adherence levels were poor (mean score 2 of 6), and levels of adherence to non-pharmacological habits did not significantly differ between patients with and without hypertension diagnoses. However, overall adherence levels improved significantly among patients with hypertension diagnoses: from 2.09 in 1998 to 2.27 in 2012 (p = 0.007), particularly regarding sufficient vegetable/seaweed consumption (p = 0.03), maintaining a normal weight (p = 0.03), and avoidance of smoking (p < 0.001). Awareness of hypertension is increasing, but hypertensive Korean patients demonstrate poor overall adherence to non-pharmacological hypertension management guidelines. These findings suggest that well-planned education programs should be continued after hypertension is diagnosed. PMID:27561006

  15. Changes in Adherence to Non-Pharmacological Guidelines for Hypertension

    PubMed Central

    Park, Kyong; Cho, Sukyung; Bower, Julie K.

    2016-01-01

    This study aimed to compare levels of adherence to non-pharmacological guidelines between patients with and without hypertension diagnoses, and examined temporal changes in adherence during recent decades. We used data from the Korean National Health and Nutrition Examination Survey (1998–2012), including 13,768 Korean hypertensive patients aged ≥ 30 years who were categorized according to the presence or absence of a hypertension diagnosis, based on blood pressure and self-reported information. Adherence to the guidelines was calculated for 6 components, including dietary and lifestyle habits. A multivariable generalized linear regression model was used. The proportion of hypertensive patients aware of their condition increased from 33.4% in 1998 to 74.8% in 2012 (p < 0.001), although these increments plateaued during recent survey years. Patients with hypertension diagnoses were older, and more likely to be female,and have lower education levels than those without hypertension diagnoses, for most survey years. Overall adherence levels were poor (mean score 2 of 6), and levels of adherence to non-pharmacological habits did not significantly differ between patients with and without hypertension diagnoses. However, overall adherence levels improved significantly among patients with hypertension diagnoses: from 2.09 in 1998 to 2.27 in 2012 (p = 0.007), particularly regarding sufficient vegetable/seaweed consumption (p = 0.03), maintaining a normal weight (p = 0.03), and avoidance of smoking (p < 0.001). Awareness of hypertension is increasing, but hypertensive Korean patients demonstrate poor overall adherence to non-pharmacological hypertension management guidelines. These findings suggest that well-planned education programs should be continued after hypertension is diagnosed. PMID:27561006

  16. Interaction of polyacrylates with porcine pepsin and the gastric mucus barrier: a mechanism for mucosal protection.

    PubMed

    Foster, S N; Pearson, J P; Hutton, D A; Allen, A; Dettmar, P W

    1994-12-01

    1. The mechanism of interaction of the polyacrylates, carbopols with the mucus barrier in vivo has been investigated in vitro. 2. Carbopol caused a dramatic increase in the viscosity of porcine gastric mucin solutions that was up to 19-fold greater than that of the sum of the individual polymers. 3. The mucin-carbopol interaction was stable after an initial 30 min period for up to 36 h at 25 degrees C or 37 degrees C. It was reduced by increasing the temperature from 20 degrees C to 45 degrees C, was unaffected by pH and ionic strength, but was enhanced by Ca2+. 4. The magnitude of the interaction between mucin and carbopol depended on the polymeric structure of the mucin and the molecular size and level of cross-linking of the carbopol. 5. The interactions were reversible and increased with increasing carbopol and mucin concentration. The dramatic increase in viscosity can be explained in terms of space filling by the mucin molecules leading to predominantly carbopol-carbopol interactions. 6. Carbopol 934P inhibits pepsin hydrolysis and therefore has potential as a mucosal protective agent in vivo. PMID:7874865

  17. A parametric study of mucociliary transport by numerical simulations of 3D non-homogeneous mucus.

    PubMed

    Chatelin, Robin; Poncet, Philippe

    2016-06-14

    Mucociliary clearance is the natural flow of the mucus which covers and protects the lung from the outer world. Pathologies, like cystic fibrosis, highly change the biological parameters of the mucus flow leading to stagnation situations and pathogens proliferation. As the lung exhibits a complex dyadic structure, in-vivo experimental study of mucociliary clearance is almost impossible and numerical simulations can bring important knowledge about this biological flow. This paper brings a detailed study of the biological parameters influence on the mucociliary clearance, in particular for pathological situations such as cystic fibrosis. Using recent suitable numerical methods, a non-homogeneous mucus flow (including non-linearities) can be simulated efficiently in 3D, allowing the identification of the meaningful parameters involved in this biological flow. Among these parameters, it is shown that the mucus viscosity, the stiffness transition between pericilliary fluid and mucus, the pericilliary fluid height as well as both cilia length and beating frequency have a great influence on the mucociliary transport. PMID:27126985

  18. The effect of N-acetyl-L-cysteine on the viscosity of ileal neobladder mucus.

    PubMed

    Schrier, B P; Lichtendonk, W J; Witjes, J A

    2002-05-01

    N-acetyl-L-cysteine (NAC) proved to be an effective mucolytic in pulmonary secretions. Our goal was to investigate the in vitro effect of NAC on viscosity of ileal neobladder mucus. The urine of a patient with an ileal neobladder was collected during the first 7 days postoperatively and stored in a refrigerator. After precipitation, the urine was decanted. The residue was stirred to a homogeneous suspension. To samples of 4.5 ml mucus, 0.5 ml NAC 10% was added. To the control sample, 0.5 ml water was added. The samples were incubated in a water bath at 37 degrees C for 5, 30 and 60 min. Viscosity was measured in the Bohlin VOR Rheometer. The viscosity of the ileal neobladder mucus decreased quickly after incubating with NAC 10%. Viscosity increased slightly after I h of incubation. The viscosity in the control sample was higher than in the other incubated samples. NAC was found to decrease the viscosity of ileal neobladder mucus, supporting the in vivo experience that NAC can be useful in patients with an ileal neobladder to facilitate the evacuation of mucus by decreasing viscosity. PMID:12088194

  19. Glycosylation and sulphation of colonic mucus glycoproteins in patients with ulcerative colitis and in healthy subjects.

    PubMed Central

    Morita, H; Kettlewell, M G; Jewell, D P; Kent, P W

    1993-01-01

    Studies have been made of mucus glycoprotein biosynthesis in different regions of the lower gastrointestinal tract in normal patients and those with ulcerative colitis (UC), active or inactive, by means of 3H-glucosamine (3H-GlcNH2)--35S-sulphate double labelling of epithelial biopsy specimens under culture conditions. The time based rate of 3H-GlcNH2 labelling of mucus in rectal tissue was similar to that in active or inactive UC whereas the rate of 35SO4(2) labelling was significantly increased in active disease. The 3H specific activities measuring the amount of isotopic incorporation into surface and tissue mucus glycoproteins were increased in patients with active UC compared with normal or inactive subjects. The 35S specific activities did not differ significantly between patients with active UC and those in remission. In the rectum, glycosylation of mucus glycoproteins decreases with the increasing age of the patient. Regional differences in 3H-labelling of mucus components are reported for ascending colon, transverse colon, sigmoid colon, and rectum. Sulphation (35S-labelling) was higher in all parts of the colon in left sided UC. Results point to accelerated glycosylation of core proteins in the active phase of UC. PMID:8344580

  20. Mucus retention in heterotopic pancreas of the gastric antrum. A lesion mimicking mucinous carcinoma.

    PubMed

    Nopajaroonsri, C

    1994-09-01

    This report describes mucus retention developing in heterotopic pancreas of the gastric antrum. This unusual complication of heterotopic pancreas was seen in a 54-year-old black man who presented with postprandial nausea, vomiting, and weight loss. Gastroscopy revealed a 2-cm pyloric polyp, which was seen to intermittently obstruct the pylorus. Exploratory laparotomy confirmed an intramural mass in the antrum with serosal thickening and nodules. Frozen-section examination of the serosal nodule revealed a pool of mucus containing epithelial clusters and chronic inflammatory cells with no verifiable pancreatic tissue. These findings suggested the possibility of a mucinous carcinoma involving the serosa. Following gastrectomy, however, heterotopic pancreatic tissue was identified in the outer muscular propria extending to the mucosa of the antrum with no evidence of carcinoma. This heterotopic pancreatic tissue showed ductal obstruction and mucus retention. As a result, some ducts were ruptured and transformed into small nodules of mucus lakes with clusters of residual ductal epithelium. We therefore concluded that the mucous extravasation nodules on the antral serosa represented a benign lesion resulting from mucus retention in the heterotopic pancreas. In contrast to mucinous carcinoma, these benign mucous extravasation nodules were closely associated with the heterotopic pancreas, and showed significant inflammation and fibrosis but no overt epithelial anaplasia. The significance of the mucous extravasation nodule in the heterotopic pancreas is its potential confusion with mucinous carcinoma. PMID:8067516

  1. Tensiometric and Phase Domain Behavior of Lung Surfactant on Mucus-like Viscoelastic Hydrogels.

    PubMed

    Schenck, Daniel M; Fiegel, Jennifer

    2016-03-01

    Lung surfactant has been observed at all surfaces of the airway lining fluids and is an important contributor to normal lung function. In the conducting airways, the surfactant film lies atop a viscoelastic mucus gel. In this work, we report on the characterization of the tensiometric and phase domain behavior of lung surfactant at the air-liquid interface of mucus-like viscoelastic gels. Poly(acrylic acid) hydrogels were formulated to serve as a model mucus with bulk rheological properties that matched those of tracheobronchial mucus secretions. Infasurf (Calfactant), a commercially available pulmonary surfactant derived from calf lung extract, was spread onto the hydrogel surface. The surface tension lowering ability and relaxation of Infasurf films on the hydrogels was quantified and compared to Infasurf behavior on an aqueous subphase. Infasurf phase domains during surface compression were characterized by fluorescence microscopy and phase shifting interferometry. We observed that increasing the bulk viscoelastic properties of the model mucus hydrogels reduced the ability of Infasurf films to lower surface tension and inhibited film relaxation. A shift in the formation of Infasurf condensed phase domains from smaller, more spherical domains to large, agglomerated, multilayer structures was observed with increasing viscoelastic properties of the subphase. These studies demonstrate that the surface behavior of lung surfactant on viscoelastic surfaces, such as those found in the conducting airways, differs significantly from aqueous, surfactant-laden systems. PMID:26894883

  2. Adherence of sputtered titanium carbides

    NASA Technical Reports Server (NTRS)

    Brainard, W. A.; Wheeler, D. R.

    1979-01-01

    Sputtered coatings of the refractory metal carbides are of great interest for applications where hard wear-resistant materials are desired. The usefulness of sputtered refractory carbides is often limited, in practice, by spalling or interfacial separation. In this work improvements in the adherence of refractory carbides on iron, nickel and titanium based alloys were obtained by using oxidation, reactive sputtering or sputtered interlayers to alter the coating-substrate interfacial region. X-ray photoelectron spectroscopy and argon ion etching were used to characterize the interfacial regions, and an attempt was made to correlate adherence as measured in wear tests with the chemical nature of the interface.

  3. Carbachol-induced colonic mucus formation requires transport via NKCC1, K⁺ channels and CFTR.

    PubMed

    Gustafsson, Jenny K; Lindén, Sara K; Alwan, Ala H; Scholte, Bob J; Hansson, Gunnar C; Sjövall, Henrik

    2015-07-01

    The colonic mucosa protects itself from the luminal content by secreting mucus that keeps the bacteria at a distance from the epithelium. For this barrier to be effective, the mucus has to be constantly replenished which involves exocytosis and expansion of the secreted mucins. Mechanisms involved in regulation of mucus exocytosis and expansion are poorly understood, and the aim of this study was to investigate whether epithelial anion secretion regulates mucus formation in the colon. The muscarinic agonist carbachol was used to induce parallel secretion of anions and mucus, and by using established inhibitors of ion transport, we studied how inhibition of epithelial transport affected mucus formation in mouse colon. Anion secretion and mucin exocytosis were measured by changes in membrane current and epithelial capacitance, respectively. Mucus thickness measurements were used to determine the carbachol effect on mucus growth. The results showed that the carbachol-induced increase in membrane current was dependent on NKCC1 co-transport, basolateral K(+) channels and Cftr activity. In contrast, the carbachol-induced increase in capacitance was partially dependent on NKCC1 and K(+) channel activity, but did not require Cftr activity. Carbachol also induced an increase in mucus thickness that was inhibited by the NKCC1 blocker bumetanide. However, mice that lacked a functional Cftr channel did not respond to carbachol with an increase in mucus thickness, suggesting that carbachol-induced mucin expansion requires Cftr channel activity. In conclusion, these findings suggest that colonic epithelial transport regulates mucus formation by affecting both exocytosis and expansion of the mucin molecules. PMID:25139191

  4. A clinical assessment of the Mucus Shaver, a device to keep the endotracheal tube free from secretions

    PubMed Central

    Berra, Lorenzo; Coppadoro, Andrea; Bittner, Edward A; Kolobow, Theodor; Laquerriere, Patrice; Pohlmann, Joshua R; Bramati, Simone; Moss, Joel; Pesenti, Antonio

    2011-01-01

    Objective We evaluated a new device designed to clean the endotracheal tube (ETT) in mechanically ventilated patients: the Mucus Shaver. Design Prospective, randomized trial. Setting University hospital intensive care unit. Patients We enrolled 24 patients, expected to remain ventilated for more than 72 hours. Interventions The Mucus Shaver is a concentric, inflatable catheter for the removal of mucus and secretions from the interior surface of the ETT. The Mucus Shaver is advanced to the distal ETT tip, inflated and subsequently withdrawn over a period of 3–5 seconds. Patients were prospectively randomized, within 2 hours of intubation, to receive standard ETT suctioning treatment or standard suctioning plus Mucus Shaver use, until extubation. Measurements and Main Results During the study period, demographic data, recent medical history, adverse events and staff evaluation of the Mucus Shaver were recorded. At extubation, each ETT was removed, cultured and analyzed by Scanning Electron Microscopy (SEM). 12 patients were assigned to the study group and 12 to the control group. No adverse events related to the use of the Mucus Shaver were observed. At extubation, only 1 ETT from the Mucus Shaver group was colonized, while in the control group, 10 ETTs were colonized (8% vs. 83%; p<0.001). SEM showed little secretions on the ETTs from the study group, while thick bacterial deposits were present on all the ETTs from the control group (p<0.001 by Fisher’s exact test, using a maximum biofilm thickness of 30 µm as cut-off). The nursing staff was satisfied by the overall safety, feasibility, and efficacy of the Mucus Shaver. Conclusions The Mucus Shaver is a safe, feasible and efficient device for ETT cleaning in the clinical setting. The Mucus Shaver is helpful in preventing ETT colonization by potentially harmful microorganisms. PMID:21926595

  5. Program Spending to Increase Adherence: South African Cervical Cancer Screening

    PubMed Central

    Goldhaber-Fiebert, Jeremy D.; Denny, Lynette A.; De Souza, Michelle; Kuhn, Louise; Goldie, Sue J.

    2009-01-01

    Background Adherence is crucial for public health program effectiveness, though the benefits of increasing adherence must ultimately be weighed against the associated costs. We sought to determine the relationship between investment in community health worker (CHW) home visits and increased attendance at cervical cancer screening appointments in Cape Town, South Africa. Methodology/Principal Findings We conducted an observational study of 5,258 CHW home visits made in 2003–4 as part of a community-based screening program. We estimated the functional relationship between spending on these visits and increased appointment attendance (adherence). Increased adherence was noted after each subsequent CHW visit. The costs of making the CHW visits was based on resource use including both personnel time and vehicle-related expenses valued in 2004 Rand. The CHW program cost R194,018, with 1,576 additional appointments attended. Adherence increased from 74% to 90%; 55% to 87%; 48% to 77%; and 56% to 80% for 6-, 12-, 24-, and 36-month appointments. Average per-woman costs increased by R14–R47. The majority of this increase occurred with the first 2 CHW visits (90%, 83%, 74%, and 77%; additional cost: R12–R26). Conclusions/Significance We found that study data can be used for program planning, identifying spending levels that achieve adherence targets given budgetary constraints. The results, derived from a single disease program, are retrospective, and should be prospectively replicated. PMID:19492097

  6. Primary Relationships, HIV Treatment Adherence, and Virologic Control

    PubMed Central

    Dilworth, Samantha E.; Taylor, Jonelle M.; Darbes, Lynae A.; Comfort, Megan L.; Neilands, Torsten B.

    2013-01-01

    To identify factors associated with antiretroviral therapy (ART) adherence and virologic control among HIV-positive men on ART in primary relationships, data were collected from 210 male couples (420 men). Dyadic actor–partner analyses investigated associations with three levels of adherence-related dependent variables: self-efficacy (ASE), self-reported adherence, and virologic control. Results indicated that higher patient ASE was related to his own positive beliefs about medications, higher relationship autonomy and intimacy, and fewer depressive symptoms. Fewer depressive symptoms and less relationship satisfaction in the partner were linked to higher ASE in the patient. Better self-reported adherence was related to the patient’s positive appraisal of the relationship and the partner’s positive treatment efficacy beliefs. Greater medication concerns of both patient and partner were associated with less adherence. The partner’s higher relationship commitment was associated with lower viral load in the patient. Findings suggest that depressive symptoms, treatment beliefs, and relationship quality factors of both partners may influence adherence-related outcomes. PMID:21811842

  7. Surveillance of medication use: early identification of poor adherence

    PubMed Central

    Jonikas, Magdalena A

    2011-01-01

    Background We sought to measure population-level adherence to antihyperlipidemics, antihypertensives, and oral hypoglycemics, and to develop a model for early identification of subjects at high risk of long-term poor adherence. Methods Prescription-filling data for 2 million subjects derived from a payor's insurance claims were used to evaluate adherence to three chronic drugs over 1 year. We relied on patterns of prescription fills, including the length of gaps in medication possession, to measure adherence among subjects and to build models for predicting poor long-term adherence. Results All prescription fills for a specific drug were sequenced chronologically into drug eras. 61.3% to 66.5% of the prescription patterns contained medication gaps >30 days during the first year of drug use. These interrupted drug eras include long-term discontinuations, where the subject never again filled a prescription for any drug in that category in the dataset, which represent 23.7% to 29.1% of all drug eras. Among the prescription-filling patterns without large medication gaps, 0.8% to 1.3% exhibited long-term poor adherence. Our models identified these subjects as early as 60 days after the first prescription fill, with an area under the curve (AUC) of 0.81. Model performance improved as the predictions were made at later time-points, with AUC values increasing to 0.93 at the 120-day time-point. Conclusions Dispensed medication histories (widely available in real time) are useful for alerting providers about poorly adherent patients and those who will be non-adherent several months later. Efforts to use these data in point of care and decision support facilitating patient are warranted. PMID:22101969

  8. Allopurinol use in a New Zealand population: prevalence and adherence.

    PubMed

    Horsburgh, Simon; Norris, Pauline; Becket, Gordon; Arroll, Bruce; Crampton, Peter; Cumming, Jacqueline; Keown, Shirley; Herbison, Peter

    2014-07-01

    Allopurinol is effective for the control of gout and its long-term complications when taken consistently. There is evidence that adherence to allopurinol therapy varies across population groups. This may exacerbate differences in the burden of gout on population groups and needs to be accurately assessed. The aim of this study was to describe the prevalence of allopurinol use in a region of New Zealand using community pharmacy dispensing data and to examine the levels of suboptimal adherence in various population groups. Data from all community pharmacy dispensing databases in a New Zealand region were collected for a year covering 2005/2006 giving a near complete picture of dispensings to area residents. Prevalence of allopurinol use in the region by age, sex, ethnicity and socioeconomic position was calculated. Adherence was assessed using the medication possession ratio (MPR), with a MPR of 0.80 indicative of suboptimal adherence. Multiple logistic regression was used to explore variations in suboptimal adherence across population groups. A total of 953 people received allopurinol in the study year (prevalence 3%). Prevalence was higher in males (6%) than in females (1%) and Māori (5%) than non-Māori (3%). The overall MPR during the study was 0.88, with 161 (22%) of patients using allopurinol having suboptimal adherence. Non-Māori were 54% less likely to have suboptimal allopurinol adherence compared to Māori (95% CI 0.30-0.72, p = 0.001). These findings are consistent with those from other studies nationally and internationally and point to the important role for health professionals in improving patient adherence to an effective gout treatment. PMID:24390636

  9. Human cervicovaginal mucus contains an activity that hinders HIV-1 movement.

    PubMed

    Shukair, S A; Allen, S A; Cianci, G C; Stieh, D J; Anderson, M R; Baig, S M; Gioia, C J; Spongberg, E J; Kauffman, S M; McRaven, M D; Lakougna, H Y; Hammond, C; Kiser, P F; Hope, T J

    2013-03-01

    Cervical and vaginal epithelia are primary barriers against HIV type I (HIV-1) entry during male-to-female transmission. Cervical mucus (CM) is produced by the endocervix and forms a layer locally as well as in the vaginal compartment in the form of cervicovaginal mucus (CVM). To study the potential barrier function of each mucus type during HIV-1 transmission, we quantified HIV-1 mobility in CM and CVM ex vivo using fluorescent microscopy. Virions and 200-nm PEGylated beads were digitally tracked and mean-squared displacement was calculated. The mobility of beads increased significantly in CVM compared with CM, consistent with the known decreased mucin concentration of CVM. Unexpectedly, HIV-1 diffusion was significantly hindered in the same CVM samples in which bead diffusion was unhindered. Inhibition of virus transport was envelope-independent. Our results reveal a previously unknown activity in CVM that is capable of impeding HIV-1 mobility to enhance mucosal barrier function. PMID:22990624

  10. Bacterial communities and species-specific associations with the mucus of Brazilian coral species.

    PubMed

    Carlos, Camila; Torres, Tatiana T; Ottoboni, Laura M M

    2013-01-01

    We investigated the existence of species-specific associations between Brazilian coral species and bacteria. Pyrosequencing of the V3 region of the 16S rDNA was used to analyze the taxonomic composition of bacterial communities associated with the mucus of four coral species (Madracis decactis, Mussismilia hispida, Palythoa caribaeorum, and Tubastraea coccinea) in two seasons (winter and summer), which were compared with the surrounding water and sediment. The microbial communities found in samples of mucus, water, and sediment differed according to the composition and relative frequency of OTUs. The coral mucus community seemed to be more stable and resistant to seasonal variations, compared to the water and sediment communities. There was no influence of geographic location on the composition of the communities. The sediment community was extremely diverse and might act as a "seed bank" for the entire environment. Species-specific OTUs were found in P. caribaeorum, T. coccinea, and M. hispida. PMID:23567936

  11. Bacterial communities and species-specific associations with the mucus of Brazilian coral species

    PubMed Central

    Carlos, Camila; Torres, Tatiana T.; Ottoboni, Laura M. M.

    2013-01-01

    We investigated the existence of species-specific associations between Brazilian coral species and bacteria. Pyrosequencing of the V3 region of the 16S rDNA was used to analyze the taxonomic composition of bacterial communities associated with the mucus of four coral species (Madracis decactis, Mussismilia hispida, Palythoa caribaeorum, and Tubastraea coccinea) in two seasons (winter and summer), which were compared with the surrounding water and sediment. The microbial communities found in samples of mucus, water, and sediment differed according to the composition and relative frequency of OTUs. The coral mucus community seemed to be more stable and resistant to seasonal variations, compared to the water and sediment communities. There was no influence of geographic location on the composition of the communities. The sediment community was extremely diverse and might act as a "seed bank" for the entire environment. Species-specific OTUs were found in P. caribaeorum, T. coccinea, and M. hispida. PMID:23567936

  12. Bacteroides in the Infant Gut Consume Milk Oligosaccharides via Mucus-Utilization Pathways

    PubMed Central

    Marcobal, A.; Barboza, M.; Sonnenburg, E.D.; Pudlo, N.; Martens, E.C.; Desai, P.; Lebrilla, C.B.; Weimer, B.C.; Mills, D.A.; German, J.B.; Sonnenburg, J.L.

    2011-01-01

    Summary Newborns are colonized with an intestinal microbiota shortly after birth but the factors governing the retention and abundance of specific microbial lineages are unknown. Nursing infants consume human milk oligosaccharides (HMOs) that pass undigested to the distal gut where they may be digested by microbes. We determined that the prominent neonate gut residents, Bacteroides thetaiotaomicron and Bacteroides fragilis, induce the same genes during HMO consumption that are used to harvest host mucus glycans, which are structurally similar to HMOs. Lacto-N-neotetraose, a specific HMO component, selects for HMO-adapted species such as Bifidobacterium infantis, which cannot use mucus, and provides a selective advantage to B. infantis in vivo when bi-associated with B. thetaiotaomicron in the gnotobiotic mouse gut. This indicates that the complex oligosaccharide mixture within HMOs attracts both mutualistic mucus-adapted species and HMO-adapted bifidobacteria to the infant intestine that likely facilitate both milk and future solid food digestion. PMID:22036470

  13. Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis.

    PubMed

    Hoegger, Mark J; Fischer, Anthony J; McMenimen, James D; Ostedgaard, Lynda S; Tucker, Alex J; Awadalla, Maged A; Moninger, Thomas O; Michalski, Andrew S; Hoffman, Eric A; Zabner, Joseph; Stoltz, David A; Welsh, Michael J

    2014-08-15

    Lung disease in people with cystic fibrosis (CF) is initiated by defective host defense that predisposes airways to bacterial infection. Advanced CF is characterized by a deficit in mucociliary transport (MCT), a process that traps and propels bacteria out of the lungs, but whether this deficit occurs first or is secondary to airway remodeling has been unclear. To assess MCT, we tracked movement of radiodense microdisks in airways of newborn piglets with CF. Cholinergic stimulation, which elicits mucus secretion, substantially reduced microdisk movement. Impaired MCT was not due to periciliary liquid depletion; rather, CF submucosal glands secreted mucus strands that remained tethered to gland ducts. Inhibiting anion secretion in non-CF airways replicated CF abnormalities. Thus, impaired MCT is a primary defect in CF, suggesting that submucosal glands and tethered mucus may be targets for early CF treatment. PMID:25124441

  14. Impact of an exercise program on adherence and fitness indicators.

    PubMed

    Carpenter, Roger; Gilleland, Diana

    2016-05-01

    Adherence to exercise is one of the most problematic health behaviors. This pilot study describes the impact of an exercise program on adherence to exercise and fitness indicators for overweight and obese adults enrolled in an insurance reimbursed exercise plan. Chart reviews were conducted retrospectively in a convenience sample of 77 subjects from a human performance lab (HPL) at a large southern university. Charts from 2004 to 2009 were reviewed for health history, fitness indicators (fitness level, weight, BMI, hip/waist ratio, % body fat, BP, HR, cholesterol), and adherence (number of exercise sessions/month). Exercise supervision was operationalized in two phases over 12months: Phase I (3months supervised exercise) and Phase II (9months unsupervised exercise). Fifty-eight participants completed Phase I, and 8 completed Phase II. Six-nine percent of those completing Phase I visited the gym at least 8 times/month with significant (α=.05) improvement in all fitness indicators. Those visiting <8 times/month had improvement in fitness level, weight, BMI, and % body fat. Twenty-four subjects continued into Phase II, with only eight completing Phase II. Of those eight, only one subject visited the HPL at least 8 times/month. Health history data including co-morbidities, symptoms, habits, perceived tension, job stress, and fitness level were not associated with adherence. Symptoms of swollen, stiff, painful joints, and swollen ankles and legs were associated with decreased adherence to exercise. Supervised exercise was positively related to adherence and improved fitness indicators. Adults with joint symptoms may require more support. Based on these pilot data, designing a study with a larger sample and the inclusion of barriers and facilitators for adherence to self-directed exercise would allow additional analysis. Innovative interventions are needed that mimic the supervised environment, shifting responsibility for the exercise plan from the supervisor to those

  15. Predictors and Correlates of Follow-up Visit Adherence among Adolescents Receiving Laparoscopic Adjustable Gastric Banding

    PubMed Central

    Sysko, Robyn; Hildebrandt, Tom B.; Kaplan, Simona; Brewer, Stephanie K.; Zitsman, Jeffrey L.; Devlin, Michael J.

    2014-01-01

    Background Adherence behaviors have not been examined among adolescents undergoing laparoscopic adjustable gastric banding (LAGB). In addition, studies of youth receiving bariatric surgery have not considered the influence of psychopathology on postoperative adherence. Objective The purpose of this study was to evaluate predictors and correlates of adherence to post-surgery visits among a sample of adolescents undergoing LAGB. Setting Psychiatry Department, University Medical Center, United States. Methods Postoperative visits with surgical staff were analyzed over the two years following surgery (n= 101 adolescents). Growth mixture modeling examined trends in adherence. Results A three-class solution provided the best fit to the data. The classes from the final model were characterized by class 1 (61.6%) demonstrating high levels of adherence over the 24 months following LAGB, class 2 (28.5%) showing a more gradual decline in adherence, and class 3 (9.9%) with an accelerated decline in adherence. Higher levels of preoperative depressive symptoms and more preoperative episodes of loss of control over eating decreased the likelihood of adherence. Class 3 adolescents had significantly higher estimated 24-month body mass indices than Classes 1 or 2. Conclusions Variable patterns of follow-up visit adherence were identified among adolescents receiving LAGB, which were predicted by depressive symptoms and loss of control over eating. The trajectory characterized by a rapid decline in adherence to follow-up visits was also associated with less weight loss. PMID:25066443

  16. Improving Patient's Primary Medication Adherence

    PubMed Central

    Leguelinel-Blache, Géraldine; Dubois, Florent; Bouvet, Sophie; Roux-Marson, Clarisse; Arnaud, Fabrice; Castelli, Christel; Ray, Valérie; Kinowski, Jean-Marie; Sotto, Albert

    2015-01-01

    Abstract Quality of transitions of care is one of the first concerns in patient safety. Redesigning the discharge process to incorporate clinical pharmacy activities could reduce the incidence of postdischarge adverse events by improving medication adherence. The present study investigated the value of pharmacist counseling sessions on primary medication adherence after hospital discharge. This study was conducted in a 1844-bed hospital in France. It was divided in an observational period and an interventional period of 3 months each. In both periods, ward-based clinical pharmacists performed medication reconciliation and inpatient follow-up. In interventional period, initial counseling and discharge counseling sessions were added to pharmaceutical care. The primary medication adherence was assessed by calling community pharmacists 7 days after patient discharge. We compared the measure of adherence between the patients from the observational period (n = 201) and the interventional period (n = 193). The rate of patients who were adherent increased from 51.0% to 66.7% between both periods (P < 0.01). When discharge counseling was performed (n = 78), this rate rose to 79.7% (P < 0.001). The multivariate regression performed on data from both periods showed that age of at least 78 years old, and 3 or less new medications on discharge order were predictive factors of adherence. New medications ordered at discharge represented 42.0% (n = 1018/2426) of all medications on discharge order. The rate of unfilled new medications decreased from 50.2% in the observational period to 32.5% in the interventional period (P < 10−7). However, patients included in the observational period were not significantly more often readmitted or visited the emergency department than the patients who experienced discharge counseling during the interventional period (45.3% vs. 46.2%; P = 0.89). This study highlights that discharge counseling sessions are

  17. Automated detection of mucus plugs within bronchial tree in MSCT images

    NASA Astrophysics Data System (ADS)

    Odry, Benjamin L.; Guiliguian, Diran; Kiraly, Atilla P.; Novak, Carol L.; Naidich, David P.; Lerallut, Jean-Francois

    2007-03-01

    Pulmonary diseases characterized by chronic airway inflammation, such as Chronic Obstructive Pulmonary (COPD), result in abnormal bronchial wall thickening, lumen dilatation and mucus plugs. Multi-Slice Computed Tomography (MSCT) allows for assessment of these abnormalities, even in airways that are obliquely oriented to the scan plane. Chronic airway inflammation typically results in limitations of airflow, allowing for the accumulation of mucus, especially in the distal airways. In addition to obstructing airways, retained secretions make the airways prone to infection. Patients with chronic airway disease are clinically followed over time to assess disease progression and response to treatment. In this regard, the ability to obtain an automatic standardized method to rapidly and objectively assess the entire airway tree morphologically, including the extent of mucus plugging, would be of particular clinical value. We have developed a method to automatically detect the presence and location of mucus plugs within the peripheral airways. We first start with segmentation of the bronchial tree using a previously developed method. The skeleton-based tree structure is then computed and each terminal branch is individually extended using an adaptive threshold algorithm. We compute a local 2-dimensional model, based on airway luminal diameter and wall thickness. We then select a few points along the principal axis beyond the terminal branches, to extract 2D cross sections for correlation with a model of mucus plugging. Airway shape is validated with a correlation value, and the lumen distribution is analyzed and compared to the model. A high correlation indicates the presence of a mucus plug. We tested our method on 5 datasets containing a total of 40 foci of mucoid impaction. Preliminary results show sensitivity of 77.5% with a specificity of 98.2% and positive predictive value of 66%.

  18. Nanoparticles decorated with proteolytic enzymes, a promising strategy to overcome the mucus barrier.

    PubMed

    Pereira de Sousa, Irene; Cattoz, Beatrice; Wilcox, Matthew D; Griffiths, Peter C; Dalgliesh, Robert; Rogers, Sarah; Bernkop-Schnürch, Andreas

    2015-11-01

    The intestinal mucus gel layer represents a stumbling block for drug adsorption. This study is aimed to formulate a nanoparticulate system able to overcome this barrier by cleaving locally the glycoprotein substructures of the mucus. Mucolytic enzymes such as papain (PAP) and bromelain (BRO) were covalently conjugated to poly(acrylic acid) (PAA). Nanoparticles (NPs) were then formulated via ionic gelation method and characterized by particle size, zeta potential, enzyme content and enzymatic activity. The NPs permeation quantified by rotating tube studies was correlated with changes in the mucus gel layer structure determined by pulsed-gradient-spin-echo NMR (PGSE-NMR), small-angle neutron scattering (SANS) and spin-echo SANS (SESANS). PAP and BRO functionalized NPs had an average size in the range of 250 and 285 nm and a zeta potential that ranged between -6 and -5 mV. The enzyme content was 242 μg enzyme/mg for PAP modified NPs and 253 μg enzyme/mg for BRO modified NPs. The maintained enzymatic activity was 43% for PAP decorated NPs and 76% for BRO decorated NPs. The rotating tube technique revealed a better performance of BRO decorated NPs compared to PAA decorated NPs, with a 4.8-fold higher concentration of NPs in the inner slice of mucus. Addition of 0.5 wt% of enzyme functionalized NPs to 5 wt% intestinal mucin led to c.a. 2-fold increase in the mobility of the mucin as measured by PGSE-NMR indicative of a significant break-up of the structure of the mucin. SANS and SESANS measurements further revealed a change in structure of the intestinal mucus induced by the incorporation of the functionalized NPs mostly occurring at a length scale longer than 0.5 μm. Accordingly, BRO decorated NPs show higher potential than PAP functionalized NPs as mucus permeating drug delivery systems. PMID:25661320

  19. Functional C1q is present in the skin mucus of Siberian sturgeon (Acipenser baerii).

    PubMed

    Fan, Chunxin; Wang, Jian; Zhang, Xuguang; Song, Jiakun

    2015-01-01

    The skin mucus of fish acts as the first line of self-protection against pathogens in the aquatic environment and comprises a number of innate immune components. However, the presence of the critical classical complement component C1q, which links the innate and adaptive immune systems of mammalians, has not been explored in a primitive actinopterygian fish. In this study, we report that C1q is present in the skin mucus of the Siberian sturgeon (Acipenser baerii). The skin mucus was able to inhibit the growth of Escherichia coli. The bacteriostatic activity of the skin mucus was reduced by heating and by pre-incubation with EDTA or mouse anti-human C1q antibody. We also detected C1q protein in skin mucus using the western blot procedure and isolated a cDNA that encodes the Siberian sturgeon C1qC, which had 44.7-51.4% identity with C1qCs in teleosts and tetrapods. A phylogenetic analysis revealed that Siberian sturgeon C1qC lies at the root of the actinopterygian branch and is separate from the tetrapod branch. The C1qC transcript was expressed in many tissues as well as in skin. Our data indicate that C1q is present in the skin mucus of the Siberian sturgeon to protect against water-borne bacteria, and the C1qC found in the sturgeon may represent the primitive form of teleost and tetrapod C1qCs. PMID:24920077

  20. Mucus glycoprotein secretion by duodenal mucosa in response to luminal arachidonic acid.

    PubMed

    Kosmala, M; Carter, S R; Konturek, S J; Slomiany, A; Slomiany, B L

    1986-12-10

    The effect of luminal application of arachidonic acid on the alkaline secretion, prostaglandin generation, and mucus glycoprotein output and composition was studied in proximal and distal duodenum of conscious dogs. Surgically prepared duodenal loops were instilled in vivo for up to 2 h with saline (control) followed by various concentrations (12.5-100 micrograms/ml) of arachidonic acid. The experiments were conducted with and without intravenous pretreatment with indomethacin. The recovered instillates were assayed for the content of prostaglandin and HCO3-, and used for the isolation of mucus glycoprotein. Exposure of duodenal mucosa to arachidonic acid led to concentration-dependent increase in the output of HCO3- and prostaglandin generation. In both cases this response was greater in the proximal duodenum. Pretreatment with indomethacin caused reduction in the basal HCO3- and prostaglandin output, and prevented the increments evoked by arachidonic acid. The proximal and distal duodenum displayed similar basal output and composition of mucus glycoprotein. Comparable increases in these glycoproteins were also obtained with arachidonic acid, the effect of which was abolished by indomethacin. Compared to basal conditions, mucus glycoproteins elaborated in response to arachidonic acid exhibited higher contents of associated lipids and covalently bound fatty acids, and contained less protein. The associated lipids of mucus glycoproteins elaborated in the presence of arachidonic acid showed enrichment in phospholipids and decrease in neutral lipids. The carbohydrate components in these glycoproteins also exhibited higher proportions of sialic acid and sulfate. The changes brought about by arachidonic acid were prevented by indomethacin pretreatment, and in both cases the glycoprotein composition returned to that obtained under basal conditions. The enrichment of mucus glycoprotein in lipids, sialic acid and sulfate in response to endogenous prostaglandin may be of

  1. Loss of the intestinal mucus layer in the normal rat causes gut injury but not toxic mesenteric lymph nor lung injury.

    PubMed

    Sharpe, Susan M; Qin, Xiaofa; Lu, Qi; Feketeova, Eleonora; Palange, David C; Dong, Wei; Sheth, Sharvil U; Lee, Marlon A; Reino, Diego; Xu, Da-Zhong; Deitch, Edwin A

    2010-11-01

    There is substantial evidence that gut barrier failure is associated with distant organ injury and systemic inflammation. After major trauma or stress, the factors and mechanisms involved in gut injury are unknown. Our primary hypothesis is that loss of the intestinal mucus layer will result in injury of the normal gut that is exacerbated by the presence of luminal pancreatic proteases. Our secondary hypothesis is that the injury produced in the gut will result in the production of biologically active mesenteric lymph and consequently distant organ (i.e., lung) injury. To test this hypothesis, five groups of rats were studied: 1) uninstrumented naive rats; 2) control rats in which a ligated segment of distal ileum was filled with saline; 3) rats with pancreatic proteases placed in their distal ileal segments; 4) rats with the mucolytic N-acetylcysteine (NAC) placed in their distal ileal segments; and 5) rats exposed to NAC and pancreatic proteases in their ileal segments. The potential systemic consequences of gut injury induced by NAC and proteases were assessed by measuring the biological activity of mesenteric lymph as well as gut-induced lung injury. Exposure of the normal intestine to NAC, but not saline or proteases, led to increased gut permeability, loss of mucus hydrophobicity, a decrease in the mucus layer, as well as morphological evidence of villous injury. Although proteases themselves did not cause gut injury, the combination of pancreatic proteases with NAC caused more severe injury than NAC alone, suggesting that once the mucus barrier is impaired, luminal proteases can injure the now vulnerable gut. Because comparable levels of gut injury caused by systemic insults are associated with gut-induced lung injury, which is mediated by biologically active factors in mesenteric lymph, we next tested whether this local model of gut injury would produce active mesenteric lymph or lead to lung injury. It did not, suggesting that gut injury by itself may not

  2. LOSS OF THE INTESTINAL MUCUS LAYER IN THE NORMAL RAT CAUSES GUT INJURY, BUT NOT TOXIC MESENTERIC LYMPH NOR LUNG INJURY

    PubMed Central

    Sharpe, Susan M.; Qin, Xiaofa; Lu, Qi; Feketeova, Eleonora; Palange, David C.; Dong, Wei; Sheth, Sharvil U.; Lee, Marlon A.; Reino, Diego; Xu, Da-Zhong; Deitch, Edwin A.

    2010-01-01

    Background and Aims There is substantial evidence that gut barrier failure is associated with distant organ injury and systemic inflammation. After major trauma or stress, the factors and mechanisms involved in gut injury are unknown. Our primary hypothesis is that loss of the intestinal mucus layer will result in injury of the normal gut that is exacerbated by the presence of luminal pancreatic proteases. Our secondary hypothesis is that the injury produced in the gut will result in the production of biologically active mesenteric lymph and consequently distant organ (i.e., lung) injury. Methods To test this hypothesis, five groups of rats were studied: 1) un-instrumented naïve rats; 2) control rats, in which a ligated segment of distal ileum was filled with saline; 3) rats with pancreatic proteases placed in their distal ileal segments; 4) rats with the mucolytic N-acetylcysteine (NAC) placed in their distal ileal segments and 5) rats exposed to NAC and pancreatic proteases in their ileal segments. The potential systemic consequences of gut injury induced by NAC and proteases were assessed by measuring the biologic activity of mesenteric lymph as well as gut-induced lung injury. Results Exposure of the normal intestine to NAC, but not saline or proteases, led to increased gut permeability, loss of mucus hydrophobicity, a decrease in the mucus layer as well as morphologic evidence of villous injury. Although proteases themselves did not cause gut injury, the combination of pancreatic proteases with NAC caused more severe injury than NAC alone, suggesting that once the mucus barrier is impaired, luminal proteases can injure the now vulnerable gut. Since comparable levels of gut injury caused by systemic insults are associated with gut-induced lung injury which is mediated by biologically active factors in mesenteric lymph, we next tested whether this local model of gut injury would produce active mesenteric lymph or lead to lung injury. It did not, suggesting that

  3. Colonization of the streptomycin-treated mouse large intestine by a human fecal Escherichia coli strain: role of growth in mucus.

    PubMed Central

    Wadolkowski, E A; Laux, D C; Cohen, P S

    1988-01-01

    The relative colonizing abilities of Escherichia coli F-18, isolated from the feces of a healthy human, and E. coli F-18col-, a strain derived from it which does not make the E. coli F-18 colicin, were studied. In a previous report, it was shown that when each strain was fed individually to streptomycin-treated mice, at approximately 10(10) CFU per mouse, each colonized the large intestine at between 10(7) and 10(8) CFU/g of feces indefinitely. However, when simultaneously fed to mice, although E. coli F-18 colonized at about 10(8) CFU/g of feces, E. coli F-18col- dropped to a level of 10(3) CFU/g of feces within 3 to 5 days. In the present investigation, we show that when given enough time to establish a state of colonization, E. coli F-18col- persists in feces in high numbers despite subsequent challenge by E. coli F-18. Therefore, a major defect in the ability of E. coli F-18col- to colonize in the presence of E. coli F-18 appears to be in initiating that state. In addition, when mucus was scraped from the cecal wall and, without further treatment, was inoculated with E. coli F-18 or F-18col-, both strains grew well. However, when cecal mucus was inoculated with both strains simultaneously, E. coli F-18 grew far more rapidly than E. coli F-18col-. Moreover, neither strain grew in cecal luminal contents. Together, these data suggest the possibility that both E. coli F-18 and F-18col- must grow in mucus to colonize the streptomycin-treated mouse large intestine, that E. coli F-18col- is eliminated by E. coli F-18 because it does not grow in mucus as well as E. coli F-18, and that E. coli F-18col- can resist elimination by E. coli F-18 if it is allowed enough time to establish itself within the mucus layer. PMID:3281898

  4. Development and evaluation of a novel mucus diffusion test system approved by self-nanoemulsifying drug delivery systems.

    PubMed

    Friedl, Heike; Dünnhaupt, Sarah; Hintzen, Fabian; Waldner, Claudia; Parikh, Shruti; Pearson, Jeffrey P; Wilcox, Matthew D; Bernkop-Schnürch, Andreas

    2013-12-01

    The aim of this study was the development of a novel mucus diffusion model and the approval thereof by self-nanoemulsifying drug delivery systems (SNEDDSs). For diffusion experiments, various SNEDD formulations were developed, spiked with fluorescein diacetate, and evaluated for their mucus diffusion behavior through an intestinal mucus layer within the novel setup. In brief, SNEDD formulations resulting in particle sizes of 12.0 nm produced 70.3% of diffused model drug through the mucus layer. In comparison, SNEDDSs with particle sizes of 455.5 nm led to a permeation of 8.3% only. Apart from this size dependence, two SNEDDS excipients namely Cremophor RH 40 and triacetin were identified to strongly affect the permeation through mucus. Hence, it could be demonstrated that particle size and single excipients can positively influence mucus diffusion of SNEDDSs. Furthermore, it could be shown that the developed mucus diffusion model is a promising tool for pharmaceutical research in comparison with already established systems as it allows an easy handling coupled with the possibility to test different kinds of mucus in parallel within one setup. PMID:24258284

  5. The Microstructure and Bulk Rheology of Human Cervicovaginal Mucus are Remarkably Resistant to Changes in pH

    PubMed Central

    Wang, Ying-Ying; Lai, Samuel K.; Ensign, Laura; Zhong, Weixi; Cone, Richard; Hanes, Justin

    2014-01-01

    The protective barrier, lubricant and clearance functions of mucus are intimately coupled to its microstructure and bulk rheology. Mucus gels consist of a network of mucin biopolymers along with lipids, salts and other proteins, and exhibit similar biochemical and physical properties across diverse mucosal surfaces. Nevertheless, mucus is exposed to a broad range of pH throughout the human body. Protein functions are typically sensitive to small changes in pH, and prior investigations using reconstituted, purified mucin gels suggested mucus transitions from a low viscosity liquid at neutral pH to a highly viscoelastic solid at low pH. We sought to determine whether those observations hold for fresh, minimally-perturbed human mucus ex vivo, by using different-sized muco-inert nanoparticles to probe microstructure, and cone-and-plate rheometry to measure bulk rheology. We demonstrate that both the microstructure and bulk rheology of fresh, undiluted and minimally perturbed cervicovaginal mucus exhibit relatively minor changes from pH 1–2 to 8–9, in marked contrast with the pH sensitivity of purified mucin gels. Our work also suggests additional components in mucus secretions, typically eliminated during mucin purification and reconstitution, may play an important role in maintaining the protective properties of mucus. PMID:24266646

  6. The microstructure and bulk rheology of human cervicovaginal mucus are remarkably resistant to changes in pH.

    PubMed

    Wang, Ying-Ying; Lai, Samuel K; Ensign, Laura M; Zhong, Weixi; Cone, Richard; Hanes, Justin

    2013-12-01

    The protective barrier, lubricant, and clearance functions of mucus are intimately coupled to its microstructure and bulk rheology. Mucus gels consist of a network of mucin biopolymers along with lipids, salts, and other proteins and exhibit similar biochemical and physical properties across diverse mucosal surfaces. Nevertheless, mucus is exposed to a broad range of pH values throughout the human body. Protein functions are typically sensitive to small changes in pH, and prior investigations using reconstituted, purified mucin gels suggested mucus undergoes a transition from a low-viscosity liquid at neutral pH to a highly viscoelastic solid at low pH. We sought to determine whether those observations hold for fresh, minimally perturbed human mucus ex vivo by using different-sized muco-inert nanoparticles to probe microstructure and cone-and-plate rheometry to measure bulk rheology. We demonstrate that both the microstructure and bulk rheology of fresh, undiluted, and minimally perturbed cervicovaginal mucus exhibit relatively minor changes from pH 1-2 to 8-9, in marked contrast with the pH sensitivity of purified mucin gels. Our work also suggests additional components in mucus secretions, typically eliminated during mucin purification and reconstitution, may play an important role in maintaining the protective properties of mucus. PMID:24266646

  7. Interfacial dilational properties of tea polyphenols and milk proteins with gut epithelia and the role of mucus in nutrient adsorption.

    PubMed

    Guri, Anilda; Li, Yang; Corredig, Milena

    2015-12-01

    By interacting with nutrients, the mucus layer covering the intestinal epithelium may mediate absorption. This study aimed to determine possible interactions between epigallocatechin-3-gallate (EGCG), skim milk proteins or their complexes with human intestinal mucin films. The films were extracted from postconfluent monolayers of HT29-MTX, a human intestinal cell line, and a model system was created using drop shape tensiometry. The EGCG uptake tested in vitro on postconfluent Caco-2 cells or co-cultures of Caco-2/HT29-MTX (mucus producing) showed recovery of bioavailable EGCG only for Caco-2 cell monolayers, suggesting an effect of mucus on absorption. Interfacial dilational rheology was employed to characterize the properties of the interface mixed with mucus dispersion. Adsorption of polyphenols greatly enhanced the viscoelastic modulus of the mucus film, showing the presence of interactions between the nutrient molecules and mucus films. On the other hand, in situ digestion of milk proteins using trypsin showed higher surface activities as a result of protein unfolding and competitive adsorption of the hydrolyzed products. There was an increase of viscoelastic modulus over the drop ageing time for the mixed interfaces, indicating the formation of a stiffer interfacial network. These results bring new insights into the role of the mucus layer in nutrient absorption and the interactions of mucus and dairy products. PMID:26328543

  8. Improving medication adherence in migraine treatment.

    PubMed

    Seng, Elizabeth K; Rains, Jeanetta A; Nicholson, Robert A; Lipton, Richard B

    2015-06-01

    Medication adherence is integral to successful treatment of migraine and other headache. The existing literature examining medication adherence in migraine is small, and the methodologies used to assess adherence are limited. However, these studies broadly suggest poor adherence to both acute and preventive migraine medications, with studies using more objective monitoring reporting lower adherence rates. Methods for improving medication adherence are described, including organizational strategies, provider-monitoring and self-monitoring of adherence, regimen strategies, patient education, self-management skills training (e.g., stimulus control, behavioral contracts), and cognitive-behavioral therapy techniques. The article concludes by discussing the future of research regarding adherence to medications for migraine and other headaches. PMID:26040703

  9. Factors influencing human leukocyte adherence in vitro.

    PubMed

    Stepniewicz, W; Tchórzewski, H; Luciak, M

    1983-01-01

    Studies were performed on factors influencing leucocyte adherence in vitro. Blood condensation was found to increase leukocyte adherence. Addition of heparin, dextran or ethanol caused a significant reduction of white blood cell count in blood samples in comparison with blood mixed with sodium EDTA or ACD solution. This suggests the existence of two granulocyte subpopulations; viz, rapidly adhering and slowly adhering. Heparin enhanced granulocyte adherence, while dextran and ethanol decreased it. Five-day storage of ACD blood led to a decrease in granulocyte adherence, while addition of heparin or histamine to ACD blood prevented this change to occur. The glucose concentration of 1,000 mg/dl augmented granulocyte adherence, while higher glucose concentrations induced its progressive fall below the control values. There was no significant change of lymphocyte adherence during the experiments. PMID:6194070

  10. Differentially expressed proteins in the skin mucus of Atlantic cod (Gadus morhua) upon natural infection with Vibrio anguillarum

    PubMed Central

    2013-01-01

    Background Vibriosis caused by V. anguillarum is a commonly encountered disease in Atlantic cod farms and several studies indicate that the initiation of infection occurs after the attachment of the pathogen to the mucosal surfaces (gut, skin and gills) of fish. Therefore it is necessary to investigate the role of different mucosal components in fish upon V. anguillarum infection. The present study has two parts; in the first part we analyzed the differential expression of skin mucus proteins from Atlantic cod naturally infected with V. anguillarum using two dimensional gel electrophoresis coupled with mass spectrometry. In the second part, a separate bath challenge experiment with V. anguillarum was conducted to assess the mRNA levels of the genes in skin tissue, corresponding to the selected proteins identified in the first part. Results Comparative proteome analysis of skin mucus of cod upon natural infection with V. anguillarum revealed key immune relevant proteins like calpain small subunit 1, glutathione-S-transferase omega 1, proteasome 26S subunit, 14-kDa apolipoprotein, beta 2-tubulin, cold inducible RNA binding protein, malate dehydrogenase 2 (mitochondrial) and type II keratin that exhibited significant differential expression. Additionally a number of protein spots which showed large variability amongst individual fish were also identified. Some of the proteins identified were mapped to the immunologically relevant JNK (c-Jun N-terminal kinases) signalling pathway that is connected to cellular events associated with pathogenesis. A bath challenge experiment with V. anguillarum showed differential expression of beta 2-tubulin, calpain small subunit 1, cold inducible RNA binding protein, flotillin1, and glutathione S-transferase omega 1 transcripts in the skin tissue of cod during early stages of infection. Conclusions Differentially expressed proteins identified in the cod skin mucus point towards their possible involvement in V. anguillarum pathogenesis

  11. Topical Ocular Drug Delivery to the Back of the Eye by Mucus-Penetrating Particles

    PubMed Central

    Schopf, Lisa R.; Popov, Alexey M.; Enlow, Elizabeth M.; Bourassa, James L.; Ong, Winston Z.; Nowak, Pawel; Chen, Hongming

    2015-01-01

    Purpose: Enhanced drug exposure to the ocular surface typically relies on inclusion of viscosity-enabling agents, whereas delivery to the back of the eye generally focuses on invasive means, such as intraocular injections. Using our novel mucus-penetrating particle (MPP) technology, which rapidly and uniformly coats and penetrates mucosal barriers, we evaluated if such drug formulations could increase ocular drug exposure and improve topical drug delivery. Methods: Pharmacokinetic (PK) profiling of topically administered loterprednol etabonate formulated as MPP (LE-MPP) was performed in rabbits and a larger species, the mini-pig. Pharmacodynamic evaluation was done in a rabbit model of VEGF-induced retinal vascular leakage. Cellular potency and PK profile were determined for a second compound, KAL821, a novel receptor tyrosine kinase inhibitor (RTKi). Results: We demonstrated in animals that administration of LE-MPP increased exposure at the ocular surface and posterior compartments. Furthermore using a rabbit vascular leakage model, we demonstrated that biologically effective drug concentrations of LE were delivered to the back of the eye using the MPP technology. We also demonstrated that a novel RTKi formulated as MPPs provided drug levels to the back of the eye above its cellular inhibitory concentration. Conclusions: Topical dosing of MPPs of LE or KAL821 enhanced drug exposure at the front of the eye, and delivered therapeutically relevant drug concentrations to the back of the eye, in animals. Translational Relevance: These preclinical data support using MPP technology to engineer topical formulations to deliver therapeutic drug levels to the back of the eye and could provide major advancements in managing sight-threatening diseases. PMID:26101724

  12. Alcohol use, antiretroviral therapy adherence, and preferences regarding an alcohol-focused adherence intervention in patients with human immunodeficiency virus

    PubMed Central

    Kekwaletswe, Connie T; Morojele, Neo K

    2014-01-01

    Background The primary objectives of this study were to determine the association between alcohol and antiretroviral therapy (ART) adherence and the perceived appropriateness and acceptability of elements of an adherence counseling program with a focus on alcohol-related ART nonadherence among a sample of ART recipients in human immunodeficiency virus (HIV) clinics in Tshwane, South Africa. Methods We conducted a cross-sectional study with purposive sampling. The sample comprised 304 male and female ART recipients at two President’s Emergency Plan For AIDS Relief-supported HIV clinics. Using an interview schedule, we assessed patients’ alcohol use (Alcohol Use Disorders Identification Test), other drug use, level of adherence to ART, and reasons for missing ART doses (AIDS Clinical Trials Group adherence instrument). Additionally, patients’ views were solicited on: the likely effectiveness of potential facilitators; the preferred quantity, duration, format, and setting of the sessions; the usefulness of having family members/friends attend sessions along with the patient; and potential skill sets to be imparted. Results About half of the male drinkers’ and three quarters of the female drinkers’ Alcohol Use Disorders Identification Test scores were suggestive of hazardous or harmful drinking. Average self-reported ART adherence was 89.7%. There was a significant association between level of alcohol use and degree of ART adherence. Overall, participants perceived two clinic-based sessions, each of one hour’s duration, in a group format, and facilitated by a peer or adherence counselor, as most appropriate and acceptable. Participants also had a favorable attitude towards family and friends accompanying them to the sessions. They also favored an alcohol-focused adherence counseling program that employs motivational interviewing and cognitive behavioral therapy-type approaches. Conclusion The association between alcohol use and ART nonadherence points to a

  13. Accurate reporting of adherence to inhaled therapies in adults with cystic fibrosis: methods to calculate “normative adherence”

    PubMed Central

    Hoo, Zhe Hui; Curley, Rachael; Campbell, Michael J; Walters, Stephen J; Hind, Daniel; Wildman, Martin J

    2016-01-01

    Background Preventative inhaled treatments in cystic fibrosis will only be effective in maintaining lung health if used appropriately. An accurate adherence index should therefore reflect treatment effectiveness, but the standard method of reporting adherence, that is, as a percentage of the agreed regimen between clinicians and people with cystic fibrosis, does not account for the appropriateness of the treatment regimen. We describe two different indices of inhaled therapy adherence for adults with cystic fibrosis which take into account effectiveness, that is, “simple” and “sophisticated” normative adherence. Methods to calculate normative adherence Denominator adjustment involves fixing a minimum appropriate value based on the recommended therapy given a person’s characteristics. For simple normative adherence, the denominator is determined by the person’s Pseudomonas status. For sophisticated normative adherence, the denominator is determined by the person’s Pseudomonas status and history of pulmonary exacerbations over the previous year. Numerator adjustment involves capping the daily maximum inhaled therapy use at 100% so that medication overuse does not artificially inflate the adherence level. Three illustrative cases Case A is an example of inhaled therapy under prescription based on Pseudomonas status resulting in lower simple normative adherence compared to unadjusted adherence. Case B is an example of inhaled therapy under-prescription based on previous exacerbation history resulting in lower sophisticated normative adherence compared to unadjusted adherence and simple normative adherence. Case C is an example of nebulizer overuse exaggerating the magnitude of unadjusted adherence. Conclusion Different methods of reporting adherence can result in different magnitudes of adherence. We have proposed two methods of standardizing the calculation of adherence which should better reflect treatment effectiveness. The value of these indices can

  14. Factors that Influence Adherence to a Gluten-Free Diet in Adults with Celiac Disease

    PubMed Central

    Edwards-George, Jessica; Dennis, Melinda; Schuppan, Detlef; Cook, Francis; Franko, Debra L.; Blom-Hoffman, Jessica; Kelly, Ciaran P.

    2013-01-01

    Objective The only treatment for celiac disease is lifelong adherence to a gluten-free diet, yet adherence is limited and factors influencing adherence are poorly understood. The purpose of this study was to determine factors influencing gluten-free diet adherence in adults with celiac disease. Methods A questionnaire was developed and administered to 154 adults with celiac disease who then underwent a standardized gluten-free diet evaluation by an experienced nutritionist. Multivariate analysis was conducted to determine factors associated with adherence level. Results Thirteen factors hypothesized to contribute to gluten-free diet adherence were found to be significantly associated with improved adherence including: understanding of the gluten-free diet, membership of a celiac disease advocacy group, and perceived ability to maintain adherence despite travel or changes in mood or stress (P < 0.001). Conclusions This study identified specific factors correlated with gluten-free diet adherence. These results provide a foundation for the design of educational interventions to improve adherence. PMID:17990115

  15. Monitoring medication adherence in multiple sclerosis using a novel web-based tool: A pilot study.

    PubMed

    Settle, Jill R; Maloni, Heidi W; Bedra, McKenzie; Finkelstein, Joseph; Zhan, Min; Wallin, Mitchell T

    2016-06-01

    Monitoring medication adherence in multiple sclerosis (MS) can be time consuming and expensive; however, non-adherence is common and is very costly in terms of lost therapeutic benefit and unused medications. To address this problem, we employed a web-based system to monitor and potentially modify medication adherence. Participants (n = 30) were randomized either to routine care or to the MS Home Automated Telehealth (MS HAT) system. Weekly interferon beta-1a intramuscular (INFbeta-1a IM) injections and daily vitamin D adherence were tracked over a six-month period using multiple modalities: self-reported adherence, calendar diaries, pharmacy refill rates, blood serum levels, and MS HAT alerts. Weekly INFbeta-1a IM adherence was highly correlated across measures; however, vitamin D adherence was not as consistent. Healthcare providers were able to efficiently monitor adherence in a patient-centered way by using the MS HAT system to monitor adherence rather than employing chart reviews and phone calls. In addition, patients with more preserved cognitive function appeared to benefit more from use of the MS HAT system than those with cognitive impairment. While further research is needed to understand the differential effects of MS HAT on specific medications and for different individuals, it is a promising tool for monitoring medication adherence in patients with MS. PMID:26253748

  16. Determinants of CPAP Adherence in Hispanics with Obstructive Sleep Apnea.

    PubMed

    Diaz-Abad, Montserrat; Chatila, Wissam; Lammi, Matthew R; Swift, Irene; D'Alonzo, Gilbert E; Krachman, Samuel L

    2014-01-01

    Purpose. We hypothesized that socioeconomic factors and a language barrier would impact adherence with continuous positive airway pressure (CPAP) among Hispanics with obstructive sleep apnea (OSA). Methods. Patients with OSA who were prescribed CPAP for at least 1 year and completed a questionnaire evaluating demographic data, socioeconomic status, and CPAP knowledge and adherence participated in the study. Results. Seventy-nine patients (26 males; 53 ± 11 yrs; body mass index (BMI) = 45 ± 9 kg/m(2)) with apnea-hypopnea index (AHI) 33 ± 30 events/hr completed the study. Included were 25 Hispanics, 39 African Americans, and 15 Caucasians, with no difference in age, AHI, CPAP use, or BMI between the groups. While there was a difference in educational level (P = 0.006), income level (P < 0.001), and employment status (P = 0.03) between the groups, these did not influence CPAP adherence. Instead, overall improvement in quality of life and health status and perceived benefit from CPAP influenced adherence, both for the group as a whole (P = 0.03, P = 0.004, and P = 0.001, resp.), as well as in Hispanics (P = 0.02, P = 0.02, P = 0.03, resp.). Conclusion. In Hispanic patients with OSA, perceived benefit with therapy, rather than socioeconomic status or a language barrier, appears to be the most important factor in determining CPAP adherence. PMID:24649371

  17. Enhancing Adherence in Clinical Exercise Trials.

    ERIC Educational Resources Information Center

    O'Neal, Heather A.; Blair, Steven N.

    2001-01-01

    Discusses exercise adherence from the perspective of adhering to an exercise treatment in a controlled trial, focusing on: adherence (to intervention and measurement); the development of randomized clinical trials; exemplary randomized clinical trials in exercise science (exercise training studies and physical activity interventions); and study…

  18. Topography Influences Adherent Cell Regulation of Osteoclastogenesis.

    PubMed

    Nagasawa, M; Cooper, L F; Ogino, Y; Mendonca, D; Liang, R; Yang, S; Mendonca, G; Uoshima, K

    2016-03-01

    The importance of osteoclast-mediated bone resorption in the process of osseointegration has not been widely considered. In this study, cell culture was used to investigate the hypothesis that the function of implant-adherent bone marrow stromal cells (BMSCs) in osteoclastogenesis is influenced by surface topography. BMSCs isolated from femur and tibia of Sprague-Dawley rats were seeded onto 3 types of titanium surfaces (smooth, micro, and nano) and a control surface (tissue culture plastic) with or without osteogenic supplements. After 3 to 14 d, conditioned medium (CM) was collected. Subsequently, rat bone marrow-derived macrophages (BMMs) were cultured in media supplemented with soluble receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) as well as BMSC CM from each of the 4 surfaces. Gene expression levels of soluble RANKL, osteoprotegerin, tumor necrosis factor α, and M-CSF in cultured BMSCs at different time points were measured by real-time polymerase chain reaction. The number of differentiated osteoclastic cells was determined after tartrate-resistant acid phosphatase staining. Analysis of variance and t test were used for statistical analysis. The expression of prominent osteoclast-promoting factors tumor necrosis factor α and M-CSF was increased by BMSCs cultured on both micro- and nanoscale titanium topographies (P < 0.01). BMSC CM contained a heat-labile factor that increased BMMs osteoclastogenesis. CM from both micro- and nanoscale surface-adherent BMSCs increased the osteoclast number (P < 0.01). Difference in surface topography altered BMSC phenotype and influenced BMM osteoclastogenesis. Local signaling by implant-adherent cells at the implant-bone interface may indirectly control osteoclastogenesis and bone accrual around endosseous implants. PMID:26553885

  19. Adherence with Electronic Monitoring and Symptoms in Children with Attention Deficit Hyperactivity Disorder

    PubMed Central

    Yang, Jaewon; Yoon, Byung-Moon; Lee, Moon-Soo; Joe, Sook-Haeng; Jung, In-Kwa

    2012-01-01

    Objective The primary aim of this study was to compare electronic monitoring with other measures of adherence to Osmotic-controlled Release Oral delivery System methylphenidate in children with attention-deficit hyperactivity disorder (ADHD). The secondary aim was to analyze the relationships between adherence and clinical factors, including ADHD symptoms. Methods Thirty-nine children diagnosed with ADHD were monitored for adherence to medication over the course of eight weeks. Medication adherence was assessed using the Medication Event Monitoring System (MEMS), which is a bottle cap with a microprocessor that records all instances and times that the bottle is opened; patient self-report; clinician rating; and pill count. Information, including demographic and clinical characteristics, symptom rating scale, and psychological test results, were also collected. The relationships between adherence and clinical factors, including ADHD rating scores of baseline and of the changes, were assessed. Results The rate of non-adherence measured by the MEMS was found to be 46.2%, which was considerably higher than those of the patient self-report (17.9%), clinician rating (31.7%), and pill count (12.8%) of non-adherence. The rate of adherence measured by the MEMS was not significantly associated with baseline symptom severity or symptom changes over the eight weeks, although non-adherent group showed more severe baseline symptoms and inferior improvement. Conclusion Adherence as measured by the MEMS showed a discrepancy with other measures of adherence in patients with ADHD. The symptom severity and level of improvement were not related to adherence with MEMS. Further studies are needed to evaluate the variables that may impact medication adherence in children with ADHD. PMID:22993526

  20. Evaluation of Adherence and Factors Affecting Adherence to Combination Antiretroviral Therapy among White, Hispanic, and Black Men in the MACS Cohort

    PubMed Central

    Oh, Debora Lee; Sarafian, Farjad; Silvestre, Anthony; Brown, Todd; Jacobson, Lisa; Badri, Sheila; Detels, Roger

    2009-01-01

    This study investigated levels of adherence to antiretroviral therapy in White, Hispanic and Black men, and isolated factors associated with adherence among each racial group. Data were collected from 1102 men enrolled in the Multicenter AIDS Cohort Study (MACS) followed between April 2002 and October 2006. Self-reported 100% adherence was defined as taking all doses and pills over the previous four-day period, reporting not typically skipping any medications, and reporting always following the medication schedule. Variables associated with adherence were determined by multi-level logistic regression for each racial group. Adherence was also analyzed by ethnicity within racial groups. After controlling for confounders, we found that Hispanics were 2.16 times and Blacks were 1.37 more likely than Whites to not report 100% adherence (95% CI (1.47, 3.18), (1.05, 1.79)). Hispanics with ethnic backgrounds from Central and South America and the Caribbean had lower rates of adherence. Blacks with ethnic backgrounds from the Caribbean had lower rates of adherence than those from other regions. PMID:19521251

  1. Lung protease/anti-protease network and modulation of mucus production and surfactant activity.

    PubMed

    Garcia-Verdugo, Ignacio; Descamps, Delphyne; Chignard, Michel; Touqui, Lhousseine; Sallenave, Jean-Michel

    2010-11-01

    Lung epithelium guarantees gas-exchange (performed in the alveoli) and protects from external insults (pathogens, pollutants…) present within inhaled air. Both functions are facilitated by secretions lining airway surface liquid, mucus (in the upper airways) and pulmonary surfactant (in the alveoli). Mucins, the main glycoproteins present within the mucus, are responsible for its rheologic properties and participate in lung defense mechanisms. In parallel, lung collectins are pattern recognition molecules present in pulmonary surfactant that also modulate lung defense. During chronic airways diseases, excessive protease activity can promote mucus hypersecretion and degradation of lung collectins and therefore contribute to the pathophysiology of these diseases. Importantly, secretion of local and systemic anti-proteases might be crucial to equilibrate the protease/anti-protease unbalance and therefore preserve the function of lung host defense compounds and airway surface liquid homeostasis. In this review we will present information relative to proteases able to modulate mucin production and lung collectin integrity, two important compounds of innate immune defense. One strategy to preserve physiological mucus production and collectin integrity during chronic airways diseases might be the over-expression of local 'alarm' anti-proteases such as SLPI and elafin. Interestingly, a cross-talk between lung collectins and anti-protease activity has recently been described, implicating the presence within the lung of a complex network between proteases, anti-proteases and pattern recognition molecules, which aims to keep or restore homeostasis in resting or inflamed lungs. PMID:20493919

  2. Role of Mechanical Stress in Regulating Airway Surface Hydration and Mucus Clearance Rates

    PubMed Central

    Button, Brian; Boucher, Richard C.

    2008-01-01

    Effective clearance of mucus is a critical innate airway defense mechanism, and under appropriate conditions, can be stimulated to enhance clearance of inhaled pathogens. It has become increasingly clear that extracellular nucleotides (ATP and UTP) and nucleosides (adenosine) are important regulators of mucus clearance in the airways as a result of their ability to stimulate fluid secretion, mucus hydration, and cilia beat frequency (CBF). One ubiquitous mechanism to stimulate ATP release is through external mechanical stress. This article addresses the role of physiologically-relevant mechanical forces in the lung and their effects on regulating mucociliary clearance (MCC). The effects of mechanical forces on the stimulating ATP release, fluid secretion, CBF, and MCC are discussed. Also discussed is evidence suggesting that airway hydration and stimulation of MCC by stress-mediated ATP release may play a role in several therapeutic strategies directed at improving mucus clearance in patients with obstructive lung diseases, including cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). PMID:18585484

  3. Mucus: a new tissue fraction for rapid determination of fish diet switching using stable isotope analysis.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stable isotope analysis of diet switching by fishes is often hampered by slow turnover rates of the tissues analyzed (usually muscle or fins). We examined epidermal mucus as a potentially faster turnover “tissue” that might provide a more rapid assessment of diet switching. In a controlled hatchery...

  4. Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma.

    PubMed

    Kuperman, Douglas A; Huang, Xiaozhu; Koth, Laura L; Chang, Grace H; Dolganov, Gregory M; Zhu, Zhou; Elias, Jack A; Sheppard, Dean; Erle, David J

    2002-08-01

    Asthma is an increasingly common disease that remains poorly understood and difficult to manage. This disease is characterized by airway hyperreactivity (AHR, defined by exaggerated airflow obstruction in response to bronchoconstrictors), mucus overproduction and chronic eosinophilic inflammation. AHR and mucus overproduction are consistently linked to asthma symptoms and morbidity. Asthma is mediated by Th2 lymphocytes, which produce a limited repertoire of cytokines, including interleukin-4 (IL-4), IL-5, IL-9 and IL-13. Although each of these cytokines has been implicated in asthma, IL-13 is now thought to be especially critical. In animal models of allergic asthma, blockade of IL-13 markedly inhibits allergen-induced AHR, mucus production and eosinophilia. Furthermore, IL-13 delivery to the airway causes all of these effects. IL-13 is thus both necessary and sufficient for experimental models of asthma. However, the IL-13-responsive cells causing these effects have not been identified. Here we show that mice lacking signal transducer and activator of transcription 6 (STAT6) were protected from all pulmonary effects of IL-13. Reconstitution of STAT6 only in epithelial cells was sufficient for IL-13-induced AHR and mucus production in the absence of inflammation, fibrosis or other lung pathology. These results demonstrate the importance of direct effects of IL-13 on epithelial cells in causing two central features of asthma. PMID:12091879

  5. In Vitro Microfluidic Models of Mucus-Like Obstructions in Small Airways

    NASA Astrophysics Data System (ADS)

    Mulligan, Molly K.; Grotberg, James B.; Sznitman, Josué

    2012-11-01

    Liquid plugs can form in the lungs as a result of a host of different diseases, including cystic fibrosis and chronic obstructive pulmonary disease. The existence of such fluid obstructions have been found as far down in the bronchiole tree as the sixteenth generation, where bronchiole openings have diameters on the order of a hundred to a few hundred microns. Understanding the propagation of liquid plugs within the bifurcating branches of bronchiole airways is important because their presence in the lungs, and their rupture and break-up, can cause injury to the epithelial cells lining the airway walls as a result of high wall shear stresses. In particular, liquid plug rupture and break-up frequently occurs at airway bifurcations. Until present, however, experimental studies of liquid plugs have generally been restricted to Newtonian fluids that do not reflect the actual pseudoplastic properties of lung mucus. The present work attempts to uncover the propagation, rupture and break-up of mucus-like liquid plugs in the lower generations of the airway tree using microfluidic models. Our approach allows the dynamics of mucus-like plug break-up to be studied in real-time, in a one-to-one in vitro model, as a function of mucus rheology and bronchial tree geometry.

  6. Flow cytometric enumeration of bacterial in the coral surface mucus layer.

    PubMed

    Bettarel, Yvan; Thanh, Mai Chi; Patrice, Got; Antoinette, Adingra; Nadège, Kouadio-Ngbesso; Bui, Van Ngoc; Thierry, Bouvier

    2016-09-01

    The direct counts of bacteria inhabiting coral mucus were performed by flow cytometry testing four fluorescent dyes (SYBR®Green I, HCS, TOPRO®3, SYTO®62) with three different scleractinian species. Results obtained with SYTO62 were the most reliable based on the comparison with standardized epifluorescence counts and the resolution of cytograms. PMID:27302040

  7. Growth and survival of Flavobacterium columnare in fish mucus and porcine gastric mucin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare, an economically important gram negative bacterium of freshwater farmed fish, colonizes the skin and gills in the initial steps of pathogenesis. The surface of fish is coated with mucus made up of high molecular weight glycoproteins. Limited studies have described the abili...

  8. Proteomic Analysis of Pure Human Airway Gland Mucus Reveals a Large Component of Protective Proteins

    PubMed Central

    Joo, Nam Soo; Evans, Idil Apak T.; Cho, Hyung-Ju; Park, Il-Ho; Engelhardt, John F.; Wine, Jeffrey J.

    2015-01-01

    Airway submucosal glands contribute to innate immunity and protect the lungs by secreting mucus, which is required for mucociliary clearance and which also contains antimicrobial, anti-inflammatory, anti-proteolytic and anti-oxidant proteins. We stimulated glands in tracheal trimmings from three lung donors and collected droplets of uncontaminated mucus as they formed at the gland orifices under an oil layer. We analyzed the mucus using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Analysis identified 5486 peptides and 441 proteins from across the 3 samples (269–319 proteins per subject). We focused on 269 proteins common to at least 2 0f 3 subjects, of which 102 (38%) had protective or innate immunity functions. While many of these have long been known to play such roles, for many others their cellular protective functions have only recently been appreciated in addition to their well-studied biologic functions (e.g. annexins, apolipoproteins, gelsolin, hemoglobin, histones, keratins, and lumican). A minority of the identified proteins are known to be secreted via conventional exocytosis, suggesting that glandular secretion occurs via multiple mechanisms. Two of the observed protective proteins, major vault protein and prohibitin, have not been observed in fluid from human epithelial cultures or in fluid from nasal or bronchoalveolar lavage. Further proteomic analysis of pure gland mucus may help clarify how healthy airways maintain a sterile environment. PMID:25706550

  9. Analysis of stable isotopes in fish mucus during a controlled diet switch

    EPA Science Inventory

    We have used a controlled diet switch in steelhead trout (Oncorhynchus mykiss) at the Oregon Hatchery Research Center to study the time rates of changes in stable isotopes of carbon and nitrogen (13C and 15N) in epidermal mucus, a rapidly responding “tissue.” Because of the ra...

  10. Stable isotope analysis of fish mucus during a controlled diet switch

    EPA Science Inventory

    We have used a controlled diet switch in steelhead trout (Oncorhynchus mykiss) at the Oregon Hatchery Research Center to study the time rates of changes in stable isotopes of carbon and nitrogen (13C and 15N) in epidermal mucus, a rapidly responding “tissue.” Because of the ra...

  11. Mucus-secreting 'signet-ring' cells in CSF revealing the site of primary cancer.

    PubMed Central

    Agnelli, G.; Gresele, P.

    1980-01-01

    A case is reported of leptomeningeal carcinomatosis in which identification of mucus-secreting 'signet-ring' carcinoma cells in the CSF allowed diagnosis of an otherwise asymptomatic gastric cancer. When lumbar puncture is performed, careful cytological examination of the CSF should be carried out in any undiagnosed patient with neurological symptoms and signs. Images Fig. 1 Fig. 2 PMID:6267573

  12. STABLE ISOTOPE SIGNATURES OF MUCUS OF STEELHEAD TROUT IN A CONTROLLED DIET SWITCH EXPERIMENT

    EPA Science Inventory

    Our work has shown that fish mucus can serve as a very rapid indicator of diet switching in fish. We performed diet switching studies of steelhead trout in a controlled hatchery setting using specially formulated low delta 15N signature and high delta 15N signature diets. To ou...

  13. Mucus: A new tissue fraction for rapid determination of fish diet switching using stable isotope analysis

    EPA Science Inventory

    Stable isotope analysis of diet switching by fishes often is hampered by slow turnover rates of the tissues analyzed (usually muscle or fins). We examined epidermal mucus as a potentially faster turnover “tissue” that might provide a more rapid assessment of diet switching. In a ...

  14. A validated measure of adherence to antibiotic prophylaxis in children with sickle cell disease

    PubMed Central

    Duncan, Natalie A; Kronenberger, William G; Hampton, Kisha C; Bloom, Ellen M; Rampersad, Angeli G; Roberson, Christopher P; Shapiro, Amy D

    2016-01-01

    Background Antibiotic prophylaxis is a mainstay in sickle cell disease management. However, adherence is estimated at only 66%. This study aimed to develop and validate a Sickle Cell Antibiotic Adherence Level Evaluation (SCAALE) to promote systematic and detailed adherence evaluation. Methods A 28-item questionnaire was created, covering seven adherence areas. General Adherence Ratings from the parent and one health care provider and medication possession ratios were obtained as validation measures. Results Internal consistency was very good to excellent for the total SCAALE (α=0.89) and four of the seven subscales. Correlations between SCAALE scores and validation measures were strong for the total SCAALE and five of the seven subscales. Conclusion The SCAALE provides a detailed, quantitative, multidimensional, and global measurement of adherence and can promote clinical care and research. PMID:27354768

  15. Measuring the adherence to medication of elderly patients with heart failure: is there a gold standard?

    PubMed

    Smith, Helen; Hankins, Matthew; Hodson, Andrew; George, Charles

    2010-11-01

    ACE inhibitors and loop diuretics are treatments of first choice for heart failure, but patients must take their medications regularly to achieve maximum benefit. Adherence is commonly assessed using pill counts, self-report or electronic monitoring, with the latter widely considered the 'gold standard'. We assessed the concordance of these three methods in a sample of 52 elderly patients with heart failure over a six-week period. Substantial differences in adherence were found between the three methods. Adherence by self-report was very high for both ACE-I and diuretic, with little between-person variation. This was, however, uncorroborated by pill count and electronic monitoring. Closer examination of the electronic record suggested that the mean level of adherence overlooked patterns of openings more consistent with adherent behaviour. There seems to be no gold standard for measurement of adherence in this population. PMID:19615767

  16. Communication and culture: predictors of treatment adherence among Mexican immigrant patients.

    PubMed

    Villagran, Melinda; Hajek, Christopher; Zhao, Xiaoquan; Peterson, Emily; Wittenberg-Lyles, Elaine

    2012-04-01

    This study examined communication and culture in clinicians' interactions with Mexican immigrants in Texas. Specifically, we explore the unique interplay among levels of acculturation, beliefs about culturally-based medical practices, perceptions of medical encounters, and the likelihood of adherence to medical therapy recommendations from US providers. Results suggest that: (a) acculturation predicts perceptions of out-group membership in the patient-provider interaction; (b) beliefs about complementary and alternative medicine are negatively related to medical adherence; (c) quality of care mediates the relationship between physician accommodation and medical adherence; and (d) there exists a complex relationship between out-group perceptions and adherence. PMID:21900335

  17. Direct Visualization of Mucus Production by the Cold-Water Coral Lophelia pertusa with Digital Holographic Microscopy

    PubMed Central

    Zetsche, Eva-Maria; Baussant, Thierry; Meysman, Filip J. R.; van Oevelen, Dick

    2016-01-01

    Lophelia pertusa is the dominant reef-building organism of cold-water coral reefs, and is known to produce significant amounts of mucus, which could involve an important metabolic cost. Mucus is involved in particle removal and feeding processes, yet the triggers and dynamics of mucus production are currently still poorly described because the existing tools to study these processes are not appropriate. Using a novel microscopic technique—digital holographic microscopy (DHM)–we studied the mucus release of L. pertusa under various experimental conditions. DHM technology permits μm-scale observations and allows the visualization of transparent mucoid substances in real time without staining. Fragments of L. pertusa were first maintained in flow-through chambers without stressors and imaged with DHM, then exposed to various stressors (suspended particles, particulate food and air exposure) and re-imaged. Under non-stressed conditions no release of mucus was observed, whilst mucus strings and sheaths were produced in response to suspended particles (activated charcoal and drill cuttings sediment) i.e. in a stressed condition. Mucus strings and so-called ‘string balls’ were also observed in response to exposure to particulate food (brine shrimp Artemia salina). Upon air-exposure, mucus production was clearly visible once the fragments were returned to the flow chamber. Distinct optical properties such as optical path length difference (OPD) were measured with DHM in response to the various stimuli suggesting that different mucus types are produced by L. pertusa. Mucus produced to reject particles is similar in refractive index to the surrounding seawater, suggesting that the energy content of this mucus is low. In contrast, mucus produced in response to either food particle addition or air exposure had a higher refractive index, suggesting a higher metabolic investment in the production of these mucoid substances. This paper shows for the first time the

  18. Continuity of airway goblet cells and intraluminal mucus in the airways of patients with bronchial asthma.

    PubMed

    Shimura, S; Andoh, Y; Haraguchi, M; Shirato, K

    1996-07-01

    The aim of this study was to elucidate the mechanism of the formation of the widespread mucous-plugging observed in autopsied lungs from patients with bronchial asthma. We performed morphometric analysis of airways of autopsied lungs from eight patients with bronchial asthma (Group BA), and compared it with those of six chronic bronchitics (Group CB) and four control patients (Control). The following parameters were measured in paraffin sections: volume proportion of bronchial glands to bronchial wall (Gland%); goblet cell granules to total epithelial layer (Goblet %); intraluminal mucus expressed as the mucus occupying ratio (MOR); volume ratio of intraluminal mucus continuous with goblet cells to total intraluminal mucus (Vc/Vtol %); and surface ratio of the contact surface of intraluminal mucus continuous with goblet cells to the total luminal surface (Sc/Stot %). Gland%, Goblet %, and MOR or inflammatory cell numbers in the airway walls both from Group BA and CB were larger than those from the Control group. However, no significant differences were observed between Group BA and CB in Gland%, Goblet %, MOR or inflammatory cell numbers, except for the eosinophil number: i.e. 23 +/- 3, 22 +/- 3 and 6 +/- 2% in Gland%; 22 +/- 9, 5 +/- 4 and 2 +/- 2% in Goblet%; 10 +/- 3, 18 +/- 3 and 0.3 +/- 0.5% in MOR; 199 +/- 68, 10 +/- 3 and 2 +/- 2 cells. mm-2 in eosinophil number of the peripheral airways from Groups BA, CB and Control, respectively. In contrast, marked and significant increases were observed both in Vc/Vtot% and Sc/Stot% in Group BA compared to Groups CB and Control both in central and peripheral airways: i.e. Vc/Vtot% in the peripheral airways was 53 +/- 5, 4 +/- 3 and 0.8 +/- 0.8% from Groups BA, CB and Control, respectively (BA vs CB or BA vs Control, p < 0.01 each). These findings suggest that the continuity of goblet cells and intraluminal mucus or lack of full release of mucus, from goblet cells, is peculiar to asthmatic airways, and may contribute to

  19. Mucus trail tracking in a predatory snail: olfactory processing retooled to serve a novel sensory modality

    PubMed Central

    Patel, Kinjal; Shaheen, Nagma; Witherspoon, Jessica; Robinson, Natallia; Harrington, Melissa A

    2014-01-01

    Introduction The rosy wolfsnail (Euglandina rosea), a predatory land snail, finds prey snails and potential mates by following their mucus trails. Euglandina have evolved unique, mobile lip extensions that detect mucus and aid in following trails. Currently, little is known of the neural substrates of the trail-following behavior. Methods To investigate the neural correlates of trail following we used tract-tracing experiments in which nerves were backfilled with either nickel-lysine or Lucifer yellow, extracellular recording of spiking neurons in snail procerebra using a multielectrode array, and behavioral assays of trail following and movement toward the source of a conditioned odor. Results The tract-tracing experiments demonstrate that in Euglandina, the nerves carrying mucus signals innervate the same region of the central ganglia as the olfactory nerves, while the electrophysiology studies show that mucus stimulation of the sensory epithelium on the lip extensions alters the frequency and pattern of neural activity in the procerebrum in a manner similar to odor stimulation of the olfactory epithelium on the optic tentacles of another land snail species, Cantareus aspersa (previously known as Helix aspersa). While Euglandina learn to follow trails of novel chemicals that they contact with their lip extensions in one to three trials, these snails proved remarkably resistant to associative learning in the olfactory modality. Even after seven to nine pairings of odorant molecules with food, they showed no orientation toward the conditioned odor. This is in marked contrast to Cantareus snails, which reliably oriented toward conditioned odors after two to three trials. Conclusions The apparent inability of Euglandina to learn to associate food with odors and use odor cues to drive behavior suggests that the capability for sophisticated neural processing of nonvolatile mucus cues detected by the lip extensions has evolved at the expense of processing of odorant

  20. The Influence of Mucus Microstructure and Rheology in Helicobacter pylori Infection

    PubMed Central

    Bansil, Rama; Celli, Jonathan P.; Hardcastle, Joseph M.; Turner, Bradley S.

    2013-01-01

    The bacterium Helicobacter pylori (H. pylori), has evolved to survive in the highly acidic environment of the stomach and colonize on the epithelial surface of the gastric mucosa. Its pathogenic effects are well known to cause gastritis, peptic ulcers, and gastric cancer. In order to infect the stomach and establish colonies on the mucus epithelial surface, the bacterium has to move across the gel-like gastric mucus lining of the stomach under acidic conditions. In this review we address the question of how the bacterium gets past the protective mucus barrier from a biophysical perspective. We begin by reviewing the molecular structure of gastric mucin and discuss the current state of understanding concerning mucin polymerization and low pH induced gelation. We then focus on the viscoelasticity of mucin in view of its relevance to the transport of particles and bacteria across mucus, the key first step in H. pylori infection. The second part of the review focuses on the motility of H. pylori in mucin solutions and gels, and how infection with H. pylori in turn impacts the viscoelastic properties of mucin. We present recent microscopic results tracking the motion of H. pylori in mucin solutions and gels. We then discuss how the biochemical strategy of urea hydrolysis required for survival in the acid is also relevant to the mechanism that enables flagella-driven swimming across the mucus gel layer. Other aspects of the influence of H. pylori infection such as, altering gastric mucin expression, its rate of production and its composition, and the influence of mucin on factors controlling H. pylori virulence and proliferation are briefly discussed with references to relevant literature. PMID:24133493

  1. Bisphosphonates adherence for treatment of osteoporosis

    PubMed Central

    2013-01-01

    Background Osteoporosis is a disease of bone metabolism in which bisphosphonates (BPS) are the most common medications used in its treatment, whose main objective is to reduce the risk of fractures. The aim of this study was to conduct a systematic review on BPs adherence for treatment of osteoporosis. Methods Systematic review of articles on BPs adherence for treatment of osteoporosis, indexed on MEDLINE (via PubMed) databases, from inception of databases until January 2013. Search terms were “Adherence, Medication” (MeSH term), “Bisphosphonates” (MeSH term), and “Osteoporosis” (MeSH term). Results Of the 78 identified studies, 27 met the eligibility criteria. Identified studies covered a wide range of aspects regarding adherence and associated factors, adherence and fracture, adherence and BPs dosage. The studies are mostly observational, conducted with women over 45 years old, showing low rates of adherence to treatment. Several factors may influence adherence: socio-economic and cultural, participation of physicians when guidance is given to the patient, the use of bone turnover markers, and use of generic drugs. The monthly dosage is associated with greater adherence compared to weekly dosage. Conclusions Considering the methodological differences between the studies, the results converge to show that adherence to treatment of osteoporosis with BPs is still inadequate. Further experimental studies are needed to evaluate the adherence and suggest new treatment options. PMID:23705998

  2. Microbial-induced meprin β cleavage in MUC2 mucin and a functional CFTR channel are required to release anchored small intestinal mucus

    PubMed Central

    Schütte, André; Ermund, Anna; Becker-Pauly, Christoph; Johansson, Malin E. V.; Rodriguez-Pineiro, Ana M.; Bäckhed, Fredrik; Müller, Stefan; Lottaz, Daniel; Bond, Judith S.; Hansson, Gunnar C.

    2014-01-01

    The mucus that covers and protects the epithelium of the intestine is built around its major structural component, the gel-forming MUC2 mucin. The gel-forming mucins have traditionally been assumed to be secreted as nonattached. The colon has a two-layered mucus system where the inner mucus is attached to the epithelium, whereas the small intestine normally has a nonattached mucus. However, the mucus of the small intestine of meprin β-deficient mice was now found to be attached. Meprin β is an endogenous zinc-dependent metalloprotease now shown to cleave the N-terminal region of the MUC2 mucin at two specific sites. When recombinant meprin β was added to the attached mucus of meprin β-deficient mice, the mucus was detached from the epithelium. Similar to meprin β-deficient mice, germ-free mice have attached mucus as they did not shed the membrane-anchored meprin β into the luminal mucus. The ileal mucus of cystic fibrosis (CF) mice with a nonfunctional cystic fibrosis transmembrane conductance regulator (CFTR) channel was recently shown to be attached to the epithelium. Addition of recombinant meprin β to CF mucus did not release the mucus, but further addition of bicarbonate rendered the CF mucus normal, suggesting that MUC2 unfolding exposed the meprin β cleavage sites. Mucus is thus secreted attached to the goblet cells and requires an enzyme, meprin β in the small intestine, to be detached and released into the intestinal lumen. This process regulates mucus properties, can be triggered by bacterial contact, and is nonfunctional in CF due to poor mucin unfolding. PMID:25114233

  3. Adherence to preventive medications in asthmatic children at a tertiary care teaching hospital in Malaysia

    PubMed Central

    Md Redzuan, Adyani; Lee, Meng Soon; Mohamed Shah, Noraida

    2014-01-01

    Purpose Asthma affects an estimated 300 million people worldwide. Poor adherence to prescribed preventive medications, especially among children with asthma, leads to increased mortality and morbidity. The purpose of this study was to assess the adherence and persistence levels of asthmatic children at the Universiti Kebangsaan Malaysia Medical Center (UKMMC), a tertiary care teaching hospital, and to determine the factors that influence adherence to prescribed preventive medications. Patients and methods Participants were asthmatic patients aged 18 years and younger with at least one prescription for a preventive medication refilled between January and December 2011. Refill records from the pharmacy dispensing database were used to determine the medication possession ratio (MPR) and continuous measure of gaps (CMG), measures of adherence and persistence levels, respectively. Results The sample consisted of 218 children with asthma from the General and Respiratory pediatric clinics at UKMMC. The overall adherence level was 38% (n=83; MPR ≥80%), and the persistence level was 27.5% (n=60; CMG ≤20%). We found a significant association between the adherence and persistence levels (r=0.483, P<0.01). The presence of comorbidities significantly predicted the adherence (odds ratio [OR] =16.21, 95% confidence interval [CI]: 7.76–33.84, P<0.01) and persistence level (OR =2.63, 95% CI: 0.13–52.79, P<0.01). Other factors, including age, sex, ethnicity, duration of asthma diagnosis, and number of prescribed preventive medications did not significantly affect adherence or persistence (P>0.05). Conclusion In conclusion, the adherence level among children with asthma at UKMMC was low. The presence of comorbidities was found to influence adherence towards preventive medications in asthmatic children. PMID:24600208

  4. Religiosity and adherence to antiretroviral therapy among patients attending a public hospital-based HIV/AIDS clinic in Uganda.

    PubMed

    Kisenyi, Rita N; Muliira, Joshua K; Ayebare, Elizabeth

    2013-03-01

    In Uganda, the prevalence of non-adherence to antiretroviral therapy (ART) by HIV/AIDS patients remains high and sometimes this is blamed on patients' religious behavior. A descriptive design was used to examine the relationship between religiosity and ART adherence in a sample of 220 patients attending a HIV/AIDS clinic in a Ugandan public hospital. Participants who self-identified as Pentecostal and Muslim had the highest percentage of members with high religiosity scores and ART adherence. Among Muslim participants (34), 82% reported high religiosity scores and high levels of ART adherence. Of the fifty Pentecostals participants, 96% reported high religiosity scores and 80% reported high levels of ART adherence. Correlation analysis showed a significant relationship between ART adherence and religiosity (r = 0.618, P ≤ 0.01). Therefore, collaboration between religious leaders and HIV/AIDS healthcare providers should be encouraged as one of the strategies for enhancing ART adherence. PMID:21360222

  5. Effect of plastic catheter material on bacterial adherence and viability.

    PubMed

    Lopez-Lopez, G; Pascual, A; Perea, E J

    1991-06-01

    The kinetics of adherence of single isolates of Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa and Escherichia coli to catheters made of polyvinyl chloride (PVC), Teflon, siliconised latex, polyurethane and Vialon was evaluated by a radiometric assay. Radiolabelled bacteria (10(8) cfu/ml) were incubated in vials containing 1-cm lengths of catheter for up to 3 days. The peak of maximal adherence to each biomaterial was reached after 24 h for P. aeruginosa and after 72 h for the other strains. Bacterial adherence to PVC and siliconised latex was significantly higher (2-6 times; p less than 0.05) than to the other biomaterials for all the strains. The lowest values of adherence were observed with polyurethane and Vialon for the staphylococci but with Teflon for E. coli and P. aeruginosa. Bacterial viability and growth was evaluated in eluates obtained from incubation of segments of each catheter in buffer for 24 h. None of the eluates affected the viability of the staphylococci. However, all of them, significantly increased the growth of E. coli and P. aeruginosa with the exception of the eluate from siliconised latex, in which the inoculum count was reduced to an undetectable level for E. coli. We conclude that bacterial adherence to catheters may depend in part on the nature of the biomaterial and that certain substances eluted from the catheters may affect the viability and growth of different micro-organisms. PMID:1905357

  6. Adherence to Methotrexate therapy in Rheumatoid Arthritis

    PubMed Central

    Arshad, Nasim; Ahmad, Nighat Mir; Saeed, Muhammad Ahmed; Khan, Saira; Batool, Shabnam; Farman, Sumaira

    2016-01-01

    Objective: To determine adherence to methotrexate (MTX) therapy in patients with Rheumatoid Arthritis (RA) and to identify factors that promote either adherence or non adherence. Methods: One hundred Rheumatoid Arthritis patients on MTX for at least two months were enrolled. Questionnaire was completed by direct interview. Details recorded were, demographics (age, sex, education, monthly income), disease duration, duration on MTX and current dose. Disease Activity Score on 28 joint counts (DAS 28) at the current visit, concomitant drugs taken and number of doses of MTX missed in the previous 8 weeks were noted. Non adherence was defined as omission of any three or more prescribed doses of MTX in previous 8 week. Patients were asked for the factors that motivated their adherence to MTX as well as factors for non adherence. Presence of side effects due to MTX was also recorded. Result: Non adherence was found among 23% of cases. Patients of low socioeconomic group (p <0.0001) and on MTX for longer duration (p <0.001) had higher non adherence. Non adherent patients had significantly higher disease activity as measured by DAS 28 (p<0.001). Good counseling and education by the doctor was a strong predictor of adherence (p <0.001). Lack of affordability (p <0.001); lack of availability at local pharmacy (p <0.001); lack of family support (p <0.001) and lack of awareness regarding need and importance of MTX (p < 0.001were found as significant factors for non adherence. Conclusion: MTX non adherence in RA is noted in about one fourth of study group. Various economical and social issues lead to non adherence but good patient education and counseling by doctor could promote adherence in this study group. PMID:27182251

  7. 77 FR 20637 - Request for Information on Prescription Medication Adherence

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-05

    ...The Office of the Assistant Secretary for Health is seeking information about causes, impact and potential solutions associated with the public health problem of prescription medication non-adherence in adults with chronic conditions. The purpose of this notice is to provide individuals and organizations with the opportunity to identify issues relevant to all levels of government, as well as......

  8. Adherence with Universal Precautions after Immediate, Personalized Performance Feedback

    ERIC Educational Resources Information Center

    Luke, Molli M.; Alavosius, Mark

    2011-01-01

    We evaluated the effects of immediate, personalized performance feedback on adherence with hand hygiene by health-care staff in the context of a multiple baseline design across participants. Target behaviors reached mastery levels and were maintained near 100% throughout 2 months of maintenance probes. (Contains 1 table and 1 figure.)

  9. A Patient Education Program to Improve Adherence Rates with Antituberculosis Drug Regimens.

    ERIC Educational Resources Information Center

    Morisky, Donald E.; And Others

    1990-01-01

    An incentive scheme to reward positive health behaviors (adherence to antituberculosis drug regimens) was tested with 88 active and 117 preventive patients randomly assigned to intervention and control groups. Preventive patients who received incentives were significantly more likely to continue care and had higher adherence levels. Actives showed…

  10. Body Consciousness, Illness-Related Impairment, and Patient Adherence in Hemodialysis.

    ERIC Educational Resources Information Center

    Christensen, Alan J.; And Others

    1996-01-01

    Examined the joint effects of private body consciousness (PBC) and degree of illness-related physical impairment on treatment regimen adherence in a sample of 52 hemodialysis patients. Predicted the effect of PBC on adherence would vary as a function of patients' level of illness-related physical impairment. Results are discussed in terms of…

  11. The effects of psychological factors in sports medicine rehabilitation adherence.

    PubMed

    Lampton, C C; Lambert, M E; Yost, R

    1993-09-01

    This study investigated the influence of achievement motivation and self-esteem on injury treatment adherence in a general sample of injured patients receiving treatment in a sports medicine clinic. Subjects consisted of both injured athletes and workers who had incurred an on-the-job injury. Based on scales of self-esteem and achievement motivation, patients were categorized as either high or low in self-esteem certainty, self-esteem level, tendency to be task-involved, and tendency to ego-involved in tasks. Treatment adherence was measured by number of missed appointments and by physical therapist ratings of effort and progress. It was found that patients low in self-esteem certainty and high in ego-involvement tended to miss the most treatment appointments. Contrary to previous findings, task-involvement was not found to be related to treatment adherence. PMID:8107483

  12. Denaturing gradient gel electrophoresis for nonlethal detection of Aeromonas salmonicida in salmonid mucus and its potential for other bacterial fish pathogens.

    PubMed

    Quinn, Robert A; Stevenson, Roselynn M W

    2012-05-01

    Denaturing gradient gel electrophoresis (DGGE) of 16S rDNA was used to nonlethally detect Aeromonas salmonicida and other bacteria in salmonid skin mucus. Mucus samples from wild spawning coho salmon (Oncorhynchus kisutch) with endemic A. salmonicida and from cultured lake trout (Salvelinus namaycush) were tested by PCR-DGGE and were compared with mucus culture on Coomassie brilliant blue agar and internal organ culture. PCR-DGGE gave a highly reproducible 4-band pattern for 9 strains of typical A. salmonicida, which was different from other Aeromonas spp. Aeromonas salmonicida presence in mucus was evident as a band that comigrated with the bottom band of the A. salmonicida 4-band pattern and was verified by sequencing. PCR-DGGE found 36 of 52 coho salmon positive for A. salmonicida, compared with 31 positive by mucus culture and 16 by organ culture. Numerous other bacteria were detected in salmonid mucus, including Pseudomonas spp., Shewanella putrefaciens, Aeromonas hydrophila and other aeromonads. However, Yersinia ruckeri was not detected in mucus from 27 lake trout, but 1 fish had a sorbitol-positive Y. ruckeri isolated from organ culture. Yersinia ruckeri seeded into a mucus sample suggested that PCR-DGGE detection of this bacterium from mucus was possible. PCR-DGGE allows nonlethal detection of A. salmonicida in mucus and differentiation of some Aeromonas spp. and has the potential to allow simultaneous detection of other pathogens present in fish mucus. PMID:22506865

  13. Medication Adherence in People With Parkinson Disease.

    PubMed

    Shin, Ju Young; Habermann, Barbara

    2016-01-01

    Parkinson disease (PD) is the second most common neurodegenerative disorder in the United States. Because there is no cure for PD currently, pharmacological therapy is the mainstay of PD symptom management. Despite the importance of medication adherence in PD, several studies have reported medication nonadherence and/or suboptimal adherence. This literature review provides an overview of medication adherence issues in people with PD. Articles were identified for this study using computerized database searches and journal hand searches. Of the 72 medication adherence articles reviewed, the following articles were eligible for this review: (a) 10 articles measuring medication adherence in people with PD, (b) four medication adherence intervention articles, and (c) six studies of medication adherence in hospitalized settings. The importance of adherence assessment and strategies in improving medication adherence are discussed with the goal of improving symptom management and clinical outcomes in people with PD. Because medication taking is a complex and multifaceted phenomena, patient-centered, theory-driven interventions are needed to improve medication adherence and quality of care and life in people with PD. PMID:27224682

  14. Characterization of Binding of Candida albicans to Small Intestinal Mucin and Its Role in Adherence to Mucosal Epithelial Cells

    PubMed Central

    de Repentigny, Louis; Aumont, Francine; Bernard, Karine; Belhumeur, Pierre

    2000-01-01

    In order to approximate and adhere to mucosal epithelial cells, Candida must traverse the overlying mucus layer. Interactions of Candida species with mucin and human buccal epithelial cells (BECs) were thus investigated in vitro. Binding of the Candida species to purified small intestinal mucin showed a close correlation with their hierarchy of virulence. Significant differences (P < 0.05) were found among three categories of Candida species adhering highly (C. dubliniensis, C. tropicalis, and C. albicans), moderately (C. parapsilosis and C. lusitaniae) or weakly (C. krusei and C. glabrata) to mucin. Adherence of C. albicans to BECs was quantitatively inhibited by graded concentrations of mucin. However, inhibition of adherence was reversed by pretreatment of mucin with pronase or C. albicans secretory aspartyl proteinase Sap2p but not with sodium periodate. Saturable concentration- and time-dependent binding of mucin to C. albicans was abrogated by pronase or Sap2p treatment of mucin but was unaffected by β-mercaptoethanol, sodium periodate, neuraminidase, lectins, or potentially inhibitory sugars. Probing of membrane blots of the mucin with C. albicans revealed binding of the yeast to the 66-kDa cleavage product of the 118-kDa C-terminal glycopeptide of mucin. Although no evidence was found for the participation of C. albicans cell surface mannoproteins in specific receptor-ligand binding to mucin, inhibition of binding by p-nitrophenol (1 mM) and tetramethylurea (0.36 M) revealed that hydrophobic interactions are involved in adherence of C. albicans to mucin. These results suggest that C. albicans may both adhere to and enzymatically degrade mucins by the action of Saps, and that both properties may act to modulate Candida populations in the oral cavity and gastrointestinal tract. PMID:10816460

  15. Adherence to Antiretroviral Therapy in India: A Systematic Review and Meta-Analysis

    PubMed Central

    Mhaskar, Rahul; Alandikar, Vaibhav; Emmanuel, Patricia; Djulbegovic, Benjamin; Patel, Sangita; Patel, Atul; Naik, Eknath; Mohapatra, Shyam; Kumar, Ambuj

    2013-01-01

    Objective: To assess the adherence to antiretroviral therapy (ART) in the human immunodeficiency virus (HIV)-infected population in India. Design: Systematic review and meta-analysis. Materials and Methods: The Medline and Cochrane library database were searched. Any prospective or retrospective study enrolling a minimum of 10 subjects with a primary objective of assessing ART adherence in the HIV population in India was included. Data were extracted on adherence definition, adherence estimates, study design, study population characteristics, recall period and assessment method. For metaanalysis, the pooled proportion was calculated as a back-transform of the weighted mean of the transformed proportions (calculated according to the Freeman-Tukey variant of the arcsine square root) using the random effects model. Results: There were seven cross-sectional studies and one retrospective study enrolling 1666 participants. Publication bias was significant (P = 0.003). Pooled results showed an ART adherence rate of 70% (95% confidence interval: 59–81%, I2 = 96.3%). Sensitivity analyses based on study design, adherence assessment method and study region did not influence adherence estimates. Fifty percent (4/8) of the studies reported cost of medication as the most common obstacle for ART adherence. Twenty-five percent (2/8) reported lack of access to medication as the reason for non-adherence and 12% (1/8) cited adverse events as the most prevalent reason for non-adherence. The overall methodological quality of the included studies was poor. Conclusion: Pooled results show that overall ART adherence in India is below the required levels to have an optimal treatment effect. The quality of studies is poor and cannot be used to guide policies to improve ART adherence. PMID:23878418

  16. Antiretroviral adherence and use of alternative therapies among older HIV-infected adults.

    PubMed Central

    Wutoh, A. K.; Brown, C. M.; Kumoji, E. K.; Daftary, M. S.; Jones, T.; Barnes, N. A.; Powell, N. J.

    2001-01-01

    OBJECTIVE: To investigate adherence to antiretroviral therapy and use of alternative therapies among older human immunodeficiency virus (HIV)-infected adults, and to assess relationships between antiretroviral adherence and clinical outcomes. METHODS: One hundred older HIV-infected patients, aged 50 and over, treated at two large HIV clinics in Washington, DC, were enrolled. A cross-sectional methodology used structured interviews to investigate antiretroviral regimens, use of alternative therapies, and demographics. Medical records provided viral load and CD4 count within 3 months of interview. RESULTS: The mean self-reported adherence was 94%, and 55 patients reported 100% adherence to antiretroviral therapy. Correlation analysis showed a significant negative correlation between adherence and viral load (r = -312, p = 0.005). There was no significant difference in adherence based on race, gender, mode of transmission, or education. Twenty-one patients (21%) reported the use of an alternative therapy, with several patients using multiple alternative therapies. There was no significant difference in adherence score (p = 0.514) or viral load (p = 0.860) based upon use of alternative therapies. CONCLUSIONS: Older HIV-infected study patients reported high levels of adherence to antiretroviral regimens, and adherence was highly correlated with HIV viral load. Use of alternative therapies did not significantly impact adherence to antiretroviral agents or viral load. High adherence among this older population may be related to older patients' familiarity with medication usage, their increasing awareness of HIV as a disease that requires optimal adherence, and educational efforts promoted by the two clinics in which they are clients. PMID:11491273

  17. Adherence to directly observed antiretroviral therapy among human immunodeficiency virus-infected prison inmates.

    PubMed

    Wohl, David A; Stephenson, Becky L; Golin, Carol E; Kiziah, C Nichole; Rosen, David; Ngo, Bich; Liu, Honghu; Kaplan, Andrew H

    2003-06-15

    Directly observed therapy (DOT) for human immunodeficiency virus (HIV) infection is commonly used in correctional settings; however, the efficacy of DOT for treating HIV infection has not been determined. We prospectively assessed adherence to antiretroviral therapy regimens among 31 HIV-infected prison inmates who were receiving >or=1 antiretrovirals via DOT. Adherence was measured by self-report, pill count, electronic monitoring caps, and, for DOT only, medication administration records. Overall, median adherence was 90%, as measured by pill count; 86%, by electronic monitoring caps; and 100%, by self-report. Adherence, as measured by electronic monitoring caps, was >90% in 32% of the subjects. In 91% of cases, adherence, as measured by medication administration records, was greater than that recorded by electronic monitoring caps for the same medications administered by DOT. Objective methods of measurement revealed that adherence to antiretroviral regimens administered wholly or in part by DOT was adherence revealed significantly different levels of adherence. These findings suggest that use of DOT does not ensure adherence to antiretroviral therapy. PMID:12802758

  18. Optimal Treatment Adherence Counseling Outcomes for People Living with HIV and Limited Health Literacy.

    PubMed

    Pellowski, Jennifer A; Kalichman, Seth C; Grebler, Tamar

    2016-01-01

    Limited health literacy has been shown to contribute to poor adherence to antiretroviral therapy (ART) in people living with HIV/AIDS. Given the mixed results of previous interventions for people with HIV and low health literacy, investigating possible targets for improved adherence is warranted. The present study aims to identify the correlates of optimal and suboptimal outcomes among participants of a recent skills-based medication adherence intervention. This secondary analysis included 188 men and women living with HIV who had low health literacy and who had complete viral load data. Adherence was assessed by unannounced pill count and follow-up viral loads were assessed by blood draw. Results showed that higher levels of health literacy and lower levels of alcohol use were the strongest predictors of achieving HIV viral load optimal outcomes. The interplay between lower health literacy and alcohol use on adherence should be the focus of future research. PMID:25211524

  19. Soil adherence to human skin

    SciTech Connect

    Driver, J.H.; Konz, J.J.; Whitmyre, G.K. )

    1989-12-01

    Dermal exposure to soils contaminated with toxic chemicals represents a potential public health hazard. These soils, contaminated with chemicals such as PCBs and dioxins, may be found at various locations throughout the US. Furthermore, dermal contact with pesticide-containing particles and contaminated soil particles is of importance for exposures to agricultural workers who reenter fields after pesticide application. With respect to dermal exposure to pesticide-contaminated particulate matter, several occurrences of human toxicity to ethyl parathion in citrus groves have been reported. These exposures resulted from dermal contact with high concentrations of the toxic transformation product paraoxon in soil dust contaminated as a result of application of pesticide to the overhead foliage of trees. To assess dermal exposure to chemically-contaminated soil at sites of concern, dermal adherence of soil must be determined prior to the assessment of dermal absorption. The purpose of the experiment reported herein was to determine the amount of soil (mg/cm{sup 2}) that adheres to adult hands under various soil conditions. These conditions include the type of soil, the organic content of the soil, and the particle size of the soil.

  20. Multilevel factors associated with long-term adherence to screening mammography in older women in the U.S.

    PubMed

    Hubbard, Rebecca A; O'Meara, Ellen S; Henderson, Louise M; Hill, Deirdre; Braithwaite, Dejana; Haas, Jennifer S; Lee, Christoph I; Sprague, Brian L; Alford-Teaster, Jennifer; Tosteson, Anna N A; Wernli, Karen J; Onega, Tracy

    2016-08-01

    In the U.S., guidelines recommend that women continue mammography screening until at least age 74, but recent evidence suggests declining screening rates in older women. We estimated adherence to screening mammography and multilevel factors associated with adherence in a longitudinal cohort of older women. Women aged 66-75years receiving screening mammography within the Breast Cancer Surveillance Consortium were linked to Medicare claims (2005-2010). Claims data identified baseline adherence, defined as receiving subsequent mammography within approximately 2years, and length of time adherent to guidelines. Characteristics associated with adherence were investigated using logistic and Cox proportional hazards regression models. Analyses were stratified by age to investigate variation in relationships between patient factors and adherence. Among 49,775 women, 89% were adherent at baseline. Among women 66-70years, those with less than a high school education were more likely to be non-adherent at baseline (odds ratio [OR] 1.96; 95% confidence interval [CI] 1.65-2.33) and remain adherent for less time (hazard ratio [HR] 1.41; 95% CI 1.11-1.80) compared to women with a college degree. Women with ≥1 versus no Charlson co-morbidities were more likely to be non-adherent at baseline (OR 1.46; 95% CI 1.31-1.62) and remain adherent for less time (HR 1.44; 95% CI 1.24-1.66). Women aged 71-75 had lower adherence overall, but factors associated with non-adherence were similar. In summary, adherence to guidelines is high among Medicare-enrolled women in the U.S. receiving screening mammography. Efforts are needed to ensure that vulnerable populations attain these same high levels of adherence. PMID:27261409

  1. Improving hand hygiene adherence among nursing staff.

    PubMed

    Harne-Britner, Sarah; Allen, Marianne; Fowler, Kimberly A

    2011-01-01

    This quasi-experimental study explored initial and sustained effects of educational and behavioral interventions on hand hygiene adherence and the relationships between hand hygiene adherence and health care-associated infections. Education paired with positive reinforcement behavioral interventions significantly improved hand hygiene adherence after the first month (χ² = 4.27; P = .039); however, the improvement was not sustained over 6 months. There were no significant differences in infection rates between the treatment and control groups. PMID:20407392

  2. Patient Characteristics Associated with Medication Adherence

    PubMed Central

    Rolnick, Sharon J; Pawloski, Pamala A.; Hedblom, Brita D.; Asche, Stephen E.; Bruzek, Richard J.

    2013-01-01

    Objective Despite evidence indicating therapeutic benefit for adhering to a prescribed regimen, many patients do not take their medications as prescribed. Non-adherence often leads to morbidity and to higher health care costs. The objective of the study was to assess patient characteristics associated with medication adherence across eight diseases. Design Retrospective data from a repository within an integrated health system was used to identify patients ≥18 years of age with ICD-9-CM codes for primary or secondary diagnoses for any of eight conditions (depression, hypertension, hyperlipidemia, diabetes, asthma or chronic obstructive pulmonary disease, multiple sclerosis, cancer, or osteoporosis). Electronic pharmacy data was then obtained for 128 medications used for treatment. Methods Medication possession ratios (MPR) were calculated for those with one condition and one drug (n=15,334) and then for the total population having any of the eight diseases (n=31,636). The proportion of patients adherent (MPR ≥80%) was summarized by patient and living-area (census) characteristics. Bivariate associations between drug adherence and patient characteristics (age, sex, race, education, and comorbidity) were tested using contingency tables and chi-square tests. Logistic regression analysis examined predictors of adherence from patient and living area characteristics. Results Medication adherence for those with one condition was higher in males, Caucasians, older patients, and those living in areas with higher education rates and higher income. In the total population, adherence increased with lower comorbidity and increased number of medications. Substantial variation in adherence was found by condition with the lowest adherence for diabetes (51%) and asthma (33%). Conclusions The expectation of high adherence due to a covered pharmacy benefit, and to enhanced medication access did not hold. Differences in medication adherence were found across condition and by

  3. Study on the increment of the production of gastric mucus in rats treated with Opuntia ficus indica (L.) Mill. cladodes.

    PubMed

    Galati, E M; Pergolizzi, S; Miceli, N; Monforte, M T; Tripodo, M M

    2002-12-01

    Opuntia ficus indica cladodes are used in traditional medicine of many countries for their cicatrisant activity. The major components of cladodes are carbohydrate-containing polymers, which consist of a mixture of mucilage and pectin. In this paper we studied the cytoprotective effects of cladodes on experimental ethanol-induced ulcer in rat. The O. ficus indica cladodes administration gives rise to cytoprotection phenomena by breaking up the epithelial cells and stimulating an increase in mucus production. When O. ficus indica cladodes are administered as a preventive therapy, keep the gastric mucosa under normal condition by preventing mucus dissolution caused by ethanol and favouring mucus production. An increase of mucus production is also observed during the course of the curative treatment. The treatment with O. ficus indica cladodes provokes an increase in the number of secretory cells. Probably, the gastric fibroblasts are involved in the antiulcer activity. PMID:12426090

  4. Chemotactic Activity of Cyclophilin A in the Skin Mucus of Yellow Catfish (Pelteobagrus fulvidraco) and Its Active Site for Chemotaxis.

    PubMed

    Dawar, Farman Ullah; Tu, Jiagang; Xiong, Yang; Lan, Jiangfeng; Dong, Xing Xing; Liu, Xiaoling; Khattak, Muhammad Nasir Khan; Mei, Jie; Lin, Li

    2016-01-01

    Fish skin mucus is a dynamic barrier for invading pathogens with a variety of anti-microbial enzymes, including cyclophilin A (CypA), a multi-functional protein with peptidyl-prolyl cis/trans isomerase (PPIase) activity. Beside various other immunological functions, CypA induces leucocytes migration in vitro in teleost. In the current study, we have discovered several novel immune-relevant proteins in yellow catfish skin mucus by mass spectrometry (MS). The CypA present among them was further detected by Western blot. Moreover, the CypA present in the skin mucus displayed strong chemotactic activity for yellow catfish leucocytes. Interestingly, asparagine (like arginine in mammals) at position 69 was the critical site in yellow catfish CypA involved in leucocyte attraction. These novel efforts do not only highlight the enzymatic texture of skin mucus, but signify CypA to be targeted for anti-inflammatory therapeutics. PMID:27589721

  5. Medication Adherence: A Call for Action

    PubMed Central

    Bosworth, Hayden B.; Granger, Bradi B.; Mendys, Phil; Brindis, Ralph; Burkholder, Rebecca; Czajkowski, Susan M.; Daniel, Jodi G.; Ekman, Inger; Ho, Michael; Johnson, Mimi; Kimmel, Stephen E.; Liu, Larry Z; Musaus, John; Shrank, William H.; Buono, Elizabeth Whalley; Weiss, Karen; Granger, Christopher B.

    2013-01-01

    Poor adherence to efficacious cardiovascular related medications has led to considerable morbidity, mortality, and avoidable health care costs. This paper provides results of a recent think tank meeting in which various stakeholder groups representing key experts from consumers, community health providers, the academic community, decision-making government officials (FDA, NIH, etc), and industry scientists met to evaluate the current status of medication adherence and provide recommendations for improving outcomes. Below, we review the magnitude of the problem of medication adherence, prevalence, impact, and cost. We then summarize proven effective approaches and conclude with a discussion of recommendations to address this growing and significant public health issue of medication non adherence. PMID:21884856

  6. Family interaction and treatment adherence after stroke.

    PubMed

    Evans, R L; Bishop, D S; Matlock, A L; Stranahan, S; Smith, G G; Halar, E M

    1987-08-01

    Caregivers of 60 stroke patients were assessed five months after patient discharge from a stroke care unit to determine the relationship between family function and poststroke treatment adherence. Areas of family interaction which were significantly related to ratings of treatment adherence included problem solving, communication, and affective involvement. Better functioning families were consistently high on signs of treatment adherence. Findings suggest that families with specific dysfunction may not be as capable of helping patients comply with rehabilitation efforts as families who function more effectively. Thorough family assessment to identify which areas of family interaction are most problematic in relation to adherence issues is recommended. PMID:3619615

  7. Treatment adherence redefined: a critical analysis of technotherapeutics

    PubMed Central

    Gagnon, Marilou; Jacob, Jean Daniel; Guta, Adrian

    2013-01-01

    GAGNON M, JACOB JD and GUTA A. Nursing Inquiry 2013; 20: 60–70 Treatment adherence redefined: a critical analysis of technotherapeutics Treatment adherence issues in the context of chronic illnesses have become an important concern worldwide and a top priority in the field of health-care. The development of devices that will allow healthcare providers to track treatment adherence and monitor physiological parameters with exact precision raises important questions and concerns. The aim of this study is to interrogate the use of these new technological devices which allow for previously unavailable data to be recorded on an ongoing basis and transmitted via a tiny microchip inserted into the body. Drawing on the work of Michel Foucault, we analyze how this anatomo-political and bio-political instrument serves to discipline chronically ill individuals and govern the health of entire populations who suffer from chronic conditions. To support our analysis, this article comprises three sections. First, we provide an overview of treatment adherence and technotherapeutics. Then, we explain how technotherapeutics concern the government of bodies and conducts at the individual level and population level more generally. Lastly, we provide an example of how this analysis can be connected to routine nursing practice in the field of HIV. PMID:22381079

  8. Glycan profiling of gel forming mucus layer from the scleractinian symbiotic coral Oculina arbuscula.

    PubMed

    Coddeville, Bernadette; Maes, Emmanuel; Ferrier-Pages, Christine; Guerardel, Yann

    2011-06-13

    The gel forming mucus layer surrounding scleractinian corals play fundamental functions in the maintenance of a favorable microenvironment required for the survival of these organisms. In particular, it harbors a rich partially species-specific symbiotic community through yet poorly understood molecular interactions. However, removal or contamination of this community by exogenous bacteria is closely linked to the worldwide bleaching events that are presently devastating coral colonies. The present study investigates the structure of major high molecular weight glycoconjugates that are responsible for both rheological properties of mucus and sugar-protein interactions with microbial communities. We demonstrated that it is composed by two distinct types of sulfated macromolecules: mucin type glycoproteins densely substituted by short unusual O-linked glycans and repetitive polysaccharides. PMID:21517058

  9. A new paradigm in respiratory hygiene: modulating respiratory secretions to contain cough bioaerosol without affecting mucus clearance

    PubMed Central

    Zayas, Gustavo; Valle, Juan C; Alonso, Mauricio; Alfaro, Henry; Vega, Daniel; Bonilla, Gloria; Reyes, Miguel; King, Malcolm

    2007-01-01

    Background Several strategies and devices have been designed to protect health care providers from acquiring transmissible respiratory diseases while providing care. In modulating the physical characteristics of the respiratory secretions to minimize the aerosolization that facilitates transmission of airborne diseases, a fundamental premise is that the prototype drugs have no adverse effect on the first line of respiratory defense, clearance of mucus by ciliary action. Methods To assess and demonstrate the primary mechanism of our mucomodulators (XLs), we have built our evidence moving from basic laboratory studies to an ex-vivo model and then to an in-vivo large animal model. We exposed anesthetized dogs without hypersecretion to different dose concentrations of aerosolized XL "B", XL "D" and XL "S". We assessed: cardio-respiratory pattern, tracheal mucus clearance, airway patency, and mucus viscoelastic changes. Results Exposure of frog palate mucus to XLs did not affect the clearance of mucus by ciliary action. Dogs maintained normal cardio-respiratory pattern with XL administration. Tracheal mucociliary clearance in anesthetized dogs indicated a sustained 40% mean increase. Tracheal mucus showed increased filance, and there was no mucus retention in the airways. Conclusion The ex-vivo frog palate and the in-vivo mammalian models used in this study, appear to be appropriate and complement each other to better assess the effects that our mucomodulators exert on the mucociliary clearance defence mechanism. The physiological function of the mucociliary apparatus was not negatively affected in any of the two epithelial models. Airway mucus crosslinked by mucomodulators is better cleared from an intact airway and normally functioning respiratory system, either due to enhanced interaction with cilia or airflow-dependent mechanisms. Data obtained in this study allow us to assure that we have complied with the fundamental requirement criteria established in the initial

  10. Capacity of the bovine intestinal mucus and its components to support growth of Escherichia coli O157:H7.

    PubMed

    Aperce, C C; Heidenreich, J M; Drouillard, J S

    2014-05-01

    Colonization of the gastrointestinal tract of cattle by Shiga toxin-producing Escherichia coli increases the risk of contamination of food products at slaughter. Our study aimed to shed more light on the mechanisms used by E. coli O157:H7 to thrive and compete with other bacteria in the gastrointestinal tract of cattle. We evaluated, in vitro, bovine intestinal mucus and its constituents in terms of their capacity to support growth of E. coli O157:H7 in presence or absence of fecal inoculum, with and without various enzymes. Growth of E. coli O157:H7 and total anaerobic bacteria were proportionate to the amount of mucus added as substrate. Growth of E. coli O157:H7 was similar for small and large intestinal mucus as substrate, and was partially inhibited with addition of fecal inoculum to cultures, presumably due to competition from other organisms. Whole mucus stimulated growth to the greatest degree compared with other compounds evaluated, but the pathogen was capable of utilizing all substrates to some extent. Addition of enzymes to cultures failed to impact growth of E. coli O157:H7 except for neuraminidase, which resulted in greater growth of E. coli O157 when combined with sialic acid as substrate. In conclusion, E. coli O157 has capacity to utilize small or large intestinal mucus, and growth is greatest with whole mucus compared with individual mucus components. There are two possible explanations for these findings (i) multiple substrates are needed to optimize growth, or alternatively, (ii) a component of mucus not evaluated in this experiment is a key ingredient for optimal growth of E. coli O157:H7. PMID:24606840

  11. Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by opening the mucus barrier in colon.

    PubMed

    Ijssennagger, Noortje; Belzer, Clara; Hooiveld, Guido J; Dekker, Jan; van Mil, Saskia W C; Müller, Michael; Kleerebezem, Michiel; van der Meer, Roelof

    2015-08-11

    Colorectal cancer risk is associated with diets high in red meat. Heme, the pigment of red meat, induces cytotoxicity of colonic contents and elicits epithelial damage and compensatory hyperproliferation, leading to hyperplasia. Here we explore the possible causal role of the gut microbiota in heme-induced hyperproliferation. To this end, mice were fed a purified control or heme diet (0.5 μmol/g heme) with or without broad-spectrum antibiotics for 14 d. Heme-induced hyperproliferation was shown to depend on the presence of the gut microbiota, because hyperproliferation was completely eliminated by antibiotics, although heme-induced luminal cytotoxicity was sustained in these mice. Colon mucosa transcriptomics revealed that antibiotics block heme-induced differential expression of oncogenes, tumor suppressors, and cell turnover genes, implying that antibiotic treatment prevented the heme-dependent cytotoxic micelles to reach the epithelium. Our results indicate that this occurs because antibiotics reinforce the mucus barrier by eliminating sulfide-producing bacteria and mucin-degrading bacteria (e.g., Akkermansia). Sulfide potently reduces disulfide bonds and can drive mucin denaturation and microbial access to the mucus layer. This reduction results in formation of trisulfides that can be detected in vitro and in vivo. Therefore, trisulfides can serve as a novel marker of colonic mucolysis and thus as a proxy for mucus barrier reduction. In feces, antibiotics drastically decreased trisulfides but increased mucin polymers that can be lysed by sulfide. We conclude that the gut microbiota is required for heme-induced epithelial hyperproliferation and hyperplasia because of the capacity to reduce mucus barrier function. PMID:26216954

  12. [Quantitative determination of IgA from human bronchial mucus (author's transl)].

    PubMed

    Hayem, A; Laine, A; Bailleul, V; Lebas, J

    1975-05-15

    Before quantitative analysis of bronchial mucus proteins, sputum must be transformed into a homogeneous medium: this is done by ultrasonic action and contact with cationic resin AG 50 W X 2. Then, acid mucins are fixed on Ecteola-cellulose, and proteins extracted by a phosphate/saline buffer at pH 5. IgA is estimated by electroimmunodiffusion. Reproducibility of the method is discussed: the accuracy for IgA values is 4%. PMID:238765

  13. Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by opening the mucus barrier in colon

    PubMed Central

    Ijssennagger, Noortje; Belzer, Clara; Hooiveld, Guido J.; Dekker, Jan; van Mil, Saskia W. C.; Müller, Michael; Kleerebezem, Michiel; van der Meer, Roelof

    2015-01-01

    Colorectal cancer risk is associated with diets high in red meat. Heme, the pigment of red meat, induces cytotoxicity of colonic contents and elicits epithelial damage and compensatory hyperproliferation, leading to hyperplasia. Here we explore the possible causal role of the gut microbiota in heme-induced hyperproliferation. To this end, mice were fed a purified control or heme diet (0.5 μmol/g heme) with or without broad-spectrum antibiotics for 14 d. Heme-induced hyperproliferation was shown to depend on the presence of the gut microbiota, because hyperproliferation was completely eliminated by antibiotics, although heme-induced luminal cytotoxicity was sustained in these mice. Colon mucosa transcriptomics revealed that antibiotics block heme-induced differential expression of oncogenes, tumor suppressors, and cell turnover genes, implying that antibiotic treatment prevented the heme-dependent cytotoxic micelles to reach the epithelium. Our results indicate that this occurs because antibiotics reinforce the mucus barrier by eliminating sulfide-producing bacteria and mucin-degrading bacteria (e.g., Akkermansia). Sulfide potently reduces disulfide bonds and can drive mucin denaturation and microbial access to the mucus layer. This reduction results in formation of trisulfides that can be detected in vitro and in vivo. Therefore, trisulfides can serve as a novel marker of colonic mucolysis and thus as a proxy for mucus barrier reduction. In feces, antibiotics drastically decreased trisulfides but increased mucin polymers that can be lysed by sulfide. We conclude that the gut microbiota is required for heme-induced epithelial hyperproliferation and hyperplasia because of the capacity to reduce mucus barrier function. PMID:26216954

  14. Lung collapse secondary to mucus plug in a gynecologic patient after reconstructive pelvic surgery.

    PubMed

    Lazarou, George; Slavin, Stephen; Cui, Nuan; Mitchell, Kaitlyn

    2014-01-01

    This is the case of a 45-year-old woman with a history of asthma and smoking who developed complete left lung and right upper lobe collapse secondary to mucus plugs that developed immediately postoperatively after an uncomplicated reconstructive pelvic surgery. This rare intraoperative complication was successfully treated in the recovery room with bedside fiber-optic bronchoscopy. This resulted in complete resolution of her pulmonary findings within 24 hours of bronchoscopy. PMID:24566216

  15. A non-redundant role for mouse Serpinb3a in the induction of mucus production in asthma

    PubMed Central

    Sivaprasad, Umasundari; Askew, David J.; Ericksen, Mark B.; Gibson, Aaron M.; Stier, Matthew T.; Brandt, Eric; Bass, Stacey A.; Daines, Michael O.; Chakir, Jamila; Stringer, Keith F.; Wert, Susan E.; Whitsett, Jeffrey A.; Le Cras, Timothy D.; Wills-Karp, Marsha; Silverman, Gary A.; Khurana Hershey, Gurjit K.

    2010-01-01

    Background Asthma is a major public health burden worldwide. Studies from our group and others have demonstrated that SERPINB3 and B4 are induced in asthmatics; however their mechanistic role in asthma has yet to be determined. Objective To evaluate the role of Serpin3a, the murine homolog of human SERPINB3 and B4, in asthma. Methods We studied wild type Balb/c and Serpinb3a null mice in house dust mite or IL-13 induced asthma models and evaluated airway hyperresponsiveness, inflammation, and goblet cell hyperplasia. Results Airway hyperresponsiveness and goblet cell hyperplasia were markedly attenuated in the Serpinb3a null mice compared to the wild type mice following allergen challenge, with minimal effects on inflammation. Expression of SPDEF, a transcription factor that mediates goblet cell hyperplasia, was decreased in the absence of Serpinb3a. IL-13 treated Serpinb3a null mice showed attenuated AHR, inflammation, and mucus production. Conclusions Excessive mucus production and mucus plugging are key pathologic features of asthma, yet the mechanisms responsible for mucus production are not well understood. Our data reveal a novel non-redundant role for Serpinb3a in mediating mucus production through regulation of SPDEF expression. This pathway may be used to effectively target mucus hypersecretion. PMID:21126757

  16. A poly(ethylene glycol)-based surfactant for formulation of drug-loaded mucus penetrating particles.

    PubMed

    Mert, Olcay; Lai, Samuel K; Ensign, Laura; Yang, Ming; Wang, Ying-Ying; Wood, Joseph; Hanes, Justin

    2012-02-10

    Mucosal surfaces are protected by a highly viscoelastic and adhesive mucus layer that traps most foreign particles, including conventional drug and gene carriers. Trapped particles are eliminated on the order of seconds to hours by mucus clearance mechanisms, precluding sustained and targeted drug and nucleic acid delivery to mucosal tissues. We have previously shown that polymeric coatings that minimize adhesive interactions with mucus constituents lead to particles that rapidly penetrate human mucus secretions. Nevertheless, a particular challenge in formulating drug-loaded mucus penetrating particles (MPP) is that many commonly used surfactants are either mucoadhesive, or do not facilitate efficient drug encapsulation. We tested a novel surfactant molecule for particle formulation composed of Vitamin E conjugated to 5 kDa poly(ethylene glycol) (VP5k). We show that VP5k-coated poly(lactide-co-glycolide) (PLGA) nanoparticles rapidly penetrate human cervicovaginal mucus, whereas PLGA nanoparticles coated with polyvinyl alcohol or Vitamin E conjugated to 1 kDa PEG were trapped. Importantly, VP5k facilitated high loading of paclitaxel, a frontline chemo drug, into PLGA MPP, with controlled release for at least 4 days and negligible burst release. Our results offer a promising new method for engineering biodegradable, drug-loaded MPP for sustained and targeted delivery of therapeutics at mucosal surfaces. PMID:21911015

  17. Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure

    PubMed Central

    Wu, Na; Zhang, Xinxin; Li, Feifei; Zhang, Tao; Gan, Yong; Li, Juan

    2015-01-01

    Vaginal small interfering RNA (siRNA) delivery provides a promising strategy for the prevention and treatment of vaginal diseases. However, the densely cross-linked mucus layer on the vaginal wall severely restricts nanoparticle-mediated siRNA delivery to the vaginal epithelium. In order to overcome this barrier and enhance vaginal mucus penetration, we prepared spray-dried powders containing siRNA-loaded nanoparticles. Powders with Pluronic F127 (F127), hydroxypropyl methyl cellulose (HPMC), and mannitol as carriers were obtained using an ultrasound-assisted spray-drying technique. Highly dispersed dry powders with diameters of 5–15 μm were produced. These powders showed effective siRNA protection and sustained release. The mucus-penetrating properties of the powders differed depending on their compositions. They exhibited different potential of opening mesh size of molecular sieve in simulated vaginal mucus system. A powder formulation with 0.6% F127 and 0.1% HPMC produced the maximum increase in the pore size of the model gel used to simulate vaginal mucus by rapidly extracting water from the gel and interacting with the gel; the resulting modulation of the molecular sieve effect achieved a 17.8-fold improvement of siRNA delivery in vaginal tract and effective siRNA delivery to the epithelium. This study suggests that powder formulations with optimized compositions have the potential to alter the steric barrier posed by mucus and hold promise for effective vaginal siRNA delivery. PMID:26347257

  18. Altered Mucus Glycosylation in Core 1 O-Glycan-Deficient Mice Affects Microbiota Composition and Intestinal Architecture

    PubMed Central

    Sommer, Felix; Adam, Nina; Johansson, Malin E. V.; Xia, Lijun; Hansson, Gunnar C.; Bäckhed, Fredrik

    2014-01-01

    A functional mucus layer is a key requirement for gastrointestinal health as it serves as a barrier against bacterial invasion and subsequent inflammation. Recent findings suggest that mucus composition may pose an important selection pressure on the gut microbiota and that altered mucus thickness or properties such as glycosylation lead to intestinal inflammation dependent on bacteria. Here we used TM-IEC C1galt-/- mice, which carry an inducible deficiency of core 1-derived O-glycans in intestinal epithelial cells, to investigate the effects of mucus glycosylation on susceptibility to intestinal inflammation, gut microbial ecology and host physiology. We found that TM-IEC C1galt-/- mice did not develop spontaneous colitis, but they were more susceptible to dextran sodium sulphate-induced colitis. Furthermore, loss of core 1-derived O-glycans induced inverse shifts in the abundance of the phyla Bacteroidetes and Firmicutes. We also found that mucus glycosylation impacts intestinal architecture as TM-IEC C1galt-/- mice had an elongated gastrointestinal tract with deeper ileal crypts, a small increase in the number of proliferative epithelial cells and thicker circular muscle layers in both the ileum and colon. Alterations in the length of the gastrointestinal tract were partly dependent on the microbiota. Thus, the mucus layer plays a role in the regulation of gut microbiota composition, balancing intestinal inflammation, and affects gut architecture. PMID:24416370

  19. Coral-mucus-associated Vibrio integrons in the Great Barrier Reef: genomic hotspots for environmental adaptation

    PubMed Central

    Koenig, Jeremy E; Bourne, David G; Curtis, Bruce; Dlutek, Marlena; Stokes, H W; Doolittle, W Ford; Boucher, Yan

    2011-01-01

    Integron cassette arrays in a dozen cultivars of the most prevalent group of Vibrio isolates obtained from mucus expelled by a scleractinian coral (Pocillopora damicornis) colony living on the Great Barrier Reef were sequenced and compared. Although all cultivars showed >99% identity across recA, pyrH and rpoB genes, no two had more than 10% of their integron-associated gene cassettes in common, and some individuals shared cassettes exclusively with distantly-related members of the genus. Of cassettes shared within the population, a number appear to have been transferred between Vibrio isolates, as assessed by phylogenetic analysis. Prominent among the mucus Vibrio cassettes with potentially inferable functions are acetyltransferases, some with close similarity to known antibiotic-resistance determinants. A subset of these potential resistance cassettes were shared exclusively between the mucus Vibrio cultivars, Vibrio coral pathogens and human pathogens, thus illustrating a direct link between these microbial niches through exchange of integron-associated gene cassettes. PMID:21270840

  20. Quantitative study of Helicobacter pylori in gastric mucus by competitive PCR using synthetic DNA fragments.

    PubMed Central

    Furuta, T; Kaneko, E; Suzuki, M; Arai, H; Futami, H

    1996-01-01

    Helicobacter pylori is closely related to upper gastrointestinal diseases, and the precise evaluation of H. pylori infection is necessary for the treatment of these diseases. The aim of the present study was to establish a method for the quantitative detection of H. pylori. We applied a competitive PCR method using various amounts of synthetic DNA fragments containing the same primer-binding and a subset of the same template sequences as the target competing for primer binding and amplification in order to quantify H. pylori in gastric mucus. The results obtained by this method were compared with the results of histological examination, the rapid urease test, bacterial culture, the [13C]urea breath test, and urea and ammonia measurements in gastric juice. As the quantity of H. pylori in gastric mucus increased, the rates of positivity of histological examination, the rapid urease test, and bacterial culture increased. The quantity of H. pylori in gastric mucus was also significantly correlated with the results of the [13C]urea breath test and was negatively correlated with the urea/ammonia ratio in gastric juice. The competitive PCR method provides an objective measure of the quantity of H. pylori and makes it possible to distinguish true negatives from false negatives due to incomplete PCR and true positives from false positives due to contamination. This method is very useful for the precise evaluation of gastric H. pylori infection. PMID:8880492

  1. Angiotensins processing activities in the venom and epidermic mucus of Scorpaena plumieri.

    PubMed

    Tenório, Humberto de Araújo; Costa, Ricardo Bezerra; Costa Marques, Maria Elizabeth; Victor Dos Santos, Claudio Wilian; Gomes, Francis Soares; Vieira Pereira, Hugo Juarez

    2016-09-01

    The venom of marine animals is a rich source of compounds with remarkable selectivity and functional diversity. Scorpaena plumieri is the most venomous fish in the Brazilian fauna and is responsible for relatively frequent accidents involving anglers and bathers. In humans, its venom causes edema, erythema, ecchymoses, anxiety, nausea, vomiting, and syncope. The venom is chemically characterized by Sp-CTx, a enzyme able to generate an initial endothelium-dependent relaxation response, followed by a contraction response. This study sought to investigate the proteolytic activities regarding vasopeptides angiotensin I and II. Both the venom and the epidermal mucus presented angiotensin conversion activity for angiotensin I, as well as a capacity to form Ang 1-7 directly via Ang I and II. Captopril (10 μM) and EDTA (1 mM) were able to abolish the converting activity of the venom and the epidermal mucus, representing the first description of a converting activity in S. plumieri venom and epidermal mucus. PMID:27215174

  2. Coral-mucus-associated Vibrio integrons in the Great Barrier Reef: genomic hotspots for environmental adaptation.

    PubMed

    Koenig, Jeremy E; Bourne, David G; Curtis, Bruce; Dlutek, Marlena; Stokes, H W; Doolittle, W Ford; Boucher, Yan

    2011-06-01

    Integron cassette arrays in a dozen cultivars of the most prevalent group of Vibrio isolates obtained from mucus expelled by a scleractinian coral (Pocillopora damicornis) colony living on the Great Barrier Reef were sequenced and compared. Although all cultivars showed >99% identity across recA, pyrH and rpoB genes, no two had more than 10% of their integron-associated gene cassettes in common, and some individuals shared cassettes exclusively with distantly-related members of the genus. Of cassettes shared within the population, a number appear to have been transferred between Vibrio isolates, as assessed by phylogenetic analysis. Prominent among the mucus Vibrio cassettes with potentially inferable functions are acetyltransferases, some with close similarity to known antibiotic-resistance determinants. A subset of these potential resistance cassettes were shared exclusively between the mucus Vibrio cultivars, Vibrio coral pathogens and human pathogens, thus illustrating a direct link between these microbial niches through exchange of integron-associated gene cassettes. PMID:21270840

  3. Potamotrygon cf. henlei stingray mucus: biochemical features of a novel antimicrobial protein.

    PubMed

    Conceição, Katia; Monteiro-dos-Santos, Juliane; Seibert, Carla Simone; Silva, Pedro Ismael; Marques, Elineide Eugênio; Richardson, Michael; Lopes-Ferreira, Mônica

    2012-10-01

    Antimicrobial molecules are important components of the innate immune system in vertebrates. They have been studied widely in several fishes, but little is known about these defence factors in stingrays, which are thought to have less sophisticated adaptive immune systems when compared to other teleosts. Stingrays from the specie Potamotrygon cf. henlei are distributed throughout the rivers of central-west Brazil, being the cause of numerous envenomations occurring in the dry seasons. In a previous study, we reported that the mucus of the stingray P. cf. henlei shows antimicrobial effects. Here, to analyze the antimicrobial compounds from the mucus of P. cf. henlei, we employed solid-phase extraction, chromatographic separation followed by ESI-MS, and Edman degradation. A protein similar to the β-chain of hemoglobin was identified, isolated and partially sequenced by Edman degradation. This protein has a molecular weight of 16072.8 Da, and was shown to be active against bacteria (Micrococcus luteus and Escherichiacoli) and yeast (Candida tropicalis) without hemolytic activity. Effects of this new protein in the microcirculation environment were also evaluated. The results obtained provide fundamental information for future basic research, clinical diagnosis and development of new therapies to accident treatment. To the best of our knowledge, this is the first description of a bioactive polypeptide from the mucus of a stingray. PMID:22683678

  4. Beyond the mucus escalator: Complex ciliary hydrodynamics in disease and function

    NASA Astrophysics Data System (ADS)

    Nawroth, Janna; Guo, Hanliang; John, Dabiri; Kanso, Eva; McFall-Ngai, Margaret

    2015-11-01

    Cilia are microscopic, hair-like structures lining external and internal body surfaces where they interact with fluids. The main function of motile cilia is often described as that of a ``mucus escalator'', i.e., a homogeneous ciliary carpet moving along layer of mucus along the surface to transport food, germ cells, debris, or pathogens. Accordingly, the performance of ciliary systems is usually measured in terms of a single metric, transport velocity, or its presumed proxy, ciliary beat frequency. We challenge this simple view through the observation that both healthy and diseased biological systems exhibit a variety of cilia morphologies, beat patterns, and arrangements, resulting in complex flow patterns and transport phenomena that cannot be reduced to a single parameter. Here we present two case studies. In one system, the ciliated surface creates two distinct flow regimes for first trapping and then sheltering potential symbiont bacteria for further biochemical screening. In the other system, chronic disease induces a misalignment of ciliary beat, leading to a pathological transition from uniform mucus transport to a pattern of stagnation and circulation. These studies suggest that (a), we need to develop a wider range of metrics for describing ciliary transport in biological and clinical contexts, and (b), engineered ciliated systems exploiting a variety of design parameters could provide novel ways of manipulating fluids at the microscale.

  5. Helicobacter pylori Couples Motility and Diffusion to Actively Create a Heterogeneous Complex Medium in Gastric Mucus

    NASA Astrophysics Data System (ADS)

    Mirbagheri, Seyed Amir; Fu, Henry Chien

    2016-05-01

    Helicobacter pylori swims through mucus gel by generating ammonia that locally neutralizes the acidic gastric environment, turning nearby gel into a fluid pocket. The size of the fluid zone is important for determining the physics of the motility: in a large zone swimming occurs as in a fluid through hydrodynamic principles, while in a very small zone the motility could be strongly influenced by nonhydrodynamic cell-mucus interactions including chemistry and adhesion. Here, we calculate the size of the fluid pocket. We model how swimming depends on the de-gelation range using a Taylor sheet swimming through a layer of Newtonian fluid bounded by a Brinkman fluid. Then, we model how the de-gelation range depends on the swimming speed by considering the advection-diffusion of ammonia exuded from a translating sphere. Self-consistency between both models determines the values of the swimming speed and the de-gelation range. We find that H. pylori swims through mucus as if unconfined, in a large pocket of Newtonian fluid.

  6. Mucolysis of the colonic mucus barrier by faecal proteinases: inhibition by interacting polyacrylate.

    PubMed

    Hutton, D A; Pearson, J P; Allen, A; Foster, S N

    1990-03-01

    1. Mucolytic (mucus solubilizing) activity in human faeces has been characterized with both purified human and pig colonic mucin and shown to be mediated by proteolysis. 2. Mucolytic activity was demonstrated by: (i) a drop in mucin viscosity; (ii) a substantial reduction in mucin size, from polymer to degraded subunit, as assessed by Sepharose CL-2B gel filtration; (iii) formation of new N-terminal peptides. 3. Mucolytic activity was also followed in faecal extracts by its proteolytic activity using standard succinyl albumin substrate. Proteolysis extended over the pH range 4.5-11.0. Proteolysis was inhibited at pH 7.5 by soybean trypsin inhibitor and phenylmethanesulphonyl fluoride, suggesting the presence of serine proteinases. 4. The polyacrylate carbomer (934P) inhibited both mucolysis of pig colonic mucin and proteolysis of succinyl albumin. 5. Interaction between the polyacrylate (carbomer 934P) and purified human and pig colonic mucin was demonstrated by a marked synergistic increase in solution viscosity (360% above control). 6. The results demonstrate the presence of a mucolytic activity in the human colonic lumen that has the potential to degrade the mucus barrier, and that polyacrylates inhibit this mucolysis and interact to strengthen the colonic mucus barrier. Polyacrylates may therefore have therapeutic potential in inflammatory bowel disease where luminal proteolytic activity can be raised. PMID:2156646

  7. Adherence to hormone therapy among women with breast cancer

    PubMed Central

    2014-01-01

    Background Despite the excellent results obtained with hormone therapy, the long treatment period and the side effects associated with its use make patient adherence difficult. Moreover, certain aspects of health care can mitigate or exacerbate non-adherence. This study aimed to identify the factors associated with adherence to hormone therapy for breast cancer, with the goal of contributing to the reformulation of the care process and to improvements in outcomes. Method This was a retrospective longitudinal study based on secondary data. The study integrated and analyzed data from a cohort of 5,861 women with breast cancer who were identified in the databases of the Brazilian National Cancer Institute [Instituto Nacional de Câncer - INCA] and the Unified Health System [Sistema Único de Saúde - SUS]. All of the patients were treated at INCA, which dispenses free medication, and the follow-up period lasted from 01/01/2004 to 10/29/2010. The outcome of interest was hormone treatment adherence, which was defined as the possession of medication, and a logistic regression model was employed to identify the socio-demographic, behavioral, clinical, and health care variables that were independently associated with the variations in this outcome. Results The proportion of women who adhered to hormone therapy was 76.3%. The likelihood of adherence to hormone therapy increased with each additional year of age, as well as among women with a secondary or higher level education, those with a partner, those who underwent surgery, those who had more consultations with a breast specialist and clinical oncologist, and those who underwent psychotherapy; the effect for the latter increased with each additional consultation. Conversely, the likelihood of adherence was lower among patients at a non-curable stage, those who were alcohol drinkers, those who received chemotherapy, those who had undergone more tests and had more hospitalizations, and those who used tamoxifen and combined

  8. Entry of (/sup 3/H)water and (1,2-/sup 14/C)polyethylene glycol 4000 into normal and cystic fibrosis salivary mucus

    SciTech Connect

    Lukie, B.E.

    1983-03-01

    This investigation was performed to compare the entry of (/sup 3/H)water and (/sup 14/C)PEG into samples of salivary mucus from patients with CF and normal subjects. A solution containing both radioisotopes was added to samples of salivary mucus and mixed, and entry of each into mucus was determined by their dilution in the supernatant at 1, 2, 4, and 24 hr. (/sup 3/H)water rapidly entered and equilibrated with the water content of both normal and CF mucus. (/sup 14/C)PEG entered mucus more slowly than (/sup 3/H)water and by 24 hr had entered at a ratio of only 0.794 +/- 0.108 and 0.766 +/- 0.039 of the water space accessible to (/sup 3/H)water in normal and CF mucus, respectively. The mechanisms responsible for the partial exclusion of the large polyethylene glycol molecule were not explored but may reflect steric restriction of access to a portion of mucus water. Thus water entry and solute exclusion, both determinants of permeability, were unaltered in CF mucus, which fact provides evidence against the presence of a generalized defect of mucus permeability in this disease. The techniques developed for this study may be adaptable to the study of the permeability properties of mucus from other sources and other gels.

  9. Entry of (/sup 3/H)water and (1,2-/sup 14/C)polyethylene glycol 4000 into normal and cystic fibrosis salivary mucus

    SciTech Connect

    Lukie, B.E.

    1983-03-01

    This investigation was performed to compare the entry of (/sup 3/H)water and (/sup 14/C)PEG into samples of salivary mucus from patients with CF and normal subjects. A solution containing both radioisotopes was added to samples and salivary mucus and mixed, and entry of each into mucus was determined by their dilution in the supernatant at 1, 2, 4, and 24 hr. (/sup 3/H)water rapidly entered and equilibrated with the water content of both normal and CF mucus. (/sup 14/C)PEG entered mucus more slowly than (/sup 3/H)water and by 24 hr had entered at a ratio of only 0.794 +/- 0.108 and 0.766 +/- 0.039 of the water space accessible to (/sup 3/H)water in normal and CF mucus, respectively. The mechanisms responsible for the partial exclusion of the large polyethylene glycol molecule were not explored but may reflect restriction of access to a portion of mucus water. Thus water entry and solute exclusion, both determinants of permeability, were unaltered in CF mucus, which fact provides evidence against the presence of a generalized defect of mucus permeability in this disease. The techniques developed for this study may be adaptable to the study of the permeability properties of mucus from other sources and other gels.

  10. Adherence of sputtered titanium carbides

    NASA Technical Reports Server (NTRS)

    Brainard, W. A.; Wheeler, D. R.

    1979-01-01

    The study searches for interface treatment that would increase the adhesion of TiC coating to nickel- and titanium-base alloys. Rene 41 (19 wt percent Cr, 11 wt percent Mo, 3 wt percent Ti, balance Ni) and Ti-6Al-4V (6 wt percent Al, 4 wt percent V, balance Ti) are considered. Adhesion of the coatings is evaluated in pin-and disk friction tests. The coatings and interface regions are examined by X-ray photoelectron spectroscopy. Results suggest that sputtered refractory compound coatings adhere best when a mixed compound of coating and substrate metals is formed in the interfacial region. The most effective type of refractory compound interface appears to depend on both substrate and coating material. A combination of metallic interlayer deposition and mixed compound interface formation may be more effective for some substrate coating combinations than either alone.

  11. The Association Between Patient-Reported and Objective Oral Anticancer Medication Adherence Measures: A Systematic Review

    PubMed Central

    Atkinson, Thomas M.; Rodríguez, Vivian M.; Gordon, Mallorie; Avildsen, Isabelle K.; Emanu, Jessica C.; Jewell, Sarah T.; Anselmi, Kimberly A.; Ginex, Pamela K.

    2016-01-01

    Problem Identification Oral anticancer medication (OAM) use has been steadily increasing, leading to several patient benefits. A notable challenge for nurses is accurate monitoring of patient OAM regimens because nonadherence is associated with poor health outcomes and decreased survival. Currently, no gold standard measure of OAM adherence exists. The authors conducted a systematic review of the association between objective and patient-reported measures of OAM adherence. Literature Search A systematic electronic literature search was conducted using PubMed, EMBASE, Scopus, PsycINFO®, Cochrane Library, Web of Science, and CINAHL® databases through November 2014. Data Evaluation Articles were independently reviewed to determine whether they included an original characterization of the level of association between objective and patient-reported measures of OAM adherence. Synthesis From a total of 11,135 articles retrieved, eight studies met inclusion criteria. Objective adherence was primarily assessed using pill counts or Medication Event Monitoring System (MEMSCap™). Patient-reported adherence was most commonly assessed using study-specific questionnaires. Significant positive correlations were observed between objective and patient-reported adherence across most studies, with three studies reporting higher rates of adherence via patient reporting. Conclusions Despite variation in the OAMs and measures used, patient-reported adherence rates were equal to or higher than objective adherence measures across studies. Social desirability bias may be a concern; however, given the significant concordance observed, using patient-reported methods in future studies of OAM adherence may be justified. Implications for Nursing This review provides evidence to support nursing use of patient-reported measures to accurately monitor OAM adherence and potentially improve the quality of patient–provider communication. PMID:27541550

  12. Explaining Adherence Success in Sub-Saharan Africa: An Ethnographic Study

    PubMed Central

    Ware, Norma C; Idoko, John; Kaaya, Sylvia; Biraro, Irene Andia; Wyatt, Monique A; Agbaji, Oche; Chalamilla, Guerino; Bangsberg, David R

    2009-01-01

    Background Individuals living with HIV/AIDS in sub-Saharan Africa generally take more than 90% of prescribed doses of antiretroviral therapy (ART). This number exceeds the levels of adherence observed in North America and dispels early scale-up concerns that adherence would be inadequate in settings of extreme poverty. This paper offers an explanation and theoretical model of ART adherence success based on the results of an ethnographic study in three sub-Saharan African countries. Methods and Findings Determinants of ART adherence for HIV-infected persons in sub-Saharan Africa were examined with ethnographic research methods. 414 in-person interviews were carried out with 252 persons taking ART, their treatment partners, and health care professionals at HIV treatment sites in Jos, Nigeria; Dar es Salaam, Tanzania; and Mbarara, Uganda. 136 field observations of clinic activities were also conducted. Data were examined using category construction and interpretive approaches to analysis. Findings indicate that individuals taking ART routinely overcome economic obstacles to ART adherence through a number of deliberate strategies aimed at prioritizing adherence: borrowing and “begging” transport funds, making “impossible choices” to allocate resources in favor of treatment, and “doing without.” Prioritization of adherence is accomplished through resources and help made available by treatment partners, other family members and friends, and health care providers. Helpers expect adherence and make their expectations known, creating a responsibility on the part of patients to adhere. Patients adhere to promote good will on the part of helpers, thereby ensuring help will be available when future needs arise. Conclusion Adherence success in sub-Saharan Africa can be explained as a means of fulfilling social responsibilities and thus preserving social capital in essential relationships. PMID:19175285

  13. Practice what you preach? An exploratory multilevel study on rheumatoid arthritis guideline adherence by rheumatologists

    PubMed Central

    Lesuis, N; den Broeder, A A; Hulscher, M E J L; van Vollenhoven, R F

    2016-01-01

    Objectives To assess variation in and determinants of rheumatologist guideline adherence in patients with rheumatoid arthritis (RA), in daily practice. Methods In this retrospective observational study, guideline adherence in the first year of treatment was assessed for 7 predefined parameters on diagnostics, treatment and follow-up in all adult patients with RA with a first outpatient clinic visit at the study centre, from September 2009 to March 2011. Variation in guideline adherence was assessed on parameter and rheumatologist level. Determinants for guideline adherence were assessed in patients (demographic characteristics, rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibody (aCCP) positivity, erythrocyte sedimentation rate, erosive disease, comorbidity and the number of available disease modifying anti-rheumatic drug (DMARD) treatment options) and rheumatologists (demographic and practice characteristics, guideline knowledge and agreement, outcome expectancy, cognitive bias, thinking style, numeracy and personality). Results A total of 994 visits in 137 patients with RA were reviewed. Variation in guideline adherence among parameters was present (adherence between 21% and 72%), with referral to the physician assistant as lowest scoring and referral to a specialised nurse as highest scoring parameter. Variation in guideline adherence among rheumatologists was also present (adherence between 22% and 100%). Patient sex, the number of DMARD options, presence of erosions, comorbidity, RF/aCCP positivity, type of patient and the rheumatologists' scientific education status were associated with adherence to 1 or more guideline parameters. Conclusions Guideline adherence varied considerably among the guideline parameters and rheumatologists, showing that there is room for improvement. Guideline adherence in our sample was related to several patient and rheumatologist determinants. PMID:27252892

  14. Medication adherence: a review of pharmacy education, research, practice and policy in Finland

    PubMed Central

    Bell, J. Simon; Enlund, Hannes; Vainio, Kirsti

    2010-01-01

    Aims To describe pharmacy education, research, practice and policy related to medication adherence in Finland since the year 2000. Methods The three universities that provide pharmacy education (Åbo Akademi, University of Eastern Finland, and University of Helsinki) completed a structured pro-forma questionnaire regarding education related to medication adherence. A MEDLINE and EMBASE literature search was performed to identify English language peer-reviewed research that reported medication compliance, adherence or persistence. The Ministry of Social Affairs and Health was invited to nominate policies and documents related to medication adherence. A narrative review of medication counselling practices and professional service delivery through Finnish community pharmacies was undertaken. Results Medication adherence was a theme integrated into obligatory and elective courses for bachelors and masters degree students. The literature search identified 33 English language peer-reviewed research articles reporting medication compliance, adherence or persistence published since the year 2000. Policy documents of the Ministry of Social Affairs and Health recognise that poor medication adherence may lead to suboptimal treatment outcomes, and encourage patient participation in treatment decision making. Adherence practice in Finnish pharmacies has been strongly linked to the development of medication counselling services. Conclusions Adherence research and education has focused on understanding and addressing the contextual factors that contribute to medication nonadherence. Adherence practice in community pharmacies has tended to focus on medication counselling and programs specific to particular disease states. Medication adherence is a topic that is integrated into courses for bachelor’s and master’s level pharmacy students in Finland. PMID:25126134

  15. Patient Characteristics and Variability in Adherence and Competence in Cognitive-Behavioral Therapy for Panic Disorder

    PubMed Central

    Boswell, James F.; Gallagher, Matthew W.; Sauer-Zavala, Shannon E.; Bullis, Jacqueline; Gorman, Jack M.; Shear, M. Katherine; Woods, Scott; Barlow, David H.

    2013-01-01

    Although associations with outcome have been inconsistent, therapist adherence and competence continues to garner attention, particularly within the context of increasing interest in the dissemination, implementation, and sustainability of evidence-based treatments. To date, research on therapist adherence and competence has focused on average levels across therapists. With a few exceptions, research has failed to address multiple sources of variability in adherence and competence, identify important factors that might account for variability, or take these sources of variability into account when examining associations with symptom change. Objective (a) statistically demonstrate between- and within-therapist variability in adherence and competence ratings and examine patient characteristics as predictors of this variability and (b) examine the relationship between adherence/competence and symptom change. Method Randomly selected audiotaped sessions from a randomized controlled trial of cognitive-behavioral therapy for panic disorder were rated for therapist adherence and competence. Patients completed a self-report measure of panic symptom severity prior to each session and the Inventory of Interpersonal Problems-Personality Disorder Scale prior to the start of treatment. Results Significant between- and within-therapist variability in adherence and competence were observed. Adherence and competence deteriorated significantly over the course of treatment. Higher patient interpersonal aggression was associated with decrements in both adherence and competence. Neither adherence nor competence predicted subsequent panic severity. Conclusions Variability and “drift” in adherence and competence can be observed in controlled trials. Training and implementation efforts should involve continued consultation over multiple cases in order to account for relevant patient factors and promote sustainability across sessions and patients. PMID:23339537

  16. Far from superficial: microbial diversity associated with the skin and mucus of fish

    USGS Publications Warehouse

    Cipriano, Rocco C.; Dove, Alistair

    2011-01-01

    During horizontal or water-borne infection involving an obligate pathogen (e.g. – Aeromonas salmonicida, cause of furunculosis), the pathogen interacted with and influenced the microbial diversity of the dermal mucus of fish. Prior to infection, the prevalent bacterial flora cultured from juvenile Atlantic salmon (Salmo salar) included Pseudomonas fluorescens, Comomonas terrigenia, Acinetobacter sp., Moraxella sp., Pseudomonas dimunita, Alcaligenes denitrificans, Pseudomonas pseudoalcaligenes, and Pseudomonas alcaligenes, Serratia liquefaciens, Aeromonas hydrophila, other motile Aeromonas spp., and Corynebacterium aquaticum. After A. salmonicida was initially detected in this population as an external mucus infection, Acinetobacter sp., Moraxella sp., C. terrigenia, P. fluorescens, and P. dimunita, Staphylococcus sp., and A. hydrophila, were also present in appreciable numbers. Within several weeks, however, the A. salmonicida infection amplified and composed 78% of the total flora in the mucus. Only P. dimunita (4%). P. fluorescens (2%), and C. terrigenia (1%) were cultured at that time and more than a third of these fish showed evidence of a systemic A. salmonicida infection within their kidneys. Eight weeks after oral oxytetracycline treatments, A. salmonicida was no longer isolated from the mucus or kidneys of any fish and glucose inert or other oxidative microbes (e.g., P. fluorescens, C. terrigenia, Acinetobacter sp., Moraxella sp.) were beginning to repopulate the external surface of the salmon in increasing frequency. Still present and composing fairly large percentages of the total flora were A. hydrophila, as well as Enterobacter sp., and P. putrefaciens. A normal microbial diversity was re-established as the fish recovered. In another investigation, reduced biological diversity was noted in the dermal mucus among smallmouth bass that were sampled from the Jackson River (Covington, VA). In these fish, A. hydrophila and P. putrefaciens were the two

  17. Psychological Determinants of Adolescent Exercise Adherence.

    ERIC Educational Resources Information Center

    Douthitt, Vicki L.

    1994-01-01

    High school physical education students completed questionnaires which represented four psychological variables, and one physical activity variable (exercise adherence) in classroom setting (n=132) and in summer setting (n=110). Found Perceived Romantic Appeal predictive of male exercise adherence and Perceived Athletic Competency, Perceived…

  18. Predicting asthma exacerbations employing remotely monitored adherence.

    PubMed

    Killane, Isabelle; Sulaiman, Imran; MacHale, Elaine; Breathnach, Aoife; Taylor, Terence E; Holmes, Martin S; Reilly, Richard B; Costello, Richard W

    2016-03-01

    This Letter investigated the efficacy of a decision-support system, designed for respiratory medicine, at predicting asthma exacerbations in a multi-site longitudinal randomised control trial. Adherence to inhaler medication was acquired over 3 months from patients with asthma employing a dose counter and a remote monitoring adherence device which recorded participant's inhaler use: n = 184 (23,656 audio files), 61% women, age (mean ± sd) 49.3 ± 16.4. Data on occurrence of exacerbations was collected at three clinical visits, 1 month apart. The relative risk of an asthma exacerbation for those with good and poor adherence was examined employing a univariate and multivariate modified Poisson regression approach; adjusting for age, gender and body mass index. For all months dose counter adherence was significantly (p < 0.01) higher than remote monitoring adherence. Overall, those with poor adherence had a 1.38 ± 0.34 and 1.42 ± 0.39 (remotely monitored) and 1.25 ± 0.32 and 1.18 ± 0.31 (dose counter) higher relative risk of an exacerbation in model 1 and model 2, respectively. However, this was not found to be statistically significantly different. Remotely monitored adherence holds important clinical information and future research should focus on refining adherence and exacerbation measures. Decision-support systems based on remote monitoring may enhance patient-physician communication, possibly reducing preventable adverse events. PMID:27222733

  19. A Review of Treatment Adherence Measurement Methods

    ERIC Educational Resources Information Center

    Schoenwald, Sonja K.; Garland, Ann F.

    2013-01-01

    Fidelity measurement is critical for testing the effectiveness and implementation in practice of psychosocial interventions. Adherence is a critical component of fidelity. The purposes of this review were to catalogue adherence measurement methods and assess existing evidence for the valid and reliable use of the scores that they generate and the…

  20. Secondary preventive medication persistence and adherence 1 year after stroke

    PubMed Central

    Olson, D.M.; Zhao, X.; Pan, W.; Zimmer, L.O.; Goldstein, L.B.; Alberts, M.J.; Fagan, S.C.; Fonarow, G.C.; Johnston, S.C.; Kidwell, C.; LaBresh, K.A.; Ovbiagele, B.; Schwamm, L.; Peterson, E.D.

    2011-01-01

    Objective: Data on long-term use of secondary prevention medications following stroke are limited. The Adherence eValuation After Ischemic stroke–Longitudinal (AVAIL) Registry assessed patient, provider, and system-level factors influencing continuation of prevention medications for 1 year following stroke hospitalization discharge. Methods: Patients with ischemic stroke or TIA discharged from 106 hospitals participating in the American Heart Association Get With The Guidelines–Stroke program were surveyed to determine their use of warfarin, antiplatelet, antihypertensive, lipid-lowering, and diabetes medications from discharge to 12 months. Reasons for stopping medications were ascertained. Persistence was defined as continuation of all secondary preventive medications prescribed at hospital discharge, and adherence as continuation of prescribed medications except those stopped according to health care provider instructions. Results: Of the 2,880 patients enrolled in AVAIL, 88.4% (2,457 patients) completed 1-year interviews. Of these, 65.9% were regimen persistent and 86.6% were regimen adherent. Independent predictors of 1-year medication persistence included fewer medications prescribed at discharge, having an adequate income, having an appointment with a primary care provider, and greater understanding of why medications were prescribed and their side effects. Independent predictors of adherence were similar to those for persistence. Conclusions: Although up to one-third of stroke patients discontinued one or more secondary prevention medications within 1 year of hospital discharge, self-discontinuation of these medications is uncommon. Several potentially modifiable patient, provider, and system-level factors associated with persistence and adherence may be targets for future interventions. PMID:21900638

  1. Cold-inducible RNA-binding protein mediates airway inflammation and mucus hypersecretion through a post-transcriptional regulatory mechanism under cold stress.

    PubMed

    Juan, Yang; Haiqiao, Wu; Xie, Wenyao; Huaping, Huang; Zhong, Han; Xiangdong, Zhou; Kolosov, Victor P; Perelman, Juliy M

    2016-09-01

    Acute or chronic cold exposure exacerbates chronic inflammatory airway diseases, such as chronic obstructive pulmonary disease (COPD) and asthma. Cold-inducible RNA-binding protein (CIRP) is a cold-shock protein and is induced by various environmental stressors, such as hypothermia and hypoxia. In this study, we showed that CIRP gene and protein levels were significantly increased in patients with COPD and in rats with chronic airway inflammation compared with healthy subjects. Similarly, inflammatory cytokine production and MUC5AC secretion were up-regulated in rats following cigarette smoke inhalation. Cold temperature-induced CIRP overexpression and translocation were shown to be dependent on arginine methylation in vitro. CIRP overexpression promoted stress granule (SG) assembly. In the cytoplasm, the stability of pro-inflammatory cytokine mRNAs was increased through specific interactions between CIRP and mediator mRNA 3'-UTRs; these interactions increased the mRNA translation, resulting in MUC5AC overproduction in response to cold stress. Conversely, CIRP silencing and a methyltransferase inhibitor (adenosine dialdehyde) promoted cytokine mRNA degradation and inhibited the inflammatory response and mucus hypersecretion. These findings indicate that cold temperature can induce an airway inflammatory response and excess mucus production via a CIRP-mediated increase in mRNA stability and protein translation. PMID:27477308

  2. Composition and Functional Characterization of Microbiome Associated with Mucus of the Coral Fungia echinata Collected from Andaman Sea.

    PubMed

    Badhai, Jhasketan; Ghosh, Tarini S; Das, Subrata K

    2016-01-01

    This study describes the community composition and functions of the microbiome associated with the mucus of the coral Fungia echinata based on metagenomic approach. Metagenome sequence data showed a dominance of the class Gammaproteobacteria followed by Alphaproteobacteria, Betaproteobacteria, Deltaproteobacteria, Flavobacteriia, Bacilli, and Clostridia. At the order level, the most abundant groups were Pseudomonadales, Oceanospirillales, Alteromonadales, and Rhodobacterales. The genus Psychrobacter was the most predominant followed by Thalassolituus and Cobetia, although other genera were also present, such as Sulfitobacter, Pseudoalteromonas, Oleispira, Halomonas, Oceanobacter, Acinetobacter, Pseudomonas, Vibrio, and Marinobacter. The metabolic profile of the bacterial community displayed high prevalence of genes associated with core-housekeeping processes, such as carbohydrates, amino acids, proteins, and nucleic acid metabolism. Further, high abundance of genes coding for DNA replication and repair, stress response, and virulence factors in the metagenome suggested acquisition of specific environmental adaptation by the microbiota. Comparative analysis with other coral metagenome exhibits marked differences at the taxonomical and functional level. This study suggests the bacterial community compositions are influenced by the specific coral micro-niche and the oligotrophic marine environment. PMID:27379066

  3. Phylogenetic characterization of culturable actinomycetes associated with the mucus of the coral Acropora digitifera from Gulf of Mannar.

    PubMed

    Nithyanand, Paramasivam; Manju, Sivalingam; Karutha Pandian, Shunmugiah

    2011-01-01

    The marine environment is a virtually untapped source of novel actinomycete diversity and its metabolites. Investigating the diversity of actinomycetes in other marine macroorganisms, like seaweeds and sponges, have resulted in isolation of novel bioactive metabolites. Actinomycetes diversity associated with corals and their produced metabolites have not yet been explored. Hence, in this study we attempted to characterize the culturable actinomycetes population associated with the coral Acropora digitifera. Actinomycetes were isolated from the mucus of the coral wherein the actinomycetes count was much higher when compared with the surrounding seawater and sediment. Actinobacteria-specific 16S rRNA gene primers were used for identifying the isolates at the molecular level in addition to biochemical tests. Amplified ribosomal DNA restriction analysis using three restriction enzymes revealed several polymorphic groups within the isolates. Sequencing and blast analysis of the isolates revealed that some isolates had only 96.7% similarity with its nearest match in GenBank indicating that they may be novel isolates at the species level. The isolated actinomycetes exhibited good antibacterial activity against various human pathogens. This study offers for the first time a prelude about the unexplored culturable actinomycetes diversity associated with a scleractinian coral and their bioactive capabilities. PMID:21105906

  4. Composition and Functional Characterization of Microbiome Associated with Mucus of the Coral Fungia echinata Collected from Andaman Sea

    PubMed Central

    Badhai, Jhasketan; Ghosh, Tarini S.; Das, Subrata K.

    2016-01-01

    This study describes the community composition and functions of the microbiome associated with the mucus of the coral Fungia echinata based on metagenomic approach. Metagenome sequence data showed a dominance of the class Gammaproteobacteria followed by Alphaproteobacteria, Betaproteobacteria, Deltaproteobacteria, Flavobacteriia, Bacilli, and Clostridia. At the order level, the most abundant groups were Pseudomonadales, Oceanospirillales, Alteromonadales, and Rhodobacterales. The genus Psychrobacter was the most predominant followed by Thalassolituus and Cobetia, although other genera were also present, such as Sulfitobacter, Pseudoalteromonas, Oleispira, Halomonas, Oceanobacter, Acinetobacter, Pseudomonas, Vibrio, and Marinobacter. The metabolic profile of the bacterial community displayed high prevalence of genes associated with core-housekeeping processes, such as carbohydrates, amino acids, proteins, and nucleic acid metabolism. Further, high abundance of genes coding for DNA replication and repair, stress response, and virulence factors in the metagenome suggested acquisition of specific environmental adaptation by the microbiota. Comparative analysis with other coral metagenome exhibits marked differences at the taxonomical and functional level. This study suggests the bacterial community compositions are influenced by the specific coral micro-niche and the oligotrophic marine environment. PMID:27379066

  5. relA enhances the adherence of enteropathogenic Escherichia coli.

    PubMed

    Spira, Beny; Ferreira, Gerson Moura; de Almeida, Luiz Gustavo

    2014-01-01

    Enteropathogenic Escherichia coli (EPEC) is a known causative agent of diarrhea in children. In the process of colonization of the small intestine, EPEC synthesizes two types of adhesins, the bundle-forming pilus (BFP) and intimin. The BFP pilus is an adhesin associated with the initial stages of adherence of EPEC to epithelial cells, while the outer membrane protein intimin carries out the intimate adherence that takes place at the third stage of infection. BFP is encoded by the bfp operon located in plasmid EAF, present only in typical EPEC isolates, while eae, the gene that encodes intimin is situated in the LEE, a chromosomal pathogenicity island. Transcription of bfp and eae is regulated by the products of the perABC operon, also present in plasmid EAF. Here we show that deletion of relA, that encodes a guanosine penta and tetraphosphate synthetase impairs EPEC adherence to epithelial cells in vitro. In the absence of relA, the transcription of the regulatory operon perABC is reduced, resulting in lower levels of BFP and intimin. Bacterial adherence, BFP and intimin synthesis and perABC expression are restored upon complementation with the wild-type relA allele. PMID:24643076

  6. Improving illiterate patients understanding and adherence to discharge medications

    PubMed Central

    Clayton, Matthew; Syed, Faizan; Rashid, Amjid; Fayyaz, Umer

    2012-01-01

    Abstract Adherence to a hospital discharge medication regime is crucial for successful treatment and to avoid increasing rates of drug resistance. A patient's success in adhering to their medication regime is dependent on many social, cultural, economic, illness and therapy-related factors, and these are often more pronounced in the developing world. Anecdotal evidence in Services Hospital, Lahore (Pakistan) suggested that the relatively high levels of illiteracy in the patient population was a major factor in poor adherence. Baseline measurement revealed that 48% of all the hospital's patients were illiterate with just 5%–12% of illiterate patients being able to interpret their handwritten discharge prescription after leaving hospital. Unsurprisingly follow-up clinics reported very poor adherence. This quality improvement project intervened by designing a new discharge prescription proforma which used pictures and symbols rather than words to convey the necessary information. Repeated surveys demonstrated large relative increases in comprehension of the new proformas amongst illiterate patients with between 23%–35% of illiterate patients understanding the new proformas. PMID:26734151

  7. Behavioral economics strategies for promoting adherence to sleep interventions.

    PubMed

    Stevens, Jack

    2015-10-01

    Cognitive-behavioral treatment for insomnia and continuous positive airway pressure therapy for obstructive sleep apnea are among the most efficacious sleep interventions. Unfortunately, adherence levels are disappointingly low for these interventions. Behavioral economics offers a promising framework for promoting adherence, often through relatively brief and straightforward strategies. The assumptions, goals, and key strategies of behavioral economics will be introduced. These strategies include providing social norms information, changing defaults, using the compromise effect, utilizing commitment devices, and establishing lottery-based systems. Then, this review will highlight specific behavioral economic approaches to promote patient adherence for three major sleep interventions: 1) behavioral treatment for pediatric insomnia, 2) cognitive-behavioral treatment for adult insomnia, and 3) continuous positive airway pressure for obstructive sleep apnea. Next, behavioral economic strategies will be discussed as ways to improve health care provider adherence to clinical practice guidelines regarding appropriate prescribing of hypnotics and ordering sleep-promoting practices for hospitalized inpatients. Finally, possible concerns that readers may have about behavioral economics strategies, including their efficacy, feasibility, and sustainability, will be addressed. PMID:25645127

  8. Treatment Adherence, Competence, and Outcome in Individual and Family Therapy for Adolescent Behavior Problems

    PubMed Central

    Hogue, Aaron; Henderson, Craig E.; Dauber, Sarah; Barajas, Priscilla C.; Fried, Adam; Liddle, Howard A.

    2010-01-01

    This study examined the impact of treatment adherence and therapist competence on treatment outcome in a controlled trial of individual cognitive–behavioral therapy (CBT) and multidimensional family therapy (MDFT) for adolescent substance use and related behavior problems. Participants included 136 adolescents (62 CBT, 74 MDFT) assessed at intake, discharge, and 6-month follow-up. Observational ratings of adherence and competence were collected on early and later phases of treatment (192 CBT sessions, 245 MDFT sessions) by using a contextual measure of treatment fidelity. Adherence and competence effects were tested after controlling for therapeutic alliance. In CBT only, stronger adherence predicted greater declines in drug use (linear effect). In CBT and MDFT, (a) stronger adherence predicted greater reductions in externalizing behaviors (linear effect) and (b) intermediate levels of adherence predicted the largest declines in internalizing behaviors, with high and low adherence predicting smaller improvements (curvilinear effect). Therapist competence did not predict outcome and did not moderate adherence–outcome relations; however, competence findings are tentative due to relatively low interrater reliability for the competence ratings. Clinical and research implications for attending to both linear and curvilinear adherence effects in manualized treatments for behavior disorders are discussed. PMID:18665684

  9. A multifaceted prospective memory intervention to improve medication adherence: design of a randomized control trial.

    PubMed

    Insel, Kathleen C; Einstein, Gilles O; Morrow, Daniel G; Hepworth, Joseph T

    2013-01-01

    Adherence to prescribed antihypertensive agents is critical because control of elevated blood pressure is the single most important way to prevent stroke and other end organ damage. Unfortunately, nonadherence remains a significant problem. Previous interventions designed to improve adherence have demonstrated only small benefits of strategies that target single facets such as understanding medication directions. The intervention described here is informed by prospective memory theory and performance of older adults in laboratory-based paradigms and uses a comprehensive, multifaceted approach to improve adherence. It incorporates multiple strategies designed to support key components of prospective remembering involved in taking medication. The intervention is delivered by nurses in the home with an education control group for comparison. Differences between groups in overall adherence following the intervention and 6 months later will be tested. Systolic and diastolic blood pressure levels also will be examined between groups and as they relate to adherence. Intra-individual regression is planned to examine change in adherence over time and its predictors. Finally, we will examine the association between executive function/working memory and adherence, predicting that adherence will be related to executive/working memory in the control group but not in the intervention group. PMID:23010608

  10. Impact of an adherence intervention on the effectiveness of tenofovir gel in the CAPRISA 004 trial.

    PubMed

    Mansoor, Leila Essop; Karim, Quarraisha Abdool; Werner, Lise; Madlala, Bernadette; Ngcobo, Nelisiwe; Cornman, Deborah H; Amico, K Rivet; Fisher, Jeffrey; Fisher, William A; Macqueen, Kathleen M; Karim, Salim S Abdool

    2014-05-01

    High adherence is important in microbicide trials, but no adherence interventions to date have demonstrated empiric improvements in microbicide adherence or effectiveness. Approximately midway during the CAPRISA 004 trial, we implemented a novel adherence intervention (Adherence Support Program-ASP), based on an Information-Motivation-Behavioral Skills model and incorporating a Motivational Interviewing approach. We assessed the impact of the ASP on adherence and tenofovir gel effectiveness using a before-and-after comparison. Of the 889 women in the trial, 774 contributed 486.1 women-years of follow-up pre-ASP and 828 contributed 845.7 women-years of follow-up post-ASP. Median adherence rose from 53.6 % pre-ASP to 66.5 % post-ASP. Detectable tenofovir levels increased from 40.6 % pre-ASP to 62.5 % post-ASP in 64 women who had paired tenofovir drug samples. Gel effectiveness improved post-ASP; HIV incidence in the tenofovir gel arm was 24 % lower pre-ASP compared to 47 % lower post-ASP. Following implementation of the ASP, microbicide adherence improved with a concomitant increase in the effectiveness of tenofovir gel. PMID:24633717

  11. Descriptions and Correlates of Medication Adherence, Attitudes, and Self-Efficacy in Outpatients With Schizophrenia Spectrum Disorders (SSDs).

    PubMed

    Beebe, Lora Humphrey; Smith, Kathleen; Phillips, Chad

    2016-06-01

    The problem of medication adherence in schizophrenia spectrum disorders (SSDs) has challenged researchers and clinicians for decades. Few investigations have examined non-psychiatric adherence in this group. We conducted a descriptive correlational investigation of adherence and related factors in 185 stable outpatients with SSDs. Fifty-seven percent of participants had antipsychotic medication levels within therapeutic range and 42% had levels below therapeutic range. Pill count percentage adherence to antipsychotic medications ranged from 0-100% with a mean of 70% and SD 34.9. Mean non-psychiatric medication adherence ranged from 0 to 100 with a mean of 61% and SD 31.8. The following characteristics were not significantly associated with adherence: age, diagnosis, gender, race, living arrangement, educational level, typical versus atypical antipsychotic medication. Level of symptoms was correlated negatively and significantly with self-reported medication adherence and medication adherence self-efficacy. Our next project will examine the effectiveness of a telephone-delivered intervention designed to support adherence in this group. PMID:27256948

  12. Immersed boundary-lattice Boltzmann method for simulation of muco-ciliary transport: effect of mucus depth at various amounts of cilia beat frequency

    NASA Astrophysics Data System (ADS)

    Shahmardan, M. M.; Sedaghat, M. H.; Norouzi, M.; Nazari, M.

    2015-12-01

    Numerical simulation based on immersed boundary-lattice Boltzmann method has been employed to study 2D muco-ciliary transport problem. The periciliary liquid (PCL) and mucus layers in this study are considered as the Newtonian and viscoelastic fluid respectively. An Oldroyd-B model is used as the constitutive equations of mucus layer. To simulate accurate effects of the cilia and PCL-mucus interface on the fluid, immersed boundary method is used. Numerical simulations have been performed to investigate the effects of mucus depth on the muco-ciliary clearance at various values of cilia beat frequencies. Our results show that, by increasing mucus depth, which results from air pollution and smoking, mean mucus velocity decreases. But it can be completely modified by increasing cilia beat frequency and the cilia beat frequency has great effect on the muco-ciliary clearance.

  13. A Brief Adherence Intervention that Improved Glycemic Control: Mediation by Patterns of Adherence

    PubMed Central

    de Vries McClintock, Heather F.; Morales, Knashawn H.; Small, Dylan S.; Bogner, Hillary R.

    2014-01-01

    This study examined whether longitudinal adherence profiles mediated the relationship between a brief adherence intervention and glycemic control among patients with Type 2 diabetes. Adherence was assessed using the Medication Event Monitoring System (MEMS). Longitudinal analysis via growth curve mixture modeling was carried out to classify patients according to patterns of adherence to oral hypoglycemic agents. Hemoglobin A1c (HbA1c) assays were used to measure glycemic control as the clinical outcome. Across the whole sample, longitudinal adherence profiles mediated 35.2% (13.2%, 81.0%) of the effect of a brief adherence intervention on glycemic control (from odds ratio (OR) = 8.48, 95% CI (3.24, 22.2) to 4.00, 95% CI (1.34, 11.93)). Our results suggest that patients in the intervention had better glycemic control largely due to their greater likelihood of adherence to oral hypoglycemic agents. PMID:24913600

  14. Episodic medication adherence in adolescents and young adults with perinatally acquired HIV: a within-participants approach.

    PubMed

    Hawkins, Amy; Evangeli, Michael; Sturgeon, Kate; Le Prevost, Marthe; Judd, Ali

    2016-01-01

    Due to the success of antiretroviral (ART) medications, young people living with perinatally acquired HIV (PHIV+) are now surviving into adolescence and young adulthood. Understanding factors influencing ART non-adherence in this group is important in developing effective adherence interventions. Most studies of ART adherence in HIV-positive populations assess differences in adherence levels and adherence predictors between participants, over a period of time (global adherence). Many individuals living with HIV, however, including PHIV+ young people, take medication inconsistently. To investigate this pattern of adherence, a within-participants design, focussing on specific episodes of adherence and non-adherence, is suitable (episodic adherence). A within-participants design was used with 29 PHIV+ young people (17 female, median age 17 years, range 14-22 years), enrolled in the UK Adolescents and Adults Living with Perinatal HIV cohort study. Participants were eligible if they could identify one dose of medication taken and one dose they had missed in the previous two months. For each of the two episodes (one adherent, one non-adherent), behavioural factors (whom they were with, location, routine, day, reminders) and psychological factors at the time of the episode (information about medication, adherence motivation, perceived behavioural skills to adhere to medication - derived from the Information-Motivation-Behavioural Skills (IMB) Model - and affect) were assessed in a questionnaire. Non-adherence was significantly associated with weekend days (Friday to Sunday versus Monday to Thursday, p = .001), lack of routine (p = .004), and being out of the home (p = .003), but not with whom the young person was with or whether they were reminded to take medication. Non-adherence was associated with lower levels of behavioural skills (p < .001), and lower positive affect (p = .005). Non-adherence was not significantly associated with negative affect

  15. Episodic medication adherence in adolescents and young adults with perinatally acquired HIV: a within-participants approach

    PubMed Central

    Hawkins, Amy; Evangeli, Michael; Sturgeon, Kate; Le Prevost, Marthe; Judd, Ali

    2016-01-01

    ABSTRACT Due to the success of antiretroviral (ART) medications, young people living with perinatally acquired HIV (PHIV+) are now surviving into adolescence and young adulthood. Understanding factors influencing ART non-adherence in this group is important in developing effective adherence interventions. Most studies of ART adherence in HIV-positive populations assess differences in adherence levels and adherence predictors between participants, over a period of time (global adherence). Many individuals living with HIV, however, including PHIV+ young people, take medication inconsistently. To investigate this pattern of adherence, a within-participants design, focussing on specific episodes of adherence and non-adherence, is suitable (episodic adherence). A within-participants design was used with 29 PHIV+ young people (17 female, median age 17 years, range 14–22 years), enrolled in the UK Adolescents and Adults Living with Perinatal HIV cohort study. Participants were eligible if they could identify one dose of medication taken and one dose they had missed in the previous two months. For each of the two episodes (one adherent, one non-adherent), behavioural factors (whom they were with, location, routine, day, reminders) and psychological factors at the time of the episode (information about medication, adherence motivation, perceived behavioural skills to adhere to medication – derived from the Information-Motivation-Behavioural Skills (IMB) Model – and affect) were assessed in a questionnaire. Non-adherence was significantly associated with weekend days (Friday to Sunday versus Monday to Thursday, p = .001), lack of routine (p = .004), and being out of the home (p = .003), but not with whom the young person was with or whether they were reminded to take medication. Non-adherence was associated with lower levels of behavioural skills (p < .001), and lower positive affect (p = .005). Non-adherence was not significantly associated with

  16. An evaluation of coral lophelia pertusa mucus as an analytical matrix for environmental monitoring: A preliminary proteomic study.

    PubMed

    Provan, Fiona; Nilsen, Mari Mæland; Larssen, Eivind; Uleberg, Kai-Erik; Sydnes, Magne O; Lyng, Emily; Øysæd, Kjell Birger; Baussant, Thierry

    2016-01-01

    For the environmental monitoring of coral, mucus appears to be an appropriate biological matrix due to its array of functions in coral biology and the non-intrusive manner in which it can be collected. The aim of the present study was to evaluate the feasibility of using mucus of the stony coral Lophelia pertusa (L. pertusa) as an analytical matrix for discovery of biomarkers used for environmental monitoring. More specifically, to assess whether a mass-spectrometry-based proteomic approach can be applied to characterize the protein composition of coral mucus and changes related to petroleum discharges at the seafloor. Surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF MS) screening analyses of orange and white L. pertusa showed that the mucosal protein composition varies significantly with color phenotype, a pattern not reported prior to this study. Hence, to reduce variability from phenotype difference, L. pertusa white individuals only were selected to characterize in more detail the basal protein composition in mucus using liquid chromatography, mass spectrometry, mass spectrometry (LC-MS/MS). In total, 297 proteins were identified in L. pertusa mucus of unexposed coral individuals. Individuals exposed to drill cuttings in the range 2 to 12 mg/L showed modifications in coral mucus protein composition compared to unexposed corals. Although the results were somewhat inconsistent between individuals and require further validation in both the lab and the field, this study demonstrated preliminary encouraging results for discovery of protein markers in coral mucus that might provide more comprehensive insight into potential consequences attributed to anthropogenic stressors and may be used in future monitoring of coral health. PMID:27484144

  17. Molecular Dynamics Simulations of Water/Mucus Partition Coefficients for Feeding Stimulants in Fish and the Implications for Olfaction

    PubMed Central

    Rygg, Alex D.; van Duin, Adri C. T.; Craven, Brent A.

    2013-01-01

    The odorant partition coefficient is a physicochemical property that has been shown to dramatically influence odorant deposition patterns in the mammalian nose, leading to a chromatographic separation of odorants along the sensory epithelium. It is unknown whether a similar phenomenon occurs in fish. Here we utilize molecular dynamics simulations, based on a simplified molecular model of olfactory mucus, to calculate water/mucus partition coefficients for amino acid odorants (alanine, glycine, cysteine, and valine) that are known to elicit feeding behavior in fish. Both fresh water and salt water environments are considered. In fresh water, all four amino acids prefer the olfactory mucus phase to water, and the partition coefficient is shown to correlate with amino acid hydrophobicity. In salt water, a reversal in odorant partitioning is found, where each of the feeding stimulants (except glycine) prefer the water phase to olfactory mucus. This is due to the interactions between the salt ions and the odorant molecules (in the water phase), and between the salt and simplified mucin (in the olfactory mucus phase). Thus, slightly different odorant deposition patterns may occur in the fish olfactory organ in fresh and salt water environments. However, in both underwater environments we found that the variation of the water/mucus odorant partition coefficient is approximately one order of magnitude, in stark contrast to air/mucus odorant partition coefficients that can span up to six orders of magnitude. We therefore anticipate relatively similar deposition patterns for most amino acid odorants in the fish olfactory chamber. Thus, in contrast to terrestrial species, living in an underwater environment may preclude appreciable chromatographic odorant separation that may be used for spatial coding of odor identity across the olfactory epithelium. This is consistent with the reported lack of spatial organization of olfactory receptor neurons in the fish olfactory

  18. Differential predictors of ART adherence among HIV-monoinfected versus HIV/HCV-coinfected individuals.

    PubMed

    Shuper, Paul A; Joharchi, Narges; Irving, Hyacinth; Fletcher, David; Kovacs, Colin; Loutfy, Mona; Walmsley, Sharon L; Wong, David K H; Rehm, Jürgen

    2016-08-01

    Although adherence is an important key to the efficacy of antiretroviral therapy (ART), many people living with HIV (PLWH) fail to maintain optimal levels of ART adherence over time. PLWH with the added burden of Hepatitis C virus (HCV) coinfection possess unique challenges that potentially impact their motivation and ability to adhere to ART. The present investigation sought to (1) compare ART adherence levels among a sample of HIV/HCV-coinfected versus HIV-monoinfected patients, and (2) identify whether ART-related clinical and psychosocial correlates differ by HCV status. PLWH receiving ART (N = 215: 105 HIV/HCV-coinfected, 110 HIV-monoinfected) completed a comprehensive survey assessing ART adherence and its potential correlates. Medical chart extraction identified clinical factors, including liver enzymes. Results demonstrated that ART adherence did not differ by HCV status, with 83.7% of coinfected patients and 82.4% of monoinfected patients reporting optimal (i.e., ≥95%) adherence during a four-day recall period (p = .809). Multivariable logistic regression demonstrated that regardless of HCV status, optimal ART adherence was associated with experiencing fewer adherence-related behavioral skills barriers (AOR = 0.56; 95%CI = 0.43-0.73), lower likelihood of problematic drinking (AOR = 0.15; 95%CI = 0.04-0.67), and lower likelihood of methamphetamine use (AOR = 0.14; 95%CI = 0.03-0.69). However, among HIV/HCV-coinfected patients, optimal adherence was additionally associated with experiencing fewer ART adherence-related motivational barriers (AOR = 0.23; 95%CI = 0.08-0.62) and lower likelihood of depression (AOR = 0.06; 95%CI = 0.00-0.84). Findings suggest that although HIV/HCV-coinfected patients may face additional, distinct barriers to ART adherence, levels of adherence commensurate with those demonstrated by HIV-monoinfected patients might be achievable if these barriers are addressed. PMID:26971360

  19. Complexities of Adherence and Post-Cancer Lymphedema Management

    PubMed Central

    Ostby, Pamela L.; Armer, Jane M.

    2015-01-01

    Breast cancer survivors are at increased risk for breast cancer-related lymphedema (BCRL), a chronic, debilitating, condition that is progressive and requires lifelong self-management. Up to 40% of 3 million breast cancer survivors in the US will develop BCRL, which has no cure, is irreversible, and requires self-management with regimens that may include multiple components. The complexities of treatment can negatively affect adherence to BCRL self-management which is critical to preventing progressive swelling and infection. The aim of this review of contemporary literature published from 2005–2015 is to examine the complexities of BCRL self-management, to identify adherence-focused studies relevant to BCRL, and to summarize barriers to self-management of BCRL. Six electronic indices were searched from which 120 articles were retrieved; 17 were BCRL-focused; and eight met inclusion criteria. Seventeen of 120 articles identified barriers to self-management of BCRL such as complexities of treatment regimens, symptom burden, balance of time for treatment and life demands, and lack of education and support; however, only eight studies included outcome measures of adherence to BCRL treatment regimens with a subsequent improvement in reduced limb volumes and/or perceptions of self-efficacy and self-regulation. A major limitation is the few number of rigorously developed outcome measures of BCRL adherence. In addition, randomized studies are needed with larger sample sizes to establish adequate levels of evidence for establishing best practice standards for improving adherence to BCRL self-management treatment regimens. PMID:26580657

  20. Complexities of Adherence and Post-Cancer Lymphedema Management.

    PubMed

    Ostby, Pamela L; Armer, Jane M

    2015-01-01

    Breast cancer survivors are at increased risk for breast cancer-related lymphedema (BCRL), a chronic, debilitating, condition that is progressive and requires lifelong self-management. Up to 40% of 3 million breast cancer survivors in the US will develop BCRL, which has no cure, is irreversible, and requires self-management with regimens that may include multiple components. The complexities of treatment can negatively affect adherence to BCRL self-management which is critical to preventing progressive swelling and infection. The aim of this review of contemporary literature published from 2005-2015 is to examine the complexities of BCRL self-management, to identify adherence-focused studies relevant to BCRL, and to summarize barriers to self-management of BCRL. Six electronic indices were searched from which 120 articles were retrieved; 17 were BCRL-focused; and eight met inclusion criteria. Seventeen of 120 articles identified barriers to self-management of BCRL such as complexities of treatment regimens, symptom burden, balance of time for treatment and life demands, and lack of education and support; however, only eig