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Sample records for adherent mucus levels

  1. Bacteriophage adhering to mucus provide a non–host-derived immunity

    PubMed Central

    Barr, Jeremy J.; Auro, Rita; Furlan, Mike; Whiteson, Katrine L.; Erb, Marcella L.; Pogliano, Joe; Stotland, Aleksandr; Wolkowicz, Roland; Cutting, Andrew S.; Doran, Kelly S.; Salamon, Peter; Youle, Merry; Rohwer, Forest

    2013-01-01

    Mucosal surfaces are a main entry point for pathogens and the principal sites of defense against infection. Both bacteria and phage are associated with this mucus. Here we show that phage-to-bacteria ratios were increased, relative to the adjacent environment, on all mucosal surfaces sampled, ranging from cnidarians to humans. In vitro studies of tissue culture cells with and without surface mucus demonstrated that this increase in phage abundance is mucus dependent and protects the underlying epithelium from bacterial infection. Enrichment of phage in mucus occurs via binding interactions between mucin glycoproteins and Ig-like protein domains exposed on phage capsids. In particular, phage Ig-like domains bind variable glycan residues that coat the mucin glycoprotein component of mucus. Metagenomic analysis found these Ig-like proteins present in the phages sampled from many environments, particularly from locations adjacent to mucosal surfaces. Based on these observations, we present the bacteriophage adherence to mucus model that provides a ubiquitous, but non–host-derived, immunity applicable to mucosal surfaces. The model suggests that metazoan mucosal surfaces and phage coevolve to maintain phage adherence. This benefits the metazoan host by limiting mucosal bacteria, and benefits the phage through more frequent interactions with bacterial hosts. The relationships shown here suggest a symbiotic relationship between phage and metazoan hosts that provides a previously unrecognized antimicrobial defense that actively protects mucosal surfaces. PMID:23690590

  2. Formation of a fibrin based gelatinous coat over repairing rat gastric epithelium after acute ethanol damage: interaction with adherent mucus.

    PubMed Central

    Sellers, L A; Allen, A; Bennett, M K

    1987-01-01

    A gelatinous coat, heterogeneous in appearance, was formed over damaged rat gastric mucosa recovering from acute ethanol injury. This coat, in places 1.6 mm thick (median thickness 680 microns), was 10 times thicker than the translucent layer of adherent mucus (median thickness 70 microns) covering the undamaged mucosa. Immunohistochemistry and periodic acid Schiff staining showed this gelatinous coat to be predominantly a fibrin gel with an exterior layer rich in mucus and necrotic cells. The plasma clotting time was significantly decreased in vitro by pig gastric mucus gel and soluble mucus glycoprotein (90% and 13% respectively) suggesting that in vivo the mucus layer remaining after epithelial damage could act as a template for fibrinogen-fibrin conversion. These results show that a fibrin based gelatinous coat, quite distinct from the adherent mucus layer and with considerable protective potential could be formed over the repairing rat gastric mucosa after acute ethanol damage. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:3653751

  3. Selective adherence of non-typeable Haemophilus influenzae (NTHi) to mucus or epithelial cells in the chinchilla eustachian tube and middle ear.

    PubMed

    Miyamoto, N; Bakaletz, L O

    1996-11-01

    Frozen sections of chinchilla Eustachian tube (ET) and middle ear mucosa were incubated with either FITC-labeled non-typeable Haemophilus influenzae (NTHi) or Bordetella pertussis. The number of bacteria adherent to "roof" vs "floor" regions was compared for each of three anatomic portions of the ET and for middle ear epithelium noting whether bacteria adhered to mucus or to epithelial cells. NTHi strains adhered significantly greater to mucus in the ET lumen whereas B. pertussis preferentially adhered to epithelial cells lining the ET (P < or = 0.05). A non-fimbriated isogenic mutant of NTHi adhered significantly less to mucus than the parental isolate at all sites of the ET floor (P < or = 0.05). Isolated fimbrin protein adhered to ET mucus and blocked adherence of whole organisms. Treatment with the mucolytic agent N-acetyl-L-cysteine resulted in significantly reduced adherence of NTHi to mucus (P < or = 0.001) and eliminated the ability to detect binding of isolated fimbrin protein. N-acetyl-L-cysteine treatment did not affect adherence of either B. pertussis or NTHi to epithelial cells. These data indicated that NTHi may mediate ascension of the ET from the nasopharynx primarily via adherence to and growth in mucus overlying the floor region of the tubal lumen. The OMP P5-homologous fimbriae were shown to contribute to this binding.

  4. Intestinal Mucus Gel and Secretory Antibody are Barriers to Campylobacter jejuni Adherence to INT 407 Cells

    DTIC Science & Technology

    1987-06-01

    An in vitro mucus assay was developed to study the role of mucus gel and secretory immunoglobulin A (sIgA) in preventing attachment of Campylobacter ... jejuni to INT 407 cells. An overlay of rabbit small intestinal mucus was found to impede the attachment of C. jejuni to a monolayer of INT 407 cells

  5. 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

  6. 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.

  7. Adhesion properties of potentially probiotic Lactobacillus kefiri to gastrointestinal mucus.

    PubMed

    Carasi, Paula; Ambrosis, Nicolás M; De Antoni, Graciela L; Bressollier, Philippe; Urdaci, María C; Serradell, María de los Angeles

    2014-02-01

    We investigated the mucus-binding properties of aggregating and non-aggregating potentially probiotic strains of kefir-isolated Lactobacillus kefiri, using different substrates. All the strains were able to adhere to commercial gastric mucin (MUCIN) and extracted mucus from small intestine (SIM) and colon (CM). The extraction of surface proteins from bacteria using LiCl or NaOH significantly reduced the adhesion of three selected strains (CIDCA 8348, CIDCA 83115 and JCM 5818); although a significant proportion (up to 50%) of S-layer proteins were not completely eliminated after treatments. The surface (S-layer) protein extracts from all the strains of Lb. kefiri were capable of binding to MUCIN, SIM or CM, and no differences were observed among them. The addition of their own surface protein extract increased adhesion of CIDCA 8348 and 83115 to MUCIN and SIM, meanwhile no changes in adhesion were observed for JCM 5818. None of the seven sugars tested had the ability to inhibit the adhesion of whole bacteria to the three mucus extracts. Noteworthy, the degree of bacterial adhesion reached in the presence of their own surface protein (S-layer) extract decreased to basal levels in the presence of some sugars, suggesting an interaction between the added sugar and the surface proteins. In conclusion, the ability of these food-isolated bacteria to adhere to gastrointestinal mucus becomes an essential issue regarding the biotechnological potentiality of Lb. kefiri for the food industry.

  8. Colonic mucus, smoking and ulcerative colitis.

    PubMed

    Pullan, R D

    1996-03-01

    Human colonic mucosal protection is not fully understood but may in part rely on a layer of mucus gel adherent to the mucosa. Ulcerative colitis may occur if mucosal protection breaks down. Two studies are presented, both of which relate to the aetiology of ulcerative colitis. First, a layer of adherent mucus gel was demonstrated by a simple, reliable method. Measurements of mucus layer thickness were made in freshly resected colonic specimens and shown to increase from a mean of 107 microns on the right colon to 155 microns in the rectum. In ulcerative colitis the layer is significantly thinner or absent, whereas in Crohn's disease the colonic mucus layer is significantly thicker. Second, the relationship between smoking and colitis is explored by a double-blind, randomised and placebo-controlled trial of transdermal nicotine in active disease. Significant clinical benefit was seen, indicating nicotine may be both useful therapeutically and the component of tobacco smoke that acts to protect against colitis. Since smoking and nicotine have actions on mucosae and mucus in other organs, it is argued that there is a mucus deficiency in ulcerative colitis that smoking acts to reverse.

  9. Relationship between Systems-Level Factors and Hand Hygiene Adherence

    PubMed Central

    Dunn-Navarra, Ann-Margaret; Cohen, Bevin; Stone, Patricia W.; Pogorzelska, Monika; Jordan, Sarah; Larson, Elaine

    2010-01-01

    This study was a cross sectional descriptive survey of acute care hospitals in California to describe staff hand hygiene compliance and related predictors, and explore the relationship between hand hygiene adherence to health care-associated infections. Although there was a relatively small sample size, institutions with morning huddles reported a significantly higher proportion of ≥95% hand hygiene compliance. Huddles are an organizational tool to improve teamwork and communication and may offer promise to influence hand hygiene adherence. PMID:20489659

  10. Colonization by lactobacilli of piglet small intestinal mucus.

    PubMed

    Rojas, M; Conway, P L

    1996-11-01

    The colonization potential of lactobacilli was investigated using small intestinal mucus extracts from 35-d-old pigs. Mucus-secreting tissue from the small intestine of piglets was gently rinsed to remove contents and then shaken in buffer to release mucus from the surface. Numbers of lactobacilli in different portions of the small intestine of 35-d-old pigs were enumerated. Also, mucus isolated from the small intestine of pigs was investigated for its capacity to support the growth of lactobacilli. Results indicated that Lactobacillus spp. inhabit the mucus layer of the small intestine and can grow and adhere to ileal mucus. From adhesion studies of Lactobacillus fermentum 104R to mucus analysed by Scatchard plot, it is suggested that an associating system showing positive cooperativity is involved. Proteinaceous compounds(s) involved in the adhesion to mucus were detected in the spent culture fluid from the growth of strain 104R. Studies are continuing in order to identify and characterize the adhesion-promoting protein(s). From the data, it is proposed that lactobacilli colonize the mucus layer of the small intestine of pigs.

  11. 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

  12. Hydroxychloroquine Blood Levels in SLE: Clarifying dosing controversies and improving adherence

    PubMed Central

    Durcan, Laura; Clarke, William A; Magder, Laurence S.; Petri, Michelle

    2015-01-01

    OBJECTIVES Hydroxychloroquine is used for its effect on systemic lupus erythematosus (SLE) disease activity and long-term benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is dosing controversy; rheumatologists recommend weight-based, while ophthalmologists advocate height-based ‘ideal body weight’ dosing. METHODS Patients were prescribed hydroxychloroquine not to exceed 6.5mg/kg (max400mg/day). In hemodialysis, the dose was 200mg after each session, in renal insufficiency it was 200mg/day. Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Patients were divided according to baseline blood level. To assess the impact of measurement and counseling on adherence, we compared the proportion of patients with a level of 500ng/ml or higher based on how many prior assessments the patient had. RESULTS The proportion of patients with hydroxychloroquine levels in the therapeutic range differed significantly by age, gender and vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, sub-therapeutic and therapeutic levels, disease activity decreased (SLEDAI 2.92, 2.36 and 2.20)(P=0.04, for trend). At first, 56% were therapeutic and by the third measurement this increased to 80% (p =<0.0001). CONCLUSION There was a trend towards higher disease activity with lower hydroxychloroquine levels. Renal failure dosing led to sub-optimum levels. We show that weight-based dosing (max 400mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling and repeated testing can increase adherences rates. PMID:26428205

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. Physical activity levels, duration pattern and adherence to WHO recommendations in German adults

    PubMed Central

    Luzak, Agnes; Heier, Margit; Thorand, Barbara; Laxy, Michael; Nowak, Dennis; Peters, Annette; Schulz, Holger

    2017-01-01

    Background Intensity and duration of physical activity are associated with the achievement of health benefits. Our aim was to characterize physical activity behavior in terms of intensity, duration pattern, and adherence to the WHO physical activity recommendations in a population-based sample of adults from southern Germany. Further, we investigated associations between physical activity and sex, age, and body mass index (BMI), considering also common chronic diseases. Methods We analyzed 475 subjects (47% males, mean age 58 years, range 48–68 years) who wore ActiGraph accelerometers for up to seven days. Measured accelerations per minute obtained from the vertical axis (uniaxial) and the vector magnitude of all three axes (triaxial) were classified as sedentary, light or moderate-to-vigorous physical activity (MVPA) according to predefined acceleration count cut-offs. The average minutes/day spent in each activity level per subject served as outcome. Associations of sex, age, BMI, and seven chronic diseases or health limitations, with the activity levels were analyzed by negative binomial regression. Results Most of the wear time was spent in sedentarism (median 61%/day), whereas the median time spent in MVPA was only 3%, with men achieving more MVPA than women (35 vs. 28 minutes/day, p<0.05). Almost two thirds of MVPA was achieved in short bouts of less than 5 minutes, and 35% of the subjects did not achieve a single 10-minute bout. Hence, only 14% adhered to the WHO recommendation of 2.5 hours of MVPA/week in at least 10-minute bouts. Females, older subjects and obese subjects spent less time in MVPA (p<0.05), but no clear association with hypertension, asthma, diabetes, chronic obstructive pulmonary disease, anxiety/depression, pain or walking difficulties was observed in regression analyses with MVPA as outcome. Conclusions Activity behavior among middle-aged German adults was highly insufficient, indicating a further need for physical activity promotion in

  18. Role of mucus in ischemia/reperfusion-induced gastric mucosal injury in rats.

    PubMed

    Mojzis, J; Hegedüsová, R; Mirossay, L

    2000-01-01

    Gastric mucus plays an important role in gastric mucosal protection. Apart from its "barrier" function, it has been demonstrated that mucus protects gastric epithelial cells against toxic oxygen metabolites derived from the xanthine/ xanthine oxidase system. In this study, we investigated the effect of malotilate and sucralfate (mucus production stimulators) and N-acetylcysteine (mucolytic agent) on ischemia/reperfusion-induced gastric mucosal injury. Gastric ischemia was induced by 30 min clamping of the coeliac artery followed by 30 min of reperfusion. The mucus content was determined by the Alcian blue method. Sucralfate (100 mg/kg), malotilate (100 mg/kg), and N-acetylcysteine (100 mg/kg) were given orally 30 min before surgery. Both sucralfate and malotilate increased the mucus production in control rats. On the other hand, N-acetyloysteine significantly decreased mucus content in control (sham) group. A significant decrease of mucus content was found in the control and the N-acetylcysteine pretreated group during the period of ischemia. On the other hand, sucralfate and malotilate prevented the decrease the content of mucus during ischemia. A similar result can be seen after ischemia/reperfusion. In the control group and N-acetylcysteine pretreated group a significant decrease of adherent mucus content was found. However, sucralfate and malotilate increased mucus production (sucralfate significantly). Sucralfate and malotilate also significantly protected the gastric mucosa against ischemia/reperfusion-induced injury. However, N-acetylcysteine significantly increased gastric mucosal injury after ischemia/reperfusion. These results suggest that gastric mucus may be involved in the protection of gastric mucosa after ischemia/reperfusion.

  19. The influence of health literacy level on an educational intervention to improve glaucoma medication adherence

    PubMed Central

    Muir, Kelly W.; Ventura, Alice; Stinnett, Sandra S.; Enfiedjian, Abraham; Allingham, R. Rand; Lee, Paul P.

    2013-01-01

    Objective To test an educational intervention targeted to health literacy level with the goal of improving glaucoma medication adherence. Methods One hundred and twenty-seven veterans with glaucoma were randomized to glaucoma education or standard care. The intervention included a video scripted at a 4th, 7th, or 10th grade level, depending on the subject’s literacy level. After six months, the number of days without glaucoma medicine (DWM) according to pharmacy records for the intervention and control groups was compared. Results The number of DWM in the six months following enrollment was similar for control and intervention groups (intervention, n = 67, DWM = 63 ± 198; standard care, n = 60, DWM = 65 ± 198; p = 0.708). For each subgroup of literacy (adequate, marginal, inadequate), subjects in the intervention group experienced less mean DWM than subjects in the control group and the effect size (ES) increased as literacy decreased: adequate literacy, ES 0.069; marginal, ES 0.183, inadequate, ES 0.363. Decreasing health literacy skills were associated with decreasing self-reported satisfaction with care (slope = 0.017, SE = 0.005, p = 0.002). Conclusions Patients with decreased health literacy skills may benefit from educational efforts tailored to address their health literacy level and learning style. Practice implications Providers should consider health literacy skills when engaging in glaucoma education. PMID:22000272

  20. 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.

  1. Airway mucus: From production to secretion.

    PubMed

    Williams, Olatunji W; Sharafkhaneh, Amir; Kim, Victor; Dickey, Burton F; Evans, Christopher M

    2006-05-01

    Mucus hypersecretion is a phenotype associated with multiple obstructive lung diseases. However, in spite of its nefarious reputation under pathologic conditions, there are significant benefits to having low levels of mucus present in the airways at baseline, such as the ability to trap and eliminate inhaled particles and to prevent desiccation of airway surfaces. Mucins are high-molecular-weight glycoproteins that are the chief components that render viscoelastic and gel-forming properties to mucus. Recent advances in animal models and in vitro systems have provided a wealth of information regarding the identification of the mucin genes that are expressed in the lungs, the signal transduction pathways that regulate the expression of these mucins, and the secretory pathways that mediate their release into the airways. In addition, the clinical and pathologic literature has corroborated many of the basic laboratory findings. As a result, mucin overproduction and hypersecretion are moving away from being markers of disease and toward being testable as functional components of lung disease processes.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. HEALTH LITERACY, MEDICATION ADHERENCE, AND BLOOD PRESSURE LEVEL AMONG HYPERTENSIVE OLDER ADULTS TREATED AT PRIMARY HEALTH CARE CENTERS.

    PubMed

    Wannasirikul, Phitchayaphat; Termsirikulchai, Lakkhana; Sujirarat, Dusit; Benjakul, Sarunya; Tanasugarn, Chanuantong

    2016-01-01

    We conducted this study to explore the causal relationships between health literacy, individual characteristics, literacy, culture and society, cognitive ability, medication adherence, and the blood pressure levels of hypertensive older adults receiving health care services at Primary Health Care Centers in Sa Kaeo Province, Thailand. Six hundred hypertensive older adults had their blood pressure level recorded and were interviewed using questionnaires. Structural Equation Modeling (SEM) was used to determine the effect size, both direct and indirect, among factors. Almost half (48.7%) of studied subjects had inadequate health literacy, 98.3% had good medication adherence, and 80% had good blood pressure levels. The highest effect size on health literacy was literacy, followed by cognitive ability, and culture and society. Medication adherence was affected directly and indirectly by cognitive ability, literacy, and culture and society. Health literacy had not only a direct effect on medication adherence but was also the mediator. Finally, the highest effect size on blood pressure level was critical and communicative health literacy. These findings suggest that health literacy should be considered in the Health Literacy Program of the National Public Health Policy and Plan, Ministry of Public Health.

  7. 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

  8. 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.

  9. 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).

  10. 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

  11. Skin mucus proteome map of European sea bass (Dicentrarchus labrax).

    PubMed

    Cordero, Héctor; Brinchmann, Monica F; Cuesta, Alberto; Meseguer, José; Esteban, María A

    2015-12-01

    Skin mucus is the first barrier of fish defence. Proteins from skin mucus of European sea bass (Dicentrarchus labrax) were identified by 2DE followed by LC-MS/MS. From all the identified proteins in the proteome map, we focus on the proteins associated with several immune pathways in fish. Furthermore, the real-time PCR transcript levels in skin are shown. Proteins found include apolipoprotein A1, calmodulin, complement C3, fucose-binding lectin, lysozyme and several caspases. To our knowledge, this is the first skin mucus proteome study and further transcriptional profiling of the identified proteins done on this bony fish species. This not only contributes knowledge on the routes involved in mucosal innate immunity, but also establishes a non-invasive technique based on locating immune markers with a potential use for prevention and/or diagnosis of fish diseases.

  12. 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.

  13. Discovery of Low Mucus Adhesion Surfaces

    PubMed Central

    Gu, Minghao; Yildiz, Hasan; Carrier, Rebecca; Belfort, Georges

    2014-01-01

    Mucus secretion from the body is ubiquitous and finding materials that resist mucus adhesion is a major technological challenge of medical and consumer import. Here, using a high throughput platform (HTP) with photo-induced graft polymerization, we first rapidly synthesized, screened and tested a library of 55 different surfaces from six functional monomer classes to discover porcine intestinal low mucus adhesion surfaces using a 1 hr static mucus adsorption protocol. From this preliminary screen, two chemistries, a zwitterionic ([2-(acryloyloxy)ethyl] trimethylammonium chloride) and a multiple hydroxyl (N-[tris(hydroxymethyl)methyl]acrylamide) surface, exhibited the significantly low mucus adhesion from a Langmuir-type isotherm when exposed to increasing concentrations of mucus for 24 hr. Apolar or hydrophobic interactions were likely the dominant attractive forces during mucus binding since many polar or hydrophilic monomers reduced mucus adhesion. Hansen solubility parameters were used to illustrate the importance of monomer polarity and hydrogen-bonding in reducing mucus adsorption. For a series of PEG monomers with changing molecular weight from 144 g/mol to 1100 g/mol, we observed an excellent linear correlation (R2 = 0.998) between relative amount adsorbed and the distance from a water point in a specialized HSP plot, emphasizing the role of surface-water interactions for PEG modified surfaces. PMID:23072828

  14. Discovery of low mucus adhesion surfaces.

    PubMed

    Gu, Minghao; Yildiz, Hasan; Carrier, Rebecca; Belfort, Georges

    2013-02-01

    Mucus secretion from the body is ubiquitous, and finding materials that resist mucus adhesion is a major technological challenge. Here, using a high throughput platform with photo-induced graft polymerization, we first rapidly synthesized, screened and tested a library of 55 different surfaces from six functional monomer classes to discover porcine intestinal low mucus adhesion surfaces using a 1h static mucus adsorption protocol. From this preliminary screen, two chemistries, a zwitterionic ([2-(acryloyloxy)ethyl] trimethylammonium chloride) and a multiple hydroxyl (N-[tris(hydroxymethyl)methyl]acrylamide) surface, exhibited significantly low mucus adhesion from a Langmuir-type isotherm when exposed to increasing concentrations of mucus for 24 h. Apolar or hydrophobic interactions were likely the dominant attractive forces during mucus binding since many polar or hydrophilic monomers reduced mucus adhesion. Hansen solubility parameters were used to illustrate the importance of monomer polarity and hydrogen bonding in reducing mucus adsorption. For a series of polyethylene glycol (PEG) monomers with changing molecular weight from 144 g mol⁻¹ to 1100 g mol⁻¹, we observed an excellent linear correlation (R²=0.998) between relative amount adsorbed and the distance from a water point in a specialized Hansen solubility parameter plot, emphasizing the role of surface-water interactions for PEG modified surfaces.

  15. 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

  16. Adhesion of human enterotoxigenic Escherichia coli to human mucus secreting HT-29 cell subpopulations in culture.

    PubMed Central

    Kerneis, S; Bernet, M F; Coconnier, M H; Servin, A L

    1994-01-01

    Enterotoxigenic Escherichia coli (ETEC) bearing the fimbrial colonisation factor antigens CFA/I, CFA/II, CFA/III, and the non-fimbrial antigen 2230 were tested for their ability to adhere to two cultured human intestinal HT-29 mucus secreting cell subpopulations. These populations are referred to as HT29-MTX and HT29-FU, which differ in the amount of secreted mucins and in their gastric or colonic mucin immunoreactivity respectively. Adherence of radiolabelled bacteria to cell monolayers infected apically was assessed. All ETEC strains adhered to the mucus secreting HT29-FU subpopulation, which secretes mucins of colonic immunoreactivity. Visualisation of bacteria by scanning electron microscopy showed that ETEC bound to the HT29-FU cells possessing a brush border, but not to the mucus and that ETEC binding developed as a function of cell differentiation. The adhesion of ETEC to cells possessing a brush border and to mucus secreting cells was also analysed by indirect immunofluorescence in HT29-MTX cells, which secrete mucins of gastric immunoreactivity. Fluorescein isothiocyanate labelling using specific anti-CFA/I antibody was used to show ETEC; rhodamine isothiocyanate labelling using a monoclonal antibody (designated M1) against purified human gastric mucus was used to detect secreted mucins, and rhodamine isothiocyanate labelling using a monoclonal antibody (designated 4H3) against human dipeptidylpeptidase IV was used to show cells possessing a brush border. Binding of bacteria colocalised with dipeptidylpeptidase IV of enterocytes and not with mucins. Images Figure 1 Figure 2 Figure 3 Figure 5 PMID:7959203

  17. 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

  18. 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

  19. 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

  20. 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.

  1. Levels of adherence and factors associated with adherence to option B+ prevention of mother-to-child transmission among pregnant and lactating mothers in selected government health facilities of South Wollo Zone, Amhara Region, northeast Ethiopia, 2016

    PubMed Central

    2016-01-01

    OBJECTIVES The aim of this study was to measure the levels of adherence and to identify factors associated with adherence to option B+ prevention of mother-to-child transmission (PMTCT) among pregnant and lactating mothers in selected government health facilities of South Wollo Zone, Amhara Region, northeast Ethiopia. METHODS An institution-based cross-sectional quantitative study design was employed from March 1, 2016 to April 14, 2016, using a standard structured data collection instrument. A sample of 191 human immunodeficiency virus (HIV)-positive pregnant and lactating mothers who were receiving PMTCT follow-up in the selected health facilities participated in the study. The data were entered using EpiData 3.1 and analyzed using SPSS version 21. Bivariate and multivariate logistic regression analyses were employed to identify factors associated with adherence. The p-values <0.05 and 95% confidence intervals (CIs) were used to identify associations between independent predictors and the outcome variable. RESULTS The level of adherence to option B+ PMTCT drugs was 87.9%. Women who received in-hospital treatment, who lived in rural areas, and faced challenges in initiating lifelong option B+ treatment on the same-day that they were diagnosed with HIV were less likely to adhere to the treatment (adjusted odds ratios [95% CI] of 0.3 [0.11 to 0.82], 0.26 [0.1 to 0.73], and 0.08 [0.02 to 0.37], respectively). CONCLUSIONS Collaborative efforts of zonal health departments with health facility administrators and counselors are recommended for effective and efficient interventions focusing on hospitals, rural areas, and patients who face challenges on the day of their diagnosis. PMID:27733034

  2. 21 CFR 884.1040 - Viscometer for cervical mucus.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Viscometer for cervical mucus. 884.1040 Section... Devices § 884.1040 Viscometer for cervical mucus. (a) Identification. A viscometer for cervical mucus is a device that is intended to measure the relative viscoelasticity of cervical mucus collected from a...

  3. Influence of estrogens on vascular transudation and mucus production in the rabbit endocervix.

    PubMed

    Haas, G G; Nicosia, S V; Wolf, D P

    1987-12-01

    The manner in which estrogens mediate cyclical changes in the viscoelastic properties and volume of cervical mucus is unclear. To identify the response to estrogens of each of the major mucus components (mucin[s], soluble proteins, and small electrolytes and water), the authors quantitated their accumulation rates before and during estrogen stimulation in the rabbit. Circulating radiolabeled markers (35S-sulfate and 131I-albumin) were used to monitor the incorporation of small and large molecular weight intravascular substances into the cervical mucus. The accumulation rate of mucins was unaffected by exogenous estrogen administration, despite significant increases in mucus volume. This increase in mucus volume was attributed to a significantly increased transudation of water and small electrolytes increasing mucus hydration as early as the first 2 hours of estrogen administration. Water, small electrolytes, and soluble proteins significantly increased during the third and fourth hours of estrogen administration, not only when compared with the unstimulated basal levels, but also when compared with the levels found during the first 2 hours of estrogen administration. No significant change occurred in mucin production, while significant changes occurred in the accumulation of proteins and small electrolytes, whether estrogen was given initially or terminally in the experiment protocol.

  4. Addressing Adherence Using Genotype-Specific PBPK Modeling—Impact of Drug Holidays on Tamoxifen and Endoxifen Plasma Levels

    PubMed Central

    Dickschen, Kristin J. R.; Willmann, Stefan; Hempel, Georg; Block, Michael

    2017-01-01

    Introduction: Tamoxifen is one of the most common treatment opportunities for hormonal positive breast cancer. Despite its good tolerability, patients demonstrate decreasing adherence over years impacting on therapeutic success. PBPK modeling was applied to demonstrate the impact of drug holidays on plasma levels of tamoxifen and its active metabolite endoxifen for different CYP2D6 genotypes. Materials and Methods: A virtual study with 24,000 patients was conducted in order to investigate the development of tamoxifen steady-state kinetics in patient groups of different CYP2D6 genotypes. The impact of drug holidays on steady-state kinetics was investigated assuming changing drug holiday scenarios. Results: Drug holidays in CYP2D6 extensive and intermediate metabolizers (EMs, IMs) exceeding 1 month lead to a decrease of endoxifen steady-state trough levels below the 5th percentile of the control group. Assuming drug holidays of 1, 2, or 3 months and administering a fixed-dose combination of 20 mg tamoxifen and 3 mg endoxifen EMs demonstrated re-established endoxifen steady-state trough levels after 5, 8, and 9 days. IMs receiving the same fixed-dose combination demonstrated re-established endoxifen steady-state trough levels after 7, 10, and 11 days. Discussion: The PBPK model impressively demonstrates the impact of drug holidays in different CYP2D6 genotypes on PK. Population simulation results indicate that drug holidays of more than 2 weeks cause a tremendous decrease of plasma levels despite the long half-life of tamoxifen. To improve therapeutic success, PBPK modeling allows identifying genotype-specific differences in PK following drug holidays and adequate treatment with loading doses. PMID:28382001

  5. Effects of verapamil, carbenoxolone and N-acetylcysteine on gastric wall mucus and ulceration in stressed rats.

    PubMed

    Koo, M W; Ogle, C W; Cho, C H

    1986-01-01

    The effects of verapamil on gastric wall mucus and ulceration were studied in rats which were restrained and exposed to 4 degrees C (stress). Stress for 2 h significantly depleted stomach wall mucus and produced marked gastric glandular ulcers. Verapamil pretreatment (2, 4, 8 or 16 mg/kg), injected intraperitoneally 30 min before experimentation, significantly prevented stress-induced mucus depletion and gastric ulceration; however, it did not itself influence stomach wall mucus levels in nonstressed animals. Intragastric administration of carbenoxolone (100 or 200 mg/kg), also given 30 min before stress, exhibited similar actions as verapamil. A 15% solution of N-acetylcysteine (10 ml/kg), given orally, strongly decreased the mucus content in both nonstress and stress conditions; it induced ulcers in nonstressed rats, and worsened stress ulceration. These effects were not reversed by verapamil pretreatment. The influence of multiple-dose pretreatment with verapamil or carbenoxolone on mucus content and ulceration in the gastric glandular mucosa during stress is also discussed. It is concluded that gastric wall mucus depletion is likely to play an important role in stress ulcer formation; the antiulcer action of verapamil could partly be due to the preservation of mucus.

  6. Degradation, foraging, and depletion of mucus sialoglycans by the vagina-adapted Actinobacterium Gardnerella vaginalis.

    PubMed

    Lewis, Warren G; Robinson, Lloyd S; Gilbert, Nicole M; Perry, Justin C; Lewis, Amanda L

    2013-04-26

    Bacterial vaginosis (BV) is a polymicrobial imbalance of the vaginal microbiota associated with reproductive infections, preterm birth, and other adverse health outcomes. Sialidase activity in vaginal fluids is diagnostic of BV and sialic acid-rich components of mucus have protective and immunological roles. However, whereas mucus degradation is believed to be important in the etiology and complications associated with BV, the role(s) of sialidases and the participation of individual bacterial species in the degradation of mucus barriers in BV have not been investigated. Here we demonstrate that the BV-associated bacterium Gardnerella vaginalis uses sialidase to break down and deplete sialic acid-containing mucus components in the vagina. Biochemical evidence using purified sialoglycan substrates supports a model in which 1) G. vaginalis extracellular sialidase hydrolyzes mucosal sialoglycans, 2) liberated sialic acid (N-acetylneuraminic acid) is transported into the bacterium, a process inhibited by excess N-glycolylneuraminic acid, and 3) sialic acid catabolism is initiated by an intracellular aldolase/lyase mechanism. G. vaginalis engaged in sialoglycan foraging in vitro, in the presence of human vaginal mucus, and in vivo, in a murine vaginal model, in each case leading to depletion of sialic acids. Comparison of sialic acid levels in human vaginal specimens also demonstrated significant depletion of mucus sialic acids in women with BV compared with women with a "normal" lactobacilli-dominated microbiota. Taken together, these studies show that G. vaginalis utilizes sialidase to support the degradation, foraging, and depletion of protective host mucus barriers, and that this process of mucus barrier degradation and depletion also occurs in the clinical setting of BV.

  7. Degradation, Foraging, and Depletion of Mucus Sialoglycans by the Vagina-adapted Actinobacterium Gardnerella vaginalis*

    PubMed Central

    Lewis, Warren G.; Robinson, Lloyd S.; Gilbert, Nicole M; Perry, Justin C.; Lewis, Amanda L.

    2013-01-01

    Bacterial vaginosis (BV) is a polymicrobial imbalance of the vaginal microbiota associated with reproductive infections, preterm birth, and other adverse health outcomes. Sialidase activity in vaginal fluids is diagnostic of BV and sialic acid-rich components of mucus have protective and immunological roles. However, whereas mucus degradation is believed to be important in the etiology and complications associated with BV, the role(s) of sialidases and the participation of individual bacterial species in the degradation of mucus barriers in BV have not been investigated. Here we demonstrate that the BV-associated bacterium Gardnerella vaginalis uses sialidase to break down and deplete sialic acid-containing mucus components in the vagina. Biochemical evidence using purified sialoglycan substrates supports a model in which 1) G. vaginalis extracellular sialidase hydrolyzes mucosal sialoglycans, 2) liberated sialic acid (N-acetylneuraminic acid) is transported into the bacterium, a process inhibited by excess N-glycolylneuraminic acid, and 3) sialic acid catabolism is initiated by an intracellular aldolase/lyase mechanism. G. vaginalis engaged in sialoglycan foraging in vitro, in the presence of human vaginal mucus, and in vivo, in a murine vaginal model, in each case leading to depletion of sialic acids. Comparison of sialic acid levels in human vaginal specimens also demonstrated significant depletion of mucus sialic acids in women with BV compared with women with a “normal” lactobacilli-dominated microbiota. Taken together, these studies show that G. vaginalis utilizes sialidase to support the degradation, foraging, and depletion of protective host mucus barriers, and that this process of mucus barrier degradation and depletion also occurs in the clinical setting of BV. PMID:23479734

  8. Treatment with Norplant subdermal implants inhibits sperm penetration through cervical mucus in vitro.

    PubMed

    Croxatto, H B; Díaz, S; Salvatierra, A M; Morales, P; Ebensperger, C; Brandeis, A

    1987-08-01

    Attempts were made to collect several samples of cervical mucus in each of thirty-three cycles of women using NORPLANT subdermal implants, in seven cycles from NORPLANT-2 rod users, and in 33 control cycles. The attempts to collect a mucus sample were successful on 20 of 77 and 7 of 14 occasions in NORPLANT capsule and rod users, respectively, due to the scanty amount and stickiness found in the majority. All 59 attempts in control subjects were successful. The distance travelled by the fastest sperm and by the bulk of spermatozoa through the cervical mucus in vitro was assessed after 10 min of incubation with a normal semen sample. The best score for each cycle was considered for the comparison between treated and control cases. Sperm penetration was greatly impaired in mucus samples of implant users with penetration by the fastest sperm exceeding 10 mm in only two instances and exceeding 20 mm in none. In 30 of 33 control samples, the fastest sperm travelled 21 mm or more and in 28, the bulk of spermatozoa travelled further than 10 mm. Unsuccessful attempts to collect mucus and poor sperm migration were observed in NORPLANT implant users even when circulating estradiol levels were comparable to those seen in the late follicular phase of the normal menstrual cycle. These results suggest that the principal mechanism by which NORPLANT implants prevent pregnancy is by interference of sperm migration through cervical mucus.

  9. 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.

  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. 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

  12. 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.

  13. Sperm counts in enzymatically liquefied cervical mucus: quantitative validation using donor cervical mucus.

    PubMed

    de Agostini, A; Campana, A

    1996-02-01

    The post-coital test evaluates the penetration of spermatozoa into cervical mucus; it relies on subjective measurements and therefore lacks precision. Enzymatic liquefaction of cervical mucus allows sperm concentration to be measured in post-coital test samples, but the reliability of such measurements is not known. Donor cervical mucus was used as a model to test the accuracy and sensitivity of sperm quantification in liquefied cervical mucus. Donor cervical mucus was dissolved by enzymatic treatments in the presence of known numbers of spermatozoa and the recovery of sperm cells was assessed after liquefaction of the samples. Enzymatic treatment of cervical mucus with a combination of bromelin and glycosidases resulted in reliable and fast liquefaction of the samples. The accuracy of sperm concentration measurements was 89 +/- 10% (mean +/- SD, n = 50), and the sensitivity limits were 1 x 10(6) and 0.2 x 10(6) spermatozoa/ml for quantitative concentration measurement and qualitative sperm detection respectively. This study demonstrates that liquefaction of cervical mucus by combined protease and glycosidases allows accurate and sensitive determination of sperm concentration in the sample. Therefore we believe that valuable data can be obtained for sperm concentration and total sperm counts in post-coital tests, that should help to improve the reliability of the post-coital test.

  14. 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.

  15. Ethical considerations in adherence research

    PubMed Central

    Patel, Nupur U; Moore, Blake A; Craver, Rebekah F; Feldman, Steven R

    2016-01-01

    Poor adherence to treatment is a common cause of medical treatment failure. Studying adherence is complicated by the potential for the study environment to impact adherence behavior. Studies performed without informing patients about adherence monitoring must balance the risks of deception against the potential benefits of the knowledge to be gained. Ethically monitoring a patient’s adherence to a treatment plan without full disclosure of the monitoring plan requires protecting the patient’s rights and upholding the fiduciary obligations of the investigator. Adherence monitoring can utilize different levels of deception varying from stealth monitoring, debriefing after the study while informing the subject that some information had been withheld in regard to the use of adherence monitoring (withholding), informed consent that discloses some form of adherence monitoring is being used and will be disclosed at the end of the study (authorized deception), and full disclosure. Different approaches offer different benefits and potential pitfalls. The approach used must balance the risk of nondisclosure against the potential for confounding the adherence monitoring data and the potential benefits that adherence monitoring data will have for the research subjects and/or other populations. This commentary aims to define various methods of adherence monitoring and to provide a discussion of the ethical considerations that accompany the use of each method and adherence monitoring in general as it is used in clinical research. PMID:27980394

  16. Ethical considerations in adherence research.

    PubMed

    Patel, Nupur U; Moore, Blake A; Craver, Rebekah F; Feldman, Steven R

    2016-01-01

    Poor adherence to treatment is a common cause of medical treatment failure. Studying adherence is complicated by the potential for the study environment to impact adherence behavior. Studies performed without informing patients about adherence monitoring must balance the risks of deception against the potential benefits of the knowledge to be gained. Ethically monitoring a patient's adherence to a treatment plan without full disclosure of the monitoring plan requires protecting the patient's rights and upholding the fiduciary obligations of the investigator. Adherence monitoring can utilize different levels of deception varying from stealth monitoring, debriefing after the study while informing the subject that some information had been withheld in regard to the use of adherence monitoring (withholding), informed consent that discloses some form of adherence monitoring is being used and will be disclosed at the end of the study (authorized deception), and full disclosure. Different approaches offer different benefits and potential pitfalls. The approach used must balance the risk of nondisclosure against the potential for confounding the adherence monitoring data and the potential benefits that adherence monitoring data will have for the research subjects and/or other populations. This commentary aims to define various methods of adherence monitoring and to provide a discussion of the ethical considerations that accompany the use of each method and adherence monitoring in general as it is used in clinical research.

  17. 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…

  18. Unusual protozoal infestation of the cervical mucus.

    PubMed

    Jabamoni, R; Dodson, M G; Blecka, L J; Jaskoski, B J; O'Leary, J A

    1977-08-01

    The transient colonization of the female genital tract with an unusual multiflagellated protozoan is reported. The presence of active organisms in large numbers in the mucus of the endocervical canal and their absence from the gastrointestinal tract and other areas indicates true colonization rather than contamination. The colonization resolved spontaneously. The organism has been classified as a Polymastigidan.

  19. 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.

  20. 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.

  1. A Prospective Study of Adherence and Virologic Failure in HIV-Infected Patients: Role of a Single Determination of Plasma Levels of Antiretroviral Medications.

    PubMed

    González, María J Cuevas; Valín, Luis Ortega; Pérez-Simón, María del Rosario; Fernández, José Luis Mostaza; Leza, Manuel Alcoba; Sánchez, Vicente Martin

    2007-12-01

    This study explores the contribution of a single determination of plasma levels for measuring adherence by means of forecasting virologic failure. Adherence was measured by questionnaires, punctuality at appointments to withdraw drugs, and plasma levels. Virologic failure was considered when 2 detectable consecutive viral loads were observed in 2 consecutive determinations with at least 1 month between them. Univariant analysis, logistic regression, and receiver operating characteristic curves were carried out. In 29 cases, virologic failure was observed. The lowest incidence was found in patients considered adherent by plasma levels and highest in those who declared nonfulfillment. The combination of methods increased the association of the incidence of virologic failure with nonadherence. The use of questionnaires plus pharmacy information implies a gain in sensitivity and a slight loss of specificity. There is a high incidence of virologic failure in these patients and a strong link with their classification as nonadherent with methods such as questionnaires and pharmacy collection information. Plasma levels do not contribute much to the prediction of virologic failure.

  2. Resveratrol inhibits mucus overproduction and MUC5AC expression in a murine model of asthma.

    PubMed

    Ni, Zhen-Hua; Tang, Ji-Hong; Chen, Guo; Lai, Yi-Min; Chen, Qing-Ge; Li, Zao; Yang, Wei; Luo, Xu-Min; Wang, Xiong-Biao

    2016-01-01

    Previous in vitro studies have demonstrated that resveratrol is able to significantly inhibit the upregulation of mucin 5AC (MUC5AC), a major component of mucus; thus indicating that resveratrol may have potential in regulating mucus overproduction. However, there have been few studies regarding the resveratrol‑mediated prevention of MUC5AC overproduction in vivo, and the mechanisms by which resveratrol regulates MUC5AC expression have yet to be elucidated. In the present study, an ovalbumin (OVA)‑challenged murine model of asthma was used to assess the effects of resveratrol treatment on mucus production in vivo. The results demonstrated that resveratrol significantly inhibited OVA‑induced airway inflammation and mucus production. In addition, the mRNA and protein expression levels of MUC5AC were increased in the OVA‑challenged mice, whereas treatment with resveratrol significantly inhibited this effect. The expression levels of murine calcium‑activated chloride channel (mCLCA)3, an important key mediator of MUC5AC production, were also reduced following resveratrol treatment. Furthermore, in vitro studies demonstrated that resveratrol significantly inhibited human (h)CLCA1 and MUC5AC expression in a dose‑dependent manner. These results indicated that resveratrol was effective in preventing mucus overproduction and MUC5AC expression in vivo, and its underlying mechanism may be associated with regulation of the mCLCA3/hCLCA1 signaling pathway.

  3. Decreased colonic mucus in rats with loperamide-induced constipation.

    PubMed

    Shimotoyodome, A; Meguro, S; Hase, T; Tokimitsu, I; Sakata, T

    2000-06-01

    Constipation is a risk factor of colorectal cancer. Mucin is a major component of lumenal mucus, which protects the colorectal mucosa against mechanical and chemical damage. The aim of this study was to evaluate mucus production and to quantitate lumen mucus in a rat model of spastic constipation. We induced constipation with loperamide (1.5 mg/kg), and histochemically evaluated mucus production and the thickness of the mucus layer at the fecal surface. We quantitated the mucus attached to the mucosal surface using colonic perfusion with N-acetylcysteine. While more feces remained in the colon, there was less fecal excretion and lower fecal water content in loperamide-administered rats than in control rats. Crypt epithelial cells contained less mucus in constipated rats than in control rats. The mucus layer at the fecal surface was thinner and less mucus was recovered from the mucosal surface in constipated rats than in control rats. Mucus production of crypt epithelial cells and mucus at the fecal and mucosal surface were reduced by loperamide-induced constipation.

  4. Strong Relationship between Oral Dose and Tenofovir Hair Levels in a Randomized Trial: Hair as a Potential Adherence Measure for Pre-Exposure Prophylaxis (PrEP)

    PubMed Central

    Liu, Albert Y.; Yang, Qiyun; Huang, Yong; Bacchetti, Peter; Anderson, Peter L.; Jin, Chengshi; Goggin, Kathy; Stojanovski, Kristefer; Grant, Robert; Buchbinder, Susan P.; Greenblatt, Ruth M.; Gandhi, Monica

    2014-01-01

    Background Pre-exposure prophylaxis (PrEP) trials using tenofovir-based regimens have demonstrated that high levels of adherence are required to evaluate efficacy; the incorporation of objective biomarkers of adherence in trial design has been essential to interpretation, given the inaccuracy of self-report. Antiretroviral measurements in scalp hair have been useful as a marker of long-term exposure in the HIV treatment setting, and hair samples are relatively easy and inexpensive to collect, transport, and store for analysis. To evaluate the relationship between dose and tenofovir concentrations in hair, we examined the dose proportionality of tenofovir in hair in healthy, HIV-uninfected adults. Methods A phase I, crossover pharmacokinetic study was performed in 24 HIV-negative adults receiving directly-observed oral tenofovir tablets administered 2, 4, and 7 doses/week for 6 weeks, with a ≥3-week break between periods. Small samples of hair were collected after each six-week period and analyzed for tenofovir concentrations. Geometric-mean-ratios compared levels between each pair of dosing conditions. Intensive plasma pharmacokinetic studies were performed during the daily-dosing period to calculate areas-under-the-time-concentration curves (AUCs). Results Over 90% of doses were observed per protocol. Median tenofovir concentrations in hair increased monotonically with dose. A log-linear relationship was seen between dose and hair levels, with an estimated 76% (95% CI 60–93%) increase in hair level per 2-fold dose increase. Tenofovir plasma AUCs modestly predicted drug concentrations in hair. Conclusions This study found a strong linear relationship between frequency of dosing and tenofovir levels in scalp hair. The analysis of quantitative drug levels in hair has the potential to improve adherence measurement in the PrEP field and may be helpful in determining exposure thresholds for protection and explaining failures in PrEP trials. Hair measures for

  5. [Glycoproteins of mucus of gastric and duodenal wall surface during ulcerogenesis and the impact of fenugreek].

    PubMed

    Khil'ko, T D; Iakubtsova, I V; Preobrazhens'ka, T D; Ostapchenko, L I

    2013-01-01

    The comparative evaluation of qualitative and quantitative composition of glycoproteins of gastric and duodenal wall surface layer of protective mucus in the normal, at the modeling of ulcers in rats and at the introduction to animals with ulcerative lesions of fenugreek extract carried out. It was shown in control (normally) the general level of glycosylation of glycoproteins gastric mucus is 1.7 times more than the duodenum. Under acute stress model ulceration in the stomach mucus decrease in hexosamine (1.4 times), galactose (2.2 times), fucose (1.3-fold) and an increase in NANA (3.6 times) observed. Under cysteamine model ulceration in duodenal mucus increase galactose (2.7 times), NANA (2.4 times), fucose (1.8-fold) but significant decrease in the amount of hexosamines 3 times compared to the control occurred. It was proved the protective effect of fenugreek extract to the wall surface mucus of the stomach and duodenum mucosa under conditions modeling ulceration in rats.

  6. Antibody activity to type 1 and type 2 herpes simplex virus in human cervical mucus.

    PubMed

    Coughlan, B M; Skinner, G R

    1977-08-01

    Neutralizing antibody activity in cervical mucus to type 1 herpes virus was detected in 24 of 28 patients, and to type 2 herpes simplex virus in 18 of 24 patients. The neutralizing antibody activity resisted heat inactivation for 30 minutes at 56 degrees C, was independent of complement and followed first order kinetics. There was evidence of antibody against both virus types in immunoglobulin fractions IgG and IgA, the latter containing approximately threefold greater neutralizing antibody activity per unit of immunoglobulin concentration. Type 1 and type 2 neutralizing antibody activity showed a positive but weak correlation and type 2 neutralizing antibody activity showed a positive but weak correlation and a type-common immunoprecipitin was identified in all concentrated pooled mucus samples. However, type-specific neutralizing antibody against both virus types was identified in pooled mucus samples by heterologous absorption techniques. There was a relatively higher average type 2 neutralizing antibody activity in the mucus than in the serum and there was no correlation between serum and mucus antibody levels for either virus type. These observations support the concept of an independent local antibody system for herpes simplex virus in the uterine cervix.

  7. 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

    2016-01-07

    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.

  8. [Mucus models for investigation of intestinal absorption mechanisms. 3. A mathematical simulation model of drug diffusion through enteral mucus].

    PubMed

    Fahr, A; Guitard, P; Matthes, I; Nimmerfall, F; Nüesch, E; Sucker, H

    1992-09-01

    The diffusion of drug substance in a closed three-compartment model through a mucus layer to equilibrium is simulated by available pharmacokinetic programs. The obtained curves conform very well to the values experimentally found. If mucus is replaced by buffer solution an explicit equation from the literature, the method used and the experimental findings give the same results. Examination of the rate constants k1 for the diffusion in, kD through and k2 from the mucus shows the significance of the relation k1/k2 > 1, = 1, < 1 as a measure for the affinity of the active agent to the mucus. The discussion of the kinetic parameters shows, as in previous results, no criterion for assuming specific mucus binding. Because of its unspecifity the usual term "mucus binding" should be replaced by "mucus retention".

  9. Essential role of the electroneutral Na+-HCO3- cotransporter NBCn1 in murine duodenal acid-base balance and colonic mucus layer build-up in vivo.

    PubMed

    Singh, Anurag Kumar; Xia, Weiliang; Riederer, Brigitte; Juric, Marina; Li, Junhua; Zheng, Wen; Cinar, Ayhan; Xiao, Fang; Bachmann, Oliver; Song, Penghong; Praetorius, Jeppe; Aalkjaer, Christian; Seidler, Ursula

    2013-04-15

    Duodenal epithelial cells need efficient defence strategies during gastric acidification of the lumen, while colonic mucosa counteracts damage by pathogens by building up a bacteria-free adherent mucus layer. Transport of HCO3(-) is considered crucial for duodenal defence against acid as well as for mucus release and expansion, but the transport pathways involved are incompletely understood. This study investigated the significance of the electroneutral Na(+)-HCO3(-) cotransporter NBCn1 for duodenal defence against acid and colonic mucus release. NBCn1 was localized to the basolateral membrane of duodenal villous enterocytes and of colonic crypt cells, with predominant expression in goblet cells. Duodenal villous enterocyte intracellular pH was studied before and during a luminal acid load by two-photon microscopy in exteriorized, vascularly perfused, indicator (SNARF-1 AM)-loaded duodenum of isoflurane-anaesthetized, systemic acid-base-controlled mice. Acid-induced HCO3(-) secretion was measured in vivo by single-pass perfusion and pH-stat titration. After a luminal acid load, NBCn1-deficient duodenocytes were unable to recover rapidly from intracellular acidification and could not respond adequately with protective HCO3(-) secretion. In the colon, build-up of the mucus layer was delayed, and a decreased thickness of the adherent mucus layer was observed, suggesting that basolateral HCO3(-) uptake is essential for optimal release of mucus. The electroneutral Na(+)-HCO3(-) cotransporter NBCn1 displays a differential cellular distribution in the murine intestine and is essential for HCO3(-)-dependent mucosal protective functions, such as recovery of intracellular pH and HCO3(-) secretion in the duodenum and secretion of mucus in the colon.

  10. Adherence to antiepilepsy drug therapy.

    PubMed

    Faught, Edward

    2012-11-01

    Adherence to antiepilepsy drug (AED) therapy is critical for effective disease management, yet adherence and persistence rates are low due to several barriers. The definitions of adherence (80% rate of total pills taken, medication possession ratio, and days covered by prescriptions filled) and methods of measurement (patient self-reports, serum drug levels, pill counts, electronic bottle tops, and reviews of pharmacy records) are not without limitations, and their applicability to epilepsy is not clear. The use of simple adherence scales during office visits can provide an overall impression of a patient's adherence and can serve as a basis for practitioner-patient dialog. Efforts to improve adherence should focus on provider and healthcare system determinants versus those focused only on the patient. These interventions include non-judgmental communication, patient education, simplification of the dosage regimen with once-daily therapies, and the use of patient reminders.

  11. 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.

  12. 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.

  13. Synthetic Tracheal Mucus with Native Rheological and Surface Tension Properties

    PubMed Central

    Hamed, R.; Fiegel, J.

    2016-01-01

    In this study the development of a model tracheal mucus with chemical composition and physical properties (bulk viscoelasticity and surface tension) matched to that of native tracheal mucus is described. The mucus mimetics were formulated using components that are abundant in tracheal mucus (glycoproteins, proteins, lipids, ions and water) at concentrations similar to those found natively. Pure solutions were unable to achieve the gel behavior observed with native mucus. The addition of a bi-functional crosslinking agent enabled control over the viscoelastic properties of the mucus mimetics by tailoring the concentration of the crosslinking agent and the duration of crosslinking. Three mucus mimetic formulations with different bulk viscoelastic properties, all within the normal range for non-diseased tracheal mucus, were chosen for investigation of surfactant spreading at the air-mimetic interface. Surfactant spread quickly and completely on the least viscoelastic mimetic surface, enabling the surface tension of the mimetic to be lowered to match native tracheal mucus. However, surfactant spreading on the more viscoelastic mimetics was hindered, suggesting that the bulk properties of the mimetics dictate the range of surface properties that can be achieved. PMID:23813841

  14. 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.

  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. 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.

  17. 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

  18. Short Communication: A Low-Cost Method for Analyzing Nevirapine Levels in Hair as a Marker of Adherence in Resource-Limited Settings

    PubMed Central

    Yang, Qiyun; Bacchetti, Peter; Huang, Yong

    2014-01-01

    Abstract 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

  19. Sustaining a "culture of silence" in the neonatal intensive care unit during nonemergency situations: a grounded theory on ensuring adherence to behavioral modification to reduce noise levels.

    PubMed

    Swathi, S; Ramesh, A; Nagapoornima, M; Fernandes, Lavina M; Jisina, C; Rao, P N Suman; Swarnarekha, A

    2014-01-01

    The aim of this study was to generate a substantive theory explaining how the staff in a resource-limited neonatal intensive care unit (NICU) of a developing nation manage to ensure adherence to behavioral modification components of a noise reduction protocol (NsRP) during nonemergency situations. The study was conducted after implementation of an NsRP in a level III NICU of south India. The normal routine of the NICU is highly dynamic because of various categories of staff conducting clinical rounds followed by care-giving activities. This is unpredictably interspersed with very noisy emergency management of neonates who suddenly fall sick. In-depth interviews were conducted with 36 staff members of the NICU (20 staff nurses, six nursing aides, and 10 physicians). Group discussions were conducted with 20 staff nurses and six nursing aides. Data analysis was done in line with the reformulated grounded theory approach, which was based on inductive examination of textual information. The results of the analysis showed that the main concern was to ensure adherence to behavioral modification components of the NsRP. This was addressed by using strategies to "sustain a culture of silence in NICU during nonemergency situations" (core category). The main strategies employed were building awareness momentum, causing awareness percolation, developing a sense of ownership, expansion of caring practices, evolution of adherence, and displaying performance indicators. The "culture of silence" reconditions the existing staff and conditions new staff members joining the NICU. During emergency situations, a "noisy culture" prevailed because of pragmatic neglect of behavioral modification when life support overrode all other concerns. In addition to this, the process of operant conditioning should be formally conducted once every 18 months. The results of this study may be adapted to create similar strategies and establish context specific NsRPs in NICUs with resource constraints.

  20. The gastrointestinal mucus system in health and disease

    PubMed Central

    Johansson, Malin E.V.; Sjövall, Henrik; Hansson, Gunnar C.

    2013-01-01

    Mucins—large, highly glycosylated proteins—are important for the luminal protection of the gastrointestinal tract. Enterocytes have their apical surface covered by transmembrane mucins and goblet cells produce the secreted gel-forming mucins that form mucus. The small intestine has a single unattached mucus layer. In cystic fibrosis, this layer becomes attached, accounting for the intestinal manifestations of this disease. The stomach and colon have two layers of mucus; the inner layer is attached and the outer layer is less dense and unattached. In the colon, the outer mucus layer is the habitat for commensal bacteria. The inner mucus layer is impervious to bacteria and is renewed every hour by surface goblet cells. The crypt goblet cells have the ability to restitute the mucus layer by secretion, for example after an ischaemic challenge. Proteases of certain parasites and some bacteria can cleave mucins and dissolve the mucus as part of their pathogenicity. The inner mucus layer can, however, also become penetrable to bacteria by several other mechanisms, including aberrations in the immune system. When bacteria reach the epithelial surface, the immune system is activated and inflammation is triggered. This mechanism might occur in some types of ulcerative colitis. PMID:23478383

  1. The gastrointestinal mucus system in health and disease.

    PubMed

    Johansson, Malin E V; Sjövall, Henrik; Hansson, Gunnar C

    2013-06-01

    Mucins--large, highly glycosylated proteins--are important for the luminal protection of the gastrointestinal tract. Enterocytes have their apical surface covered by transmembrane mucins and goblet cells produce the secreted gel-forming mucins that form mucus. The small intestine has a single unattached mucus layer, which in cystic fibrosis becomes attached, accounting for the intestinal manifestations of this disease. The stomach and colon have two layers of mucus; the inner layer is attached and the outer layer is less dense and unattached. In the colon, the outer mucus layer is the habitat for commensal bacteria. The inner mucus layer is impervious to bacteria and is renewed every hour by surface goblet cells. The crypt goblet cells have the ability to restitute the mucus layer by secretion, for example after an ischaemic challenge. Proteases of certain parasites and some bacteria can cleave mucins and dissolve the mucus as part of their pathogenicity. The inner mucus layer can, however, also become penetrable to bacteria by several other mechanisms, including aberrations in the immune system. When bacteria reach the epithelial surface, the immune system is activated and inflammation is triggered. This mechanism might occur in some types of ulcerative colitis.

  2. Measurement of Psychiatric Treatment Adherence

    PubMed Central

    Sajatovic, Martha; Velligan, Dawn; Weiden, Peter J.; Valenstein, Marcia; Ogedegbe, Gbenga

    2014-01-01

    Objective Nonadherence to medications for mental disorders substantially limits treatment effectiveness and results in higher rates of relapse, hospitalization, and disability. Accurate measurement of medication adherence is important not only in adherence research, but also in clinical trials in which medications are being evaluated, and in clinical practice where failure to detect nonadherence results in premature medication changes, unnecessary polypharmacy, and greater likelihoods of functional deteriorations and hospitalizations. This is a review of psychiatric treatment adherence methods and measures arising from a meeting on “Methodological Challenges in Psychiatric Treatment Adherence Research” held on September 27-28, 2007 in Bethesda, MD and organized by the National Institute of Mental Health (NIMH). Methods This paper reviews the range of modalities currently available for assessing adherence behavior including pill counts, pharmacy records, technology-assisted monitoring, biological assays, and a range of self-report and interviewer-rated scales. Measures of adherence attitudes are also reviewed. Results Each of the adherence measures described are imperfect estimates of actual medication ingestion but each provides informative estimates of adherence or the attitudinal factors associated with adherence. Measure selection depends on a range of factors including the patient sample, the context in which the measure is being used, and the clinical outcomes expected from various levels of nonadherence. The use of multiple measures of adherence is encouraged to balance the limitations of individual measures. Conclusion While adherence assessment has become increasingly sophisticated in recent years there remains a need for refinement and expansion on currently available methods and measures. PMID:21109048

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. Pathogen bacteria adhesion to skin mucus of fishes.

    PubMed

    Benhamed, Said; Guardiola, Francisco A; Mars, Mohammed; Esteban, María Ángeles

    2014-06-25

    Fish are always in intimate contact with their environment; therefore they are permanently exposed to very vary external hazards (e.g. aerobic and anaerobic bacteria, viruses, parasites, pollutants). To fight off pathogenic microorganisms, the epidermis and its secretion, the mucus acts as a barrier between the fish and the environment. Fish are surrounded by a continuous layer of mucus which is the first physical, chemical and biological barrier from infection and the first site of interaction between fish's skin cells and pathogens. The mucus composition is very complex and includes numerous antibacterial factors secreted by fish's skin cells, such as immunoglobulins, agglutinins, lectins, lysins and lysozymes. These factors have a very important role to discriminate between pathogenic and commensal microorganisms and to protect fish from invading pathogens. Furthermore, the skin mucus represents an important portal of entry of pathogens since it induces the development of biofilms, and represents a favorable microenvironment for bacteria, the main disease agents for fish. The purpose of this review is to summarize the current knowledge of the interaction between bacteria and fish skin mucus, the adhesion mechanisms of pathogens and the major factors influencing pathogen adhesion to mucus. The better knowledge of the interaction between fish and their environment could inspire other new perspectives to study as well as to exploit the mucus properties for different purposes.

  14. HIV Medication Adherence

    MedlinePlus

    HIV Treatment HIV Medication Adherence (Last updated 3/2/2017; last reviewed 3/2/2017) Key Points Medication adherence means sticking firmly to ... Before and After Starting HIV Medicines . What is medication adherence? Adherence means “to stick firmly.” So for ...

  15. Effects of drugs on mucus clearance.

    PubMed

    Houtmeyers, E; Gosselink, R; Gayan-Ramirez, G; Decramer, M

    1999-08-01

    Mucociliary clearance (MCC), the process in which airway mucus together with substances trapped within are moved out of the lungs, is an important defence mechanism of the human body. Drugs may alter this process, such that it is necessary to know the effect of the drugs on MCC. Indeed, agents stimulating MCC may be used therapeutically in respiratory medicine, especially in patients suspected of having an impairment of their mucociliary transport system. In contrast, caution should be taken with drugs depressing MCC as an undesired side-effect, independently of their therapeutic indication. Since cough clearance (CC) serves as a back-up system when MCC fails, the influence of drugs must be examined not only on MCC but also on CC. Ultimately, the clinical repercussions of alterations in mucus transport induced by drug administration must be studied. Tertiary ammonium compounds (anticholinergics), aspirin, anaesthetic agents and benzodiazepines have been shown to be capable of depressing the mucociliary transport system. Cholinergics, methylxanthines, sodium cromoglycate, hypertonic saline, saline as well as water aerosol have been shown to increase MCC. Adrenergic antagonists, guaifenesin, S-carboxymethylcysteine, sodium 2-mercapto-ethane sulphonate and frusemide have been reported not to alter the mucociliary transport significantly. Amiloride, uridine 5'-triphosphate (UTP), quaternary ammonium compounds (anticholinergics), adrenergic agonists, corticosteroids, recombinant human deoxyribonuclease (rhDNase), N-acetylcysteine, bromhexine and ambroxol have been reported either not to change or to augment MCC. Indirect data suggest that surfactant as well as antibiotics may improve the mucociliary transport system. As for the influence of drugs on CC, amiloride and rhDNase have been demonstrated to increase the effectiveness of cough. A trend towards an improved CC was noted after treatment with adrenergic agonists. The anticholinergic agent ipratropium bromide, which

  16. Glycobiome: bacteria and mucus at the epithelial interface.

    PubMed

    Ouwerkerk, Janneke P; de Vos, Willem M; Belzer, Clara

    2013-02-01

    The human gastrointestinal tract is colonised with a dense and diverse microbial community, that is an important player in human health and physiology. Close to the epithelial cells the mucosal microbiota is separated from the host with a thin lining of host derived glycans, including the cell surface glycocalyx and the extracellular secreted mucus. The mucosa-associated microbial composition differs from the luminal content and could be particularly important for nutrient exchange, communication with the host, development of the immune system, and resistance against invading pathogens. The mucosa-associated microbiota has adapted to the glycan rich environment by the production of mucus-degrading enzymes and mucus-binding extracellular proteins, and include mucus-degrading specialists such as Akkermansia muciniphila and Bacteroides thetaiotaomicron. This review is focussed on the host-microbe interactions within the glycan landscape at the epithelial interface and considers the spatial organisation and composition of the mucosa-associated microbiota in health and disease.

  17. 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

  18. 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

  19. Effective extraction of Arabidopsis adherent seed mucilage by ultrasonic treatment

    PubMed Central

    Zhao, Xianhai; Qiao, Lijun; Wu, Ai-Min

    2017-01-01

    The Arabidopsis seed coat is composed of two layers of mucilage, a water-soluble non-adherent outer layer and an adherent inner layer. The non-adherent mucilage can easily be extracted by gentle shaking. However, adherent mucilage is extremely difficult to dissociate from the seed coat. Despite various treatments to extract the adherent mucilage, including EDTA, ammonium oxalate, dilute alkali or acid washes, most of it remains on the seed coat. Here, we show for the first time the extraction of almost all of the adherent mucilage from the Arabidopsis seed coat. Our results demonstrate that ultrasonic treatment was able to extract the adherent mucilage effectively within 20 seconds. Adherent mucilage, like non-adherent mucilage, is mainly composed of rhamnogalacturonan I (RG I). The crystalline cellulose content in adherent mucilage was measured as 3.7 mg g−1 of dry seed. Compared with non-adherent mucilage, the adherent mucilage exhibits relatively stable levels of sugar under various environmental conditions. In all cases, adherent mucilage showed higher levels of sugar than non-adherent mucilage. The cell wall remnant could associate with the adherent mucilage, which could prevent the extraction of the adherent mucilage. Our results show that ultrasonic treatment is an effective method for the quick extraction of Arabidopsis adherent mucilage with little effort. PMID:28091592

  20. Isolation of the galactose-binding lectin that mediates the in vitro adherence of Entamoeba histolytica.

    PubMed Central

    Petri, W A; Smith, R D; Schlesinger, P H; Murphy, C F; Ravdin, J I

    1987-01-01

    Entamoeba histolytica adheres to human colonic mucus, colonic epithelial cells, and other target cells via a galactose (Gal) or N-acetyl-D-galactosamine (GalNAc) inhibitable surface lectin. Blockade of this adherence lectin with Gal or GalNAc in vitro prevents amebic killing of target cells. We have identified and purified the adherence lectin by two methods: affinity columns derivatized with galactose monomers or galactose terminal glycoproteins, and affinity columns and immunoblots prepared with monoclonal antibodies that inhibit amebic adherence. By both methods the adherence lectin was identified as a 170-kD secreted and membrane-bound amebic protein. The surface location of the lectin was confirmed by indirect immunofluorescence. Purified lectin competitively inhibited amebic adherence to target cells by binding to receptors on the target Chinese hamster ovary cells in a Gal-inhibitable manner. Images PMID:2890654

  1. Prophylactic exercises among head and neck cancer patients during and after swallowing sparing intensity modulated radiation: adherence and exercise performance levels of a 12-week guided home-based program.

    PubMed

    Cnossen, Ingrid C; van Uden-Kraan, Cornelia F; Witte, Birgit I; Aalders, Yke J; de Goede, Cees J T; de Bree, Remco; Doornaert, Patricia; Rietveld, Derek H F; Buter, Jan; Langendijk, Johannes A; Leemans, C René; Verdonck-de Leeuw, Irma M

    2017-02-01

    The background and purpose of this paper is to investigate adherence, exercise performance levels and associated factors in head and neck cancer (HNC) patients participating in a guided home-based prophylactic exercise program during and after treatment [swallowing sparing intensity modulated radiation therapy (SW-IMRT)]. Fifty patients were included in the study. Adherence was defined as the percentage of patients who kept up exercising; exercise performance level was categorized as low: ≤1, moderate: 1-2, and high: ≥2 time(s) per day, on average. Associations between 6- and 12-week exercise performance levels and age, gender, tumour site and stage, treatment, intervention format (online or booklet), number of coaching sessions, and baseline HNC symptoms (EORTC-QLQ-H&N35) were investigated. Adherence rate at 6 weeks was 70% and decreased to 38% at 12 weeks. In addition, exercise performance levels decreased over time (during 6 weeks: 34% moderate and 26% high; during 12 weeks: 28% moderate and 18% high). The addition of chemotherapy to SW-IMRT [(C)SW-IMRT] significantly deteriorated exercise performance level. Adherence to a guided home-based prophylactic exercise program was high during (C)SW-IMRT, but dropped afterwards. Exercise performance level was negatively affected by chemotherapy in combination with SW-IMRT.

  2. Lyn regulates mucus secretion and MUC5AC via the STAT6 signaling pathway during allergic airway inflammation

    PubMed Central

    Wang, Xiaoyun; Li, Yin; Luo, Deyu; Wang, Xing; Zhang, Yun; Liu, Zhigang; Zhong, Nanshan; Wu, Min; Li, Guoping

    2017-01-01

    Hypersecretion of mucus is an important component of airway remodeling and contributes to the mucus plugs and airflow obstruction associated with severe asthma phenotypes. Lyn has been shown to down-regulate allergen-induced airway inflammation. However, the role of Lyn in mucin gene expression remains unresolved. In this study, we first demonstrate that Lyn overexpression decreased the mucus hypersecretion and levels of the muc5ac transcript in mice exposed to ovalbumin (OVA). Lyn overexpression also decreased the infiltration of inflammatory cells and the levels of IL-13 and IL-4 in OVA-challenged airways. Whereas Lyn knockdown increased the IL-4 or IL-13-induced MUC5AC transcript and protein levels in the human bronchial epithelial cell line, 16HBE, Lyn overexpression decreased IL-4- or IL-13-induced MUC5AC transcript and protein levels. Overexpression of Lyn also decreased the expression and phosphorylation of STAT6 in OVA-exposed mice, whereas Lyn knockdown increased STAT6 and MUC5AC levels in 16HBE cells. Finally, chromatin immunoprecipitation analysis confirmed that Lyn overexpression decreased the binding of STAT6 to the promoter region of Muc5ac in mice exposed to OVA. Collectively, these findings demonstrated that Lyn overexpression ameliorated airway mucus hypersecretion by down-regulating STAT6 and its binding to the MUC5AC promoter. PMID:28205598

  3. Bacillus cereus Adhesion to Simulated Intestinal Mucus Is Determined by Its Growth on Mucin, Rather Than Intestinal Environmental Parameters.

    PubMed

    Tsilia, Varvara; Uyttendaele, Mieke; Kerckhof, Frederiek-Maarten; Rajkovic, Andreja; Heyndrickx, Marc; Van de Wiele, Tom

    2015-11-01

    Adhesion of pathogenic bacteria to intestinal mucus, the protective layer of the gastrointestinal epithelium, is often considered a virulence factor. The ability of food-poisoning Bacillus cereus strains to attach to mucus and the factors affecting this interaction have not yet been investigated. Therefore, the role of adhesion in pathogenesis of B. cereus still remains unknown. In the present study, an in vitro assay based on mucin agar was used to simulate adhesion of B. cereus to mucus. Bacterial-associated factors (e.g., strain specificity and microbial competition) known to influence adhesion to different surfaces and a variety of environmental conditions (e.g., pH and oxygen) encountered in the gastrointestinal tract were investigated. The effect of these parameters on B. cereus NVH 0500/00 mucin adhesion was generally limited even in the presence of microbial competition. This suggests that B. cereus NVH 0500/00 is a versatile pathogen. Inoculation of 4 to 5 log colony-forming units (CFU) per milliliter. B. cereus NVH 0500/00 resulted in 5-6 log CFU/mL mucin-associated bacteria after a short incubation period. This indicates that this pathogenic strain could grow in the presence of mucin agar. This growth may potentially mask the effect of the studied conditions. Yet, extensive attachment of B. cereus to mucin is not necessarily a prerequisite for virulence, because other pathogenic strains do not adhere with the same efficiency to mucin. Nevertheless, adhesion may contribute to the disease by providing close contact to nutrient sources, such as mucin, which would not only result in bacterial proliferation, but also in disruption of the protective host mucus surface.

  4. Mitomycin-C suppresses mucus secretion in an ileal neobladder rat model.

    PubMed

    Fan, Weiwei; Yu, Yang; Shu, Junjie; Ming, Hao; Li, Weiping; Fan, Zhilu

    2015-08-01

    The aim of the present study was to investigate the mucus secretion status of mature goblet cells following the application of mitomycin-C (MMC) in ileal neobladder rat models. Bladder substitution models were established in Sprague Dawley rats, which had been divided into five groups, namely the control (sham), normal saline (NS), high-dose MMC (HMMC), low-dose MMC (LMMC) and dehydrated alcohol (DA) groups. To evaluate the total protein concentration and level of sialic acid following the therapy, urine from the rats in each group was collected on days 8, 11 and 14. In addition, to observe the variances between mucus secretion and the ileum goblet cells, immunohistochemistry and hematoxylin and eosin staining were conducted in the different groups on day 17. The results indicated that the ileal neobladder mucosas in the MMC groups were clearly undamaged, as compared with the DA group. Furthermore, the MMC and DA groups were shown to inhibit the proliferation of goblet cells. The concentration of protein and sialic acid in the LMMC group was found to be lower compared with the NS group, while the concentration in the HMMC group was considerably lower. In conclusion, HMMC was demonstrated to evidently reduce the mucin and sialic acid concentration in the urine, without visible damage to the ileal neobladder mucus membrane. Therefore, MMC may provide a novel therapeutic approach for the treatment of certain bladder conditions.

  5. Mitomycin-C suppresses mucus secretion in an ileal neobladder rat model

    PubMed Central

    FAN, WEIWEI; YU, YANG; SHU, JUNJIE; MING, HAO; LI, WEIPING; FAN, ZHILU

    2015-01-01

    The aim of the present study was to investigate the mucus secretion status of mature goblet cells following the application of mitomycin-C (MMC) in ileal neobladder rat models. Bladder substitution models were established in Sprague Dawley rats, which had been divided into five groups, namely the control (sham), normal saline (NS), high-dose MMC (HMMC), low-dose MMC (LMMC) and dehydrated alcohol (DA) groups. To evaluate the total protein concentration and level of sialic acid following the therapy, urine from the rats in each group was collected on days 8, 11 and 14. In addition, to observe the variances between mucus secretion and the ileum goblet cells, immunohistochemistry and hematoxylin and eosin staining were conducted in the different groups on day 17. The results indicated that the ileal neobladder mucosas in the MMC groups were clearly undamaged, as compared with the DA group. Furthermore, the MMC and DA groups were shown to inhibit the proliferation of goblet cells. The concentration of protein and sialic acid in the LMMC group was found to be lower compared with the NS group, while the concentration in the HMMC group was considerably lower. In conclusion, HMMC was demonstrated to evidently reduce the mucin and sialic acid concentration in the urine, without visible damage to the ileal neobladder mucus membrane. Therefore, MMC may provide a novel therapeutic approach for the treatment of certain bladder conditions. PMID:26622360

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

    PubMed Central

    Ott, Brittany M.; Dacks, Andrew M.; Ryan, Kenneth J.

    2016-01-01

    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 gammaproteobacterium Aeromonas veronii is transmitted from the gut of the medicinal leech to other hosts via host mucosal castings, yet A. veronii can 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-bound A. veronii had 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 that A. veronii alters transcription of loci in a synthetic pathway that obtains and incorporates N-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

  7. Terminal carbohydrates abundance, immune related enzymes, bactericidal activity and physico-chemical parameters of the Senegalese sole (Solea senegalensis, Kaup) skin mucus.

    PubMed

    Guardiola, Francisco A; Cuartero, María; Del Mar Collado-González, María; Díaz Baños, F Guillermo; Cuesta, Alberto; Moriñigo, Miguel Ángel; Esteban, M Ángeles

    2017-01-01

    Recently, interest in mucosal surfaces, more specifically fish skin and its secreted mucus, has greatly increased among immunologists. The abundance of terminal carbohydrates, several enzymes (proteases, lysozyme, peroxidase, alkaline phosphatase, esterases and ceruloplasmin), bactericidal activity against fish pathogenic and non-pathogenic bacteria and several physico-chemical parameters (protein concentration, pH, conductivity, redox potential, osmolarity, density and viscosity) in the skin mucus of Senegalese sole (Solea senegalensis, Kaup) have been evaluated. Present results evidence the abundance of N-acetylneuraminic acid, mannose, glucose and N-acetyl-galactosamine in skin mucus. The levels of lysozyme, proteases, esterases and alkaline phosphatase were very similar (from 20 to 30 Units mg(-1) protein). However, 93 Units mg(-1) protein were detected of ceruloplasmin and only 4'88 Units mg(-1) protein of peroxidase. Skin mucus of S. senegalensis showed high bactericidal activity against the tested pathogen bacteria but weak activity against non-pathogenic bacteria. Finally, a clear relationship between mucus density and temperature was detected, while viscosity showed a direct shear- and temperature-dependent behaviour. These results could be useful for better understanding the role of the skin mucus as a key component of the innate immune system, as well as, for elucidating possible relationships between biological and physico-chemical parameters and disease susceptibility.

  8. A new role for bicarbonate in mucus formation.

    PubMed

    Chen, Eric Y T; Yang, Ning; Quinton, Paul M; Chin, Wei-Chun

    2010-10-01

    The impact of small anions on the physical properties of gel-forming mucin has been almost overlooked relative to that of cations. Recently, based on the coincident abnormalities in HCO(3)(-) secretion and abnormal mucus formed in the hereditary disease cystic fibrosis (CF), HCO(3)(-) was hypothesized to be critical in the formation of normal mucus by virtue of its ability to sequester Ca(2+) from condensed mucins being discharged from cells. However, direct evidence of the impact of HCO(3)(-) on mucus properties is lacking. Herein, we demonstrate for the first time that mucin diffusivity (∼1/viscosity) increases as a function of [HCO(3)(-)]. Direct measurements of exocytosed mucin-swelling kinetics from airway cells showed that mucin diffusivity increases by ∼300% with 20 mM extracellular HCO(3)(-) concentration. Supporting data indicate that HCO(3)(-) reduces free Ca(2+) concentration and decreases the amount of Ca(2+) that remains associated with mucins. The results demonstrate that HCO(3)(-) enhances mucin swelling and hydration by reducing Ca(2+) cross-linking in mucins, thereby decreasing its viscosity and likely increasing its transportability. In addition, HCO(3)(-) can function as a Ca(2+) chelator like EGTA to disperse mucin aggregates. This study indicates that poor HCO(3)(-) availability in CF may explain why secreted mucus remains aggregated and more viscous in affected organs. These insights bear on not only the fundamental pathogenesis in CF, but also on the process of gel mucus formation and release in general.

  9. 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.

  10. The effect of prebiotics on adherence of probiotics.

    PubMed

    Kadlec, Robert; Jakubec, Martin

    2014-01-01

    Prebiotics are generally considered to promote the function or viability of probiotics via their fermentation, but their effect on the adherence of probiotics is still unclear. In this study, we examined the effect of 4 commercially available prebiotics [Orafti GR, Orafti P95, and Orafti Synergy (Beneo GmbH, Mannheim, Germany), and Vivinal (Friesland Foods Domo, Amersfoort, the Netherlands)] and 3 simple saccharides (glucose, galactose, and lactose) on the adherence of 5 probiotic type strains, 2 lactococci starter cultures, and 5 potential dairy probiotic strains from the Culture Collection of Dairy Microorganisms (Tábor, Czech Republic). Adherence was tested in microtiter plates on the following types of substrate: polystyrene alone and polystyrene coated with either porcine mucus or cocultures of the human colon cell lines Caco2 and HT29-MXT (1:9 ratio of HT29-MXT:Caco2). Adherence was evaluated as a change in fluorescence in the well of a microtiter plate. The most commonly observed effect (with a few exceptions) of prebiotics was decreased adherence of the tested strains observed on all types of substrate. The tested saccharides, which are part of the residual compounds of the used prebiotics, had a very similar effect-eliciting a decrease in adherence ability in the majority of the probiotic strains.

  11. Inadequate cervical mucus--a cause of "idiopathic" infertility.

    PubMed

    Sher, G; Katz, M

    1976-08-01

    The purpose of this study was to investigate and treat a group of patients referred for "idiopathic" infertility in whom no apparent cause for infertility, apart from inadequate cervical mucus, was found. Hormone investigations revealed that these patients could be divided into two groups: those with low sex steroid profiles despite apparent ovulation, and a second group with normal sex steroid profiles. All patients were treated with ovulation-inducing agents in an attempt to produce "controlled" ovarian hyperstimulation and an improved cervical mucus. Four of six patients conceived. The rationale behind the use of ovulation-inducing agents in this situation is discussed.

  12. IL-13–induced airway mucus production is attenuated by MAPK13 inhibition

    PubMed Central

    Alevy, Yael G.; Patel, Anand C.; Romero, Arthur G.; Patel, Dhara A.; Tucker, Jennifer; Roswit, William T.; Miller, Chantel A.; Heier, Richard F.; Byers, Derek E.; Brett, Tom J.; Holtzman, Michael J.

    2012-01-01

    Increased mucus production is a common cause of morbidity and mortality in inflammatory airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. However, the precise molecular mechanisms for pathogenic mucus production are largely undetermined. Accordingly, there are no specific and effective anti-mucus therapeutics. Here, we define a signaling pathway from chloride channel calcium-activated 1 (CLCA1) to MAPK13 that is responsible for IL-13–driven mucus production in human airway epithelial cells. The same pathway was also highly activated in the lungs of humans with excess mucus production due to COPD. We further validated the pathway by using structure-based drug design to develop a series of novel MAPK13 inhibitors with nanomolar potency that effectively reduced mucus production in human airway epithelial cells. These results uncover and validate a new pathway for regulating mucus production as well as a corresponding therapeutic approach to mucus overproduction in inflammatory airway diseases. PMID:23187130

  13. 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…

  14. Cervical mucus characteristics and hormonal status at insemination of Holstein cows

    PubMed Central

    Bernardi, S.; Rinaudo, A.; Marini, P.

    2016-01-01

    The present study was carried out to characterize the cervical mucus (CM) collected when inseminating Holstein cows and to relate the secretion pattern with pregnancy. The mucus was collected from mid-cervix of 64 cows with spontaneus estrus (SE) and induced estrus (IE). The quantity, pattern and consistency of the mucus, pH, arborization patterns and the sperm motility were observed. The levels of progesterone and estradiol 17β in serum were also determined. Pregnancy detection was performed by means of transrectal ultrasonography 60 days after insemination. Mucous secretion of cows with SE was significantly different from those with IE, showing a lower degree of crystallization (SE 2.00; IE 2.75) and a lower level of steroid hormones (P4: SE 0.17 ng/ml and IE 0.33 ng/ml (t 1.99547 α 0.05); E2: SE 30.95 pg/ml and IE 47.76 pg/ml (t 1.99495 α 0.05). Progesterone level was significantly lower and estrogen significantly higher in pregnant cows (P) in relation to that observed in non pregnant females (N) (P4: P 0.20 ng/ml and N 0.44 ng/ml (t 1.99602 α 0.05); E2: P 54.77 pg/ml and N 40.75 pg/ml (t 1.99505 α 0.05). In conclusion pregnancy was associated with acopious, clear and watery discharge (similar to egg white), with an arborization degree of 2.25, presence of atypical fern leaves together with rosette formations and needles or thorns on rails due to low levels of progesterone accompanied by high concentrations of estrogens. PMID:27656229

  15. 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...

  16. 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

    ... Clearing Mucus From Endotracheal Tubes AGENCY: National Institutes of Health, Public Health Service, HHS...-074-2005/0 ``Mucus Slurping Endotracheal Tube''; U.S. Patent 7,503,328 to Oculus Innovative Sciences... mucus from endotracheal tubes. DATES: Only written comments and/or applications for a license...

  17. Imaging and tracking HIV viruses in human cervical mucus

    NASA Astrophysics Data System (ADS)

    Boukari, Fatima; Makrogiannis, Sokratis; Nossal, Ralph; Boukari, Hacène

    2016-09-01

    We describe a systematic approach to image, track, and quantify the movements of HIV viruses embedded in human cervical mucus. The underlying motivation for this study is that, in HIV-infected adults, women account for more than half of all new cases and most of these women acquire the infection through heterosexual contact. The endocervix is believed to be a susceptible site for HIV entry. Cervical mucus, which coats the endocervix, should play a protective role against the viruses. Thus, we developed a methodology to apply time-resolved confocal microscopy to examine the motion of HIV viruses that were added to samples of untreated cervical mucus. From the images, we identified the viruses, tracked them over time, and calculated changes of the statistical mean-squared displacement (MSD) of each virus. Approximately half of tracked viruses appear constrained while the others show mobility with MSDs that are proportional to τα+ν2τ2, over time range τ, depicting a combination of anomalous diffusion (0<α<0.4) and flow-like behavior. The MSD data also reveal plateaus attributable to possible stalling of the viruses. Although a more extensive study is warranted, these results support the assumption of mucus being a barrier against the motion of these viruses.

  18. 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...

  19. Sodium alginate decreases the permeability of intestinal mucus.

    PubMed

    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.

  20. 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

  1. 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.

  2. Medication adherence in schizophrenia.

    PubMed

    Acosta, Francisco Javier; Hernández, José Luis; Pereira, José; Herrera, Judit; Rodríguez, Carlos J

    2012-10-22

    Non-adherence is a major problem in the treatment of schizophrenia. Its high prevalence, potentially severe consequences and associated costs make the study of this phenomenon a priority issue. In this article, basic non-adherence concepts of prevalence, consequences, evaluation methods, methodological restrictions of available studies, risk factors and intervention strategies, are reviewed. Studying non-adherence risk factors is a necessary step toward designing adequately oriented intervention strategies. An operative definition of adherence and good knowledge of its evaluation methods are essential to study this phenomenon. Unfortunately, most available studies contain methodological restrictions, especially concerning the evaluation methods, and an agreed operative definition of adherence has only very recently been reached. Knowing non-adherence risk factors, intervention strategies and available evidence on their effectiveness is essential in making treatment decisions in daily clinical practice.

  3. Medication Adherence Mediates the Association between Type D Personality and High HbA1c Level in Chinese Patients with Type 2 Diabetes Mellitus: A Six-Month Follow-Up Study

    PubMed Central

    Li, Xuemei; Gao, Min; Zhang, Shengfa; Xu, Huiwen; Zhou, Huixuan; Wang, Xiaohua; Qu, Zhiyong; Guo, Jing

    2017-01-01

    Aims. To examine the association between Type D personality and HbA1c level and to explore the mediating role of medication adherence between them in patients with type 2 diabetes mellitus (T2DM). Methods. 330 patients went on to complete a self-report measure of medication adherence and the HbA1c tests. Chi-square test, T test, Ordinary Least Square Regression (OLS), and Recentered Influence Function Regression (RIF) were employed. Results. Patients with Type D personality had significantly higher HbA1c value (P < 0.01). When Type D personality was operationalized as a categorical variable, SI was associated with HbA1c (P < 0.01). When NA, SI, and their interaction term were entered into regression, all of them were no longer associated with HbA1c level (P > 0.1). On the other hand, when Type D personality was operationalized as a continuous variable, only SI trait was associated with HbA1c level (P < 0.01). When NA, SI, and NA × SI term together were entered into regression, only SI was not related to HbA1c level. Furthermore, medication adherence had a significant mediation effect between Type D personality and HbA1c, accounting for 54.43% of the total effect. Conclusion. Type D personality was associated with HbA1c in direct and indirect ways, and medication adherence acted as a mediator role. PMID:28280745

  4. Interaction of tea polyphenols and food constituents with model gut epithelia: the protective role of the mucus gel layer.

    PubMed

    D'Agostino, Eleanor M; Rossetti, Damiano; Atkins, Derek; Ferdinando, Dudley; Yakubov, Gleb E

    2012-03-28

    The luminal surface of the gastrointestinal tract is covered by a mucus gel layer that acts to protect gut epithelial cells from the harsh luminal environment. This study investigated the use of two human colonic adenocarcinoma cell lines, HT29-MTX-E12 and HT29, as a model to mimic gut epithelium with and without a mucus gel layer. The effect of adding the tea polyphenols epigallocatechin gallate (EGCG) and epicatechin (EC) to the cells with subsequent examination of cell morphology and viability was assessed. EGCG, at the concentrations tested, was very toxic to the HT29 cells, but less toxic to the HT29-MTX-E12 cells, suggesting that the mucus gel layer on the HT29-MTX-E12 cells can protect the cells against EGCG toxicity. In contrast, EC had no effect on the viability of either the HT29 or HT29-MTX-E12 cells, suggesting that proteins within the mucus gel layer on the apical surface of gut epithelial cells may bind to the galloyl ring of EGCG. The effect of adding food-related ingredients with the ability to complex with EGCG, β-casein and maltodextrin, on cell viability was also examined. The presence of β-casein was very effective in protecting the cells against the toxicity effect of EGCG, but maltodextrin, at the concentration tested, was less effective in protecting against this toxicity. In conclusion, the results demonstrate that the mucus gel layer on HT29 human colonic adenocarcinoma cells may protect these cells against EGCG toxicity. In addition, the data showing reduced toxicity of EC compared to that of EGCG suggest that the cytotoxic effects of high polyphenol levels may be associated with the ability of polyphenols to interact with cellular proteins and mucins.

  5. Composition and functional role of the mucus layers in the intestine.

    PubMed

    Johansson, Malin E V; Ambort, Daniel; Pelaseyed, Thaher; Schütte, André; Gustafsson, Jenny K; Ermund, Anna; Subramani, Durai B; Holmén-Larsson, Jessica M; Thomsson, Kristina A; Bergström, Joakim H; van der Post, Sjoerd; Rodriguez-Piñeiro, Ana M; Sjövall, Henrik; Bäckström, Malin; Hansson, Gunnar C

    2011-11-01

    In discussions on intestinal protection, the protective capacity of mucus has not been very much considered. The progress in the last years in understanding the molecular nature of mucins, the main building blocks of mucus, has, however, changed this. The intestinal enterocytes have their apical surfaces covered by transmembrane mucins and the whole intestinal surface is further covered by mucus, built around the gel-forming mucin MUC2. The mucus of the small intestine has only one layer, whereas the large intestine has a two-layered mucus where the inner, attached layer has a protective function for the intestine, as it is impermeable to the luminal bacteria.

  6. Detection of Low Adherence in Rural Tuberculosis Patients in China: Application of Morisky Medication Adherence Scale

    PubMed Central

    Xu, Minlan; Markström, Urban; Lyu, Juncheng; Xu, Lingzhong

    2017-01-01

    The detection and analysis of cases of low medication adherence is important for helping to control tuberculosis (TB). The purpose of this study was to detect low adherence in rural TB patients by using the eight-item Morisky Medication Adherence Scale of Chinese version (C-MMAS-8) and to further analyze the adherence-related variables. A total of 358 rural TB patients recruited through multi-stage randomized sampling participated in the survey. Data were collected by the use of interviewer-led questionnaires. First, the reliability and validity of the C-MMAS-8 were determined. Second, the adherence level was assessed, and factors related to low adherence were analyzed by using Pearson’s chi-square test and then in multiple logistic regression model. Finally, the prediction of the logistic model was assessed with Receiver Operating Characteristic (ROC) curves. The C-MMAS-8 could be used to detect low adherence in TB patients with good reliability and validity. By using the referred cutoff points of MMAS-8, it was found that more than one-third of the participants had low medication adherence. Further analysis revealed the variables of being older, a longer treatment time, and being depressive were significantly related to low adherence. The ROC of the model was assessed as good using the cutoff point. We conclude that appropriately tailored strategies are needed for health-care providers to help rural TB patients cope with low medication adherence. PMID:28257075

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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

  12. Parental education level is associated with clustering of metabolic risk factors in adolescents independently of cardiorespiratory fitness, adherence to the Mediterranean diet, or pubertal stage.

    PubMed

    Santos, Rute; Moreira, Carla; Abreu, Sandra; Lopes, Luís; Ruiz, Jonatan R; Moreira, Pedro; Silva, Pedro; Mota, Jorge

    2014-08-01

    Few studies have reported associations between clustering metabolic risk factors and socioeconomic status (SES) in youth. This study aimed to analyze the association between clustering metabolic risk factors and SES in adolescents. It was hypothesized that SES is inversely related to clustering metabolic risk factors. This 2009 cross-sectional school-based study investigated 517 Portuguese adolescents ages 15-18 years. The study considered the age- and sex-adjusted z-scores for the ratio of total cholesterol/high-density lipoprotein, homeostasis model, triglycerides, and systolic blood pressure, and a metabolic risk score was constructed by summing all the z-scores (≥1 standard deviation was considered high risk). Cardiorespiratory fitness was estimated by the 20 m shuttle-run test and dietary intake by a food frequency questionnaire. The best of parental education was used as a proxy measure of SES. The results showed that adolescents with low SES were more likely to have a high metabolic risk score (odds ratio [OR], 1.96; p < 0.020) regardless of cardiorespiratory fitness, adherence to the Mediterranean diet, or pubertal stage. In conclusion, a lower SES was associated with increased risk for a high metabolic risk score among Azorean adolescents after adjustment for pubertal stage, adherence to the Mediterranean diet, and cardiorespiratory fitness. Future health-promotion strategies among Azorean adolescents should consider the impact of SES on their health.

  13. Optical tweezers reveal relationship between microstructure and nanoparticle penetration of pulmonary mucus

    PubMed Central

    Kirch, Julian; Schneider, Andreas; Abou, Bérengère; Hopf, Alexander; Schaefer, Ulrich F.; Schneider, Marc; Schall, Christian; Wagner, Christian; Lehr, Claus-Michael

    2012-01-01

    In this study, the mobility of nanoparticles in mucus and similar hydrogels as model systems was assessed to elucidate the link between microscopic diffusion behavior and macroscopic penetration of such gels. Differences in particle adhesion to mucus components were strongly dependent on particle coating. Particles coated with 2 kDa PEG exhibited a decreased adhesion to mucus components, whereas chitosan strongly increased the adhesion. Despite such mucoinert properties of PEG, magnetic nanoparticles of both coatings did not penetrate through native respiratory mucus, resisting high magnetic forces (even for several hours). However, model hydrogels were, indeed, penetrated by both particles in dependency of particle coating, obeying the theory of particle mobility in an external force field. Comparison of penetration data with cryogenic scanning EM images of mucus and the applied model systems suggested particularly high rigidity of the mucin scaffold and a broad pore size distribution in mucus as reasons for the observed particle immobilization. Active probing of the rigidity of mucus and model gels with optical tweezers was used in this context to confirm such properties of mucus on the microscale, thus presenting the missing link between micro- and macroscopical observations. Because of high heterogeneity in the size of the voids and pores in mucus, on small scales, particle mobility will depend on adhesive or inert properties. However, particle translocation over distances larger than a few micrometers is restricted by highly rigid structures within the mucus mesh. PMID:23091027

  14. 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.

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

    PubMed

    Qin, Xiaofa; Deitch, Edwin A

    2015-01-22

    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.

  16. 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

  17. Comparative permeability of some acyclovir derivatives through native mucus and crude mucin dispersions.

    PubMed

    Legen; Kristl, A

    2001-08-01

    The permeability of some guanine derivatives (acyclovir [ACV], deoxyacyclovir [DCV], and their N-acetyl congeners) through native porcine mucus and crude porcine mucin dispersions (30% and 50% w/v) was investigated in two-compartment dialysis cells. High correlation between apparent permeability coefficients Papp of tested substances determined in these two models was observed, although the examined compounds permeated faster through the native mucus. It was also established that Papp values decrease with increasing hydrophilicity and molecular mass of the tested substances. Furthermore, the influence of some substances that affect mucus structure (cysteine, N-acetylcysteine [NCY], sodium taurocholate [ST], and sodium chloride) on the permeation rate of the examined compounds through mucus and mucin dispersions was examined. It was shown that the Papp values of guanine derivatives were generally lower after the addition of these substances to the native mucus and mucin dispersions, although the lowering effect was more pronounced in the case of native mucus.

  18. Simultaneous determination of allantoin and glycolic acid in snail mucus and cosmetic creams with high performance liquid chromatography and ultraviolet detection.

    PubMed

    El Mubarak, Mohamed Ahmed S; Lamari, Fotini N; Kontoyannis, Christos

    2013-12-27

    A new methodology for simultaneous quantitative analysis of allantoin and glycolic acid in snail mucus and cosmetic creams was developed. HPLC separation was achieved a Synergi-Hydro RP column within 7min using isocratic elution with potassium phosphate (pH 2.7; 10mM) at a flow rate of 0.7mL/min at 30°C. Sample pretreatment was performed by dilution of mucus or cosmetic cream in the elution buffer, heating at 60°C for 20min, adjusting the pH to 2.9 and purification with hexane extraction. Linearity was determined with spiked samples and the LLOQ values of 0.0125 and 0.2500mg/mL were determined for allantoin and glycolic acid, respectively. Accuracy and intra- and inter-day repeatability were studied at three levels of concentrations (0.04, 0.08 and 0.16mg/mL for allantoin and 0.1, 1.5 and 4.0mg/mL for glycolic acid) using spiked mucus and cream base samples; mean values of recovery were in the range of 96.81-102.42% in all matrices tested, whereas the respective RSDs (%Relative Standard Deviation) were less than 3.04% in all cases. Spiked mucus and cream samples were stable (RSD<4.16 and relative error<4.34%) at room temperature and at 4°C for 1 week and at -18°C for 6 months; samples were also stable after three freeze-thaw cycles. The method was applied to the analysis of different lots of snail mucus, and of three commercial creams containing snail mucus.

  19. A Beneficiary Role for Neuraminidase in Influenza Virus Penetration through the Respiratory Mucus

    PubMed Central

    Yang, Xiaoyun; Steukers, Lennert; Forier, Katrien; Xiong, Ranhua; Braeckmans, Kevin

    2014-01-01

    Swine influenza virus (SIV) has a strong tropism for pig respiratory mucosa, which consists of a mucus layer, epithelium, basement membrane and lamina propria. Sialic acids present on the epithelial surface have long been considered to be determinants of influenza virus tropism. However, mucus which is also rich in sialic acids may serve as the first barrier of selection. It was investigated how influenza virus interacts with the mucus to infect epithelial cells. Two techniques were applied to track SIV H1N1 in porcine mucus. The microscopic diffusion of SIV particles in the mucus was analyzed by single particle tracking (SPT), and the macroscopic penetration of SIV through mucus was studied by a virus in-capsule-mucus penetration system, followed by visualizing the translocation of the virions with time by immunofluorescence staining. Furthermore, the effects of neuraminidase on SIV getting through or binding to the mucus were studied by using zanamivir, a neuraminidase inhibitor (NAI), and Arthrobacter ureafaciens neuraminidase. The distribution of the diffusion coefficient shows that 70% of SIV particles were entrapped, while the rest diffused freely in the mucus. Additionally, SIV penetrated the porcine mucus with time, reaching a depth of 65 µm at 30 min post virus addition, 2 fold of that at 2 min. Both the microscopic diffusion and macroscopic penetration were largely diminished by NAI, while were clearly increased by the effect of exogenous neuraminidase. Moreover, the exogenous neuraminidase sufficiently prevented the binding of SIV to mucus which was reversely enhanced by effect of NAI. These findings clearly show that the neuraminidase helps SIV move through the mucus, which is important for the virus to reach and infect epithelial cells and eventually become shed into the lumen of the respiratory tract. PMID:25333824

  20. 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.

  1. 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

  2. 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

  3. Epithelial tethering of MUC5AC-rich mucus impairs mucociliary transport in asthma

    PubMed Central

    Bonser, Luke R.; Zlock, Lorna; Finkbeiner, Walter

    2016-01-01

    The development of pathologic mucus, which is not readily cleared from the airways, is an important contributor to the morbidity and mortality associated with asthma. It is not clear how the major airway mucins MUC5AC and MUC5B are organized within the mucus gel or how this gel contributes to airway obstruction in asthma. Here, we demonstrated that mucus plugs from individuals with fatal asthma are heterogeneous gels with distinct MUC5AC- and MUC5B-containing domains. Stimulation of cultured human bronchial epithelial cells with IL-13, a key mediator in asthma, induced the formation of heterogeneous mucus gels and dramatically impaired mucociliary transport. Impaired transport was not associated with defects in ciliary function but instead was related to tethering of MUC5AC-containing mucus gel domains to mucus-producing cells in the epithelium. Replacement of tethered mucus with untethered mucus restored mucociliary transport. Together, our results indicate that tethering of MUC5AC-containing domains to the epithelium causes mucostasis and likely represents a major cause of mucus plugging in asthma. PMID:27183390

  4. 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

    2016-09-06

    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.

  5. Effects of cathepsin K deficiency on intercellular junction proteins, luminal mucus layers, and extracellular matrix constituents in the mouse colon.

    PubMed

    Arampatzidou, Maria; Schütte, André; Hansson, Gunnar C; Saftig, Paul; Brix, Klaudia

    2012-12-01

    Cathepsin K has been shown to exhibit antimicrobial and anti-inflammatory activities in the mouse colon. To further elucidate its role, we used Ctsk-/- mice and demonstrated that the absence of cathepsin K was accompanied by elevated protein levels of related cysteine cathepsins (cathepsins B, L, and X) in the colon. In principle, such changes could result in altered subcellular localization; however, the trafficking of cysteine cathepsins was not affected in the colon of Ctsk-/- mice. However, cathepsin K deficiency affected the extracellular matrix constituents, as higher amounts of collagen IV and laminin were observed. Moreover, the localization pattern of the intercellular junction proteins E-cadherin and occludin was altered in the colon of Ctsk-/- mice, suggesting potential impairment of the barrier function. Thus, we used an ex vivo method for assessing the mucus layers and showed that the absence of cathepsin K had no influence on mucus organization and growth. The data of this study support the notion that cathepsin K contributes to intestinal homeostasis and tissue architecture, but the lack of cathepsin K activity is not expected to affect the mucus-depending barrier functions of the mouse colon. These results are important with regard to oral administration of cathepsin K inhibitors that are currently under investigation in clinical trials.

  6. 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

  7. Social work and medical care: electronic reminders to address adherence.

    PubMed

    Whisenhunt, Allison

    2014-01-01

    Social workers are often involved with patients and families around adherence, both to clinic appointments as well as to the medication regimen. An evidence-based practice project was created and implemented to determine the efficacy of electronic reminders such as text messaging on adherence. The implications of improving adherence can positively impact the patient on an individual level as well as reduce costs and increase revenue at a systems level.

  8. Kitchen table wisdom: a Freirian approach to medication adherence.

    PubMed

    Williams, Ann B; Burgess, Jane D; Danvers, Karina; Malone, Janice; Winfield, Subrena D; Saunders, Lois

    2005-01-01

    Most interventions to promote medication adherence are based on psychological theories of individual behavior. In contrast, this article describes the theory and practice of a socially based adherence intervention that is guided by the educational principles of Paolo Freire. This approach asserts that adherence is influenced by the patient's social context and attempts to improve adherence through identifying social constraints on adherence behavior. The program builds on the traditions of patient education through home nursing visits. Using a dialectic process of dialogue and problem solving and working with a team that includes a nurse and a peer-educator, patients are encouraged to act to change their social environment to support their desire to achieve high levels of medication adherence. This strategy does not replace, but rather supplements, traditional methods of understanding individual patient behavior and allows the patient and the nurse to consider potential solutions to adherence challenges in the larger social context.

  9. Carbachol-induced colonic mucus formation requires transport via NKCC1, K+ channels and CFTR

    PubMed Central

    Lindén, Sara K.; Alwan, Ala H.; Scholte, Bob J.; Hansson, Gunnar C.; Sjövall, Henrik

    2016-01-01

    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

  10. 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

  11. Role of nicotinic receptors and acetylcholine in mucous cell metaplasia, hyperplasia and airway mucus formation in vitro and in vivo

    PubMed Central

    Gundavarapu, Sravanthi; Wilder, Julie A.; Mishra, Neerad C.; Rir-sima-ah, Jules; Langley, Raymond J.; Singh, Shashi P.; Saeed, Ali Imran; Jaramillo, Richard J.; Gott, Katherine M.; Peña-Philippides, Juan Carlos; Harrod, Kevin S.; McIntosh, J. Michael; Buch, Shilpa; Sopori, Mohan L.

    2012-01-01

    Background Airway mucus hypersecretion is a key pathophysiological feature in number of lung diseases. Cigarette smoke/nicotine and allergens are strong stimulators of airway mucus; however, the mechanism of mucus modulation is unclear. Objectives Characterize the pathway by which cigarette smoke/nicotine regulates airway mucus and identify agents that decrease airway mucus. Methods IL-13 and gamma-aminobutyric acid receptors (GABAARs) are implicated in airway mucus. We examined the role of IL-13 and GABAARs in nicotine-induced mucus formation in normal human bronchial epithelial (NHBE) and A549 cells, and secondhand cigarette smoke and/or ovalbumin-induced mucus formation in vivo. Results Nicotine promotes mucus formation in NHBE cells; however, the nicotine-induced mucus formation is independent of IL-13 but sensitive to the GABAAR antagonist picrotoxin (PIC). Airway epithelial cells express α7/α9/α10 nicotinic acetylcholine receptors (nAChRs) and specific inhibition or knockdown of α7- but not α9/α10-nAChRs abrogates mucus formation in response to nicotine and IL-13. Moreover, addition of acetylcholine or inhibition of its degradation increases mucus in NHBE cells. Nicotinic but not muscarinic receptor antagonists block allergen or nicotine/cigarette smoke-induced airway mucus formation in NHBE cells and/or in mouse airways. Conclusions Nicotine-induced airway mucus formation is independent of IL-13 and α7-nAChRs are critical in airway mucous cell metaplasia/hyperplasia and mucus production in response to various pro-mucoid agents, including IL-13. In the absence of nicotine, acetylcholine may be the biological ligand for α7-nAChRs to trigger airway mucus formation. α7-nAChRs are downstream of IL-13 but upstream of GABAARα2 in the MUC5AC pathway. Acetylcholine and α-7-nAChRs may serve as therapeutic targets to control airway mucus. PMID:22578901

  12. 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

  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.

  14. 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.

  15. Coral mucus functions as an energy carrier and particle trap in the reef ecosystem.

    PubMed

    Wild, Christian; Huettel, Markus; Klueter, Anke; Kremb, Stephan G; Rasheed, Mohammed Y M; Jørgensen, Bo B

    2004-03-04

    Zooxanthellae, endosymbiotic algae of reef-building corals, substantially contribute to the high gross primary production of coral reefs, but corals exude up to half of the carbon assimilated by their zooxanthellae as mucus. Here we show that released coral mucus efficiently traps organic matter from the water column and rapidly carries energy and nutrients to the reef lagoon sediment, which acts as a biocatalytic mineralizing filter. In the Great Barrier Reef, the dominant genus of hard corals, Acropora, exudes up to 4.8 litres of mucus per square metre of reef area per day. Between 56% and 80% of this mucus dissolves in the reef water, which is filtered through the lagoon sands. Here, coral mucus is degraded at a turnover rate of at least 7% per hour. Detached undissolved mucus traps suspended particles, increasing its initial organic carbon and nitrogen content by three orders of magnitude within 2 h. Tidal currents concentrate these mucus aggregates into the lagoon, where they rapidly settle. Coral mucus provides light energy harvested by the zooxanthellae and trapped particles to the heterotrophic reef community, thereby establishing a recycling loop that supports benthic life, while reducing loss of energy and nutrients from the reef ecosystem.

  16. Helicobacter pylori infection does not reduce the viscosity of human gastric mucus gel.

    PubMed Central

    Markesich, D C; Anand, B S; Lew, G M; Graham, D Y

    1995-01-01

    The mechanism by which Helicobacter pylori undermines host defence mechanisms is unclear. Several in vitro studies using soluble mucins have suggested that H pylori may compromise mucus function. Gastric mucus gel was obtained from 13 H pylori infected patients; six untreated subjects and seven after eradication of the infection. Gastric mucus is a non-Newtonian substance in that its viscosity changes with changing rates of shear, requiring mucus viscosity to be measured in a rotational cone-plate microviscometer. Viscosity was measured at shear rates varying from 1.15 s-1 to 46 s-1. The gastric mucus viscosity was significantly higher in patients infected with H pylori compared with mucus gel obtained after eradication of the infection. The results of our study suggest that the previous studies using in vitro methods involving soluble mucins or its components may have lead to erroneous conclusions about the in vivo interactions of H pylori and gastric mucus gel. The present findings argue against the hypothesis that degradation of gastric mucus by H pylori is important in the pathogenesis of peptic ulcer. PMID:7698685

  17. Quantitative post-coital test: sperm counts in cervical mucus after enzymatic liquefaction.

    PubMed

    de Agostini, A; Tawfik, E; Campana, A

    1996-02-01

    The post-coital test involves direct microscopic examination of sperm number and motility in cervical mucus. The results depend on the quality of the mucus and the distribution of spermatozoa within the sample. To progress from such qualitative data to quantitative measurements of the spermatozoa present in post-coital mucus, we have developed methods to measure sperm concentrations in enzymatically liquefied post-coital cervical mucus. The mucus score and sperm motility were measured prior to mucus liquefaction, and, together with sperm concentration, they allowed the calculation of the total number of motile spermatozoa present. A combination of bromelin and glycosidases proved to be more efficient in achieving reliable mucus liquefaction than treatment with bromelin alone, and was used to liquefy a series of 36 post-coital test samples. Total sperm numbers ranged between 19 x 10(3) and 16.8 x 10(6). Of the samples, 75% contained < 3 x 10(6) spermatozoa, and 39% contained < 1 x 10(6) spermatozoa. Sperm motility was very high in these samples, except for a distinct subset of samples (19%) in which the total sperm motility was markedly decreased ( < 20%). The measurement of sperm concentration in liquefied cervical mucus will help to determine normal values for the post-coital test, and to estimate the number of motile spermatozoa reaching the upper female genital tract.

  18. 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…

  19. 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.

  20. Relation of ventilatory impairment and of chronic mucus hypersecretion to mortality from obstructive lung disease and from all causes.

    PubMed Central

    Lange, P; Nyboe, J; Appleyard, M; Jensen, G; Schnohr, P

    1990-01-01

    The relation of ventilatory impairment and chronic mucus hypersecretion to death from all causes and death from obstructive lung disease (chronic bronchitis, emphysema and asthma) was studied in 13,756 men and women randomly selected from the general population of the City of Copenhagen. During the 10 year follow up 2288 subjects died. In 164 subjects obstructive lung disease was considered to be an underlying or a contributory cause of death (obstructive lung disease related death); in 73 subjects it was considered to be the underlying cause of death (obstructive lung disease death). Forced expiratory volume in one second, expressed as a percentage of the predicted value (FEV1% pred), and the presence of chronic phlegm were used to characterise ventilatory function and chronic mucus hypersecretion respectively. For mortality analysis the proportional hazards regression model of Cox was used; it included age, sex, pack years, inhalation habit, body mass index, alcohol consumption, and the presence or absence of asthma, heart disease, and diabetes mellitus as confounding factors. By comparison with subjects with an FEV1 of 80% pred or more, subjects with an FEV1 below 40% pred had increased risk of dying from all causes (relative risk (RR) = 5.0 for women, 2.7 for men), a higher risk of obstructive lung disease related death (RR = 57 for women, 34 for men), and a higher risk of obstructive lung disease death (RR = 101 for women, 77 for men). Chronic mucus hypersecretion was associated with only a slightly higher risk of death from all causes (RR = 1.1 for women, 1.3 for men). The association between chronic mucus hypersecretion and obstructive lung disease death varied with the level of ventilatory function, being weak in subjects with normal ventilatory function (for an FEV1 of 80% pred the RR was 1.2), but more pronounced in subjects with reduced ventilatory function (for an FEV1 of 40% pred the RR was 4.2). A similar though statistically non-significant trend was

  1. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues

    PubMed Central

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

    2009-01-01

    Mucus is a viscoelastic and adhesive gel that protects the lung airways, gastrointestinal (GI) tract, vagina, eye and other mucosal surfaces. Most foreign particulates, including conventional particle-based drug delivery systems, are efficiently trapped in human mucus layers by steric obstruction and/or adhesion. Trapped particles are typically removed from the mucosal tissue within seconds to a few hours depending on anatomical location, thereby strongly limiting the duration of sustained drug delivery locally. A number of debilitating diseases could be treated more effectively and with fewer side effects if drugs and genes could be more efficiently delivered to the underlying mucosal tissues in a controlled manner. This review first describes the tenacious mucus barrier properties that have precluded the efficient penetration of therapeutic particles. It then reviews the design and development of new mucus-penetrating particles that may avoid rapid mucus clearance mechanisms, and thereby provide targeted or sustained drug delivery for localized therapies in mucosal tissues. PMID:19133304

  2. 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.

  3. Dietary Myrtle (Myrtus communis L.) improved non-specific immune parameters and bactericidal activity of skin mucus in rainbow trout (Oncorhynchus mykiss) fingerlings.

    PubMed

    Mansouri Taee, Hadis; Hajimoradloo, Abdolmajid; Hoseinifar, Seyed Hossein; Ahmadvand, Hassan

    2017-03-19

    The present study examined the effects of dietary Myrtle (Myrtus communis L.) on non-specific immune parameters and bactericidal activity of skin mucus in rainbow trout (Oncorhynchus mykiss) fingerlings. Three hundred and sixty fingerlings (6.50 ± 0.55 g (were distributed in twelve cages (65 × 65 × 65 cm) with a metal framework. The study included four treatments repeated in triplicates. The treatments were feeding trouts with experimental diets containing different levels (0, 0.5, 1 and 1.5%) of Myrtle powder. The fingerlings were fed on experimental diet for sixty days and then skin mucus non-specific immune parameters as well as bactericidal activity were measured. At the end of the trial, the highest skin mucus soluble protein level was observed in group fed with 1.5% Myrtle (P < 0.05). The alkaline phosphatase (ALP) activity was significantly increased in fish groups fed 1 and 1.5% Myrtle compared with the control group (P < 0.05). However, evaluation of skin mucus lysozyme activity showed no significant difference between treatments and control group (P > 0.05). Also, no antibacterial activity was detected against Escherichia coli, Staphylococcus aureus and Salmonella enterica in all treatments and control group. Whereas skin mucus of rainbow trout showed antimicrobial activity against fish pathogens (Aeromonas hydrophila and Yersinia ruckeri) in 1 and 1.5% Myrtle treatments. These results indicated beneficial effects of dietary Myrtle on mucosal immune parameters of fingerling rainbow trout.

  4. Antimicrobial properties of mucus from the brown garden snail Helix aspersa.

    PubMed

    Pitt, S J; Graham, M A; Dedi, C G; Taylor-Harris, P M; Gunn, A

    2015-01-01

    Research into naturally occurring antimicrobial substances has yielded effective treatments. One area of interest is peptides and proteins produced by invertebrates as part of their defence system, including the contents of mollusc mucus. Mucus produced by the African giant land snail, Achatina fulica has been reported to contain two proteins with broad-spectrum antibacterial activity. Mucus from the brown garden snail, Helix aspersa, appears to have skin regeneration properties. This study sought to investigate the antimicrobial properties of H. aspersa mucus. Mucus was collected from H. aspersa snails, diluted in phosphate-buffered saline (PBS), with the supernatant tested against a wide range of organisms in a disc-diffusion antimicrobial assay. This was followed with comparative experiments involving A. fulica, including bacteriophage assays. Mucus from both species of snail was passed through a series of protein size separation columns in order to determine the approximate size of the antimicrobial substance. Electrophoresis was also carried out on the H. aspersa mucus. Results indicated that H. aspersa mucus had a strong antibacterial effect against several strains of Pseudomonas aeruginosa and a weak effect against Staphylococcus aureus. Mucus from A. fulica also inhibited the growth of S. aureus, but the broad spectrum of activity reported by other workers was not observed. Antimicrobial activity was not caused by bacteriophage. Size separation experiments indicated that the antimicrobial substance(s) in H. aspersa were between 30 and 100 kDa. Electrophoresis revealed two proteins in this region (30-40 kDa and 50-60 kDa). These do not correspond with antimicrobial proteins previously reported in A. fulica. This study found one or more novel antimicrobial agents in H. aspersa mucus, with a strong effect against P. aeruginosa.

  5. 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

  6. 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.

  7. 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.

  8. Medication adherence: process for implementation

    PubMed Central

    Mendys, Phil; Zullig, Leah L; Burkholder, Rebecca; Granger, Bradi B; Bosworth, Hayden B

    2014-01-01

    Improving medication adherence is a critically important, but often enigmatic objective of patients, providers, and the overall health care system. Increasing medication adherence has the potential to reduce health care costs while improving care quality, patient satisfaction and health outcomes. While there are a number of papers that describe the benefits of medication adherence in terms of cost, safety, outcomes, or quality of life, there are limited reviews that consider how best to seamlessly integrate tools and processes directed at improving medication adherence. We will address processes for implementing medication adherence interventions with the goal of better informing providers and health care systems regarding the safe and effective use of medications. PMID:25114513

  9. Mannitol-guided delivery of Ciprofloxacin in artificial cystic fibrosis mucus model.

    PubMed

    Yang, Yan; Tsifansky, Michael D; Shin, Sooyoung; Lin, Qingnuo; Yeo, Yoon

    2011-06-01

    Abnormal airway mucus presents a significant challenge for inhalational drug delivery. Recognizing the thick and tenacious airway mucus seen in the cystic fibrosis (CF) patients as a critical barrier to effective drug delivery, both into the mucus layer itself as well as across that layer to the underlying airway epithelium, we hypothesize that mannitol or NaCl can form inhalable drug carriers, improve drug penetration into the mucus, and ultimately enhance the drug's therapeutic effect. The objective of this study is to test whether mannitol and NaCl particles, as inhalable drug carriers, improve drug delivery into and enhance a drug's activity within a mucus-like material. Microparticles containing Ciprofloxacin (Cipro), an active ingredient, and either mannitol or NaCl were produced by spray-drying. Cipro encapsulated in mannitol particles (Cipro-mannitol) was significantly more effective at killing Pseudomonas aeruginosa (P. aeruginosa) grown in artificial mucus (AM) than Cipro encapsulated in either NaCl particles (Cipro-NaCl) or in hydrophobic particles consisting of dipalmitoylphosphatidylcholine (DPPC), albumin, and lactose (Cipro-DAL). The relatively high antibacterial effectiveness of Cipro-mannitol was not due to the effect of mannitol on bacteria or on Cipro. Rather, the unique performance of the mannitol-based particles in AM is attributable to its ability to increase local water content in the AM and enhance drug penetration into it. Mannitol is a promising excipient for inhalable microparticles that facilitate the drug delivery into the CF mucus.

  10. An investigation into the role of mucus thickness on mucoadhesion in the gastrointestinal tract of pig.

    PubMed

    Varum, Felipe J O; Veiga, Francisco; Sousa, João S; Basit, Abdul W

    2010-07-11

    Mucoadhesion in the gastrointestinal tract is a complex phenomenon and both formulation and physiological features need to be well understood and considered. Mucus thickness has been inferred to play a role in this process; however no definitive influence has been established. This study aimed to investigate the influence of mucus thickness on the mucoadhesion process, using a large animal (pig) as a model to closely resemble the human physiological features. The mucus thickness of different regions of the gastrointestinal tract of pig was fully measured by means of a histochemical method (hematoxilin/eosin) employing cryostat sections. Mucoadhesion was evaluated ex vivo on porcine mucosa by tensiometry using a polyacrylic acid polymer (Carbopol 974P NF) as a mucoadhesive model material, both in a dry and swollen state. Mucus was thickest in the stomach (body 67.9+/-54.7 microm) and mucus thickness increased from proximal to distal segments in both the small intestine (duodenum 25.9+/-11.8 microm, ileum 31.0+/-15.7 microm) and large intestine (caecum 19.4+/-8.7 microm, ascending colon 31.9+/-17.2 microm, descending colon 35.1+/-16.0 microm and rectum 40.8+/-12.5 microm). Swollen polymer exhibited lower mucoadhesion than the dry form in all sections analysed. Mucus thickness plays a role on the mucoadhesion, as thicker mucus provides deeper polymer chain diffusion and entanglements; however, other factors are also involved in this complex process.

  11. Targeted epigenetic editing of SPDEF reduces mucus production in lung epithelial cells.

    PubMed

    Song, Juan; Cano-Rodriquez, David; Winkle, Melanie; Gjaltema, Rutger A F; Goubert, Désirée; Jurkowski, Tomasz P; Heijink, Irene H; Rots, Marianne G; Hylkema, Machteld N

    2017-03-01

    Airway mucus hypersecretion contributes to the morbidity and mortality in patients with chronic inflammatory lung diseases. Reducing mucus production is crucial for improving patients' quality of life. The transcription factor SAM-pointed domain-containing Ets-like factor (SPDEF) plays a critical role in the regulation of mucus production and, therefore, represents a potential therapeutic target. This study aims to reduce lung epithelial mucus production by targeted silencing SPDEF using the novel strategy, epigenetic editing. Zinc fingers and CRISPR/dCas platforms were engineered to target repressors (KRAB, DNA methyltransferases, histone methyltransferases) to the SPDEF promoter. All constructs were able to effectively suppress both SPDEF mRNA and protein expression, which was accompanied by inhibition of downstream mucus-related genes [anterior gradient 2 (AGR2), mucin 5AC (MUC5AC)]. For the histone methyltransferase G9A, and not its mutant or other effectors, the obtained silencing was mitotically stable. These results indicate efficient SPDEF silencing and downregulation of mucus-related gene expression by epigenetic editing, in human lung epithelial cells. This opens avenues for epigenetic editing as a novel therapeutic strategy to induce long-lasting mucus inhibition.

  12. 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.

  13. 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.

  14. Scalable method to produce biodegradable nanoparticles that rapidly penetrate human mucus.

    PubMed

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

    2013-09-10

    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 hydrophilic 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.

  15. Methods to determine the interactions of micro- and nanoparticles with mucus.

    PubMed

    Grießinger, Julia; Dünnhaupt, Sarah; Cattoz, Beatrice; Griffiths, Peter; Oh, Sejin; Borrós i Gómez, Salvador; Wilcox, Matthew; Pearson, Jeffrey; Gumbleton, Mark; Abdulkarim, Muthanna; Pereira de Sousa, Irene; Bernkop-Schnürch, Andreas

    2015-10-01

    The present review provides an overview of methods and techniques for studying interactions of micro- and nanoparticulate drug delivery system with mucus. Nanocarriers trapped by mucus are featuring a change in particle size and zeta potential that can be utilized to predict their mucus permeation behavior. Furthermore, interactions between nanoparticulate drug delivery systems and mucus layer modify the viscoelasticity of mucus which can be detected via rheological studies and quartz crystal microbalance with dissipation monitoring (QCM-D) analysis. Having a closer look at molecular interactions between drug carrier and mucus small-angle neutron scattering (SANS) is an appropriate analysis technique. Moreover, different methods to determine particle diffusion in mucus such as the newly established Transwell diffusion system, rotating silicone tube technique, multiple-particle tracking (MPT) and diffusion NMR are summarized within this review. The explanations and discussed pros and cons of collated methods and techniques should provide a good starting point for all those looking forward to move in this interesting field.

  16. Patient-related Factors Predicting HIV Medication Adherence among Men and Women with Alcohol Problems

    PubMed Central

    PARSONS, JEFFREY T.; ROSOF, ELANA; MUSTANSKI, BRIAN

    2007-01-01

    The study explored the relationship between HIV medication adherence and alcohol, cognitive, social and affective factors in 272 persons with alcohol problems. Alcohol and cognitive factors significantly differentiated those who did and did not adhere. Specifically, adherence confidence and number of drinks emerged as subfactors driving the associations to adherence. Among those who were less than perfectly adherent (n = 154), only alcohol factors predicted levels of nonadherence. Cognitive factors play a role in understanding some of the differences between those who do and do not adhere to their HIV medications, but they do not differentiate among levels of nonadherence. PMID:17284499

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

    PubMed Central

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

    2016-01-01

    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) with a layer of endogenous mucus were doped with topically deposited GNRs (80×22nm), 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. PMID:27746581

  18. 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.

  19. 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.

  20. Unraveling the Role of Surface Mucus-Binding Protein and Pili in Muco-Adhesion of Lactococcus lactis

    PubMed Central

    Duviau, Marie-Pierre; Meyrand, Mickael; Guérardel, Yann; Castelain, Mickaël; Loubière, Pascal; Chapot-Chartier, Marie-Pierre; Dague, Etienne; Mercier-Bonin, Muriel

    2013-01-01

    Adhesion of bacteria to mucus may favor their persistence within the gut and their beneficial effects to the host. Interactions between pig gastric mucin (PGM) and a natural isolate of Lactococcus lactis (TIL448) were measured at the single-cell scale and under static conditions, using atomic force microscopy (AFM). In parallel, these interactions were monitored at the bacterial population level and under shear flow. AFM experiments with a L. lactis cell-probe and a PGM-coated surface revealed a high proportion of specific adhesive events (60%) and a low level of non-adhesive ones (2%). The strain muco-adhesive properties were confirmed by the weak detachment of bacteria from the PGM-coated surface under shear flow. In AFM, rupture events were detected at short (100−200 nm) and long distances (up to 600−800 nm). AFM measurements on pili and mucus-binding protein defective mutants demonstrated the comparable role played by these two surface proteinaceous components in adhesion to PGM under static conditions. Under shear flow, a more important contribution of the mucus-binding protein than the pili one was observed. Both methods differ by the way of probing the adhesion force, i.e. negative force contact vs. sedimentation and normal-to-substratum retraction vs. tangential detachment conditions, using AFM and flow chamber, respectively. AFM blocking assays with free PGM or O-glycan fractions purified from PGM demonstrated that neutral oligosaccharides played a major role in adhesion of L. lactis TIL448 to PGM. This study dissects L. lactis muco-adhesive phenotype, in relation with the nature of the bacterial surface determinants. PMID:24260308

  1. Psychological perspective of medication adherence in transplantation

    PubMed Central

    De Pasquale, Concetta; Veroux, Massimiliano; Fornaro, Michele; Sinagra, Nunzia; Basile, Giusi; Gozzo, Cecilia; Santini, Roberta; Costa, Alessandra; Pistorio, Maria Luisa

    2016-01-01

    AIM To identify the risk factors and the post-transplant psychological symptoms that affect adherence to therapy in a population of kidney transplant recipients. METHODS The study examined the psychological variables likely responsible for the non-adherent behavior using a psychological-psychiatric assessment, evaluation of the perception of patients’ health status, and an interview regarding the anti-rejection drug therapy assumption. The study included 74 kidney transplant recipients. RESULTS Individuals with a higher level of education and more years since transplantation showed better mental balance. Regarding gender, women appeared to be less adherent to therapy. Further, the years since transplantation adversely affected the proper pharmacological assumption. Adherence to therapy did not significantly change with the mental health index. CONCLUSION The biopsychosocial illness model provides a conceptual frame of reference in which biological, psychological, and social aspects take on the same importance in the adherence to treatment protocols. For effective management, it is necessary to understand the patients’ personal experiences, their assumptions about the disease, health status perception, and mood, and to identify any “barriers” that could cause them to become noncompliant. PMID:28058225

  2. 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

  3. Bipolar disorder: medication adherence and life contentment.

    PubMed

    Darling, Carol Anderson; Olmstead, Spencer B; Lund, Victoria E; Fairclough, Jaime F

    2008-06-01

    Using family stress theory, we examined the influence of family and health stress, level of coping, and internal health locus of control upon the life contentment of individuals diagnosed with bipolar disorder (BPD) who were either adherent or nonadherent to their medication regimens. A survey-interview design was used with a sample of 100 individuals diagnosed with BPD; 50 participants were adherent to their medication and 50 were considered nonadherent. The results indicated that the adherent group had fewer health problems and more resources for coping with stress, possessed a stronger belief that their own behaviors controlled their health status, and had higher life contentment compared to nonadherent participants. For the participants in this study, internal health locus of control had the greatest total effect on life contentment followed by family coping. Implications included the need to comprehensively assess each individual regarding the multiple factors in one's life that influence an effective treatment regimen.

  4. 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...

  5. 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...

  6. Regulation of airway surface liquid volume and mucus transport by active ion transport.

    PubMed

    Tarran, Robert

    2004-01-01

    Mucus clearance is an important component of the lung's innate defense against disease, and the ability of the airways to clear mucus is strongly dependent on the volume of liquid on airway surfaces. Whether airway surface liquid (ASL) volume is maintained by passive surface forces or by active ion transport is controversial yet crucial to the understanding of how this system operates in both health and disease. In support of active ion transport being the major determinant of ASL volume, we have demonstrated that normal airway epithelia sense and autoregulate ASL height (volume) by adjusting the rates of Na+ absorption and Cl- secretion to maintain mucus transport.

  7. Clinical significance of airway mucus hypersecretion in chronic obstructive pulmonary disease

    PubMed Central

    Tian, Pan-wen; Wen, Fu-qiang

    2015-01-01

    Airway mucus hypersecretion is one of the most important features of chronic obstructive pulmonary disease (COPD). Airway mucus hypersecretion in COPD patients results in outcomes such as rapid decline of lung function, poor quality of life, and high rate of acute exacerbation, hospitalization and mortality. Nonpharmacologic treatments for airway mucus hypersecretion in COPD include smoking cessation and physical rehabilitation. Pharmacologic therapies include expectorants, mucolytics, methylxanthines, beta-adrenergic receptor agonists, anticholinergics, glucocorticoids, phosphodiesterase-4 inhibitors, antioxidants, and antibiotics. Novel drugs with promising prospects are currently under clinical trials. PMID:27847895

  8. Static friction of porous bioceramic β-TCP on intestinal mucus films

    NASA Astrophysics Data System (ADS)

    Wang, Xin-Yu; Han, Ying-Chao; Jiang, Xin; Dai, Hong-Lian; Li, Shi-Pu

    2006-09-01

    The static friction behavior between a porous bioceramic material and an intestinal mucus film was investigated in order to develop a new intestine robotic endoscope. Here, the friction couple is porous β-tricalcium phosphate (β-TCP) and an artificial intestine mucus film. The effect of pore size of the β-TCP material on the friction behavior is investigated. The results illustrated that in this friction system there is a relatively small normal force upon the intestinal mucus film of the intestine wall during locomotion. The maximum static friction force in this friction couple varies with the pore size of the porous β-TCP material.

  9. Vaginal mucus from ewes treated with progestogen sponges affects quality of ram spermatozoa.

    PubMed

    Manes, Jorgelina; Ríos, Glenda; Fiorentino, María Andrea; Ungerfeld, Rodolfo

    2016-03-15

    The use of intravaginal sponges (IS) to synchronize estrous onset in ewes provokes vaginitis, an increase in the vaginal bacterial load, and growth of bacterial species that are not present during spontaneous estrous behavior. The objective of the study was to compare the functional sperm parameters after incubating it with mucus collected from the vagina of ewes during spontaneous estrus or estrous synchronized with IS. Pooled spermatozoa were co-incubated with: (1) vaginal mucus collected from ewes in spontaneous estrus; (2) vaginal mucus collected from ewes in estrus pretreated with progestogen-impregnated IS; (3) synthetic mucus; and (4) medium without mucus as a control group. Sperm samples were evaluated after incubating it for 30 and 90 minutes. The number of colony-forming units (CFUs/mL), pH, and osmolality were greater in the mucus collected from ewes treated with IS than from those untreated (P = 0.046; P < 0.0001, and P < 0.0001, respectively). The percentage of sperm with progressive motility was lower after incubation with vaginal mucus collected from estrous ewes treated with IS than in the other three treatments both, 30 and 90 minutes after incubation (P = 0.0009 and P < 0.0001, respectively). The sample incubated for 30 minutes with mucus from ewes treated with IS had a lower percentage of sperm with intact plasma membrane than all the other treatments (P < 0.0001). The percentage of sperm with functional membrane was significantly lower in the sample incubated for 30 minutes with vaginal mucus from ewes treated with IS than in the other three treatments (P < 0.0001). After 90 minutes, the percentage was still lower than that in the sample collected from ewes during their spontaneous estrus (P = 0.0005). The lowest percentages of sperm with acrosome damage were observed in sperm incubated with mucus collected from sheep in spontaneous estrus for 30 and 90 minutes (P < 0.0001 and P = 0.008, respectively). The percentage of apoptotic spermatozoa was

  10. 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

  11. Purification and Characterization of a Surface Protein from Lactobacillus fermentum 104R That Binds to Porcine Small Intestinal Mucus and Gastric Mucin

    PubMed Central

    Rojas, Maurilia; Ascencio, Felipe; Conway, Patricia L.

    2002-01-01

    An adhesion-promoting protein involved in the binding of Lactobacillus fermentum strain 104R to small intestinal mucus from piglets and to partially purified gastric mucin was isolated and characterized. Spent culture supernatant fluid and bacterial cell wall extracts were fractionated by ammonium sulfate precipitation and gel filtration. The active fraction was purified by affinity chromatography. The adhesion-promoting protein was detected in the fractions by adhesion inhibition and dot blot assays and visualized by polyacrylamide gel electrophoresis (PAGE), sodium dodecyl sulfate-PAGE, and Western blotting with horseradish peroxidase-labeled mucus and mucin. The active fraction was characterized by estimating the relative molecular weight and by assessing the presence of carbohydrates in, and heat sensitivity of, the active region of the adhesion-promoting protein. The purified protein was digested with porcine trypsin, and the peptides were purified in a SMART system. The peptides were tested for adhesion to horseradish peroxidase-labeled mucin by using the dot blot adhesion assay. Peptides which bound mucin were sequenced. It was shown that the purified adhesion-promoting protein on the cell surface of L. fermentum 104R is extractable with 1 M LiCl and low concentrations of lysozyme but not with 0.2 M glycine. The protein could be released to the culture supernatant fluid after 24 h of growth and had affinity for both small intestinal mucus and gastric mucin. In the native state this protein was variable in size, and it had a molecular mass of 29 kDa when denatured. The denatured protein did not contain carbohydrate moieties and was not heat sensitive. Alignment of amino acids of the adhering peptides with sequences deposited in the EMBL data library showed poor homology with previously published sequences. The protein represents an important molecule for development of probiotics. PMID:11976105

  12. Adherence in the CAPRISA 004 tenofovir gel microbicide trial.

    PubMed

    Mansoor, Leila Essop; Abdool Karim, Quarraisha; Yende-Zuma, Nonhlanhla; MacQueen, Kathleen M; Baxter, Cheryl; Madlala, Bernadette T; Grobler, Anneke; Abdool Karim, Salim S

    2014-05-01

    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 17,031 monthly visits. On average women reported five 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.

  13. 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.

  14. Correlates of Pediatric CPAP Adherence

    PubMed Central

    Hawkins, Stephen M.M.; Jensen, Emily L.; Simon, Stacey L.; Friedman, Norman R.

    2016-01-01

    Study Objectives: Obstructive sleep apnea (OSA) is a common pediatric condition characterized by recurrent partial or complete cessation of airflow during sleep, typically due to inadequate upper airway patency. Continuous positive airway pressure (CPAP) is a therapeutic option that reduces morbidity. Despite efforts to promote use, CPAP adherence is poor in both pediatric and adult populations. We sought to determine whether demographics, insurance status, OSA severity, therapeutic pressure, or comorbid conditions were associated with pediatric CPAP adherence. Methods: A retrospective review of adherence download data was performed on all pediatric patients with initiation or adjustment of CPAP treatment over a one-year period with documented in-laboratory CPAP titration. Patients were grouped as CPAP adherent or non-adherent, where adherence was defined as > 70% nightly use and average usage ≥ 4 hours per night. Differences between the groups were analyzed by χ2 test. Results: Overall, nearly half of participants were CPAP adherent (49%, 69/140). Of the demographic data collected (age, ethnicity, sex, insurance status), only female sex was associated with better adherence (60.9% vs 39.5% of males adherent; odds ratio [OR] = 2.41, 95%CI = 1.20–4.85; p = 0.01). Severity of OSA (diagnostic apnea-hypopnea index [AHI] and degree of hypoxemia), therapeutic pressure, and residual AHI did not impact CPAP adherence (p > 0.05). Patients with developmental delay (DD) were more likely to be adherent with CPAP than those without a DD diagnosis (OR = 2.55, 95%CI = 1.27–5.13; p = 0.007). Female patients with trisomy 21 tended to be more adherent, but this did not reach significance or account for the overall increased adherence associated with female sex. Conclusions: Our study demonstrates that adherence to CPAP therapy is poor but suggests that female sex and developmental delay are associated with better adherence. These findings support efforts to understand the

  15. Forgiveness of non-adherence to HIV-1 antiretroviral therapy.

    PubMed

    Shuter, Jonathan

    2008-04-01

    Superior adherence to HIV-1 antiretroviral therapy is a mainstay of successful HIV management. Studies performed in the early era of highly active antiretroviral therapy demonstrated the need for > or =95% adherence in order to achieve and sustain viral suppression. High rates of viral suppression have been observed at more moderate levels of adherence with newer antiretroviral regimens. The term 'forgiveness' is being used to describe the ability of a regimen to achieve and sustain viral suppression, despite suboptimal adherence. A variety of pharmacological, viral and host properties determine the level of forgiveness of any specific regimen. As the choice of treatment options continues to expand, forgiveness of non-adherence is likely to emerge as an increasingly important factor in therapeutic decision-making.

  16. Mucus and pepsin role in gastric damage prevention by H2-receptor antagonists and antiulcer drugs.

    PubMed

    Impicciatore, M; Morini, G; Chiavarini, M; Plazzi, P V; Agosti, A; Soldani, G

    1984-01-01

    The effects of cimetidine and ranitidine, alone or combined with sulglycotide or carbenoxolone, and those of 16,16-dimethyl prostaglandin E2 were investigated on mucosal lesions induced in pylorus-ligated rats. The drugs were administered orally after pylorus ligation; 3 hr later the animals were killed, the stomachs removed and examined for the presence of mucosal lesions. Volume, pH, total acidity, pepsin, free and barrier mucus were determined. H2-antagonists both at nonantisecretory and antisecretory doses failed to prevent gastric mucosal lesions or to affect significantly mucus and pepsin. Sulglycotide and carbenoxolone inhibited pepsin secretion, the latter enhanced barrier mucus and both reduced lesion severity. A nearly complete prevention of mucosal damage was observed after anti-secretory doses of cimetidine plus sulglycotide or carbenoxolone. Data obtained compared with those of 16,16-dimethyl prostaglandin E2 suggest that mucus and pepsin might have a partial role in ulcer prevention.

  17. A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility.

    PubMed

    Desai, Mahesh S; Seekatz, Anna M; Koropatkin, Nicole M; Kamada, Nobuhiko; Hickey, Christina A; Wolter, Mathis; Pudlo, Nicholas A; Kitamoto, Sho; Terrapon, Nicolas; Muller, Arnaud; Young, Vincent B; Henrissat, Bernard; Wilmes, Paul; Stappenbeck, Thaddeus S; Núñez, Gabriel; Martens, Eric C

    2016-11-17

    Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota, and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome, and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics.

  18. Lectin histochemical aspects of mucus function in the oesophagus of the reticulated python (Python reticulatus).

    PubMed

    Meyer, W; Luz, S; Schnapper, A

    2009-08-01

    Using lectin histochemistry, the study characterizes basic functional aspects of the mucus produced by the oesophageal epithelium of the Reticulated python (Python reticulatus). Reaction staining varied as related to the two epithelium types present, containing goblet cells and ciliary cells. Remarkable intensities were achieved especially in the luminal mucus layer and the fine mucus covering the epithelial ciliary border for Con A (alpha-D-Man; alpha-D-Glc) as part of neutral glycoproteins, Limax flavus agglutinin (NeuNac = NeuNgc), emphasizing that water binding hyaluronan provides a hydrated interface conductive to the passage of material and UEA-I (alpha-L-Fuc), corroborating the view that fucose-rich highly viscous mucus is helpful against mechanical stress during prey transport.

  19. Topical corticosteroids do not revert the activated phenotype of eosinophils in eosinophilic esophagitis but decrease surface levels of CD18 resulting in diminished adherence to ICAM-1, ICAM-2, and endothelial cells.

    PubMed

    Lingblom, Christine; Bergquist, Henrik; Johnsson, Marianne; Sundström, Patrik; Quiding-Järbrink, Marianne; Bove, Mogens; Wennerås, Christine

    2014-12-01

    Swallowed topical corticosteroids are the standard therapy for eosinophilic esophagitis (EoE) in adults. Eosinophils in the blood of untreated EoE patients have an activated phenotype. Our aim was to determine if corticosteroids restore the phenotype of eosinophils to a healthy phenotype and if certain cell-surface molecules on blood eosinophils correlate with eosinophilic infiltration of the esophagus. Levels of eight surface markers on eosinophils from treated and untreated EoE patients were determined by flow cytometry and analyzed using multivariate methods of pattern recognition. Corticosteroid-treated EoE patients' eosinophils had decreased levels of CD18 compared to both untreated patients and healthy controls, but maintained their activated phenotype. CD18 expression correlated positively with eosinophil numbers in the esophagus and promoted the adherence of eosinophils to ICAM-1, ICAM-2, and to endothelial cells. The diminished expression of CD18 may be one mechanism behind the reduced entry of eosinophils into the esophagus in corticosteroid-treated EoE patients.

  20. 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

  1. [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.

  2. 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

  3. Adherence as a language game.

    PubMed

    Kolberg, Espen Skarstein

    2017-03-02

    Non-adherence, i.e. medication intake behavior not corresponding with agreed recommendations, is associated with increased morbidity and death, and it has been estimated that as many as 50% of patients in developed countries are not taking their medications as prescribed. But even as efforts in improving medication adherence over the years have increased, results are inconsistent, with only a minority of clinical trials showing any improvement in both adherence and clinical outcome. Since patient education is central to promoting good medication adherence, and language is integral to education, perhaps an exploration of the meaning and use of language, using the philosophy of Ludwig Wittgenstein, is in order.

  4. 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

  5. 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).

  6. Mucus-penetrating nanoparticles made with "mucoadhesive" poly(vinyl alcohol).

    PubMed

    Popov, Alexey; Enlow, Elizabeth; Bourassa, James; Chen, Hongming

    2016-10-01

    Nanoparticles that readily penetrate mucosal layers are desirable for a variety of biomedical applications. Nevertheless, most nanoparticles tend to be immobilized in mucus via steric and/or adhesive interactions. Contrary to the established opinion that poly(vinyl alcohol) (PVA) is mucoadhesive, we discovered that coating otherwise mucoadhesive nanoparticles with certain partially hydrolyzed PVAs can aid particle mobility in mucus. We describe two approaches to producing such mucus-penetrating particles (non-covalent modification of pre-formed nanoparticles and emulsification in the presence of PVA) and provide mobility data in human cervicovaginal mucus ex vivo as measured by multiple particle tracking and bulk permeation. When coated with PVAs that are ≥95% hydrolyzed, nanoparticles as small as ~210nm were immobilized in mucus similarly to well-established mucoadhesive controls (P>0.05). However, nanoparticles coated with PVAs that are <95% hydrolyzed penetrated mucus with velocities significantly exceeding those for the mucoadhesive controls (P<0.001) and were mobile in the bulk permeation assay.

  7. 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

  8. A new method to improve the clinical evaluation of cystic fibrosis patients by mucus viscoelastic properties.

    PubMed

    Tomaiuolo, Giovanna; Rusciano, Giulia; Caserta, Sergio; Carciati, Antonio; Carnovale, Vincenzo; Abete, Pasquale; Sasso, Antonio; Guido, Stefano

    2014-01-01

    In cystic fibrosis (CF) patients airways mucus shows an increased viscoelasticity due to the concentration of high molecular weight components. Such mucus thickening eventually leads to bacterial overgrowth and prevents mucus clearance. The altered rheological behavior of mucus results in chronic lung infection and inflammation, which causes most of the cases of morbidity and mortality, although the cystic fibrosis complications affect other organs as well. Here, we present a quantitative study on the correlation between cystic fibrosis mucus viscoelasticity and patients clinical status. In particular, a new diagnostic parameter based on the correlation between CF sputum viscoelastic properties and the severity of the disease, expressed in terms of FEV1 and bacterial colonization, was developed. By using principal component analysis, we show that the types of colonization and FEV1 classes are significantly correlated to the elastic modulus, and that the latter can be used for CF severity classification with a high predictive efficiency (88%). The data presented here show that the elastic modulus of airways mucus, given the high predictive efficiency, could be used as a new clinical parameter in the prognostic evaluation of cystic fibrosis.

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

    PubMed

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

    2015-10-05

    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.

  10. 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

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

    PubMed Central

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

    2015-01-01

    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

  12. 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.

  13. 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.

  14. Effect of Native Gastric Mucus on in vivo Hybridization Therapies Directed at Helicobacter pylori

    PubMed Central

    Santos, Rita S; Dakwar, George R; Xiong, Ranhua; Forier, Katrien; Remaut, Katrien; Stremersch, Stephan; Guimarães, Nuno; Fontenete, Sílvia; Wengel, Jesper; Leite, Marina; Figueiredo, Céu; De Smedt, Stefaan C; Braeckmans, Kevin; Azevedo, Nuno F

    2015-01-01

    Helicobacter pylori infects more than 50% of the worldwide population. It is mostly found deep in the gastric mucus lining of the stomach, being a major cause of peptic ulcers and gastric adenocarcinoma. To face the increasing resistance of H. pylori to antibiotics, antimicrobial nucleic acid mimics are a promising alternative. In particular, locked nucleic acids (LNA)/2'-OMethyl RNA (2'OMe) have shown to specifically target H. pylori, as evidenced by in situ hybridization. The success of in vivo hybridization depends on the ability of these nucleic acids to penetrate the major physical barriers—the highly viscoelastic gastric mucus and the bacterial cell envelope. We found that LNA/2'OMe is capable of diffusing rapidly through native, undiluted, gastric mucus isolated from porcine stomachs, without degradation. Moreover, although LNA/2'OMe hybridization was still successful without permeabilization and fixation of the bacteria, which is normally part of in vitro studies, the ability of LNA/2'OMe to efficiently hybridize with H. pylori was hampered by the presence of mucus. Future research should focus on developing nanocarriers that shield LNA/2'OMe from components in the gastric mucus, while remaining capable of diffusing through the mucus and delivering these nucleic acid mimics directly into the bacteria. PMID:26645765

  15. 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

  16. 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

  17. Lyn kinase represses mucus hypersecretion by regulating IL-13-induced endoplasmic reticulum stress in asthma.

    PubMed

    Wang, Xing; Yang, Xiaoqiong; Li, Yin; Wang, Xiaoyun; Zhang, Yun; Dai, Xi; Niu, Bin; Wu, Juan; Yuan, Xiefang; Xiong, Anjie; Liu, Zhigang; Zhong, Nanshan; Wu, Min; Li, Guoping

    2017-02-01

    In asthma, mucus hypersecretion is thought to be a prominent pathological feature associated with widespread mucus plugging. However, the current treatments for mucus hypersecretion are often ineffective or temporary. The potential therapeutic targets of mucus hypersecretion in asthma remain unknown. Here, we show that Lyn is a central effector of endoplasmic reticulum stress (ER stress) and mucous hypersecretion in asthma. In Lyn-transgenic mice (Lyn-TG) and wild-type (WT) C57BL/6J mice exposed to ovalbumin (OVA), Lyn overexpression attenuates mucus hypersecretion and ER stress. Interleukin 13 (IL-13) induced MUC5AC expression by enhancing ER stress in vitro. Lyn serves as a negative regulator of IL-13-induced ER stress and MUC5AC expression. We further find that an inhibitor of ER stress, which is likely involved in the PI3K p85α/Akt pathway and NFκB activity, blocked MUC5AC expression in Lyn-knockdown cells. Furthermore, PI3K/Akt signaling is required for IL-13-induced ER stress and MUC5AC expression in airway epithelial cells. The ER stress regulation of MUC5AC expression depends on NFκB in Lyn-knockdown airway epithelial cells. Our studies indicate not only a concept of mucus hypersecretion in asthma that involves Lyn kinase but also an important therapeutic candidate for asthma.

  18. Adherence and non-adherence to treatments: focus on pharmacy practice in Nepal.

    PubMed

    Bastakoti, Suresh; Khanal, Saval; Dahal, Bibek; Pun, Nirmala Tilija

    2013-04-01

    Nepal is one of the developing countries having many limitations in providing the quality health services to its population. In many countries, improvement in patients' adherence to the pharmacotherapy had been one of major outcome of quality pharmaceutical services. Till date, very less thing has been done in this area in Nepal; so it seems mandatory to improve the patient adherence to the treatment plans. Adherence to the medical therapy can be explained by the extent of the behavioral coincidence to the medication and non-medication regimen by a patient whereas compliance and concordance are two different models of patient adherence to the therapy. Compliance model suggests that patients have been brought responsible for being unable to follow 'doctor's order and concordance tempts to measure the degree of agreement between patient and his or her clinician about the nature of illness and the best possible therapy for the welfare of the patient. Non-adherence to the therapy may lead to different problems as consequences of non-adherence in four different level- individual, institutional, societal and national levels. Although some programs like, "Direct Observation Treatment, Short-course (DOTS) for tuberculosis, implementation of antiretroviral treatment schedules for HIV patients and pediatric vaccination models," are the examples of attention towards the cases of noncompliance in Nepal. It has long been faced its limitations in the forms of either untrained manpower or lack of good documentation of patients' adherence to therapy or high illiteracy rate or unaffordibility of patients to their treatment or lack of pharmaceutical care services.

  19. Clonogenic Assay: Adherent Cells

    PubMed Central

    Rafehi, Haloom; Orlowski, Christian; Georgiadis, George T.; Ververis, Katherine; El-Osta, Assam; Karagiannis, Tom C.

    2011-01-01

    The clonogenic (or colony forming) assay has been established for more than 50 years; the original paper describing the technique was published in 19561. Apart from documenting the method, the initial landmark study generated the first radiation-dose response curve for X-ray irradiated mammalian (HeLa) cells in culture1. Basically, the clonogenic assay enables an assessment of the differences in reproductive viability (capacity of cells to produce progeny; i.e. a single cell to form a colony of 50 or more cells) between control untreated cells and cells that have undergone various treatments such as exposure to ionising radiation, various chemical compounds (e.g. cytotoxic agents) or in other cases genetic manipulation. The assay has become the most widely accepted technique in radiation biology and has been widely used for evaluating the radiation sensitivity of different cell lines. Further, the clonogenic assay is commonly used for monitoring the efficacy of radiation modifying compounds and for determining the effects of cytotoxic agents and other anti-cancer therapeutics on colony forming ability, in different cell lines. A typical clonogenic survival experiment using adherent cells lines involves three distinct components, 1) treatment of the cell monolayer in tissue culture flasks, 2) preparation of single cell suspensions and plating an appropriate number of cells in petri dishes and 3) fixing and staining colonies following a relevant incubation period, which could range from 1-3 weeks, depending on the cell line. Here we demonstrate the general procedure for performing the clonogenic assay with adherent cell lines with the use of an immortalized human keratinocyte cell line (FEP-1811)2. Also, our aims are to describe common features of clonogenic assays including calculation of the plating efficiency and survival fractions after exposure of cells to radiation, and to exemplify modification of radiation-response with the use of a natural antioxidant

  20. 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.

  1. [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.

  2. 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…

  3. 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

  4. 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

  5. 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.

  6. Depression at Treatment Initiation Predicts HIV Antiretroviral Adherence in Uganda

    PubMed Central

    Wagner, Glenn J.; Slaughter, Mary; Ghosh-Dastidar, Bonnie

    2014-01-01

    We examined the relationship between depression (symptom type, diagnostic severity and change over time) and adherence to HIV antiretroviral therapy (ART) with data from three longitudinal studies (N= 1021) of patients starting ART in Uganda. The Patient Health Questionnaire (PHQ-9) was used to assess depressive symptoms (total score; somatic and cognitive subscales), and to categorize severity level. At baseline, 9% had major depression and 30% had minor depression; 82% were adherent (reported no missed ART doses in past 7 days) at Month 6 and 85% at Month 12. Controlling for demographic and medical covariates, multivariate random-effects logistic regression models revealed that change in depression was not related to adherence; however, baseline total depression symptoms, and cognitive symptoms in particular, as well as major and minor depression, were significant predictors of adherence. These findings highlight the need for early identification and aggressive treatment of depression to optimize ART adherence. PMID:28084190

  7. 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

  8. Platycodin D inhibits interleukin-13-induced the expression of inflammatory cytokines and mucus in nasal epithelial cells.

    PubMed

    Wang, Botao; Gao, Ying; Zheng, Guoxi; Ren, Xiaoyong; Sun, Bin; Zhu, Kang; Luo, Huanan; Wang, Zhenghui; Xu, Min

    2016-12-01

    Allergic rhinitis (AR) is a common chronic inflammatory condition of the nasal mucosal tissue. Platycodin D (PLD), a triterpenoid saponin isolated from the root of Platycodon grandiflorum, has anti-inflammatory effects in a mouse model of allergic asthma. However, the anti-inflammatory effects of PLD in the nasal mucosa have not been deeply investigated. The objective was to investigate the effect of PLD on inflammatory cytokines and mucus production from nasal epithelial cells. Our study showed that PLD inhibited the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and eotaxin in interleukin (IL)-13-stimulated RPMI2650 cells. PLD also suppressed IL-13-induced mucin 5AC (MUC5AC) expression in RPMI2650 cells. Moreover, PLD treatment prevented IL-13-induced p-NF-κB p65 expression in RPMI2650 cells, as well as MAPK signaling pathway activation. Taken together, our results provided evidence that PLD inhibits IL-13-induced the expression of inflammatory cytokines and mucus in nasal epithelial cells by inhibiting the activation of NF-κB and MAPK signaling pathways.

  9. 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.

  10. [Strategies to improve medication adherence].

    PubMed

    Laufs, U; Böhm, M; Kroemer, H K; Schüssel, K; Griese, N; Schulz, M

    2011-08-01

    Up to 50 % of patients with chronic diseases do not take their medication regularly. Poor adherence to drug therapy is associated with higher morbidity and mortality. A selective literature search using the terms adherence, compliance, concordance, persistence, medication management, and pharmaceutical care was performed. Evidence for improving adherence has been provided for the following principles: individual counselling of patients and care givers, medication management including simplifying dosing and use of combination tablets as well as the use of individual unit doses, e. g. blister cards. The effectiveness has only been shown for the duration of the interventions. The improvement of medication adherence represents an area of research with high impact on outcomes and cost. Measures to improve adherence may be as important as the development of novel therapies. However, prospective clinical evaluations with clinical endpoints are missing especially for the German health care system in order to develop recommendations for clinical practice. Joint efforts of physicians and pharmacists are needed.

  11. Factors affecting medication adherence in elderly people

    PubMed Central

    Jin, Hyekyung; Kim, Yeonhee; Rhie, Sandy Jeong

    2016-01-01

    Background Little is known about the functional health literacy (FHL) associated with medication adherence in elderly patients. The aim of this study was to examine the FHL among older adults and identify influencing factors that can predict medication adherence. Methods This was a cross-sectional survey. Participants (n=160) aged 65 years and older were selected from outpatient clinics of 3 tertiary care hospitals, 6 community pharmacies, and 2 senior centers between November 1 and 30, 2014. The participants’ FHL was measured using the Korean Functional Health Literacy Test, which consists of 15 items including 8 numeracy and 7 reading comprehension items. Medication adherence was measured by the Adherence to Refills and Medication Scale. Descriptive statistics, chi-square or Fisher’s exact test, and multiple regression analyses were used to analyze the data. Results The mean score of the total FHL was 7.72±3.51 (range 0–15). The percentage of the total number of correct answers for the reading comprehension subtest and numeracy subtest were 48.1% and 54.4%, respectively. Among 160 participants, 52.5% showed low adherence to medication. The factors affecting medication adherence included the patient’s degree of satisfaction with the service (β=−0.215, P=0.022), sufficient explanation of medication counseling (β=−0.335, P=0.000), education level (β=−0.153, P=0.045), health-related problems (β=−0.239, P=0.004), and dosing frequency (β=0.189, P=0.018). Conclusion In this study, we found medication adherence of elderly patients was associated with education level, health-related problems, dosing frequency, satisfaction with patient counseling, and explanation of medication, but no association was found with FHL. Pharmacists should consider elderly patients’ individual characteristics such as educational background and specific patient-related health problems, provide sufficient information and explanation of medication, and ensure patient

  12. Medication Adherence in a Comparative Effectiveness Trial for Bipolar Disorder

    PubMed Central

    Sylvia, Louisa G.; Reilly-Harrington, Noreen A.; Leon, Andrew C.; Kansky, Christine I.; Calabrese, Joseph R.; Bowden, Charles L.; Ketter, Terence A.; Friedman, Edward S.; Iosifescu, Dan V.; Thase, Michael E.; Ostacher, Michael J.; Keyes, Michelle; Rabideau, Dustin; Nierenberg, Andrew A.

    2013-01-01

    Objective Psychopharmacology remains the foundation of treatment for bipolar disorder, but medication adherence in this population is low (Range = 20% to 64%). We examined medication adherence in a multi-site, comparative effectiveness study of lithium. Method The Lithium Moderate Dose Use Study (LiTMUS) was a six-month, six-site, randomized effectiveness trial of adjunctive moderate dose lithium therapy compared to optimized treatment in adult outpatients with bipolar I or II disorder (N=283). Medication adherence was measured at each study visit with the Tablet Routine Questionnaire. Results We found that 4.50% of participants reported missing at least 30% of their medications in the past week at baseline and non-adherence remained low throughout the trial (< 7%). Poor medication adherence was associated with more manic symptoms and side effects as well as lower lithium serum levels at mid- and post-treatment, but not with poor quality of life, overall severity of illness, or depressive symptoms. Conclusion Participants in LiTMUS were highly adherent with taking their medications. The lack of association with possible predictors of adherence, such as depression and quality of life, could be explained by the limited variance or other factors as well as by not using an objective measure of adherence. PMID:24117232

  13. Treatment adherence in multiple sclerosis: a survey of Belgian neurologists

    PubMed Central

    Decoo, Danny; Vokaer, Mathieu

    2015-01-01

    Background Poor treatment adherence is common among patients with multiple sclerosis (MS). This survey evaluated neurologists’ perception of treatment adherence among MS patients. Materials and methods This questionnaire-based survey of Belgian neurologists treating MS patients was conducted between June and July 2014. Face-to-face interviews with the neurologists were based on a semistructured questionnaire containing questions regarding the perception of the treatment-adherence level. Results A total of 41 neurologists participated in the survey. Of these, 88% indicated frequent discussions about treatment adherence as beneficial for treatment efficacy. The mean time spent on the treatment-adherence discussion during the initial consultation was 11 minutes, with 24% of doctors spending 5 minutes and 24% of doctors spending 10 minutes discussing this issue. The majority of neurologists (56%) perceived the adherence level in MS as good, and 12% perceived it as excellent. The majority of neurologists (64%) indicated intolerance as a main cause of poor adherence, and all neurologists reported insufficient efficacy as a consequence of nonadherence. The importance of adherence in the neurologists’ practice was evaluated on a scale of 1–10, with 1= “not very important” and 10= “very important”: 44% of doctors indicated a score of 10, and the mean score was 9.0. Conclusion Belgian neurologists consider treatment adherence in MS as essential for the benefits of therapies. However, although neurologists are aware of the consequences of nonadherence, they generally spend limited time discussing the importance of treatment adherence with their patients. PMID:26640373

  14. Secondary Structure and Glycosylation of Mucus Glycoproteins by Raman Spectroscopies

    PubMed Central

    2016-01-01

    The major structural components of protective mucus hydrogels on mucosal surfaces are the secreted polymeric gel-forming mucins. The very high molecular weight and extensive O-glycosylation of gel-forming mucins, which are key to their viscoelastic properties, create problems when studying mucins using conventional biochemical/structural techniques. Thus, key structural information, such as the secondary structure of the various mucin subdomains, and glycosylation patterns along individual molecules, remains to be elucidated. Here, we utilized Raman spectroscopy, Raman optical activity (ROA), circular dichroism (CD), and tip-enhanced Raman spectroscopy (TERS) to study the structure of the secreted polymeric gel-forming mucin MUC5B. ROA indicated that the protein backbone of MUC5B is dominated by unordered conformation, which was found to originate from the heavily glycosylated central mucin domain by isolation of MUC5B O-glycan-rich regions. In sharp contrast, recombinant proteins of the N-terminal region of MUC5B (D1-D2-D′-D3 domains, NT5B), C-terminal region of MUC5B (D4-B-C-CK domains, CT5B) and the Cys-domain (within the central mucin domain of MUC5B) were found to be dominated by the β-sheet. Using these findings, we employed TERS, which combines the chemical specificity of Raman spectroscopy with the spatial resolution of atomic force microscopy to study the secondary structure along 90 nm of an individual MUC5B molecule. Interestingly, the molecule was found to contain a large amount of α-helix/unordered structures and many signatures of glycosylation, pointing to a highly O-glycosylated region on the mucin. PMID:27791356

  15. 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.

  16. Addition of mucin to the growth medium triggers mucus-binding activity in different strains of Lactobacillus reuteri in vitro.

    PubMed

    Jonsson, H; Ström, E; Roos, S

    2001-10-16

    We have examined the ability of a number of Lactobacillus reuteri strains to bind immobilised mucus material. After growth in MRS broth, some strains showed high binding activity towards mucus whilst many strains exhibited a very low binding activity. In order to simulate the intestinal milieu, we grew the bacteria in MRS supplemented with the glycoprotein mucin, the main component of mucus. Growth under these conditions dramatically improved the mucus-binding activity of most strains that initially showed very poor binding when grown in MRS broth. In addition, there was a strong induction of mucus binding in some strains after growth on solid substrate as compared to growth in liquid culture. Protease treatment of bacteria grown in the presence of mucin eliminated the adhesion, suggesting that mucin induces the production of cell surface proteins that possess mucus-binding properties.

  17. 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

  18. Characterization of vibrios diversity in the mucus of the polychaete Myxicola infundibulum (Annellida, Polichaeta).

    PubMed

    Stabili, Loredana; Giangrande, Adriana; Pizzolante, Graziano; Caruso, Giorgia; Alifano, Pietro

    2014-01-01

    Vibrios are among the most abundant culturable microbes in aquatic environments. They can be either free-living in the water column or associated with several marine organisms as mutualists, saprophytes, or parasites. In the present study we analysed vibrios abundance and diversity in the mucus of the polychaete Myxicola infundibulum, complementing culture-based with molecular methods. Vibrios reached 4.6 × 10(3) CFU mL(-1) thus representing a conspicuous component of the heterotrophic culturable bacteria. In addition, luminous vibrios accounted for about 60% of the total culturable vibrios in the mucus. The isolates were assigned to: Vibrio gigantis, Vibrio fischeri, Vibrio jasicida, Vibrio crassostreae, Vibrio kanaloae, and Vibrio xuii. Two Vibrio isolates (MI-13 and MI-15) may belong to a new species. We also tested the ability of the Vibrio isolates to grow on M. infundibulum mucus as the sole carbon source. All strains showed appreciable growth in the presence of mucus, leading us to conclude that this matrix, which is abundant and covers the animal entirely, may represent a microcosm and a food source for some bacteria, playing a crucial role in the structuring of a mucus-associated beneficial microbial community. Moreover, the trophic relationship between vibrios and M. infundibulum mucus could be enhanced by the protection that mucus offers to vibrios. The results of this study represent a contribution to the growing evidence for complex and dynamic invertebrate-microbe associations present in nature and highlight the importance of exploring relationships that Vibrio species establish with marine invertebrates.

  19. Morbidly adherent placenta.

    PubMed

    Abuhamad, Alfred

    2013-10-01

    Morbidly adherent placenta, which describes placenta accreta, increta, and percreta, implies an abnormal implantation of the placenta into the uterine wall. The incidence of placenta accreta has increased significantly over the past several decades, with the main risk factors include prior cesarean section and placental previa. Sonographic markers of placenta accreta can be present as early as the first trimester and include a low uterine implantation of a gestational sac, multiple vascular lacunae within the placenta, loss of the normal hypoechoic retroplacental zone, and abnormality of the uterine serosa-bladder interface, among others. Ultrasound has high sensitivity and specificity for the diagnosis of placenta accreta and MRI should be reserved for rare cases in which the ultrasound is non-diagnostic. The optimum time for planned delivery for a patient with placenta accreta is around 34-35 weeks following a course of corticosteroid injection. The successful management of placenta accreta includes a multidisciplinary care team approach with the successful management relying heavily on the prenatal diagnosis of this entity and preparing for the surgical management in a multidisciplinary approach by assuring the most skilled team is available for those patients.

  20. Reinforcing adherence to antihypertensive medications.

    PubMed

    Petry, Nancy M; Alessi, Sheila M; Byrne, Shannon; White, William B

    2015-01-01

    This pilot study evaluated a reinforcement intervention to improve adherence to antihypertensive therapy. Twenty-nine participants were randomized to standard care or standard care plus financial reinforcement for 12 weeks. Participants in the reinforcement group received a cell phone to self-record videos of adherence, for which they earned rewards. These participants sent videos demonstrating on-time adherence 97.8% of the time. Pill count adherence differed significantly between the groups during treatment, with 98.8%±1.5% of pills taken during treatment in the reinforcement condition vs 92.6%±9.2% in standard care (P<.002). Benefits persisted throughout a 3-month follow-up, with 93.8%±9.3% vs 78.0%±18.5% of pills taken (P<.001). Pill counts correlated significantly (P<.001) with self-reports of adherence, which also differed between groups over time (P<.01). Systolic blood pressure decreased modestly over time in participants overall (P<.01) but without significant time-by-group effects. These results suggest that reinforcing medication adherence via cellular phone technology and financial reinforcement holds potential to improve adherence.

  1. 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

  2. Marital satisfaction and adherence to religion

    PubMed Central

    Jafari, F; Neisani Samani, L; Fatemi, N; Ta’avoni, S; Abolghasemi, J

    2015-01-01

    Background: One of the most important determinants of health and marital satisfaction, the family and religious adherence can be effective because religion includes guidelines for life and providing a system of beliefs and values make these features can affect family life. Approach: This descriptive research - an analysis performed to assess the level of satisfaction of 47 questionnaires marital satisfaction questionnaire whose validity and reliability were evaluated and a couple of them asked to assess adherence to religion. The study population included 382 couples in Tehran that a cluster of 22 districts of Tehran were the selected. To analyze the data, ANOVA, Chi-square, and Pearson correlation coefficient using the software SPSS (version 22) became all tests were performed at the 5% level. Results: The data showed that the average age is 34 for women and 38 years for men and the majority of couples are in appropriate level in religiosity (40.5 percent). The results showed a main direct relation among religiosity and marital satisfaction of men and women (p ≤ 0.001). The correlation among religiosity and marital satisfaction of women r = 0.271 and this factor in men r = 0.200 was obtained indicating a direct relationship was significant. Conclusion: couples who were both committed to religion, their marital satisfaction score was more than couples without adherence to religion, and thus promoting religious beliefs and commitment can increase their marital satisfaction in couples. PMID:28316734

  3. Gastroprotective effect of ranitidine bismuth citrate is associated with increased mucus bismuth concentration in rats.

    PubMed Central

    Tanaka, S; Guth, P H; Paulsen, G; Kaunitz, J D

    1996-01-01

    BACKGROUND: Antisecretory and bismuth compounds protect the gastric mucosa from injury resulting from non-steroidal anti-inflammatory drugs. AIM: To study the mechanism underlying the gastroprotective effects of ranitidine bismuth citrate (GG311) in rats. METHODS: Indomethacin rat injury model and in vivo microscopy in which acid output, surface cell intracellular pH (pHi), gastric mucus gel thickness, and mucosal blood flow were measured simultaneously. RESULTS: In injury studies, GG311 dose dependently protected against severe injury induced by indomethacin (60 mg/kg subcutaneously). In in vivo microscopic studies, indomethacin significantly decreased mucus gel thickness and increased the initial rate of acidification of gastric surface cells when the superfusate pH was lowered from 7.4 to 1.0, and impaired pHi during acid exposure. Indomethacin had no effect on mucosal blood flow or acid output. GG311 alone had no effect on gel thickness, blood flow, or pHi homeostasis during acid exposure, but improved the initial acidification rate and pHi during superfusion with pH 1.0 solutions in the presence of indomethacin. In separate experiments, indomethacin pretreatment considerably increased gastric mucus bismuth concentrations in rats given GG311. CONCLUSIONS: The gastroprotective effect of GG311 against indomethacin induced gastric injury is associated with high and prolonged gastric mucus bismuth concentrations, which may impair proton permeation across the mucus gel. PMID:8977335

  4. Some effects of tripotassium dicitrato bismuthate on gastric secretion and the mucus barrier.

    PubMed

    Sidebotham, R L; Batten, J J; Li, K; Spencer, J; Baron, J H

    1990-10-01

    The effect of tripotassium dicitrato bismuthate (De-Nol) on the breakdown of the gastric mucus barrier was investigated by measuring the output of mucus glycoprotein in pentagastrin-stimulated secretion from 13 patients before and after treatment for peptic ulcer, and by examining the accumulation of dialysable peptides and amino acids (DPAA) in stimulated secretion from ten of these patients. The accumulation of DPAA was significantly reduced after De-Nol (by 54%) and to a greater extent than was the output of mucus glycoprotein (by 27%). These observations are consistent with a decrease in the rate of breakdown of the mucus barrier as a result of De-Nol treatment. De-Nol significantly reduced pepsin output (by 32%) in the same group of patients. Comparison of the change in pepsin output with the change in accumulation of DPAA in stimulated juice indicated that De-Nol increases the resistance of the mucus barrier to acid-pepsin proteolysis and/or inhibits the secretion of amino acids and peptides from gastric mucosa.

  5. 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

  6. Clearance of viscoelastic mucus simulant with airflow in a rectangular channel, an experimental study.

    PubMed

    Hassan, Amgad A; Evrensel, Cahit A; Krumpe, Peter E

    2006-01-01

    Interaction of mucus simulant with airflow in a rectangular channel is investigated experimentally. Two different viscoelastic gel mucus simulants are prepared by cross linking Borax with Locust Bean Gum (LBG) solution; liquid-like (LM) with lower storage modulus and semi-solid (SM). The rheological difference between LM and SM represent the qualitative change from liquid-like healthy mucus to the one with higher storage modulus found in a person with lung disease. The study concentrates on the effect of viscoelastic layer thickness and rheology on the wave formation and clearance due to its interaction with airflow. The results indicate that the onset air velocity for wave initiation reduces by increasing layer thickness. This effect is more pronounced for SM. Slowly propagating waves initiate at a lower air velocity for LM compared to SM for thinner layer thickness and this behavior reverses for a thicker layer. Although SM clears at a critical air velocity, LM does not show clearance behavior, defined as separation of layer section from rest and movement in the downstream flow direction. This seems to suggest that thicker mucus with higher elastic modulus, similar to the mucus for a person with lung disease, may clear easier with a two-phase air-liquid flow, as in cough.

  7. Proteomics profiling of epidermal mucus secretion of a cichlid (Symphysodon aequifasciata) demonstrating parental care behavior.

    PubMed

    Chong, Kenny; Joshi, Shashikant; Jin, Lam Toong; Shu-Chien, Alexander Chong

    2006-04-01

    The discus fish (Symphysodon aequifasciata) is a cichlid demonstrating advanced mode of parental care towards fry. Both male and female fish utilized epidermal mucus secreted from specialized epidermal cells to feed developing fry. We utilized proteomics to compare protein profile from parental and nonparental fish. Gel analysis revealed a total of 35 spots that were up-regulated in parental mucus. In tandem, another 18 spots were uniquely expressed in parental mucus. MS analysis of these spots identified proteins such as fructose biphosphate aldolase, nucleoside diphosphate kinase, and heat shock proteins, which are essential to support energy provision, cell repair and proliferation, stress mediation, and defense mechanism in parental fish during parental-care period. Concurrently, the detection of several antioxidant-related proteins such as thioredoxin peroxidase and hemopexin suggests a need to overcome oxidative stress during hypermucosal production in parental-care behavior. A C-type lectin was also found to be uniquely expressed in parental mucus and could have important role in providing antimicrobial defense to both parental fish and fry. In summary, our study shows that discus mucus proteome undergoes changes in protein expression during parental-care period.

  8. 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.

  9. Response of a viscoelastic layer (mucus) to turbulent airflow in a rigid tube.

    PubMed

    Evrensel, Cahit A; Khan, Raquib U; Krumpe, Peter E

    2008-01-01

    Basic interaction mechanism between the air flow and viscoelastic mucus layer lining a rigid tube is computationally studied. Linear wave instability theory is applied to the coupled air-mucus system to explore the stability of the interface. Primary velocity profile is taken to be the mean profile of turbulent flow and turbulent fluctuations are neglected. The model predicts that the instability initiates in the form of slow propagating waves on the mucus surface. Onset flow speed at which these waves initiate is very sensitive to mucus viscosity to elasticity ratio at lower range and it approaches to an asymptotic value for higher values. The results indicate that while the wave length increases, wave speed decreases with increasing mucus viscosity to elasticity ratio. Model also predicts that the waves initiate at lower flow velocities for the turbulent case compared to the published laminar case. Turbulent onset flow speed is only 34% Flow is considered to be turbulent during forced expiration and coughing in central and upper airways. Model predicts that this flow behavior tends to favor wave initiation at lower flow rates and may facilitate cough clearance.

  10. Effect of D-002 on gastric mucus composition in ethanol-induced ulcer.

    PubMed

    Carbajal, D; Molina, V; Noa, M; Valdés, S; Arruzazabala, M L; Aguilar, C; Más, R

    2000-10-01

    This study was designed to determine the effect of D-002, a natural product isolated and purified from beeswax (Apis mellifera), on gastric mucus composition on ethanol-induced ulcer in rats. The morphology of the lesions was analysed histologically, and morphometric analysis of gastric-gland content in total glycoprotein and sulphated macromolecules were done. Oral pretreatment with D-002 at 5 and 25 mgkg(-1)1 before oral administration of ethanol at 60%, produced a significant increase in the amount of gastric mucus and total protein. The histomorphometric evaluation of the gastric damage at the same doses showed a significant increase in neutral glycoproteins and sulfated macromolecules. It is concluded that enhancement of the quantity and quality of the mucus could partly explain the gastroprotective effect of D-002.

  11. Immunoglobulin concentrations in cervical mucus in patients with normal and abnormal cervical cytology.

    PubMed

    Coughlan, B M; Skinner, G R

    1977-02-01

    The cervical mucus of 31 patients with normal and 16 patients with abnormal cervical cytology was investigated at each stage of the menstrual cycle for immunoglobulin IgG, IgA and IgM. IgG and IgA were present in every mucus sample, while IgM was only occasionally found in trace amounts. IgG and IgA increased towards the last week of the menstrual cycle, the increase being in general more marked for IgA. Patients with abnormal cervical cytology showed increased IgG and, more strikingly, IgA concentrations in their cervical mucus, but there was no correlation between the IgG and IgA concentrations at any stage of the menstrual cycle. Whereas in patients with normal cervical cytology the IgG and IgA concentrations correlated throughout the menstrual cycle.

  12. 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

  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.

  14. 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

  15. Nanoparticle penetration of human cervicovaginal mucus: The effect of polyvinyl alcohol

    PubMed Central

    Yang, Ming; Lai, Samuel K.; Yu, Tao; Wang, Ying-Ying; Happe, Christina; Zhong, Weixi; Zhang, Michael; Anonuevo, Abraham; Fridley, Colleen; Hung, Amy; Fu, Jie; Hanes, Justin

    2014-01-01

    Therapeutic nanoparticles must rapidly penetrate the mucus secretions lining the surfaces of the respiratory, gastrointestinal and cervicovaginal tracts to efficiently reach the underlying tissues. Whereas most polymeric nanoparticles are highly mucoadhesive, we previously discovered that a dense layer of low MW polyethylene glycol (PEG) conferred a sufficiently hydrophilic and uncharged surface to effectively minimize mucin-nanoparticle adhesive interactions, allowing well-coated particles to rapidly diffuse through human mucus. Here, we sought to investigate the influence of surface coating by polyvinyl alcohol (PVA), a relatively hydrophilic and uncharged polymer routinely used as a surfactant to formulate drug carriers, on the transport of nanoparticles in fresh human cervicovaginal mucus. We found that PVA-coated polystyrene (PS) particles were immobilized, with speeds at least 4,000-fold lower in mucus than in water, regardless of the PVA molecular weight or incubation concentration tested. Nanoparticles composed of poly(lactide-co-glycolide) (PLGA) or diblock copolymers of PEG-PLGA were similarly immobilized when coated with PVA (slowed 29,000- and 2,500-fold, respectively). PVA coatings could not be adequately removed upon washing, and the residual PVA prevented sufficient coating with Pluronic F127 capable of reducing particle mucoadhesion. In contrast to PVA-coated particles, the similar sized PEG-coated formulations were slowed only ~6- to 10-fold in mucus compared to in water. Our results suggest incorporating PVA in the particle formulation process may lead to the formation of mucoadhesive particles for many nanoparticulate systems. Thus, alternative methods for particle formulation, based on novel surfactants or changes in the formulation process, should be identified and developed in order to produce mucus-penetrating particles for mucosal applications. PMID:25090196

  16. Quantitative study of changes in intestinal morphology and mucus gel on total parenteral nutrition in rats.

    PubMed

    Sakamoto, K; Hirose, H; Onizuka, A; Hayashi, M; Futamura, N; Kawamura, Y; Ezaki, T

    2000-12-01

    Quantification of changes in gastrointestinal morphology and mucus gel has been difficult to study. In the present study, we investigated changes in rat intestine under total parenteral nutrition (TPN) using fluoresceinated lectin staining and image analysis. Wistar rats (n = 34) were divided into two groups: one group received TPN for 2 weeks, and a control group received standard rat chow and water ad libitum for the same period. A 1-cm segment of distal ileum was removed and cut into cross sections. Sections were stained with hematoxylin and eosin, and to stain the mucus, periodic acid-Schiff (PAS), alcian blue (AB), and fluoresceinated lectin, that is, FITC-labeled Ulex europaeus agglutinin I (FITC-UEA-I), were used. Light microscope images were stored in a personal computer and analyzed using image analysis. We measured perimeter length, mucosal thickness, villus area, villus surface area index, mucus stain-positive area, mucosal area ratio, and mucosal surface area ratio. Perimeter length, mucosal thickness, villus area, and villus surface area index in the TPN group were significantly less than those in the control group (P < 0.001 for each parameter). In all mucus stainings, the stain-positive area in the TPN group was significantly less than that in the control group. However, there were no significant differences in mucosal area or mucosal surface area ratios between the two groups. The FITC-UEA-I-positive area was significantly greater than the PAS- or and AB-positive area. There were significant positive correlations between the FITC-UEA-I-positive area and both the PAS-positive and AB-positive areas. TPN for 2 weeks promoted intestinal atrophy and decreased absolute quantity of mucus gel. We successfully introduced the FITC-UEA-I staining method to evaluate changes in mucus gel.

  17. 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.

  18. 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%.

  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.

  20. Unravelling adherence to prophylaxis in haemophilia: a patients' perspective.

    PubMed

    Schrijvers, L H; Kars, M C; Beijlevelt-van der Zande, M; Peters, M; Schuurmans, M J; Fischer, K

    2015-09-01

    Given the lifelong therapy in haemophilia patients, insight in non-adherence behaviour from a patient perspective is important to understand patients' difficulties with the following treatment recommendations. The aim of this study was to clarify the process underlying adherence (behaviour) to prophylactic treatment, from a patients' perspective. To develop a grounded theory, a qualitative study using individual in-depth interviews was performed to understand experiences, perceptions and beliefs concerning adherence to prophylaxis. From two Dutch treatment centres, 21 adults with haemophilia using prophylaxis were interviewed. Patients were asked how they experience their task to administer prophylaxis and how they adhere to this. The interviews were transcribed, coded and analysed in an iterative process, leading to the development of the grounded theory. Adherence was determined by the position of prophylaxis in life. The position of prophylaxis was determined by the perception of prophylaxis and the ability to exert prophylaxis. Patients' perception was influenced by two main factors: acceptance of haemophilia and feeling/fearing symptoms. The ability to exert prophylaxis was influenced by understanding haemophilia and prophylaxis and planning/infusion skills. The combination of different perceptions and skills led to four main positions of prophylaxis in life: (i) prophylaxis integrated in life, (ii) prophylaxis according to doctors' advice, struggling with irregular situations, (iii) prophylaxis is too much to handle, (iv) prophylaxis is a confrontation with illness. The adherence level gradually decreased from position 1 to 4. This information can be used to design tailored interventions to promote adherence.

  1. Relationship between colonial morphology and adherence of Streptococcus pneumoniae.

    PubMed Central

    Cundell, D R; Weiser, J N; Shen, J; Young, A; Tuomanen, E I

    1995-01-01

    Phase variants in colonial opacity of pneumococci differ in the ability to colonize the nasopharynx of infant rats. To explain this observation at a cellular level, we compared the ability of opacity variants to adhere to buccal epithelial cells, type II pneumocytes, or vascular endothelial cells and to the glycoconjugates that represent the cognate receptors at each of these sites. The transparent phenotype was associated with enhanced adherence to buccal cells (approximately 100%) and their receptor relative to that of the opaque variants. Only modest differences in adherence (< 45%) were demonstrated to resting lung and vascular cells. In contrast, adherence of transparent variants increased by 90% to lung cells stimulated with interleukin-1 and by 130% to endothelial cells stimulated with tumor necrosis factor. In contrast, cytokine stimulation did not influence the adherence of opaque pneumococci. This difference correlated with the unique ability of transparent variants to adhere to immobilized GlcNAc and to cells bearing transfected platelet-activating factor receptors. These results suggest that the mechanism of enhanced colonization of the nasopharynx in vivo by transparent as compared with opaque phase variants involves a greater ability to adhere to both GlcNAc beta 1-3Gal on buccal epithelial cells and GlcNAc and PAF receptors on cytokine-activated, as opposed to resting, lung and endovascular cells. PMID:7868244

  2. Fungal colonization with Pneumocystis correlates to increasing chloride channel accessory 1 (hCLCA1) suggesting a pathway for up-regulation of airway mucus responses, in infant lungs

    PubMed Central

    Pérez, Francisco J.; Ponce, Carolina A.; Rojas, Diego A.; Iturra, Pablo A.; Bustamante, Rebeca I.; Gallo, Myriam; Hananias, Karime; Vargas, Sergio L.

    2014-01-01

    Fungal colonization with Pneumocystis is associated with increased airway mucus in infants during their primary Pneumocystis infection, and to severity of COPD in adults. The pathogenic mechanisms are under investigation. Interestingly, increased levels of hCLCA1 – a member of the calcium-sensitive chloride conductance family of proteins that drives mucus hypersecretion – have been associated with increased mucus production in patients diagnosed with COPD and in immunocompetent rodents with Pneumocystis infection. Pneumocystis is highly prevalent in infants; therefore, the contribution of Pneumocystis to hCLCA1 expression was examined in autopsied infant lungs. Respiratory viruses that may potentially increase mucus, were also examined. hCLCA1 expression was measured using actin-normalized Western-blot, and the burden of Pneumocystis organisms was quantified by qPCR in 55 autopsied lungs from apparently healthy infants who died in the community. Respiratory viruses were diagnosed using RT-PCR for RSV, metapneumovirus, influenza, and parainfluenza viruses; and by PCR for adenovirus. hCLCA1 levels in virus positive samples were comparable to those in virus-negative samples. An association between Pneumocystis and increased hCLCA1 expression was documented (P=0.028). Additionally, increasing Pneumocystis burden correlated with increasing hCLCA1 protein expression levels (P=0.017). Results strengthen the evidence of Pneumocystis-associated up-regulation of mucus-related airway responses in infant lungs. Further characterization of this immunocompetent host-Pneumocystis-interaction, including assessment of potential clinical significance, is warranted. PMID:25379375

  3. Growth and survival of the fish pathogenic bacterium, Flavobacterium columnare, in tilapia mucus and porcine gastric mucin.

    PubMed

    Shoemaker, Craig A; LaFrentz, Benjamin R

    2015-02-01

    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 ability of bacterial pathogens to grow in fish mucus. Our objective was to determine if F. columnare isolates could grow and survive in formulated water (FW) containing autoclaved tilapia mucus or porcine gastric mucin. We demonstrated the ability of F. columnare genomovars I, II, II-B and III to replicate (2-3 logs) and survive (21 to >100 days) in FW containing tilapia mucus. In a second experiment, genomovar I and II isolates were found to replicate in FW containing tilapia mucus or porcine mucin but not in FW only. From a practical standpoint, fish handling and/or hauling results in stress that leads to mucus sloughing often with subsequent F. columnare infection. Flavobacterium columnare utilizes fish mucus as a nutrient source, and studies are underway to determine if growth in mucus or mucin results in differential protein expression and/or increased virulence of F. columnare towards fish.

  4. 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

    2013-12-09

    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.

  5. 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

  6. 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

  7. [Drug prescriptions: Adherence and understanding in Madagascar].

    PubMed

    Raharinjatovo, L; Ralandison, S

    2015-01-01

    Frequently ignored or neglected, poor adherence is an important cause of treatment failure and a major public health problem. We assessed the factors involved in adherence in a hospital in Madagascar. This long-term study evaluated two groups of variables: patients' level of understanding of their disease and drug prescriptions, and the information on the prescription written by the doctor. We interviewed 93 in-patients (mean age: 50 years) and found that 16% were illiterate. Overall, 27% did not know the name of their illness, 34% were unaware of the treatment objectives, and 14% did not understand the drug prescription. On 20% of the prescriptions, the patients' name was not included, and the daily dose information and schedule was omitted from 16%. A day after receiving the prescription, only 64% had purchased the medication and only 53% of all patients had taken any. A correlation was observed between illiteracy, knowledge of the disease/treatment goals, and non-purchase of drugs. The poor quality of information contained in the prescriptions and patients' poor understanding of what they were supposed to do are obvious. Using pre-completed health forms and text messages might improve adherence.

  8. The challenge of patient adherence

    PubMed Central

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

    2005-01-01

    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

  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.

  10. Adherence of Staphylococcus epidermidis to biomaterials is augmented by PIA.

    PubMed

    Olson, M E; Garvin, K L; Fey, P D; Rupp, M E

    2006-10-01

    Staphylococcus epidermidis is the most common cause of orthopaedic prosthetic device infections. Polysaccharide intercellular adhesin (PIA) is important in the pathogenesis of intravascular catheter-associated infection, and has an essential role in cellular aggregation and biofilm formation. However, the role of PIA in orthopaedic infections is less well understood. We used genetically defined strains of S. epidermidis in an in vitro adherence assay to assess the importance of PIA in the adherence to various orthopaedic biomaterials. On all biomaterials tested (zirconia, ultra-high molecular weight polyethylene, polymethylmethacrylate, cobalt chromium, titanium, stainless steel, and silastic), PIA-positive S. epidermidis 1457 exhibited greater levels of adherence thanS. epidermidis 1457 M10, an isogenic icaA Tn917 mutant. PIA appears to play a critical role in the adherence of S. epidermidis to orthopaedic biomaterials, and may serve as an important virulence determinant in orthopaedic prosthetic device infections.

  11. 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

  12. BopA Does Not Have a Major Role in the Adhesion of Bifidobacterium bifidum to Intestinal Epithelial Cells, Extracellular Matrix Proteins, and Mucus

    PubMed Central

    Kainulainen, Veera; Reunanen, Justus; Hiippala, Kaisa; Guglielmetti, Simone; Vesterlund, Satu; Palva, Airi

    2013-01-01

    The ability of bifidobacteria to adhere to the intestine of the human host is considered to be important for efficient colonization and achieving probiotic effects. Bifidobacterium bifidum strains DSM20456 and MIMBb75 adhere well to the human intestinal cell lines Caco-2 and HT-29. The surface lipoprotein BopA was previously described to be involved in mediating adherence of B. bifidum to epithelial cells, but thioacylated, purified BopA inhibited the adhesion of B. bifidum to epithelial cells in competitive adhesion assays only at very high concentrations, indicating an unspecific effect. In this study, the role of BopA in the adhesion of B. bifidum was readdressed. The gene encoding BopA was cloned and expressed without its lipobox and hydrophobic signal peptide in Escherichia coli, and an antiserum against the recombinant BopA was produced. The antiserum was used to demonstrate the abundant localization of BopA on the cell surface of B. bifidum. However, blocking of B. bifidum BopA with specific antiserum did not reduce adhesion of bacteria to epithelial cell lines, arguing that BopA is not an adhesin. Also, adhesion of B. bifidum to human colonic mucin and fibronectin was found to be BopA independent. The recombinant BopA bound only moderately to human epithelial cells and colonic mucus, and it failed to bind to fibronectin. Thus, our results contrast the earlier findings on the major role of BopA in adhesion, indicating that the strong adhesion of B. bifidum to epithelial cell lines is BopA independent. PMID:24014530

  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. 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

  15. Draft Genome Sequence of a Novel Luteimonas sp. Strain from Coral Mucus, Hawai‘i

    PubMed Central

    Miller, James M.; Rowley, Sonia J.

    2016-01-01

    Luteimonas sp. strain JM171 was cultivated from mucus collected around the coral Porites lobata. The JM171 draft genome of 2,992,353 bp contains 2,672 protein-coding open reading frames, 45 tRNA coding regions, and encodes a putative globin-coupled diguanylate cyclase, JmGReg. PMID:27811107

  16. 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...

  17. 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...

  18. 76 FR 52961 - Prospective Grant of Exclusive License: Devices for Clearing Mucus From Endotracheal Tubes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-24

    ...-061-2004/0 ``Mucus Shaving Apparatus for Endotracheal Tubes''; U.S. Patent 7,051,737 to EndOclear, LLC.... SUPPLEMENTARY INFORMATION: The patent intended for licensure covers an endotracheal tube cleaning apparatus...). The preferred embodiment as recited in the claims is a cleaning apparatus with a flexible central...

  19. 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.

  20. 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.

  1. 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...

  2. 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...

  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. Evidence that ferritin is associated with light production in the mucus of the marine worm Chaetopterus

    PubMed Central

    Rawat, Renu; Deheyn, Dimitri D.

    2016-01-01

    The blue glow of the mucus from Chaetopterus involves a photoprotein, iron and flavins. Identity and respective role of these components remain, however, largely unresolved today, likely because of viscosity issues and inhibition of this system by oxidizers conventionally used to track bioluminescence activity. Here, we used gentle centrifugation to obtain a mucus supernatant showing no inhibition to oxidizers, allowing for further analysis. We applied conventional chromatographic techniques to isolate major proteins associated with light emission. Luminescence ability of elutriate fractions was tested with hydrogen peroxide to track photoprotein and/or protein-bound chromophore. Fractions producing light contained few major proteins, one with similarity to ferritin. Addition to the mucus of elements with inhibitory/potentiary effect on ferritin ferroxidase activity induced corresponding changes in light production, emphasizing the possible role of ferritin in the worm bioluminescence. DNA of the protein was cloned, sequenced, and expressed, confirming its identity to a Chaetopterus Ferritin (ChF). Both ferric and ferrous iron were found in the mucus, indicating the occurrence of both oxidase and reductase activity. Biochemical analysis showed ChF has strong ferroxidase activity, which could be a source of biological iron and catalytic energy for the worm bioluminescence when coupled to a reduction process with flavins. PMID:27830745

  5. Characterization of a novel hemagglutinin of diarrhea-associated Escherichia coli that has characteristics of diffusely adhering E. coli and enteroaggregative E. coli.

    PubMed Central

    Yamamoto, T; Wakisaka, N; Nakae, T; Kamano, T; Serichantalergs, O; Echeverria, P

    1996-01-01

    Escherichia coli 73-1 (serotype O73:H33) and 5-2 (serotype O89:H-) isolated from patients with diarrhea adhered to tissue culture cells (HeLa and HEp-2) as well as coverslips (plastic and glass) in a diffuse pattern. Adherence of strain 73-1 was mediated by a 110-kbp plasmid designated pEDA1 and correlated with D-mannose-resistant hemagglutinin (MRHA) detected with bovine, sheep, or human erythrocytes. The MRHA region was duplicated on pEDA1 and mediated the production of the 57-kDa outer membrane protein whose N-terminal amino acid sequence was hydrophobic. In accordance with MRHA and adherence, the 57-kDa outer membrane protein was observed best at 37 degrees C and to a lesser extent at 25 degrees C. In human intestine, adherence to mucus and colonic epithelium was obvious. No detectable pili were observed. The enteroaggregative E. coli heat-stable enterotoxin 1 (EAST1) gene, whose nucleotide sequence was 99.1% homologous to that of enteroaggregative E. coli, was present adjacent to the MRHA region on pEDA1. Strain 5-2 also exhibited MRHA activities and adherence and had sequences corresponding to those of the MRHA region and EAST1 gene. The data suggest that strain 73-1 (and strain 5-2), which has characteristics of both diffusely adhering E. coli and enteroaggregative E. coli, possesses a novel hemagglutinin associated with diffuse adherence. PMID:8751919

  6. [Expression and role of sugar chains on airway mucus during the exacerbation of airway inflammation].

    PubMed

    Ishibashi, Yuji; Inouye, Yoshio; Taniguchi, Akiyoshi

    2012-01-01

    Human bronchial mucins, such as MUC5AC, have traditionally been defined as a family of high-molecular weight glycoproteins. Changes in the contents of sugar chains on MUC5AC are among the fundamental features in inflammatory respiratory disease. The changes have been shown to lead to unfavorable alterations in the viscosity of mucus, resulting in impairment of mucociliary transport, vulnerability to viral/bacterial infection as sugar chains play an important role in adhesion of some viruses and bacteria to the epithelium, and finally inflammatory cell infiltration in the airway. Recently, we found that expression of some glycosyltransferases associated with the contents and structure of sugar chains is regulated by phosphatidylinositol-phospholipase (PI-PL) C signaling in cells. L-Carbocisteine, a mucoregulatory drug, normalized or balanced fucosylated and sialylated sugar chains, such as sialyl Lewis x through inhibition of PI-PL C signaling. We prepared MUC5AC fusion protein with tandem repeats associated with MUC5AC, and confirmed that L-carbocisteine inhibited the increases in viscosity associated with sialyl Lewis x expression levels. In addition, the clinical study (2008) noted that L-carbocisteine reduced the frequency of common colds and exacerbation of symptoms in patients with COPD. These favorable effects in patients may be due to normalization of sugar chain contents on mucins. We suggest that the inhibitory effect on infection of airway epithelial cells by rhinoviruses, respiratory syncytial virus, and influenza viruses by treatment with L-carbocisteine may also be based on the regulation of sugar chain contents or structures on mucins.

  7. Interrelationship between milk constituents, serum oestradiol and vaginal mucus indicators of oestrus in Egyptian buffaloes.

    PubMed

    Kandiel, M M M; El-Naggar, R A M; Abdel-Ghaffar, A E; Sosa, G A M; Abou El-Roos, N A

    2014-02-01

    The intensity of heat signs in buffaloes is generally low and the incidence of suboestrus varied from 15 to 73% (Buffalopedia). The objective of this study was to investigate the feasibility of monitoring the changes in some milk constituents, oestradiol levels and electrical conductivity of vaginal mucus during peri-oestrous period in prediction of the timing of oestrus in buffaloes. Twenty-one Egyptian buffaloes aged 3-9 year, 1st-6th lactations, were examined by oestrous detector and ultrasonographically for monitoring the ovarian and uterine activity for 7 days around the time of standing oestrus. Sodium, potassium, chloride and lactose were assayed in aqueous phase of milk; besides, oestradiol was estimated in serum. Current results declared highly significant acute changes in milk constituents at the time of oestrus characterized by peaking of chloride and sodium levels and lowering of potassium and lactose values. The alternation in milk composition when arranged in decreasing order of magnitude, sodium was the highest (77.78 ± 0.69%), followed by chloride (61.60 ± 1.52%) and potassium (-58.14 ± 10.89%). Concomitantly, milk lactose decreased by 26.07 ± 7.97% compared to baseline levels. Synchronously, vaginal electrical resistance (VER) showed a significant (p < 0.01) decrease, but serum oestradiol 17β levels surged (59.93 ± 7.29 pg/ml) on day of oestrus. Serum oestradiol level was negatively correlated with VER (r = -0.577), potassium (r = -0.661), positively correlated with chloride (r = 0.707) and sodium (r = 0.579) and not correlated with lactose levels. These results for the first time suggested that the changes in constituents of milk during peri-oestrous period may be used as a practical non-invasive indicator for oestrous detection and prediction of ovulation in Egyptian buffaloes.

  8. 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

  9. Actinobacillus actinomycetemcomitans adheres to human gingival fibroblasts and modifies cytoskeletal organization.

    PubMed

    Gutiérrez-Venegas, Gloria; Kawasaki-Cárdenas, Perla; Garcés, Carla Portillo; Román-Alvárez, Patricia; Barajas-Torres, Carolina; Contreras-Marmolejo, Luis Arturo

    2007-09-01

    Adherence of Actinobacillus actinomycetemcomitans to human gingival fibroblast cells induces cytoskeletal reorganization. A. actinomycetemcomitans is considered a pathogenic bacteria involved in localized aggressive periodontitis. Studies with epithelial cells have shown an adherent capacity of bacteria that is increased under anaerobic conditions. For adherence to take place, there is a need for interaction between extracellular vesicles and bacterial fimbriae. However, molecular events associated with the adherence process are still unknown. The aim of this study was to investigate whether A. actinomycetemcomitans adherence to human gingival fibroblasts promotes cytoskeletal reorganization. Adherence was determined with light microscopy and scanning electron microscopy. For F-actin visualization, cells were treated with fluorescein-isothiocyanate-phalloidin and samples were examined with epifluorescence optics. Fluorescent was recorded on Kodak T-Max 400 film. We showed that A. actinomycetemcomitans adheres to human gingival fibroblast primary cultures, this property stimulating an increase in the intracellular calcium levels. In human gingival fibroblast primary cultures, we observed that maximal A. actinomycetemcomitans adherence took place 1.5h after culture infection occurred and remained for 6h. The adherence was associated with morphologic alterations and an increased in the intracellular calcium levels. These experiments suggest that A. actinomycetemcomitans adherence cause morphological alterations, induce actin stress fibers and recruitment of intracellular calcium levels.

  10. Pilot study examining the efficacy of an electronic intervention to promote HIV medication adherence.

    PubMed

    Claborn, Kasey R; Leffingwell, Thad R; Miller, Mary Beth; Meier, Ellen; Stephens, Johnny R

    2014-01-01

    Widespread dissemination of current interventions designed to improve HIV medication adherence is limited by several barriers, including additional time and expense burdens on the health care systems. Electronic interventions could aid in dissemination of interventions in the clinic setting. This study developed and tested the feasibility and acceptability of a computer-based adaption of an empirically supported face-to-face adherence promotion intervention. HIV-positive individuals (N = 92) on antiretroviral therapy with self-reported adherence <95% were randomized to the electronic intervention + treatment as usual (TAU) or TAU only. Study outcome variables which included treatment self-efficacy and self-reported medication adherence were assessed at baseline and follow-up. Time × condition interaction effects in mixed model analysis of variance (ANOVAs) examined the differences in patterns of change in the outcome variables over time between the two groups. Participants in the electronic intervention condition reported higher levels of self-efficacy to adhere to their medication at follow-up compared to the control condition. Although nonsignificant, levels of adherence tended to improve over time in the intervention condition, while TAU adherence remained constant. This was the first study to investigate a single-session, computer-based adherence intervention. Results suggest that electronic interventions are feasible and this method may be effective at increasing self-efficacy and adherence among patients reporting suboptimal adherence levels.

  11. Understanding Dutch practice nurses' adherence to evidence-based smoking cessation guidelines and their needs for web-based adherence support: results from semistructured interviews

    PubMed Central

    de Ruijter, D; Smit, E S; de Vries, H; Goossens, L; Hoving, C

    2017-01-01

    Objectives Practice nurses in general practices suboptimally adhere to smoking cessation guidelines. Since the effectiveness of their smoking cessation support is greatest when full adherence to these guidelines is achieved, interventions need to be developed to improve practice nurses' guideline adherence, for example, by tailoring their content to adherence determinants. However, the sociocognitive determinants explaining adherence have not yet been investigated. Therefore, this qualitative needs assessment aimed to explore practice nurses' current counselling practices, as well as their sociocognitive beliefs related to their smoking cessation guideline adherence and their needs regarding web-based adherence support. Setting Primary care; general practices in the Netherlands. Participants 19 practice nurses, actively involved in smoking cessation counselling. Methods Semistructured individual interviews, based on the I-Change Model and the Diffusion of Innovations Theory, were conducted from May to September 2014. Data were systematically analysed using the Framework Method and considered reliable (κ 0.77; % agreement 99%). Results Respondents felt able to be empathic and collaborative during smoking cessation consultations. They also reported psychological (eg, low self-efficacy to increase patient motivation and arranging adequate follow-up consultations) and practical barriers (eg, outdated information on quit support compensation and a perceived lack of high-quality trainings for practice nurses) to smoking cessation guideline adherence. Most respondents were interested in web-based adherence support to overcome these barriers. Conclusions Sociocognitive determinants influence practice nurses' smoking cessation guideline adherence. To improve their adherence, web-based tailored adherence support can provide practice nurses with personally relevant feedback tailored to individually perceived barriers to smoking cessation guideline adherence. More

  12. 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

  13. Predicting adherence to antiretroviral therapy among pregnant women in Guyana: Utility of the Health Belief Model.

    PubMed

    Vitalis, Deborah

    2016-08-29

    Barriers to antiretroviral therapy (ART) adherence among pregnant women are varied and complex. This study explored the constructs of a theoretical model, the Health Belief Model (HBM) to understand and predict ART adherence among pregnant women in Guyana. A cross-sectional study surveyed 108 pregnant women attending 11 primary care clinics. ART adherence ranging from the past weekend to three months was assessed through self-reports, and health beliefs with the Adherence Determinants Questionnaire (ADQ). Constructs with sufficient variation in responses were tested for association with the level of adherence using Spearman's rank correlation coefficient and test. Sixty-seven per cent (72) of the women reported being always adherent. Although there was positive endorsement of ART treatment and adherence, the HBM did not help in understanding or predicting ART adherence in this population. Only one item from the perceived susceptibility construct was significantly associated (p = 0.009) with adherence. Interventions are warranted to address ART adherence in this population, as 19% of the women were recently non-adherent. Although the ADQ did not contribute to a deeper understanding or provide insight into pathways that can be targeted for intervention, theoretical models can play a key role in identifying these pathways.

  14. Improving adherence and outcomes in diabetic patients

    PubMed Central

    Joshi, Renu; Joshi, Disha; Cheriyath, Pramil

    2017-01-01

    Objective Nonadherence in diabetes is a problem leading to wasted resources and preventable deaths each year. Remedies for diminishing nonadherence are many but marginally effective, and outcomes remain suboptimal. Aim The aim of this study was to test a new iOS “app”, PatientPartner. Derived from complexity theory, this novel technology has been extensively used in other fields; this is the first trial in a patient population. Methods Physicians referred patients who were “severely non-adherent” with HbA1c levels >8. After consent and random assignment (n=107), subjects in the intervention group were immersed in the 12-min PatientPartner game, which assesses and trains subjects on parameters of thinking that are critical for good decision making in health care: information management, stress coping, and health strategies. The control group did not play PatientPartner. All subjects were called each week for 3 weeks and self-reported on their medication adherence, diet, and exercise. Baseline and 3-month post-intervention HbA1c levels were recorded for the intervention group. Results Although the control group showed no difference on any measures at 3 weeks, the intervention group reported significant mean percentage improvements on all measures: medication adherence (57%, standard deviation [SD] 18%–96%, SD 9), diet (50%, SD 33%–75%, SD 28), and exercise (29%, SD 31%–43%, SD 33). At 3 months, the mean HbA1c levels in the intervention group were significantly lower (9.6) than baseline (10.7). Conclusion Many programs to improve adherence have been proved to be expensive and marginally effective. Therefore, improvements from the single use of a 12-min-long “app” are noteworthy. This is the first ever randomized, controlled trial to demonstrate that an “app” can impact the gold standard biological marker, HbA1c, in diabetes. PMID:28243070

  15. Relationship of race-, sexual orientation-, and HIV-related discrimination with adherence to HIV treatment: a pilot study.

    PubMed

    Boarts, Jessica M; Bogart, Laura M; Tabak, Melanie A; Armelie, Aaron P; Delahanty, Douglas L

    2008-10-01

    Adherence to highly active antiretroviral therapy (HAART) must be close to perfect in order to maintain suppression of HIV viral load, and to prevent the development of drug resistant strains of HIV. People living with HIV (PLWH) often report low levels of adherence. One variable that has been linked to poor adherence is perceived discrimination; however, research has generally not considered the possible unique effects of different types of discrimination on adherence. The present pilot study aimed to examine the association of three types of discrimination (due to HIV+ status, race, or sexual orientation) with adherence among 57 PLWH. Logistic regression analyses were conducted to demonstrate the relationships between each type of discrimination and self-reported adherence. Racial discrimination significantly predicted lower adherence levels, whereas sexual orientation- and HIV-related discrimination did not. Results underscore the importance of addressing discrimination issues, specifically racial, when designing interventions to improve adherence to HAART.

  16. Carbocisteine normalizes the viscous property of mucus through regulation of fucosylated and sialylated sugar chain on airway mucins.

    PubMed

    Ishibashi, Yuji; Takayama, Goh; Inouye, Yoshio; Taniguchi, Akiyoshi

    2010-09-01

    Almost all of fucose and sialic acid in mucus are found on the mucus glycoproteins (mucins), and these sugar components on mucins are known to be associated with the viscous property of mucus. We have reported some aspects of carbocisteine, a mucoregulatory drug, correcting fucose and sialic acid contents in mucus. At present, carbocisteine's expectorant action of airway mucus is postulated to involve - the regulation of fucose and sialic acid contents on mucins. However little information is available about the relationship between the viscosity and sugar contents on mucins when treated with carbocisteine. To investigate further the mechanism behind the action of carbocisteine, the present study prepared MUC5AC fusion protein which has tandem repeat regions associated with MUC5AC, and evaluated the effects of carbocisteine on tumor necrosis factor (TNF)-alpha-induced increases of mucus viscosity and sialyl-Lewis x-epitopes antigen, an antigen which consists of fucosylated and sialylated sugar chains on the MUC5AC fusion proteins. Carbocisteine inhibited the TNF-alpha-induced increases of the viscosity and sialyl-Lewis x-epitopes on MUC5AC fusion protein. These findings suggest that carbocisteine may normalize the viscosity of mucus through "balancing" of fucose and sialic acid contents on airway mucins.

  17. 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.

  18. Differentially expressed proteins in gill and skin mucus of Atlantic salmon (Salmo salar) affected by amoebic gill disease.

    PubMed

    Valdenegro-Vega, Victoria A; Crosbie, Phil; Bridle, Andrew; Leef, Melanie; Wilson, Richard; Nowak, Barbara F

    2014-09-01

    The external surfaces of fish, such as gill and skin, are covered by mucus, which forms a thin interface between the organism and water. Amoebic gill disease (AGD) is a parasitic condition caused by Neoparamoeba perurans that affects salmonids worldwide. This disease induces excessive mucus production in the gills. The host immune response to AGD is not fully understood, and research tools such as genomics and proteomics could be useful in providing further insight. Gill and skin mucus samples were obtained from Atlantic salmon (Salmo salar) which were infected with N. perurans on four successive occasions. NanoLC tandem mass spectrometry (MS/MS) was used to identify proteins in gill and skin mucus of Atlantic salmon affected by AGD. A total of 186 and 322 non-redundant proteins were identified in gill and skin mucus respectively, based on stringent filtration criteria, and statistics demonstrated that 52 gill and 42 skin mucus proteins were differentially expressed in mucus samples from AGD-affected fish. By generating protein-protein interaction networks, some of these proteins formed part of cell to cell signalling and inflammation pathways, such as C-reactive protein, apolipoprotein 1, granulin, cathepsin, angiogenin-1. In addition to proteins that were entirely novel in the context in the host response to N. perurans, our results have confirmed the presence of protein markers in mucus that have been previously predicted on the basis of modified mRNA expression, such as anterior gradient-2 protein, annexin A-1 and complement C3 factor. This first proteomic analysis of AGD-affected salmon provides new information on the effect of AGD on protein composition of gill and skin mucus. Future research should focus on better understanding of the role these components play in the response against infection with N. perurans.

  19. 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 12 months: Phase I (3 months supervised exercise) and Phase II (9 months 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

  20. Dietary Lactobacillus acidophilus modulated skin mucus protein profile, immune and appetite genes expression in gold fish (Carassius auratus gibelio).

    PubMed

    Hosseini, Marjan; Kolangi Miandare, Hamed; Hoseinifar, Seyed Hossein; Yarahmadi, Peyman

    2016-12-01

    The objective of the present study was to investigate the effect of dietary Lactobacillus acidophilus on skin mucus protein pattern, immune and appetite related genes expression as well as growth performance in gold fish (Carassius auratus gibelio). Three hundred healthy gold fish (2.5 ± 0.05) juveniles were randomly distributed in 12 glass aquariums (400-L; 25 fish per aquaria) and fed experimental diets contain different levels of L. acidophilus (0, 1.5 × 10(8), 3 × 10(8) and 6 × 10(8)) for 8 weeks. SDS-PAGE analysis of skin mucus protein profile at the end of the feeding trial revealed differences in protein profile of probiotic fed fish and control group; even three new bands were observed in L. acidophilus treated groups. Furthermore, fish fed 6 × 10(8) CFU g(-1) supplemented diet showed up-regulation of both TNF-1α and TNF-2α gene expression (P < 0.05). Evaluation of appetite related gene expression showed down-regulation of ghrelin in probiotic fed fish compared those of control treatment (P < 0.05). However, administration of different levels of L. acidophilus had no significant effects on growth performance (P > 0.05). These results demonstrated that while no beneficial effects on growth performance, dietary L. acidophilus affects immune and appetite related genes expression as well as skin mucus protein profile.

  1. Antiretroviral concentrations in small hair samples as a feasible marker of adherence in rural Kenya

    PubMed Central

    Hickey, Matthew D; Salmen, Charles R; Tessler, Robert A; Omollo, Dan; Bacchetti, Peter; Magerenge, Richard; Mattah, Brian; Salmen, Marcus R; Zoughbie, Daniel; Fiorella, Kathryn J; Geng, Elvin; Njoroge, Betty; Jin, Chengshi; Huang, Yong; Bukusi, Elizabeth A; Cohen, Craig R; Gandhi, Monica

    2014-01-01

    Antiretroviral hair levels objectively quantify drug exposure over time and predict virologic responses. We assessed the acceptability and feasibility of collecting small hair samples in a rural Kenyan cohort. 95% of participants (354/373) donated hair. Although median self-reported adherence was 100% (IQR 96–100%), a wide range of hair concentrations likely indicates overestimation of self-reported adherence and the advantages of a pharmacologic adherence measure. Higher nevirapine (NVP) hair concentrations observed in women and older adults require further study to unravel behavioral versus pharmacokinetic contributors. In resource-limited settings, hair antiretroviral levels may serve as a low-cost quantitative biomarker of adherence. PMID:24694932

  2. Trauma, Dissociation, and Antiretroviral Adherence among Persons Living with HIV/AIDS

    PubMed Central

    Keuroghlian, Alex S.; Kamen, Charles S.; Neri, Eric; Lee, Susanne; Liu, Rhianon; Gore-Felton, Cheryl

    2011-01-01

    Background There are approximately 1,000,000 persons living with HIV/AIDS (PLH) in the United States; to reduce rates of new infection and curb disease progression, adherence to HIV medication among PLH is critical. Despite elevated trauma rates in PLH, no studies to date have investigated the relationship between dissociation, a specific symptom of trauma, and HIV medication adherence. We hypothesized that Post-Traumatic Stress Disorder (PTSD) symptoms would be associated with lower adherence, and that dissociation would moderate this relationship. Methods Forty-three individuals with HIV were recruited from community-based clinics to participate in a cross-sectional study. The relationship of trauma, dissociation, and their interaction to the probability of antiretroviral adherence was assessed using a hierarchical binary logistic regression analysis. Results Among 38 eligible participants, greater PTSD was associated with lower odds of adherence (OR = .92, p < .05). Dissociation moderated the effect of PTSD on adherence, resulting in lower odds of adherence (OR = .95, p < .05). PTSD symptoms were significantly associated with lower odds of adherence in individuals reporting high levels of dissociation (OR = .86, p < .05) but not in those reporting low levels of dissociation (OR = 1.02, p > .05). Conclusions This is the first study to demonstrate a relationship between dissociation and medication adherence. Findings are discussed in the context of clinical management of PLH with trauma histories and the need for interventions targeting dissociative symptomatology to optimize adherence. PMID:21636097

  3. Current Concepts for PrEP Adherence

    PubMed Central

    Haberer, Jessica E.

    2016-01-01

    Purpose of review This review describes 1) the current understanding of adherence to oral PrEP, 2) methods for adherence measurement, 3) approaches to supporting PrEP adherence, and 4) guidance for defining PrEP adherence goals within the larger context of HIV prevention. Recent findings PrEP adherence has generally been higher in recent trials, open-label extensions, and demonstration projects compared to the initial clinical trials; potential explanations include known PrEP efficacy and different motivations to take PrEP. Recent studies have explored adherence monitoring through electronic pill containers, short message service (SMS), and drug concentrations in hair and dried blood spots. The few PrEP adherence interventions developed to date include combinations of enhanced counseling, feedback of objective adherence measurement, and SMS. Conceptualization of PrEP adherence is evolving. The goal is not 100% adherence indefinitely, as it was in clinical trials. PrEP adherence should be defined with respect to HIV exposure, which varies over time by sexual behavior and use of other prevention strategies. Summary PrEP adherence beyond clinical trials has generally been high enough to achieve reliable HIV prevention. Future efforts to measure and support PrEP adherence should focus on the context of risk for HIV acquisition, accounting for dynamic behaviors and choices among HIV prevention options. PMID:26633638

  4. An Application of School-Based Intervention Implementation Adherence Monitoring and Performance Feedback Procedures

    ERIC Educational Resources Information Center

    Mayer, Julia Elizabeth

    2012-01-01

    The current study examined the application of implementation adherence monitoring and group feedback procedures with teachers implementing the Leveled Literacy Intervention (LLI; Fountas & Pinnell, 2008a). Using a repeated measures design across time, changes in implementation adherence levels were examined as teachers participated in…

  5. Decisional capacity and medication adherence among youth with HIV.

    PubMed

    Chenneville, Tiffany; Clutter, Michiko Otsuki; Hintz, Stephanie; Walsh, Audra; Emmanuel, Patricia; Lujan-Zilberman, Jorge; Rodriguez, Carina

    2015-01-01

    This exploratory study examined the degree to which decisional capacity (DC) is associated with measures of self-reported medication adherence. We hypothesized that youth with higher levels of DC would report greater levels of antiretroviral medication adherence. Seventy-two (72) youth with HIV aged 13-24 participated in this study. Data collection included administration of the MacArthur Competence Tool for Treatment and measures of adherence (i.e., seven-day self-report interview, visual analog scale, and biological indicators). Data were analyzed using descriptive statistics, intercorrelations, and multiple and Poisson regression analyses. Youth with HIV who exhibited greater understanding of their disease were more likely to report fewer missed doses in the last seven days. Findings build upon literature in the areas of DC and health literacy and highlight the potential utility of enhancing HIV disease understanding among youth with HIV.

  6. 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…

  7. It's the adherence, stupid (that determines asthma control in preschool children)!

    PubMed

    Klok, Ted; Kaptein, Adrian A; Duiverman, Eric J; Brand, Paul L

    2014-03-01

    Although guideline-based asthma care and adherence to inhaled corticosteroids are predictors of asthma control, the role of adherence in maintaining long-term asthma control is largely unknown. This study was designed to explore the relationship between adherence to inhaled corticosteroids and long-term asthma control in young children with asthma. In this observational study, 81 2-6-year-old asthmatic children, using inhaled corticosteroids, closely followed-up in a programme with extensive self-management training, were enrolled. Adherence was measured daily for 12 months using Smartinhaler (Nexus6 Ltd, Auckland, New Zealand) devices. Long-term asthma control was assessed by parents and physicians and included clinical assessment, an asthma control questionnaire and lung function measurement. We examined the association of adherence to asthma control, adjusting for seasonal influences and clinical characteristics. Median (interquartile range) adherence was 87% (70-94%), and 64 (79%) children had well-controlled asthma throughout follow-up. Adherence >80% was associated with better asthma control, and we found no important confounders of this association. Children with persistent mild symptoms had lower adherence rates (p=0.028). Guideline-based asthma care was associated with good asthma control in most children. Adherence to inhaled corticosteroids was an independent strong predictor of long-term asthma control, with highest levels of asthma control found in children with adherence >80% of doses prescribed.

  8. 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.

  9. ADHERENCE AND QUALITY OF LIFE IN PATIENTS WITH TYPE II DIABETES MELLITUS IN NORTHERN GREECE

    PubMed Central

    Zioga, Efrosini; Kazakos, Kyriakos; Dimopoulos, Evagelos; Koutras, Christos; Marmara, Kalliopi; Marmara, Eleni-Efrosini; Marmaras, Athanasios; Lavdaniti, Maria

    2016-01-01

    Introduction: Adherence as a concept includes various types of health-related behavior. Better medical adherence leads to improved disease control and fewer diabetes–related complications. Quality of life and medication adherence are interrelated. Patients with diabetes who adhere to their treatment can experience an improvement in quality of life and vice versa. Aim: To assess treatment adherence in patients with type II diabetes, as well as the connection between adherence and quality of life. Methodology: A descriptive non-experimental study was conducted in a provincial hospital in Northern Greece. The sample examined was a convenience sample consisting of 108 patients with type II diabetes mellitus. They completed the “Diabetes Self-Care Activities Questionnaire” and SF-36 “Quality of Life Questionnaire”. Results: Participants demonstrated good adherence to diet and blood test / blood glucose test routines, but did not experience high levels of quality of life. The type of treatment affected the adherence to blood tests with a statistically significant difference (p=0,000). Also, marital status affected mental health with a statistically significant difference (p=0,032). The adherence sub scales are correlated with the all domains of quality of life. Conclusions: According to our findings, it is important to plan interventions to enhance adherence to other types of treatment and to help patients to further improve their quality of life. PMID:27698597

  10. An observational study of hand hygiene adherence following the introduction of an education intervention

    PubMed Central

    Arthur, Antony; Vaughan, Natalie; Wharrad, Heather; Windle, Richard

    2014-01-01

    Hand hygiene adherence needs to be increased and sustained in order to prevent and reduce healthcare associated infections. We implemented an educational intervention and observed the adherence of healthcare workers, patients and visitors over 24 hour periods at four observation points. For healthcare workers a total of 2,294 opportunities were observed and for patients and visitors, a total of 597 opportunities were observed. Healthcare worker adherence increased following the introduction of the educational intervention, with 53.0% (282/532) adherence at baseline (observation point 1), and was sustained varying between 67.7% and 70.8% in the post-intervention points (p=0.0007). The greatest increase in adherence was observed between baseline and the observation point 2. Adherence varied according to type of opportunity (p<0.0001) with the lowest level of adherence observed after contact with patient surroundings, however there was no obvious trend across the observation points. There was an interaction between point of study and ward (p=0.0001). For patients and visitors, adherence did differ according to the point of study (p=0.0074) with adherence prior to the intervention being 49.1% and then ranging from 43.5–61.8%. We suggest that future educational interventions should be implemented as this study implies that there is potential for increased and sustained adherence to hand hygiene protocols.

  11. Which psychosocial factors are related to chelation adherence in thalassemia? A systematic review.

    PubMed

    Evangeli, Michael; Mughal, Kulsoom; Porter, John B

    2010-06-01

    Good adherence to iron chelation therapy in thalassemia is crucial. Although there is evidence that adherence is related to regimen factors, there has been less emphasis on the relationship between psychosocial (psychological, demographic and social) factors and adherence. We present a systematic review of psychosocial correlates of chelation adherence in thalassemia. Nine studies met the inclusion criteria. Information was extracted regarding the study characteristics and the relationship between psychosocial factors and chelation adherence. Methodological quality was rated. The studies took place in a range of countries, were mostly cross sectional in design, and examined adherence to deferoxamine (DFO) only. Sample sizes ranged from 15 to 1573. A variety of psychosocial variables were examined. Definitions of adherence varied between studies and non adherence rates were also variable (9 to 66%). Older age was consistently associated with lower levels of chelation adherence. There were few other consistent findings. The methodological quality of studies was variable. There is a need for more methodologically sophisticated and theoretically informed studies on psychosocial correlates of chelation adherence. We offer specific suggestions.

  12. Impact of food, housing, and transportation insecurity on ART adherence: a hierarchical resources approach.

    PubMed

    Cornelius, Talea; Jones, Maranda; Merly, Cynthia; Welles, Brandi; Kalichman, Moira O; Kalichman, Seth C

    2017-04-01

    Antiretroviral therapy (ART) has transformed HIV into a manageable illness. However, high levels of adherence must be maintained. Lack of access to basic resources (food, transportation, and housing) has been consistently associated with suboptimal ART adherence. Moving beyond such direct effects, this study takes a hierarchical resources approach in which the effects of access to basic resources on ART adherence are mediated through interpersonal resources (social support and care services) and personal resources (self-efficacy). Participants were 915 HIV-positive men and women living in Atlanta, GA, recruited from community centers and infectious disease clinics. Participants answered baseline questionnaires, and provided prospective data on ART adherence. Across a series of nested models, a consistent pattern emerged whereby lack of access to basic resources had indirect, negative effects on adherence, mediated through both lack of access to social support and services, and through lower treatment self-efficacy. There was also a significant direct effect of lack of access to transportation on adherence. Lack of access to basic resources negatively impacts ART adherence. Effects for housing instability and food insecurity were fully mediated through social support, access to services, and self-efficacy, highlighting these as important targets for intervention. Targeting service supports could be especially beneficial due to the potential to both promote adherence and to link clients with other services to supplement food, housing, and transportation. Inability to access transportation had a direct negative effect on adherence, suggesting that free or reduced cost transportation could positively impact ART adherence among disadvantaged populations.

  13. 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.

  14. 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.

  15. Chemotactic Activity of Cyclophilin A in the Skin Mucus of Yellow Catfish (Pelteobagrus fulvidraco) and Its Active Site for Chemotaxis

    PubMed Central

    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

  16. 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

  17. Respiratory mucus hypersecretion really an innocent disorder. A 22-year mortality survey of 1061 working men

    SciTech Connect

    Annesi, I.; Kauffmann, F.

    1986-10-01

    The relation of chronic air-flow limitation and respiratory mucus hypersecretion to all causes of mortality was studied in a population of 1,061 men working in the Paris area, surveyed initially in 1960/1961, and followed for 22 yr. During this period, 369 deaths occurred; VC, FEV1, FEV1/H3, and FEV1/VC were significantly associated with mortality, even when age, smoking, occupational dust exposure, and chronic phlegm were taken into account. Besides the obstructive disorder, the hypersecretory disorder (chronic phlegm) was significantly associated with mortality. Controlling, using Cox's model, for age, FEV1/H3, smoking habits, and dust exposure, all factors associated with chronic mucus hypersecretion and mortality, showed that phlegm production remained significantly related to death (relative risk, = 1.35; p less than 0.01). Although relatively weak, this relationship is not negligible in terms of public health because of the high prevalence of chronic phlegm.

  18. Cryopreservation of adherent neuronal networks.

    PubMed

    Ma, Wu; O'Shaughnessy, Thomas; Chang, Eddie

    2006-07-31

    Neuronal networks have been widely used for neurophysiology, drug discovery and toxicity testing. An essential prerequisite for future widespread application of neuronal networks is the development of efficient cryopreservation protocols to facilitate their storage and transportation. Here is the first report on cryopreservation of mammalian adherent neuronal networks. Dissociated spinal cord cells were attached to a poly-d-lysine/laminin surface and allowed to form neuronal networks. Adherent neuronal networks were embedded in a thin film of collagen gel and loaded with trehalose prior to transfer to a freezing medium containing DMSO, FBS and culture medium. This was followed by a slow rate of cooling to -80 degrees C for 24 h and then storage for up to 2 months in liquid nitrogen at -196 degrees C. The three components: DMSO, collagen gel entrapment and trehalose loading combined provided the highest post-thaw viability, relative to individual or two component protocols. The post-thaw cells with this protocol demonstrated similar neuronal and astrocytic markers and morphological structure as those detected in unfrozen cells. Fluorescent dye FM1-43 staining revealed active recycling of synaptic vesicles upon depolarizing stimulation in the post-thaw neuronal networks. These results suggest that a combination of DMSO, collagen gel entrapment and trehalose loading can significantly improve conventional slow-cooling methods in cryopreservation of adherent neuronal networks.

  19. Novel Compounds from Shark and Stingray Epidermal Mucus With Antimicrobial Activity Against Wound Infection Pathogens

    DTIC Science & Technology

    2013-03-01

    cultures have been screened against a different panel of human pathogenic tester strains, including Bacillus spp (B. anthracis and B. cereus ...classify the Gram positive bacteria as Bacillus spp or not, or members of the Bacillus cereus group. Optimal temperatures (25, 30 or 35ºC) were...Mucus Mg(TFA)2-extracted samples were screened for antibiotic activity using the tester pathogen, Bacillus subtilis. B. subtilis was grown overnight

  20. 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

  1. 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.

  2. 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.

  3. Autophagy is essential for ultrafine particle-induced inflammation and mucus hyperproduction in airway epithelium.

    PubMed

    Chen, Zhi-Hua; Wu, Yin-Fang; Wang, Ping-Li; Wu, Yan-Ping; Li, Zhou-Yang; Zhao, Yun; Zhou, Jie-Sen; Zhu, Chen; Cao, Chao; Mao, Yuan-Yuan; Xu, Feng; Wang, Bei-Bei; Cormier, Stephania A; Ying, Song-Min; Li, Wen; Shen, Hua-Hao

    2016-01-01

    Environmental ultrafine particulate matter (PM) is capable of inducing airway injury, while the detailed molecular mechanisms remain largely unclear. Here, we demonstrate pivotal roles of autophagy in regulation of inflammation and mucus hyperproduction induced by PM containing environmentally persistent free radicals in human bronchial epithelial (HBE) cells and in mouse airways. PM was endocytosed by HBE cells and simultaneously triggered autophagosomes, which then engulfed the invading particles to form amphisomes and subsequent autolysosomes. Genetic blockage of autophagy markedly reduced PM-induced expression of inflammatory cytokines, e.g. IL8 and IL6, and MUC5AC in HBE cells. Mice with impaired autophagy due to knockdown of autophagy-related gene Becn1 or Lc3b displayed significantly reduced airway inflammation and mucus hyperproduction in response to PM exposure in vivo. Interference of the autophagic flux by lysosomal inhibition resulted in accumulated autophagosomes/amphisomes, and intriguingly, this process significantly aggravated the IL8 production through NFKB1, and markedly attenuated MUC5AC expression via activator protein 1. These data indicate that autophagy is required for PM-induced airway epithelial injury, and that inhibition of autophagy exerts therapeutic benefits for PM-induced airway inflammation and mucus hyperproduction, although they are differentially orchestrated by the autophagic flux.

  4. Helicobacter pylori Couples Motility and Diffusion to Actively Create a Heterogeneous Complex Medium in Gastric Mucus

    NASA Astrophysics Data System (ADS)

    Fu, Henry; Mirbagheri, Seyed Amir

    2016-11-01

    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. 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. Funded by National Science Foundation award CBET-1252182.

  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. Characterization of gelatin/chitosan scaffold blended with aloe vera and snail mucus for biomedical purpose.

    PubMed

    López Angulo, Daniel Enrique; do Amaral Sobral, Paulo José

    2016-11-01

    Biologically active scaffolds used in tissue engineering and regenerative medicine have been generating promising results in skin replacement. The present study aims to test the hypothesis that the incorporation of Aloe vera and snail mucus into scaffolds based on gelatin and chitosan could improve their structure, composition and biodegradability, with a potential effect on bioactivity. Homogeneous pore diameter as well as pore walls in the composite scaffold could be seen in the SEM image. The pores in the scaffolds were interconnected and their sizes ranged from 93 to 296μm. The addition of Aloe vera and snail mucus enlarged the mean pore size with increased porosity and caused changes in the pore architecture. The FTIR analysis has shown good affinity and interaction between the matrix and the Aloe, which may decrease water-binding sites, so this fact hindered the water absorption capacity of the material. The mechanical properties could explain the highest swelling capacity of the snail scaffold, because the high percentage of elongation could facilitate the entry of liquid in it, generating a matrix with plenty of fluid retention. The real innovation in the present work could be the use of these substances (Aloe and snail mucus) for tissue engineering.

  7. 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.

  8. Competition for attachment of aquaculture candidate probiotic and pathogenic bacteria on fish intestinal mucus.

    PubMed

    Vine, N G; Leukes, W D; Kaiser, H; Daya, S; Baxter, J; Hecht, T

    2004-06-01

    Probiotics for aquaculture are generally only selected by their ability to produce antimicrobial metabolites; however, attachment to intestinal mucus is important in order to remain within the gut of its host. Five candidate probiotics (AP1-AP5), isolated from the clownfish, Amphiprion percula (Lacepéde), were examined for their ability to attach to fish intestinal mucus and compete with two pathogens, Aeromonas hydrophila and Vibrio alginolyticus. Two different radioactive isotopes were used to quantify competition between pathogens and probionts. Attachment of the pathogens was enhanced by the presence of the candidate probiotics. However, the addition of the candidate probiotics after the pathogens resulted in reduced pathogen attachment. Only AP5 caused lower attachment success of V. alginolyticus when added before the pathogen. When AP5 was added first, the average attachment change was 41% compared with 72% when added after V. alginolyticus, suggesting that the probiotic is displaced but that enhanced attachment of the pathogen does not occur. Conversely, when V. alginolyticus was added first, followed by AP5, attachment change was 37% while AP5 had 92% attachment change when added second. This implies that the pathogen was displaced by the candidate probiotic and therefore it appeared that, based on the ability of probiont AP5 to attach to mucus, the growth of the pathogen in the digestive tract might be suppressed by the candidate probiont's presence.

  9. 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

  10. A poly(ethylene glycol)-based surfactant for formulation of drug-loaded mucus penetrating particles

    PubMed Central

    Mert, Olcay; Lai, Samuel K.; Ensign, Laura; Yang, Ming; Wang, Ying-Ying; Wood, Joseph; Hanes, Justin

    2011-01-01

    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 polyethylene 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

  11. 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.

  12. 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

  13. Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure.

    PubMed

    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.

  14. An observational study of health literacy and medication adherence in adult kidney transplant recipients

    PubMed Central

    Demian, Maryam N.; Shapiro, R. Jean

    2016-01-01

    Background There is a high prevalence of non-adherence to immunosuppressants in kidney transplant recipients. Although limited health literacy is common in kidney recipients and is linked to adverse outcomes in other medical populations, its effect on medication adherence in kidney transplant recipients remains poorly understood. The objective was to investigate the effect of lower health literacy on immunosuppressant adherence. Methods Kidney recipients who were at least 6 months post-transplant and outpatients of Vancouver General Hospital in B.C., Canada were recruited through invitation letters. A total of 96 recipients completed the Health Literacy Questionnaire, which provides a multifactorial profile of self-reported health literacy and the Transplant Effects Questionnaire-Adherence subscale measuring self-reported immunosuppressant adherence. Hierarchical linear regression was used to analyze the association between health literacy and adherence after controlling for identified risk factors of non-adherence. Results Our sample was on average 53 years old, 56% male and 9 years post-transplant. Kidney recipients reported low levels of health literacy on scales measuring active health management and critical appraisal of information and 75% reported non-perfect adherence. Worse adherence was associated with poorer overall health literacy (ΔR2 = 0.08, P = 0.004) and lower scores on six of nine of the health literacy factors. Conclusions Poorer health literacy is associated with lower immunosuppressant adherence in adult kidney transplant recipients suggesting the importance of considering a recipient's level of health literacy in research and clinical contexts. Medication adherence interventions can target the six factors of health literacy identified as being risk factors for lower medication adherence. PMID:27994867

  15. Far from superficial: microbial diversity associated with the skin and mucus of fish

    USGS Publications Warehouse

    Cipriano, Rocco C.; Dove, Alistair; Cipriano, R.C.; Bruckner, A.W.; Shchelkunov, I.S.

    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

  16. 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.)

  17. 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.

  18. 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…

  19. 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

  20. 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.

  1. Adherence of Pseudomonas aeruginosa to contact lenses

    SciTech Connect

    Miller, M.J.

    1988-01-01

    The purpose of this research was to examined the interactions of P. aeruginosa with hydrogel contact lenses and other substrata, and characterize adherence to lenses under various physiological and physicochemical conditions. Isolates adhered to polystyrene, glass, and hydrogel lenses. With certain lens types, radiolabeled cells showed decreased adherence with increasing water content of the lenses, however, this correlation with not found for all lenses. Adherence to rigid gas permeable lenses was markedly greater than adherence to hydrogels. Best adherence occurred near pH 7 and at a sodium chloride concentration of 50 mM. Passive adhesion of heat-killed cells to hydrogels was lower than the adherence obtained of viable cells. Adherence to hydrogels was enhanced by mucin, lactoferrin, lysozyme, IgA, bovine serum albumin, and a mixture of these macromolecules. Adherence to coated and uncoated lenses was greater with a daily-wear hydrogel when compared with an extended-wear hydrogel of similar polymer composition. Greater adherence was attributed to a higher concentration of adsorbed macromolecules on the 45% water-content lens in comparison to the 55% water-content lens.

  2. Predictors of Positive Airway Pressure Therapy Adherence in Children: A Prospective Study

    PubMed Central

    DiFeo, Natalie; Meltzer, Lisa J.; Beck, Suzanne E.; Karamessinis, Laurie R.; Cornaglia, Mary Anne; Traylor, Joel; Samuel, John; Gallagher, Paul R.; Radcliffe, Jerilynn; Beris, Heidi; Menello, Mary Kate; Marcus, Carole L.

    2012-01-01

    Study Objectives: Children with obstructive sleep apnea are increasingly being treated with positive airway pressure (PAP), particularly if they have underlying medical conditions. Although PAP is an effective treatment, its use is challenging due to poor adherence. We hypothesized that demographic, psychosocial, and polysomnographic parameters would be related to PAP adherence. We therefore prospectively collected data potentially pertaining to PAP adherence, and correlated it with PAP use. Methods: Fifty-six patients and their parents completed a series of psychosocial questionnaires prior to PAP initiation. Objective adherence data were obtained after 1 and 3 months of PAP use. Results: The population was primarily obese; 23% had neurodevelopmental disabilities. PAP adherence varied widely, with PAP being worn 22 ± 8 nights in month-1, but mean use was only 3 ± 3 h/night. The greatest predictor of use was maternal education (p = 0.002 for nights used; p = 0.033 for mean h used/night). Adherence was lower in African American children vs other races (p = 0.021). In the typically developing subgroup, adherence correlated inversely with age. Adherence did not correlate with severity of apnea, pressure levels, or psychosocial parameters other than a correlation between family social support and nights of PAP use in month-3. Conclusions: PAP adherence in children and adolescents is related primarily to family and demographic factors rather than severity of apnea or measures of psychosocial functioning. Further research is needed to determine the relative contributions of maternal education, socioeconomic status and cultural beliefs to PAP adherence in children, in order to develop better adherence programs. Citation: DiFeo N; Meltzer LJ; Beck SE; Karamessinis LR; Cornaglia MA; Traylor J; Samuel J; Gallagher PR; Radcliffe J; Beris H; Menello MK; Marcus CL. Predictors of positive airway pressure therapy adherence in children: a prospective study. J Clin Sleep Med 2012

  3. Promoting homework adherence in cognitive-behavioral therapy for adolescent depression.

    PubMed

    Jungbluth, Nathaniel J; Shirk, Stephen R

    2013-01-01

    This study used prospective, observational methods to evaluate six features of therapist behavior as predictors of homework adherence in cognitive-behavioral therapy for adolescent depression, with the goal of identifying therapist strategies with the potential to improve adolescent adherence. Therapist behaviors were expected to interact with initial levels of client resistance or adherence to predict subsequent homework completion. Participants were 50 referred adolescents (33 female, 54% ethnic minority) ages 14 to 18 (M = 15.9) meeting diagnostic criteria for a depressive disorder, and without comorbid psychotic disorder, bipolar disorder, autism spectrum disorder, intellectual disability, or concurrent treatments. Therapist homework-related behaviors were coded from audiotapes of Sessions 1 and 2 and used to predict adolescents' homework adherence, coded from audiotapes of Sessions 2 and 3. Several therapist behaviors were predictive of subsequent homework adherence, particularly for initially resistant or nonadherent adolescents. Stronger homework rationale and greater time allocated to explaining homework in Session 1 predicted greater adherence at Session 2, particularly for initially resistant adolescents. Stronger rationale and eliciting reactions/troubleshooting obstacles in Session 2 predicted greater adherence at Session 3, particularly for adolescents who were less adherent to prior homework. Strategies such as providing a strong rationale, allocating more time to assigning homework, and eliciting reactions/troubleshooting obstacles may be effective ways to bolster homework adherence among initially less engaged, depressed teens.

  4. 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.

  5. Patient perceptions of voice therapy adherence.

    PubMed

    van Leer, Eva; Connor, Nadine P

    2010-07-01

    Patient perspectives of behavioral voice therapy, including perspectives of treatment adherence, have not been formally documented. Because treatment adherence is, to a large extent, determined by patient beliefs, assessment of patient perspectives is integral to the study of adherence. Fifteen patients who had undergone at least two sessions of direct voice therapy for a variety of voice disorders/complaints were interviewed about their perspectives on voice therapy, with a particular focus on adherence. Interviews were transcribed and analyzed for content according to qualitative methods. Three common content themes emerged from the transcripts: Voice Therapy is Hard, Make it Happen, and The Match Matters. Findings were compared with reports of patient experiences in other behavioral interventions, such as diet and exercise, and related to existing theoretical models of behavior change and therapeutic process. This study yields information toward the development of scales to measure adherence-related constructs and strategies to improve treatment adherence in voice therapy.

  6. Factors influencing bacterial adherence to biomaterials.

    PubMed

    Merritt, K; Chang, C C

    1991-01-01

    The adherence of bacteria to implanted medical devices is believed to be important in the development of implant associated infections. Measures which reduce bacterial adherence should reduce the incidence of these infections. However, in order to assess the importance of adherence, the effectiveness of methods to reduce adherence, and compare data from different laboratories, the conditions of the in vitro studies on adherence need to be specified. There are currently no correct and incorrect methods, however, methods used need to be carefully described. The studies reported here indicate that the definition of adherence needs to be established, with the use of polystyrene as the reference material recommended. Since the adherent organisms lose adherence traits with culture, cultures must be selected for adherence regularly. It is important to control the number of organisms/ml but the volume used is not important. The medium used to grow the organisms and the use of stationary, rocking or flow conditions will alter adherence and need to be specified and be consistent within a set of experiments. Culture conditions, methods of rinsing the material, methods of elution and counting, or direct counting of organisms on the material need to be specified. Finally, as much information as possible on the bulk and surface properties of the material should be provided. The handling of the material for the experiments should be careful and defined. Fingerprints, contact with protein, wet surfaces vs dry surfaces, etc., will all affect the subsequent adherence. The materials should not be re-used since the removal of the adherent proteins or the biofilm is very difficult. Progress can be made in this important area if the details of procedures are specified.

  7. Inhibition of Pneumococcal Adherence to Human Nasopharyngeal Epithelial Cells by Anti-PsaA Antibodies

    PubMed Central

    Romero-Steiner, Sandra; Pilishvili, Tamar; Sampson, Jacquelyn S.; Johnson, Scott E.; Stinson, Annie; Carlone, George M.; Ades, Edwin W.

    2003-01-01

    The role of pneumococcal (Pnc) surface adhesin A (PsaA) in the adherence of Streptococcus pneumoniae (pneumococcus) to host cells is not well defined. We examined the effect of anti-PsaA antibodies in an inhibition of adherence assay using Detroit 562 nasopharyngeal human epithelial cells. Rabbit polyclonal (Pab) anti-recombinant PsaA (rPsaA) sera, a purified mouse monoclonal antibody (MAb) (MAb 6F62G8E12), and 22 healthy adult sera with known anti-PsaA IgG levels (obtained by enzyme-linked immunosorbent assay) were evaluated for their abilities to inhibit Pnc adherence to confluent monolayers (measured as percent reduction in CFU counts compared to those of uninhibited controls). Pnc adherence was dependent on capsular phenotype (no or low adherence for opaque strains). With an inoculum of 104 to 105 bacteria/well, the mean ± standard deviation count in controls was 163 ± 32 CFU/well for transparent strains. Low adherence was observed for a PsaA-minus mutant even at higher inoculum doses. Mean percent inhibitions of adherence with Pab and MAb were 54 and 50%, respectively. Adult sera showed inhibition in a dose-response fashion with a range of 98 to 8%, depending on the serum anti-PsaA antibody concentration. Absorption of Pab with rPsaA restored Pnc adherence to control levels. Absorption of sera with a PsaA-minus mutant did not result in a significant decrease (P >0.05) of inhibition of adherence activity. Additionally, nearly 100% of Pnc adherence was inhibited by lipidated rPsaA at 2.5 μg/ml. Our data support the argument that PsaA is an adhesin that mediates Pnc adherence to human nasopharyngeal cells. This functional assay may be useful in evaluating antibodies elicited in response to PsaA vaccination. PMID:12626450

  8. Self-perception of knowledge and adherence reflecting the effectiveness of antiretroviral therapy

    PubMed Central

    Dagli-Hernandez, Carolina; Lucchetta, Rosa Camila; de Nadai, Tales Rubens; Galduróz, José Carlos Fernandez; Mastroianni, Patricia de Carvalho

    2016-01-01

    Objectives To evaluate which indirect method for assessing adherence best reflects highly active antiretroviral therapy (HAART) effectiveness and the factors related to adherence. Method This descriptive, cross-sectional study was performed in 2012 at a reference center of the state of São Paulo. Self-report (simplified medication adherence questionnaire [SMAQ]) and drug refill parameters were compared to the viral load (clinical parameter of the effectiveness of pharmacotherapy [EP]) to evaluate the EP. The “Cuestionario para la Evaluación de la Adhesión al Tratamiento Antiretroviral” (CEAT-VIH) was used to evaluate factors related to adherence and the EP and, complementarily, patient self-perception of adherence was compared to the clinical parameter of the EP. Results Seventy-five patients were interviewed, 60 of whom were considered as adherent from the clinical parameter of the EP and ten were considered as adherent from all parameters. Patient self-perception about adherence was the instrument that best reflected the EP when compared to the standardized self-report questionnaire (SMAQ) and drug refill parameter. The level of education and the level of knowledge on HAART were positively correlated to the EP. Forgetfulness, alcohol use, and lack of knowledge about the medications were the factors most frequently reported as a cause of nonadherence. Conclusion A new parameter of patient self-perception of adherence, which is a noninvasive, inexpensive instrument, could be applied and assessed as easily as self-report (SMAQ) during monthly drug refill, since it allows monitoring adherence through pharmaceutical assistance. Therefore, patient adherence to HAART could be evaluated using self-perception (CEAT-VIH) and the viral load test. PMID:27695297

  9. SP 03-1 POLYPILL STRATEGY TO IMPROVED ADHERENCE.

    PubMed

    Prabhakaran, Dorairaj

    2016-09-01

    Among individuals with established CVD, multiple medications (aspirin, blood pressure lowering drugs and statins) are required to manage CVD and it is well established that non adherence to prescribed treatments is substantial in the long term. Such discontinuation of CV-preventive medications and low adherence rates has been shown to affect the success of CVD prevention efforts. In low- and middle income countries only less than 20% patients receive recommended therapy for CVD prevention, but even in high-income countries treatment coverage in the community is only about 50% in those with heart disease and 35% in those with stroke. Patients adherence to CV drugs is likely to be adversely affected by a number of factors including patients' beliefs, complexity of medication regime, lack of understanding of their condition or medication, and medication cost and associated clinic visits cost. Fixed-dose combination (FDC) polypill therapy may reduce these treatment gaps by reducing cost, complexity, therapeutic inertia, and low adherence. There are several mechanisms whereby an FDC strategy may enhance adherence. These encompass ease of prescription, overcoming physician inertia, patient acceptability, packaged delivery, and ease of taking. Recent evidence from well-designed randomized controlled trials (UMPIRE, Kanyini-GAP, IMPACT) and meta-analysis (SPACE collaboration) of RCTs have shown that access to FDC polypill in patients with CVD or similarly high risk improved adherence, BP, and cholesterol levels. These trials have shown that physicians are willing to prescribe polypill to this group of patients by involving them in the trial, and at the end of the study more patients were taking the FDC treatment. In order to achieve substantial reduction of CVD burden, immediate use of FDC/polypill in secondary prevention is indicated; however, the evidence in primary prevention needs to be adjudicated.

  10. 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

  11. Informal care and reciprocity of support are associated with HAART adherence among men in Baltimore, MD, USA.

    PubMed

    Knowlton, Amy R; Yang, Cui; Bohnert, Amy; Wissow, Lawrence; Chander, Geetanjali; Arnsten, Julia A

    2011-10-01

    Research suggests gender differences in interpersonal relationship factors important to health. This study examined relationship factors associated with HAART adherence among men. The sample (n = 154) comprised 95% African Americans and 48% current illicit drug users; 83% reported HAART adherence. Results revealed adherence was associated with comfort level taking HAART in the presence of close friends, and the interaction between informal care (having someone to care for oneself when sick in bed) and reciprocity of support. Among those with informal care, higher reciprocity of support to caregivers was associated with greater adherence. Promoting men's reciprocity of support to their caregivers and enhancing peer norms of medication taking are important strategies for improving men's adherence. The findings complement previous findings on relationship factors adversely associated with women's adherence. Results suggest the merit of interventions targeting men and their informal caregivers, particularly main partners, and gender-specific, contextually tailored strategies to promote HAART adherence.

  12. Informal Care and Reciprocity of Support are Associated with HAART Adherence among Men in Baltimore, MD, USA

    PubMed Central

    Knowlton, Amy R.; Yang, Cui; Bohnert, Amy; Wissow, Lawrence; Chander, Geetanjali; A. Arnsten, Julia

    2010-01-01

    Research suggests gender differences in interpersonal relationship factors important to health. This study examined relationship factors associated with HAART adherence among men. The sample (n=154) comprised 95% African Americans and 48% current illicit drug users; 83% reported HAART adherence. Results revealed adherence was associated with comfort level taking HAART in the presence of close friends, and the interaction between informal care (having someone to care for oneself when sick in bed) and reciprocity of support. Among those with informal care, higher reciprocity of support to caregivers was associated with greater adherence. Promoting men’s reciprocity of support to their caregivers and enhancing peer norms of medication taking are important strategies for improving men’s adherence. The findings complement previous findings on relationship factors adversely associated with women’s adherence. Results suggest the merit of interventions targeting men and their informal caregivers, particularly main partners, and gender-specific, contextually tailored strategies to promote HAART adherence. PMID:20632081

  13. 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

  14. Biofilm, adherence, and hydrophobicity as virulence factors in Malassezia furfur.

    PubMed

    Angiolella, Letizia; Leone, Claudia; Rojas, Florencia; Mussin, Javier; de Los Angeles Sosa, María; Giusiano, Gustavo

    2017-03-09

    Malassezia species are natural inhabitants of the healthy skin. However, under certain conditions, they may cause or exacerbate several skin diseases. The ability of this fungus to colonize or infect is determined by complex interactions between the fungal cell and its virulence factors. This study aims to evaluate "in vitro" the hydrophobicity levels, the adherence on a plastic surface and the biofilm formation of 16 clinical isolates of Malassezia furfur. Cellular surface hydrophobicity (CSH) levels were determined by two-phase system. The biofilm formation was determined by tetrazolium salt (XTT) reduction assay and by Scanning Electron Microscopy (SEM). Results showed many isolates were hydrophobic, adherent, and producers of biofilm on abiotic surfaces with different capacity. SEM observations confirmed an abundant extracellular matrix after 48 h of biofilm formation. About 63% of strains with high production of biofilm showed medium to high percentage of hydrophobicity and/or adherence. In addition, it has been demonstrated a correlation between hydrophobicity, adherence, and biofilm formation in about 60% of strains examined. These important virulence factors could be responsible of this yeast changing from a commensal to a pathogenic status.

  15. Pic, an autotransporter protein secreted by different pathogens in the Enterobacteriaceae family, is a potent mucus secretagogue.

    PubMed

    Navarro-Garcia, Fernando; Gutierrez-Jimenez, Javier; Garcia-Tovar, Carlos; Castro, Luis A; Salazar-Gonzalez, Hector; Cordova, Vanessa

    2010-10-01

    A hallmark of enteroaggregative Escherichia coli (EAEC) infection is a formation of biofilm, which comprises a mucus layer with immersed bacteria in the intestines of patients. While studying the mucinolytic activity of Pic in an in vivo system, rat ileal loops, we surprisingly found that EAEC induced hypersecretion of mucus, which was accompanied by an increase in the number of mucus-containing goblet cells. Interestingly, an isogenic pic mutant (EAEC Δpic) was unable to cause this mucus hypersecretion. Furthermore, purified Pic was also able to induce intestinal mucus hypersecretion, and this effect was abolished when Pic was heat denatured. Site-directed mutagenesis of the serine protease catalytic residue of Pic showed that, unlike the mucinolytic activity, secretagogue activity did not depend on this catalytic serine protease motif. Other pathogens harboring the pic gene, such as Shigella flexneri and uropathogenic E. coli (UPEC), also showed results similar to those for EAEC, and construction of isogenic pic mutants of S. flexneri and UPEC confirmed this secretagogue activity. Thus, Pic mucinase is responsible for one of the pathophysiologic features of the diarrhea mediated by EAEC and the mucoid diarrhea induced by S. flexneri.

  16. Assessment of Antiretroviral Treatment Adherence among Children Attending Care at a Tertiary Hospital in Southeastern Nigeria

    PubMed Central

    Akahara, Cletus; Okolo, Seline

    2017-01-01

    Background. Adherence is the strongest predictor of successful treatment outcome among children infected with HIV. Our aim was to assess the antiretroviral drugs adherence status of HIV-infected children attending care at a tertiary hospital in Southeastern Nigeria. Method. The study involved a cross-sectional survey of 210 HIV-infected children attending care at a tertiary hospital in Southeastern Nigeria using self-report method of assessment. Optimal ART adherence is defined as patient taking not missing more than 1 dose of combined antiretroviral therapy medication in the preceding 2 weeks prior to the study. Result. A majority of the subjects 191 (91%) had good adherence. There was a significant relationship between adherence and patient educational level (p = 0.004), duration of treatment (p = 0.001), drug administrator (p = 0.005), and orphan status (p = 0.001). The motivating factor for adherence was “not falling sick as before” while stigma was the most discouraging factor. Conclusion. The adherence level in this study was good. Stigma was an important reason given by patient/caregivers for nonadherence. There is need for concerted effort in addressing this barrier to improve adherence and prevent the emergence of drug resistance and treatment failure. PMID:28261274

  17. Assessment of Antiretroviral Treatment Adherence among Children Attending Care at a Tertiary Hospital in Southeastern Nigeria.

    PubMed

    Akahara, Cletus; Nwolisa, Emeka; Odinaka, Kelechi; Okolo, Seline

    2017-01-01

    Background. Adherence is the strongest predictor of successful treatment outcome among children infected with HIV. Our aim was to assess the antiretroviral drugs adherence status of HIV-infected children attending care at a tertiary hospital in Southeastern Nigeria. Method. The study involved a cross-sectional survey of 210 HIV-infected children attending care at a tertiary hospital in Southeastern Nigeria using self-report method of assessment. Optimal ART adherence is defined as patient taking not missing more than 1 dose of combined antiretroviral therapy medication in the preceding 2 weeks prior to the study. Result. A majority of the subjects 191 (91%) had good adherence. There was a significant relationship between adherence and patient educational level (p = 0.004), duration of treatment (p = 0.001), drug administrator (p = 0.005), and orphan status (p = 0.001). The motivating factor for adherence was "not falling sick as before" while stigma was the most discouraging factor. Conclusion. The adherence level in this study was good. Stigma was an important reason given by patient/caregivers for nonadherence. There is need for concerted effort in addressing this barrier to improve adherence and prevent the emergence of drug resistance and treatment failure.

  18. Effect of zinc on lysozyme-like activity of the seastar Marthasterias glacialis (Echinodermata, Asteroidea) mucus.

    PubMed

    Stabili, L; Pagliara, P

    2009-03-01

    Lysozyme represents the best characterized enzyme involved in the self-defense from bacteria. In this study we analysed the effects of zinc on the lysozyme-like activity of the seastar Marthasterias glacialis mucus. This activity, detected by measuring the cleared lysis area of dried Micrococcus lysodeikticus cell walls on Petri dishes, was significantly reduced in presence of zinc. The results are discussed in the light of elucidating the possible relationship between environmental contaminants and increased disease susceptibility in seastars due to the decrease of antibacterial protection. The benefits of using the test of lysozyme activity to monitoring environmental pollution are highlighted.

  19. Villous Adenoma in Renal Pelvis With Manifestation of Percutaneous Fistula and Mucus Secretion.

    PubMed

    Liu, Danqi; Tan, Jing; Huang, Kai; Jiang, Zhiqiang; He, Leye; Yin, Guangming

    2017-01-06

    A 70-year-old man, complaining of percutaneous fistula with jelly-like yellow mucus in the right kidney for a month, was admitted to our department. From computed tomography, stones and severe hydronephrosis but no suspicious mass was found in right kidney. Nephrectomy of right kidney was performed and pathological examination revealed a villous adenoma in the renal pelvis with moderate to severe atypical hyperplasia of glandular epithelium. Primary villous adenoma in renal pelvis is rare and believed to be related to chronic irritation of stone and inflammation. Mostly nephrectomy was performed before diagnosis was made.

  20. 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.

  1. HIV-infected individuals with co-occurring bipolar disorder evidence poor antiretroviral and psychiatric medication adherence.

    PubMed

    Moore, David J; Posada, Carolina; Parikh, Mili; Arce, Miguel; Vaida, Florin; Riggs, Patricia K; Gouaux, Ben; Ellis, Ronald J; Letendre, Scott L; Grant, Igor; Atkinson, J Hampton

    2012-11-01

    The contribution of bipolar disorder (BD), a prevalent serious mental illness characterized by impulsivity and mood instability, to antiretroviral (ART) and psychiatric medication adherence among HIV-infected (HIV+) individuals is unknown. We examined medication adherence among 44 HIV+/BD+ persons as compared to 33 demographically- and medically-comparable HIV+/BD- persons. Classification of adherent (≥ 90%) or non-adherent (<90%) based on proportion of correctly taken doses over 30 days was determined using electronic medication monitoring devices. HIV+/BD+ persons were significantly less likely to be ART adherent (47.7%) as compared to HIV+/BD- (90.9%) persons. Within the HIV+/BD+ group, mean psychiatric medication adherence was significantly worse than ART medication adherence, although there was a significant correlation between ART and psychiatric adherence levels. Importantly, 30-day ART adherence was associated with plasma virologic response among HIV+/BD+ individuals. Given the high overlap of HIV and BD, and the observed medication adherence difficulties for these persons, specialized adherence improvement interventions are needed.

  2. HIV-infected individuals with co-occurring bipolar disorder evidence poor antiretroviral and psychiatric medication adherence

    PubMed Central

    Moore, David J.; Posada, Carolina; Parikh, Mili; Arce, Miguel; Vaida, Florin; Riggs, Patricia K.; Gouaux, Ben; Ellis, Ronald J.; Letendre, Scott L.; Grant, Igor; Atkinson, J. Hampton

    2012-01-01

    The contribution of bipolar disorder (BD), a prevalent serious mental illness characterized by impulsivity and mood instability, to antiretroviral (ART) and psychiatric medication adherence among HIV-infected (HIV+) individuals is unknown. We examined medication adherence among 44 HIV+/BD+ persons as compared to 33 demographically- and medically-comparable HIV+/BD− persons. Classification of adherent (≥90%) or non-adherent (<90%) based on proportion of correctly taken doses over 30 days was determined using electronic medication monitoring devices. HIV+/BD+ persons were significantly less likely to be ART adherent (47.7%) as compared to HIV+/BD− (90.9%) persons. Within the HIV+/BD+ group, mean psychiatric medication adherence was significantly worse than ART medication adherence, although there was a significant correlation between ART and psychiatric adherence levels. Importantly, 30-day ART adherence was associated with plasma virologic response among HIV+/BD+ individuals. Given the high overlap of HIV and BD, and the observed medication adherence difficulties for these persons, specialized adherence improvement interventions are needed. PMID:22041931

  3. Adherence in ulcerative colitis: an overview

    PubMed Central

    Testa, Anna; Castiglione, Fabiana; Nardone, Olga Maria; Colombo, Giorgio L

    2017-01-01

    Medication adherence is an important challenge while treating chronic illnesses, such as ulcerative colitis (UC), that require a long-term management to induce and maintain clinical remission. This review provides an overview of the role that medication adherence plays in the routine management of UC, with a focus on the results of a recent Italian study reporting the perception of patients with UC regarding adherence to treatment. A literature analysis was conducted on topics, such as measurement of adherence in real practice, causes, risk factors and consequences of non-adherence and strategies, to raise patients’ adherence. Most of the data refer to adherence to 5-aminosalicylic acid, and standard of care for the induction and maintenance of remission in UC. The adherence rate to 5-aminosalicylic acid is low in clinical practice, thus resulting in fivefold higher risk of relapse, likely increased risk of colorectal cancer, reduced quality of life and higher health care costs for in- and outpatient settings. There are various causes affecting non-adherence to therapy: forgetfulness, high cost of drugs, lack of understanding of the drug regimen – which are sometimes due to insufficient explanation by the specialist – anxiety created by possible adverse events, lack of confidence in physicians’ judgment and complex dosing regimen. The last aspect negatively influences adherence to medication both in clinical trial settings and in real-world practice. Regarding this feature, mesalamine in once-daily dosage may be preferable to medications with multiple doses per day because the simplification of treatment regimens improves adherence. PMID:28260866

  4. The influence of frailty syndrome on medication adherence among elderly patients with hypertension

    PubMed Central

    Jankowska-Polańska, Beata; Dudek, Krzysztof; Szymanska-Chabowska, Anna; Uchmanowicz, Izabella

    2016-01-01

    Background Hypertension affects about 80% of people older than 80 years; however, diagnosis and treatment are difficult because about 55% of them do not adhere to treatment recommendations due to low socioeconomic status, comorbidities, age, physical limitations, and frailty syndrome. Aims The purposes of this study were to evaluate the influence of frailty on medication adherence among elderly hypertensive patients and to assess whether other factors influence adherence in this group of patients. Methods and results The study included 296 patients (mean age 68.8±8.0) divided into frail (n=198) and non-frail (n=98) groups. The Polish versions of the Tilburg Frailty Indicator (TFI) for frailty assessment and 8-item Morisky Medication Adherence Scale for adherence assessment were used. The frail patients had lower medication adherence in comparison to the non-frail subjects (6.60±1.89 vs 7.11±1.42; P=0.028). Spearman’s rank correlation coefficients showed that significant determinants with negative influence on the level of adherence were physical (rho =−0.117), psychological (rho =−0.183), and social domain (rho =−0.163) of TFI as well as the total score of the questionnaire (rho =−0.183). However, multiple regression analysis revealed that only knowledge about complications of untreated hypertension (β=0.395) and satisfaction with the home environment (β=0.897) were found to be independent stimulants of adherence level. Conclusion Frailty is highly prevalent among elderly hypertensive patients. Higher level of frailty among elderly patients can be considered as a determinant of lower adherence. However, social support and knowledge about complications of untreated hypertension are the most important independent determinants of adherence to pharmacological treatment. PMID:27994444

  5. Randomized Controlled Trial of a Personalized Cellular Phone Reminder System to Enhance Adherence to Antiretroviral Therapy

    PubMed Central

    Kumar, Vikram; Doros, Gheorghe; Farmer, Eric; Drainoni, Mari-Lynn; Rybin, Denis; Myung, Dan; Jackson, Jonathan; Backman, Elke; Stanic, Anela; Skolnik, Paul R.

    2011-01-01

    Abstract Adherence to antiretroviral therapy (ART) represents one of the strongest predictors of progression to AIDS, yet it is difficult for most patients to sustain high levels of adherence. This study compares the efficacy of a personalized cell phone reminder system (ARemind) in enhancing adherence to ART versus a beeper. Twenty-three HIV-infected subjects on ART with self-reported adherence less than 85% were randomized to a cellular phone (CP) or beeper (BP). CP subjects received personalized text messages daily; in contrast, BP subjects received a reminder beep at the time of dosing. Interviews were scheduled at weeks 3 and 6. Adherence to ART was measured by self-report (SR, 7-day recall), pill count (PC, past 30 days at baseline, then past 3 weeks), Medication Event Monitoring System (MEMS; cumulatively at 3 and 6 weeks), and via a composite adherence score constructed by combining MEMS, pill count, and self report. A mixed effects model adjusting for baseline adherence was used to compare adherence rates between the intervention groups at 3 and 6 weeks. Nineteen subjects completed all visits, 10 men and 9 females. The mean age was 42.7 ± 6.5 years, 37% of subjects were Caucasian and 89% acquired HIV heterosexually. The average adherence to ART was 79% by SR and 65% by PC at baseline in both arms; over 6 weeks adherence increased and remained significantly higher in the ARemind group using multiple measures of adherence. A larger and longer prospective study is needed to confirm these findings and to better understand optimal reminder messages and user fatigue. PMID:21323532

  6. 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

  7. 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

  8. 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

  9. 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…

  10. Current Situation of Medication Adherence in Hypertension

    PubMed Central

    Vrijens, Bernard; Antoniou, Sotiris; Burnier, Michel; de la Sierra, Alejandro; Volpe, Massimo

    2017-01-01

    Despite increased awareness, poor adherence to treatments for chronic diseases remains a global problem. Adherence issues are common in patients taking antihypertensive therapy and associated with increased risks of coronary and cerebrovascular events. Whilst there has been a gradual trend toward improved control of hypertension, the number of patients with blood pressure values above goal has remained constant. This has both personal and economic consequences. Medication adherence is a multifaceted issue and consists of three components: initiation, implementation, and persistence. A combination of methods is recommended to measure adherence, with electronic monitoring and drug measurement being the most accurate. Pill burden, resulting from free combinations of blood pressure lowering treatments, makes the daily routine of medication taking complex, which can be a barrier to optimal adherence. Single-pill fixed-dose combinations simplify the habit of medication taking and improve medication adherence. Re-packing of medication is also being utilized as a method of improving adherence. This paper presents the outcomes of discussions by a European group of experts on the current situation of medication adherence in hypertension. PMID:28298894

  11. The importance of the patient-clinician relationship in adherence to antiretroviral medication.

    PubMed

    Molassiotis, Alex; Morris, Kate; Trueman, Ian

    2007-12-01

    The aim of the study was to assess dimensions of the patient-clinician relationship in relation to adherence with antiretroviral medication in a sample of HIV patients. This was a correlational evaluation, using a cross-sectional design. Thirty-eight HIV patients in two UK HIV units provided complete data. Analysis suggested that the elements of the patient-clinician relationship contributing to adherence with medication were the patient perception of being valued and respected by the clinician, the patients' ability to initiate discussions about the treatment, empowerment and level of trust placed in the nurse. The latter, and the time since starting antiretroviral treatment, were the only two variables that could predict adherence in a regression model, explaining 41% of the variance in adherence. Building trusted relationships with the patients and investing in educational and communication techniques to improve the therapeutic relationship could strongly contribute to HIV patients to maintaining high adherence rates.

  12. Medication adherence skills training for African-American breast cancer survivors: the effects on health literacy, medication adherence, and self-efficacy.

    PubMed

    Rust, Connie F; Davis, Cindy; Moore, Matthew R

    2015-01-01

    There are gaps in research regarding medication adherence, self-efficacy in proper medication adherence, and health literacy among breast cancer survivors. This pilot randomized controlled study was conducted to provide information addressing health literacy with respect to medication adherence and self-efficacy in African American breast cancer survivors. The study sample consisted of an intervention group (n = 24) of medication adherence skills training (MST) and a control group (n = 24), with a total sample population of 48 participants. The MST workshop was a collaborative intervention between pharmacy and social work and was designed to address issues that may be encountered while taking multiple medications for various acute and chronic conditions, increase participant confidence in accessing necessary resources for improved medication usage, and enhance personal self-efficacy regarding health care. A statistically significant relationship was detected between initial health literacy and medication adherence, as well as initial health literacy and self-efficacy. These findings indicated that individuals with higher health literacy were more likely to have higher levels of self-efficacy and were more likely to adhere to medication instructions. Analysis of the intervention and treatment groups did not show a statistically significant effect on health literacy, medication adherence, or self-efficacy from pre-test to post-test.

  13. 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

  14. Adherence to hypertension medication: Quantitative and qualitative investigations in a rural Northern Vietnamese community

    PubMed Central

    Nguyen, Thi-Phuong-Lan; Schuiling-Veninga, Catharina C. M.; Nguyen, Thi Bach Yen; Vu, Thu-Hang; Wright, E. Pamela; Postma, Maarten J.

    2017-01-01

    Objectives The purposes of this study were to assess the adherence to medication of hypertensive patients visiting community health stations in a rural area in Vietnam, to examine the relationship between levels of adherence and cardiovascular risk among hypertensive patients and to further understand factors influencing adherence. Methods This study is part of a prospective one-year study conducted on hypertension management in a population aged 35 to 64 years. Data on age, sex, blood pressure and blood test results were collected at baseline. Cardiovascular risk was based on the Cardiovascular Risk Prediction Model for populations in Asia. To calculate medication adherence, the number of days the drug was taken was divided by the number of days since the first day of the prescription. A threshold of 80% was applied to differentiate between adherence and non-adherence. In-depth interviews were conducted among 18 subjects, including subjects classified as adherent and as non-adherent. Results Among 315 patients analyzed, 49.8% of the patients were adherent. Qualitative investigation revealed discrepancies in classification of adherence and non-adherence based on quantitative analysis and interviews. No significant difference in medication compliance between two cardiovascular disease risk groups (<10% vs. >10% risk) was found, also not after controlling for age, sex, and ethnicity (adjusted odds ratio at 1.068; 95% CI: 0.614 to 1.857). The odds of medication adherence in females was 1.531 times higher than in males but the difference was not statistically significant (95% CI: 0.957 to 2.448). Each one-year increase in age resulted in patients being 1.036 times more likely to be compliant (95% CI: 1.002 to 1.072). Awareness of complications related to hypertension was given as the main reason for adherence to therapy. Conclusions Medication adherence rate was relatively low among hypertensive subjects. The data suggest that rather than risk profile, the factor of

  15. Kaempferol Inhibits Endoplasmic Reticulum Stress-Associated Mucus Hypersecretion in Airway Epithelial Cells And Ovalbumin-Sensitized Mice.

    PubMed

    Park, Sin-Hye; Gong, Ju-Hyun; Choi, Yean-Jung; Kang, Min-Kyung; Kim, Yun-Ho; Kang, Young-Hee

    2015-01-01

    Mucus hypersecretion is an important pathological feature of chronic airway diseases, such as asthma and pulmonary diseases. MUC5AC is a major component of the mucus matrix forming family of mucins in the airways. The initiation of endoplasmic reticulum (ER)-mediated stress responses contributes to the pathogenesis of airway diseases. The present study investigated that ER stress was responsible for airway mucus production and this effect was blocked by the flavonoid kaempferol. Oral administration of ≥10 mg/kg kaempferol suppressed mucus secretion and goblet cell hyperplasia observed in the bronchial airway and lung of BALB/c mice sensitized with ovalbumin (OVA). TGF-β and tunicamycin promoted MUC5AC induction after 72 h in human bronchial airway epithelial BEAS-2B cells, which was dampened by 20 μM kaempferol. Kaempferol inhibited tunicamycin-induced ER stress of airway epithelial cells through disturbing the activation of the ER transmembrane sensor ATF6 and IRE1α. Additionally, this compound demoted the induction of ER chaperones such as GRP78 and HSP70 and the splicing of XBP-1 mRNA by tunicamycin. The in vivo study further revealed that kaempferol attenuated the induction of XBP-1 and IRE1α in epithelial tissues of OVA-challenged mice. TGF-β and tunicamycin induced TRAF2 with JNK activation and such induction was deterred by kaempferol. The inhibition of JNK activation encumbered the XBP-1 mRNA splicing and MUC5AC induction by tunicamycin and TGF-β. These results demonstrate that kaempferol alleviated asthmatic mucus hypersecretion through blocking bronchial epithelial ER stress via the inhibition of IRE1α-TRAF2-JNK activation. Therefore, kaempferol may be a potential therapeutic agent targeting mucus hypersecretion-associated pulmonary diseases.

  16. Effects of oral contraceptives on free fatty acids of human cervical mucus.

    PubMed

    Singh, E J; Swartwout, J R

    1973-05-01

    Amounts of individual free fatty acids were determined in human cervical mucus from 3 control women, 2 using Ovulen-21, 2 using C-Quens, and 2 using Ovral. Using a tuberculin syringe without a needle, mucus was collected daily, pooled, and frozen. After extraction by the FOLCH technique, and chromatography on a Florisil column, fatty acids were determined by gas chromatography. Fatty acids made up 10.5% of total lipids in controls, 11.8% in C-Quens users, 11.1% in Ovral users and 9.7% in Ovulen-21 users. In controls the greatest changes during the cycle were an increase in the proportion of myristic (14:0), decrease in stearic (18:0), and increase in saturated fatty acids during Cycle Days 12-16, compared to Days 5-9 or 23-27. In C-Quens users the proportion of saturated fatty acids increased on Days 23-27, compared to the rest of the cycle. Pooled results showed a slightly higher proportion of saturated fatty acids (81.2-84.0%) in samples from pill users than controls (79% saturated).

  17. Effect of chest physiotherapy on the removal of mucus in patients with cystic fibrosis

    SciTech Connect

    Rossman, C.M.; Waldes, R.; Sampson, D.; Newhouse, M.T.

    1982-07-01

    We studied the effectiveness of some of the components of a physiotherapy regimen on the removal of mucus from the lungs of 6 subjects with cystic fibrosis. On 5 randomized study days, after inhalation of a /sup 99/mTc-human serum albumin aerosol to label primarily the large airways, the removal of lung radioactivity was measured during 40 min of (a) spontaneous cough while at rest (control), (b) postural drainage, (c) postural drainage plus mechanical percussion, (d) combined maneuvers (postural drainage, deep breathing with vibrations, and percussion) administered by a physiotherapist, (e) directed vigorous cough. Measurements continued for an additional 2 h of quiet rest. Compared with the control day, all forms of intervention significantly improved the removal of mucus: cough (p less than 0.005), physiotherapy maneuvers (0.005 less than or equal to p less than 0.01), postural drainage (p less than 0.05), and postural drainage plus percussion (p less than 0.01). However, there was no significant difference between regimented cough alone and therapist-administered combined maneuvers, nor between postural drainage alone and with mechanical percussion. We conclude that in cystic fibrosis, vigorous, regimented cough sessions may be as effective as therapist-administered physiotherapy in removing pulmonary secretions. Postural drainage, although better than the control maneuver, was not as effective as cough and was not enhanced by mechanical percussion. Frequent, vigorous self-directed cough sessions are potentially as useful as more complex measures for effective bronchial toilet.

  18. Exogenous surfactant therapy and mucus rheology in chronic obstructive airway diseases.

    PubMed

    Banerjee, R; Puniyani, R R

    2000-01-01

    Exogenous surfactant is a specialized biomaterial used for substitution of the lipoprotein mixture normally present in the lungs-pulmonary surfactant. Respiratory Distress Syndrome is a disease of preterm infants mainly caused by pulmonary immaturity as evidenced by a deficiency of mature lung surfactant. Pulmonary surfactant is known to stabilize small alveoli and prevent them from collapsing during expiration. However, apart from alveoli, surfactant also lines the narrow conducting airways of the tracheobronchial tree. This paper reviews the role of this surfactant in the airways and its effect on mucus rheology and mucociliary clearance. Its potential role as a therapeutic biomaterial in chronic obstructive airway diseases, namely asthma, chronic bronchitis, and respiratory manifestations of cystic fibrosis, are discussed. This paper also attempts to elucidate the exact steps in the pathogenic pathway of these diseases which could be reversed by supplementation of exogenous surfactant formulations. It is shown that there is great potential for the use of present day surfactants (which are actually formulated for use in Respiratory Disease Syndrome) as therapy in the aforementioned diseases of altered mucus viscoelasticity and mucociliary clearance. However, for improved effectiveness, specific surfactant formulations satisfying certain specific criteria should be tailor-made for the clinical condition for which they are intended. The properties required to be fulfilled by the optimal exogenous surfactant in each of the above clinical conditions are enumerated in this paper.

  19. Consommation de lait et production de mucus chez les enfants asthmatiques

    PubMed Central

    Thiara, Gurkaran; Goldman, Ran D.

    2012-01-01

    Résumé Question De nombreux parents qui ont des enfants asthmatiques hésitent de plus en plus à leur donner du lait parce qu’ils croient que cela aggrave leur asthme en augmentant la production de mucus. Sachant que le lait fait partie d’un régime alimentaire sain qui favorise la croissance et l’apport en calcium, est-il avisé d’exclure le lait de l’alimentation? Réponse Depuis le 12e siècle, on proscrit le lait chez les patients atteints d’asthme. Ceci étant dit, jusqu’à maintenant, aucune étude n’a pu établir de lien définitif qui puisse appuyer cette recommandation. Puisqu’il faudrait des preuves plus concluantes pour déterminer l’effet qu’a la consommation de lait chez les enfants asthmatiques et qu’on doit mieux comprendre les mécanismes de production de mucus, on ne devrait pas exclure le lait ou en consommer moins. Santé Canada recommande 2 portions de lait (0,5 l) par jour pour les enfants de 2 à 8 ans et 3 à 4 portions de lait par jour (0,75 à 1 l) pour les enfants de 9 à 13 ans pour un développement et une santé optimale.

  20. Motivating patient adherence to allergic rhinitis treatments.

    PubMed

    Bender, Bruce G

    2015-03-01

    Patient nonadherence significantly burdens the treatment of allergic rhinitis (AR). Fewer than half of prescribed doses of intranasal corticosteroid medication are taken. The challenges for immunotherapies are even greater. While sustained treatment for 3 to 5 years is required for full benefit, most patients receiving immunotherapy, either subcutaneous or sublingual, stop treatment within the first year. Although research into interventions to improve AR adherence is lacking, lessons learned from adherence interventions in other chronic health conditions can be applied to AR. Two well-established, overriding models of care-the chronic care model and patient-centered care-can improve adherence. The patient-centered care model includes important lessons for allergy providers in their daily practice, including understanding and targeting modifiable barriers to adherence. Additionally, recent studies have begun to leverage health information and communication technologies to reach out to patients and promote adherence, extending patient-centered interventions initiated by providers during office visits.

  1. 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.

  2. Supportive relationships and medication adherence in HIV-infected, low-income Latinos.

    PubMed

    van Servellen, Gwen; Lombardi, Emilia

    2005-12-01

    Inadequate social support and poor communications with health care providers can affect adherence to antiretroviral therapy. The magnitude of independent effects of these factors on adherence is not fully known. This study examined the relationship of perceived emotional or informational social support from family and friends, quality of physician-patient communications and relationships, and medication adherence in a sample of low-income, Spanish-speaking, HIV-positive Latino men and women receiving treatment in community-based clinics (n = 85). Results of the study indicated that, whereas emotional or informational support was significantly associated with level of dose adherence (OR, 1.04, 95% CI, 1.01-1.08; p = .03), quality of physician-patient communications or relationships was significantly associated with adherence to medication schedule,t(6, 71) = 4.45,p < .001. Quality of patient-physician relationship accounted for 22% of the variance in adherence to medication schedule. Both kinds of support were associated with better adherence in this population but may affect adherence behaviors in different ways.

  3. A Qualitative Study Exploring Factors Associated with Provider Adherence to Severe Pediatric Traumatic Brain Injury Guidelines.

    PubMed

    Brolliar, Sarah M; Moore, Megan; Thompson, Hilaire J; Whiteside, Lauren K; Mink, Richard B; Wainwright, Mark S; Groner, Jonathan I; Bell, Michael J; Giza, Christopher C; Zatzick, Douglas F; Ellenbogen, Richard G; Ng Boyle, Linda; Mitchell, Pamela H; Rivara, Frederick P; Vavilala, Monica S

    2016-08-15

    Despite demonstrated improvement in patient outcomes with use of the Pediatric Traumatic Brain Injury (TBI) Guidelines (Guidelines), there are differential rates of adherence. Provider perspectives on barriers and facilitators to adherence have not been elucidated. This study aimed to identify and explore in depth the provider perspective on factors associated with adherence to the Guidelines using 19 focus groups with nurses and physicians who provided acute management for pediatric patients with TBI at five university-affiliated Level 1 trauma centers. Data were examined using deductive and inductive content analysis. Results indicated that three inter-related domains were associated with clinical adherence: 1) perceived guideline credibility and applicability to individual patients, 2) implementation, dissemination, and enforcement strategies, and 3) provider culture, communication styles, and attitudes towards protocols. Specifically, Guideline usefulness was determined by the perceived relevance to the individual patient given age, injury etiology, and severity and the strength of the evidence. Institutional methods to formally endorse, codify, and implement the Guidelines into the local culture were important. Providers wanted local protocols developed using interdisciplinary consensus. Finally, a culture of collaboration, including consistent, respectful communication and interdisciplinary cooperation, facilitated adherence. Provider training and experience, as well as attitudes towards other standardized care protocols, mirror the use and attitudes towards the Guidelines. Adherence was determined by the interaction of each of these guideline, institutional, and provider factors acting in concert. Incorporating provider perspectives on barriers and facilitators to adherence into hospital and team protocols is an important step toward improving adherence and ultimately patient outcomes.

  4. Psychological factors and use of antiepileptic drugs: pilot work using an objective measure of adherence.

    PubMed

    Kemp, Steven; Feely, Morgan; Hay, Alastair; Wild, Heather; Cooper, Cathryn

    2007-01-01

    Given the current emphasis on the "concordance" prescribing model, a study was designed to determine the influence of patients' beliefs about epilepsy, beliefs about medication and a range of neuroepilepsy variables on drug adherence among a sample of epilepsy patients. A special feature of the study was the use of a credible objective measure of drug adherence. Psychological health was also assessed. Thirty-seven patients were recruited from a local epilepsy clinic. Beliefs about epilepsy (illness representations), beliefs about epilepsy medication, anxiety, depression, neuroepilepsy status and adherence were all measured. Data were collected via clinical interview and questionnaire methods. Adherence with drug treatment was determined by an objective measure using low-dose phenobarbital as an indicator of adherence and, or, measurement of antiepileptic drug levels. Neither illness representations nor beliefs about epilepsy drugs were related to adherence. With the exception of time since last seizure, which was positively related to adherence, neuroepilepsy variables were unrelated to adherence. A number of significant associations between cognitive representations of epilepsy and mood were found.

  5. Antiretroviral Non-Adherence is Associated With a Retrieval Profile of Deficits in Verbal Episodic Memory.

    PubMed

    Obermeit, Lisa C; Morgan, Erin E; Casaletto, Kaitlin B; Grant, Igor; Woods, Steven Paul

    2015-01-01

    HIV-associated deficits in verbal episodic memory are commonly associated with antiretroviral non-adherence; however, the specific aspects of memory functioning (e.g., encoding, consolidation, or retrieval) that underlie this established relationship are not well understood. This study evaluated verbal memory profiles of 202 HIV+ participants who underwent a 30-day electronic monitoring of antiretroviral adherence. At the group level, non-adherence was significantly associated with lower scores on immediate and delayed passage recall and word list learning. Retention and recognition of passages and word lists were not related to adherence. Participants were then classified as having either a normal verbal memory profile, a "subcortical" retrieval profile (i.e., impaired free recall with relatively spared recognition), or a "cortical" encoding profile (e.g., cued recall intrusions) based on the Massman et al. ( 1990 ) algorithm for the California Verbal Learning Test. HIV+ participants with a classic retrieval deficit had significantly greater odds of being non-adherent than participants with a normal or encoding profile. These findings suggest that adherence to prescribed antiretroviral regimens may be particularly vulnerable to disruption in HIV+ individuals due to deficits in the complex process of efficiently accessing verbal episodic information with minimal cues. A stronger relationship between non-adherence and passage (vs. word list) recall was also found and may reflect the importance of contextual features in remembering to take medications. Targeted interventions for enhancing and supporting episodic memory retrieval processes may improve antiretroviral adherence and overall health outcomes among persons living with HIV.

  6. 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.

  7. Natural variability of in vitro adherence to fibrinogen and fibronectin does not correlate with in vivo infectivity of Staphylococcus aureus.

    PubMed

    Ythier, Mathilde; Entenza, Jose M; Bille, Jacques; Vandenesch, François; Bes, Michèle; Moreillon, Philippe; Sakwinska, Olga

    2010-04-01

    Adherence to fibrinogen and fibronectin plays a crucial role in Staphylococcus aureus experimental endocarditis. Previous genetic studies have shown that infection and carriage isolates do not systematically differ in their virulence-related genes, including genes conferring adherence, such as clfA and fnbA. We set out to determine the range of adherence phenotypes in carriage isolates of S. aureus, to compare the adherence of these isolates to the adherence of infection isolates, and to determine the relationship between adherence and infectivity in a rat model of experimental endocarditis. A total of 133 healthy carriage isolates were screened for in vitro adherence to fibrinogen and fibronectin, and 30 isolates were randomly chosen for further investigation. These 30 isolates were compared to 30 infective endocarditis isolates and 30 blood culture isolates. The infectivities of the carriage isolates, which displayed either extremely low or high adherence to fibrinogen and fibronectin, were tested using a rat model of experimental endocarditis. The levels of adherence to both fibrinogen and fibronectin were very similar for isolates from healthy carriers and members of the two groups of infection isolates. All three groups of isolates showed a wide range of adherence to fibrinogen and fibronectin. Moreover, the carriage isolates that showed minimal adherence and the carriage isolates that showed strong adherence had the same infectivity in experimental endocarditis. Adherence was proven to be important for pathogenesis in experimental endocarditis, but even the least adherent carriage strains had the ability to induce infection. We discuss the roles of differential gene expression, human host factors, and gene redundancy in resolving this apparent paradox.

  8. Transient improvement of urticaria induces poor adherence as assessed by Morisky Medication Adherence Scale-8.

    PubMed

    Kaneko, Sakae; Masuda, Koji; Hiragun, Takaaki; Inomata, Naoko; Furue, Masutaka; Onozuka, Daisuke; Takeuchi, Satoshi; Murota, Hiroyuki; Sugaya, Makoto; Saeki, Hidehisa; Shintani, Yoichi; Tsunemi, Yuichiro; Abe, Shinya; Kobayashi, Miwa; Kitami, Yuki; Tanioka, Miki; Imafuku, Shinichi; Abe, Masatoshi; Hagihara, Akihito; Morisky, Donald E; Katoh, Norito

    2015-11-01

    Poor adherence to medication is a major public health challenge. Here, we aimed to determine the adherence to oral and topical medications and to analyze underlying associated factors using the translated Japanese version of Morisky Medication Adherence Scale-8 regarding urticaria treatment. Web-based questionnaires were performed for 3096 registered dermatological patients, along with a subanalysis of 751 registered urticaria patients in this study. The adherence to oral medication was significantly associated with the frequency of hospital visits. Variables that affected the adherence to topical medication included age and experience of drug effectiveness. The rate of responses that "It felt like the symptoms had improved" varied significantly among the dermatological diseases treated with oral medications. Dermatologists should be aware that adherence to the treatment of urticaria is quite low. Regular visits and active education for patients with urticaria are mandatory in order to achieve a good therapeutic outcome by increasing the adherence.

  9. Successive shifts in the microbial community of the surface mucus layer and tissues of the coral Acropora muricata under thermal stress.

    PubMed

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

    2015-12-01

    The coral mucus may harbor commensal bacteria that inhibit growth of pathogens. Therefore, there is a need to understand the dynamics of bacterial communities between the coral mucus and tissues. Nubbins of Acropora muricata were subjected to increasing water temperatures of 26°C-33°C, to simultaneously explore the bacterial diversity in coral mucus and tissues by 16S rRNA gene amplicon sequencing. Photochemical efficiency of symbiotic dinoflagellates within the corals declined above 31°C. Both the mucus and tissues of healthy A. muricata were dominated by γ-Proteobacteria, but under thermal stress there was a shift towards bacteria from the Verrucomicrobiaceae and α-Proteobacteria. Members of Cyanobacteria, Flavobacteria and Sphingobacteria also become more prominent at higher temperatures. The relative abundance of Vibrio spp. in the coral mucus increased at 29°C, but at 31°C, there was a drop in the relative abundance of Vibrio spp. in the mucus, with a reciprocal increase in the tissues. On the other hand, during bleaching, the relative abundance of Endozoicomonas spp. decreased in the tissues with a reciprocal increase in the mucus. This is the first systematic experiment that shows the potential for a bacterial community shift between the coral surface mucus and tissues in a thermally stressed coral.

  10. 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

  11. The effects of feeding with synbiotic (Pediococcus acidilactici and fructooligosaccharide) enriched adult Artemia on skin mucus immune responses, stress resistance, intestinal microbiota and performance of angelfish (Pterophyllum scalare).

    PubMed

    Azimirad, Mahmood; Meshkini, Saeed; Ahmadifard, Nasrollah; Hoseinifar, Seyed Hossein

    2016-07-01

    The aim of this study was to evaluate the effects of feeding on synbiotic (Pediococcus acidilactici and fructooligosaccharide) enriched adult Artemia franciscana on skin mucus immune responses, stress resistance, intestinal microbiota and growth performance of angelfish (Pterophyllum scalare). Three hundred and sixty fish with initial weight 3.2 ± 0.13 g were randomly divided into twelve aquaria (50 L) assigned to four groups in triplicates. Fish were fed for 7 weeks with dietary treatments, including treatment 1: feeding adult Artemia without enrichment (control group), treatment 2: feeding adult Artemia enriched with lyophilised probiotic P. acidilactici (700 mg L(-1)), 3: feeding adult Artemia enriched with prebiotic fructooligosaccharide (FOS) (100 mg L(-1)), group 4: feeding adult Artemia enriched with synbiotic (P. acidilactici (700 mg L(-1)) + FOS (100 mg L(-1))). Skin mucus immune responses (lysozyme activity, total Immunoglobulin and protease), stress resistance against environmental stress (acute decrease of temperature and increase salinity), intestinal microbiota as well as growth indices were measured at the end of feeding trial. Artemia enriched with synbiotic significantly improved growth performance compared to other treatments (P < 0.05). The highest weight gain and specific growth rate (SGR) was observed in synbiotic fed fish (P < 0.05). Compared to the other treatments, the population of lactic acid bacteria was significantly higher in the intestinal microbiota of fish fed synbiotic supplemented diet (P < 0.05). In the environmental stress challenge test, the maximum resistance to abrupt decrease of temperature (17 °C) or elevation of salinity (12 g per liter) was observed in the synbiotic treatment. Also, the total immunoglobulin and lysozyme activity level of skin mucus was significantly elevated in fish fed Artemia enriched with synbiotic (P < 0.05). These results revealed that feeding angelfish with synbiotic

  12. 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.

  13. Adherence to Antihypertensive Medications in Iranian Patients.

    PubMed

    Behnood-Rod, Azin; Rabbanifar, Omid; Pourzargar, Pirouz; Rai, Alireza; Saadat, Zahra; Saadat, Habibollah; Moharamzad, Yashar; Morisky, Donald E

    2016-01-01

    Introduction. Appropriate adherence to medication is still a challenging issue for hypertensive patients. We determined adherence to antihypertensive(s) and its associated factors among 280 Iranian patients. Methods. They were recruited consecutively from private and university health centers and pharmacies in four cities. The validated Persian version of the 8-item Morisky Medication Adherence Scale (MMAS-8) was administered to measure adherence. Results. Mean (±SD) overall MMAS-8 score was 5.75 (±1.88). About half of the sample (139 cases, 49.6%) showed low adherence (MMAS-8 score < 6). There was a negative linear association between the MMAS-8 score and systolic BP (r = -0.231, P < 0.001) as well as diastolic BP (r = -0.280, P < 0.001). In linear regression model, overweight/obesity (B = -0.52, P = 0.02), previous history of admission to emergency services due to hypertensive crisis (B = -0.79, P = 0.001), and getting medication directly from drugstore without refill prescription in hand (B = -0.51, P = 0.04) were factors recognized to have statistically significant association with the MMAS-8 score. Conclusion. Antihypertensive adherence was unsatisfactory. We suggest that health care providers pay special attention and make use of the aforementioned findings in their routine visits of hypertensive patients to recognize those who are vulnerable to poor adherence.

  14. Adherence to Antihypertensive Medications in Iranian Patients

    PubMed Central

    Behnood-Rod, Azin; Rabbanifar, Omid; Pourzargar, Pirouz; Rai, Alireza; Saadat, Zahra; Saadat, Habibollah; Moharamzad, Yashar; Morisky, Donald E.

    2016-01-01

    Introduction. Appropriate adherence to medication is still a challenging issue for hypertensive patients. We determined adherence to antihypertensive(s) and its associated factors among 280 Iranian patients. Methods. They were recruited consecutively from private and university health centers and pharmacies in four cities. The validated Persian version of the 8-item Morisky Medication Adherence Scale (MMAS-8) was administered to measure adherence. Results. Mean (±SD) overall MMAS-8 score was 5.75 (±1.88). About half of the sample (139 cases, 49.6%) showed low adherence (MMAS-8 score < 6). There was a negative linear association between the MMAS-8 score and systolic BP (r = −0.231, P < 0.001) as well as diastolic BP (r = −0.280, P < 0.001). In linear regression model, overweight/obesity (B = −0.52, P = 0.02), previous history of admission to emergency services due to hypertensive crisis (B = −0.79, P = 0.001), and getting medication directly from drugstore without refill prescription in hand (B = −0.51, P = 0.04) were factors recognized to have statistically significant association with the MMAS-8 score. Conclusion. Antihypertensive adherence was unsatisfactory. We suggest that health care providers pay special attention and make use of the aforementioned findings in their routine visits of hypertensive patients to recognize those who are vulnerable to poor adherence. PMID:27069676

  15. 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

  16. Medication Adherence in the General Population

    PubMed Central

    Glombiewski, Julia A.; Nestoriuc, Yvonne; Rief, Winfried; Glaesmer, Heide; Braehler, Elmar

    2012-01-01

    Background Adherence to medication is low in specific populations who need chronic medication. However, adherence to medication is also of interest in a more general fashion, independent of specific populations or side effects of particular drugs. If clinicians and researchers expect patients to show close to full adherence, it is relevant to know how likely the achievement of this goal is. Population based rates can provide an estimate of efforts needed to achieve near complete adherence in patient populations. The objective of the study was to collect normative data for medication nonadherence in the general population. Methods and Findings We assessed 2,512 persons (a representative sample of German population). Adherence was measured by Rief Adherence Index. We also assessed current medication intake and side effects. We found that at least 33% of Germans repeatedly fail to follow their doctor's recommendations regarding pharmacological treatments and only 25% of Germans describe themselves as fully adherent. Nonadherence to medication occurs more often in younger patients with higher socioeconomic status taking short-term medications than in older patients with chronic conditions. Experience with medication side effects was the most prominent predictor of nonadherence. Conclusions The major strengths of our study are a representative sample and a novel approach to assess adherence. Nonadherece seems to be commonplace in the general population. Therefore adherence cannot be expected per se but needs special efforts on behalf of prescribers and public health initiatives. Nonadherence to medication should not only be considered as a drug-specific behaviour problem, but as a behaviour pattern that is independent of the prescribed medication. PMID:23272064

  17. Leveling

    USGS Publications Warehouse

    1966-01-01

    Geodetic leveling by the U.S. Geological Survey provides a framework of accurate elevations for topographic mapping. Elevations are referred to the Sea Level Datum of 1929. Lines of leveling may be run either with automatic or with precise spirit levels, by either the center-wire or the three-wire method. For future use, the surveys are monumented with bench marks, using standard metal tablets or other marking devices. The elevations are adjusted by least squares or other suitable method and are published in lists of control.

  18. Medication Adherence Interventions That Target Subjects with Adherence Problems: Systematic Review and Meta-analysis

    PubMed Central

    Conn, Vicki S.; Ruppar, Todd M.; Enriquez, Maithe; Cooper, Pam

    2015-01-01

    Background Inadequate medication adherence is a pervasive, under-recognized cause of poor health outcomes. Many intervention trials designed to improve medication adherence have targeted adults with adherence problems. No previous reviews have synthesized the effectiveness of medication adherence interventions focused on subjects with medication adherence difficulties. Objective This systematic review and meta-analysis synthesized findings from medication adherence intervention studies conducted among adults with medication adherence difficulties. Methods Primary research studies were eligible for inclusion if they tested an intervention designed to increase medication adherence among adults with documented adherence difficulties and reported medication adherence behavior outcomes. Comprehensive search strategies of 13 computerized databases, author and ancestry searches, and hand searches of 57 journals were used to locate eligible primary research. Participant demographics, intervention characteristics, and methodological features were reliably coded from reports along with medication adherence outcomes. Effect sizes for outcomes were calculated as standardized mean differences, and random effects models were used to estimate overall mean effects. Exploratory dichotomous and continuous variable moderator analyses were employed to examine potential associations between medication adherence effect size and sample, intervention, and methodological characteristics. Results Data were extracted from 53 reports of studies involving 8,243 individual primary study participants. The overall standardized mean difference effect size for treatment vs. control subjects was 0.301. For treatment pre- vs. post-intervention comparisons, the overall effect size was 0.533. Significantly larger effect sizes were associated with interventions incorporating prompts to take medications than interventions lacking medication prompts (0.497 vs. 0.234). Larger effect sizes were also found

  19. A mixed-methods study of the implementation of medication adherence policy solutions: how do European countries compare?

    PubMed Central

    Clyne, Wendy; McLachlan, Sarah

    2015-01-01

    Objectives We describe a key informant study that invited national medicines policy leads for the European Union member states to self-assess the level of implementation of medicines adherence initiatives in their country and the adequacy of that implementation. Interviews with medicines policy leads enabled in-depth understanding of the variation in adherence support across nations and the ways in which different nations prioritize, plan, and implement medicines adherence systems and services. Methods Ten national policy leads (Bulgaria, Denmark, Estonia, Finland, Germany, Ireland, Latvia, Lithuania, Malta, and the Netherlands) completed a self-assessment survey, and seven (Estonia, Finland, Germany, Ireland, Lithuania, Malta, and the Netherlands) engaged in a follow-up interview. Key findings Policy leads varied in the level of implementation of medication adherence solutions that they reported in their nations; most initiatives were aimed directly at patients with few initiatives at government or health care commissioner levels of action. Policy leads reported insufficient implementation of medication adherence initiatives across all potential domains. Barriers to implementation included lack of resources, strategic planning, evidence to support action, the “hidden” nature of medication adherence within policy work, and dispersed responsibility for medication adherence as a policy and practice theme. Conclusion This study has international significance and summarizes the emergent characteristics of nations with and without coordinated medication adherence activity. We highlight the importance of sharing good practice in policy formulation and implementation for medication adherence. PMID:26604703

  20. Acoustic response from adherent targeted contrast agents

    PubMed Central

    Zhao, Shukui; Kruse, Dustin E.; Ferrara, Katherine W.; Dayton, Paul A.

    2006-01-01

    In ultrasonic molecular imaging, encapsulated micron-sized gas bubbles are tethered to a blood vessel wall by targeting ligands. A challenging problem is to detect the echoes from adherent microbubbles and distinguish them from echoes from non-adherent agents and tissue. Echoes from adherent contrast agents are observed to include a high amplitude at the fundamental frequency, and significantly different spectral shape compared with free agents (p < 0.0003). Mechanisms for the observed acoustical difference and potential techniques to utilize these differences for molecular imaging are proposed. PMID:17225437

  1. Connection between self-stigma, adherence to treatment, and discontinuation of medication

    PubMed Central

    Kamaradova, Dana; Latalova, Klara; Prasko, Jan; Kubinek, Radim; Vrbova, Kristyna; Mainerova, Barbora; Cinculova, Andrea; Ociskova, Marie; Holubova, Michaela; Smoldasova, Jarmila; Tichackova, Anezka

    2016-01-01

    Introduction Self-stigma plays a role in many areas of the patient’s life. Furthermore, it also discourages therapy. The aim of our study was to examine associations between self-stigma and adherence to treatment and discontinuation of medication in patients from various diagnostic groups. Methods This cross-sectional study involved outpatients attending the Department of Psychiatry, University Hospital Olomouc, Czech Republic. The level of self-stigma was measured with the Internalized Stigma of Mental Illness and adherence with the Drug Attitude Inventory. The patients also anonymously filled out a demographic questionnaire which included a question asking whether they had discontinued their medication in the past. Results We examined data from 332 patients from six basic diagnostic categories (substance abuse disorders, schizophrenia, bipolar disorders, depressive disorders, anxiety disorders, and personality disorders). The study showed a statistically significant negative correlation between self-stigma and adherence to treatment in all diagnostic groups. Self-stigma correlated positively and adherence negatively with the severity of disorders. Another important factor affecting both variables was partnership. Self-stigma positively correlated with doses of antidepressants and adherence with doses of anxiolytics. Self-stigma also negatively correlated with education, and positively with a number of hospitalizations and number of psychiatrists visited. Adherence was further positively correlated with age and age of onset of disorders. Regression analysis showed that self-stigma was an important factor negatively influencing adherence to treatment and significantly contributing to voluntary discontinuation of drugs. The level of self-stigma did not differ between diagnostic categories. Patients suffering from schizophrenia had the lowest adherence to treatment. Conclusion The study showed a significant correlation between self-stigma and adherence to treatment

  2. Self-Assessment of Adherence to Medication: A Case Study in Campania Region Community-Dwelling Population

    PubMed Central

    Menditto, Enrica; Guerriero, Francesca; Orlando, Valentina; Crola, Catherine; Di Somma, Carolina; Illario, Maddalena; Morisky, Donald E.; Colao, Annamaria

    2015-01-01

    Objectives. The aim of the study was to assess self-reported medication adherence measure in patients selected during a health education and health promotion focused event held in the Campania region. The study also assessed sociodemographic determinants of adherence. Methods. An interviewer assisted survey was conducted to assess adherence using the Italian version of the 8-item Morisky Medication Adherence Scale (MMAS-8). Participants older than 18 years were interviewed by pharmacists while waiting for free-medical checkup. Results. A total of 312 participants were interviewed during the Health Campus event. A total of 187 (59.9%) had low adherence to medications. Pearson's bivariate correlation showed positive association between the MMAS-8 score and gender, educational level and smoking (P < 0.05). A multivariable analysis showed that the level of education and smoking were independent predictors of adherence. Individuals with an average level of education (odds ratio (OR), 2.21, 95% confidence interval (CI), 1.08–4.52) and nonsmoker (odds ratio (OR) 1.87, 95% confidence interval (CI), 1.04–3.35) were found to be more adherent to medication than those with a lower level of education and smoking. Conclusion. The analysis showed very low prescription adherence levels in the interviewed population. The level of education was a relevant predictor associated with that result. PMID:26346487

  3. Interplay between Oral Hypoglycemic Medication Adherence and Quality of Life among Elderly Type 2 Diabetes Mellitus Patients

    PubMed Central

    Manan, Mohamed Mansor; Husin, Akhma Radzuanna; Alkhoshaiban, Ali Saleh; Al-Worafi, Yaser Mohammed Ali

    2014-01-01

    Background: Adherence to medications is an important factor that contributes to therapeutic success. With the current increase in the elderly population, information relating to adherence to treatment and quality of life (QoL) of diabetic elderly patients will help the healthcare provider to improve their treatment. Thus, this study aims to determine the factors affecting adherence to medications and the consequence of non adherence to QoL. Materials and Methods: This was a cross-sectional study using validated Morisky Medication Adherence Scale (MMAS) Questionnaire. This study was conducted to assess the level of adherence on oral hypoglycemic medications (OHM) and quality of life of the Type 2 diabetes mellitus (T2DM) elderly patients in an urban health centre in Malaysia. A retrospective medication record review was also conducted to collect and confirm data on patients’ demographics, diagnosis, treatments, and outcomes. Results: One hundred and seventy nine patients were recruited in this study. Median adherence score was 7.75 (IQR 6.50- 8.00). Good adherer was observed in 48.00% of the participants. A Chi-square test indicated significant correlation between adherence and HbA1c (p= 0.010). The mean elderly diabetes mellitus Problem Areas in Diabetes (PAID) score was 6.30 ±SD 8.50. A significant inversed association was observed between PAID score and the level of adherence (r = - 0.175, p< 0.05). A highly significant difference in the low adherence group (p = 0.002). PAID score significantly correlated with age (years), female gender and HbA1c (p <0.05). A negative association between HbA1c levels and adherence was identified where a 1% increase in HbA1c was associated with a 30% decrease in the likelihood of being adherent. Conclusion: A medication adherence rate of 48% was obtained among elderly T2DM patients treated in the primary care clinic. This study showed that HbA1c is a relevant tool to assess patient glycemic control and adherence

  4. A systematic scoping review of adherence to reporting guidelines in health care literature

    PubMed Central

    Samaan, Zainab; Mbuagbaw, Lawrence; Kosa, Daisy; Debono, Victoria Borg; Dillenburg, Rejane; Zhang, Shiyuan; Fruci, Vincent; Dennis, Brittany; Bawor, Monica; Thabane, Lehana

    2013-01-01

    Background Reporting guidelines have been available for the past 17 years since the inception of the Consolidated Standards of Reporting Trials statement in 1996. These guidelines were developed to improve the quality of reporting of studies in medical literature. Despite the widespread availability of these guidelines, the quality of reporting of medical literature remained suboptimal. In this study, we assess the current adherence practice to reporting guidelines; determine key factors associated with better adherence to these guidelines; and provide recommendations to enhance adherence to reporting guidelines for future studies. Methods We undertook a systematic scoping review of systematic reviews of adherence to reporting guidelines across different clinical areas and study designs. We searched four electronic databases (Cumulative Index to Nursing and Allied Health Literature, Web of Science, Embase, and Medline) from January 1996 to September 2012. Studies were included if they addressed adherence to one of the following guidelines: Consolidated Standards of Reporting Trials (CONSORT), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), Quality of Reporting of Meta-analysis (QUOROM), Transparent Reporting of Evaluations with Nonrandomized Designs (TREND), Meta-analysis Of Observational Studies in Epidemiology (MOOSE) and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). A protocol for this study was devised. A literature search, data extraction, and quality assessment were performed independently by two authors in duplicate. This study reporting follows the PRISMA guidelines. Results Our search retrieved 5159 titles, of which 50 were eligible. Overall, 86.0% of studies reported suboptimal levels of adherence to reporting guidelines. Factors associated with better adherence included journal impact factor and endorsement of guidelines, publication date, funding source, multisite studies, pharmacological

  5. Methamphetamine use and neuropsychiatric factors are associated with antiretroviral non-adherence.

    PubMed

    Moore, David J; Blackstone, Kaitlin; Woods, Steven Paul; Ellis, Ronald J; Atkinson, J Hampton; Heaton, Robert K; Grant, Igor

    2012-01-01

    The present study assesses the impact of methamphetamine (METH) on antiretroviral therapy (ART) adherence among HIV+ persons, as well as examines the contribution of neurocognitive impairment and other neuropsychiatric factors [i.e., major depressive disorder (MDD), antisocial personality disorder (ASPD), and attention deficit disorder (ADHD)] for ART non-adherence. We examined HIV+ persons with DSM-IV-diagnosed lifetime history of METH abuse/dependence (HIV+ /METH+ ; n=67) as compared to HIV+ participants with no history of METH abuse/dependence (HIV+ /METH - ; n=50). Ancillary analyses compared these groups with a small group of HIV+ /METH+ persons with current METH abuse/dependence (HIV+ /CU METH+ ; n=8). Non-adherence was defined as self-report of any skipped ART dose in the last four days. Neurocognitive functioning was assessed with a comprehensive battery, covering seven neuropsychological domains. Lifetime METH diagnosis was associated with higher rates of detectable levels of plasma and CSF HIV RNA. When combing groups (i.e., METH+ and METH- participants), univariate analyses indicated co-occurring ADHD, ASPD, and MDD predicted ART non-adherence (p's < 0.10; not lifetime METH status or neurocognitive impairment). A significant multivariable model including these variables indicated that only MDD uniquely predicted ART non-adherence after controlling for the other variables (p<0.05). Ancillary analyses indicated that current METH users (use within 30 days) were significantly less adherent (50% prevalence of non-adherence) than lifetime METH+ users and HIV+ /METH- participants and that neurocognitive impairment was associated with non-adherence (p's < 0.05). METH use disorders are associated with worse HIV disease outcomes and ART medication non-adherence. Interventions often target substance use behaviors alone to enhance antiretroviral treatment outcomes; however, in addition to targeting substance use behaviors, interventions to improve ART adherence may

  6. Complete genome sequence of Coriobacteriaceae Strain 68-1-3, a novel mucus- degrading isolate from the swine intestinal tract

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A novel Coriobacteriaceae bacterium (Strain 68-1-3) was isolated from the ileum of the swine intestinal tract using a selective mucus-based medium. Here we present the finished genome sequence for the swine commensal, totaling 1.97 Mb in size. Genome-wide differences and low 16S rRNA gene sequence ...

  7. Skin mucus proteome of gilthead sea bream: A non-invasive method to screen for welfare indicators.

    PubMed

    Sanahuja, Ignasi; Ibarz, Antoni

    2015-10-01

    In teleosts, the skin mucus is the first physical barrier against physical and chemical attacks. It contains components related to metabolism, environmental influences and nutritional status. Here, we study mucus and composition based on a proteome map of soluble epidermal mucus proteins obtained by 2D-electrophoresis in gilthead sea bream, Sparus aurata. Over 1300 spots were recorded and the 100 most abundant were further analysed by LC-MS/MS and identified by database retrieval; we also established the related specific biological processes by Gene Ontology enrichment. Sixty-two different proteins were identified and classified in 12 GO-groups and into three main functions: structural, metabolic and protection-related. Several of the proteins can be used as targets to determine fish physiological status: actins and keratins, and especially their catabolic products, in the structural functional group; glycolytic enzymes and ubiquitin/proteasome-related proteins in the metabolic functional group; and heat shock proteins, transferrin and hemopexins, in the protection-related group. This study analyses fish mucus, a potential non-invasive tool for characterising fish status, beyond defence capacities, and we postulate some putative candidates for future studies along similar lines.

  8. Modified-Chitosan/siRNA Nanoparticles Downregulate Cellular CDX2 Expression and Cross the Gastric Mucus Barrier

    PubMed Central

    Sadio, Ana; Gustafsson, Jenny K.; Pereira, Bruno; Gomes, Carla Pereira; Hansson, Gunnar C.; David, Leonor; Pêgo, Ana Paula; Almeida, Raquel

    2014-01-01

    Development of effective non-viral vectors is of crucial importance in the implementation of RNA interference in clinical routine. The localized delivery of siRNAs to the gastrointestinal mucosa is highly desired but faces specific problems such as the stability in gastric acidity conditions and the presence of the mucus barrier. CDX2 is a transcription factor critical for intestinal differentiation being involved in the initiation and maintenance of gastrointestinal diseases. Specifically, it is the trigger of gastric intestinal metaplasia which is a precursor lesion of gastric cancer. Its expression is also altered in colorectal cancer, where it may constitute a lineage-survival oncogene. Our main objective was to develop a nanoparticle-delivery system of siRNA targeting CDX2 using modified chitosan as a vector. CDX2 expression was assessed in gastric carcinoma cell lines and nanoparticles behaviour in gastrointestinal mucus was tested in mouse explants. We show that imidazole-modified chitosan and trimethylchitosan/siRNA nanoparticles are able to downregulate CDX2 expression and overpass the gastric mucus layer but not colonic mucus. This system might constitute a potential therapeutic approach to treat CDX2-dependent gastric lesions. PMID:24925340

  9. Phytonutrient diet supplementation promotes beneficial Clostridia species and intestinal mucus secretion resulting in protection against enteric infection

    PubMed Central

    Wlodarska, Marta; Willing, Benjamin P.; Bravo, David M.; Finlay, B. Brett

    2015-01-01

    Plant extracts, or phytonutrients, are used in traditional medicine practices as supplements to enhance the immune system and gain resistance to various infectious diseases and are used in animal production as health promoting feed additives. To date, there are no studies that have assessed their mechanism of action and ability to alter mucosal immune responses in the intestine. We characterized the immunomodulatory function of six phytonutrients: anethol, carvacrol, cinnamaldehyde, eugenol, capsicum oleoresin and garlic extract. Mice were treated with each phytonutrient to assess changes to colonic gene expression and mucus production. All six phytonutrients showed variable changes in expression of innate immune genes in the colon. However only eugenol stimulated production of the inner mucus layer, a key mucosal barrier to microbes. The mechanism by which eugenol causes mucus layer thickening likely involves microbial stimulation as analysis of the intestinal microbiota composition showed eugenol treatment led to an increase in abundance of specific families within the Clostridiales order. Further, eugenol treatment confers colonization resistance to the enteric pathogen Citrobacter rodentium. These results suggest that eugenol acts to strengthen the mucosal barrier by increasing the thickness of the inner mucus layer, which protects against invading pathogens and disease. PMID:25787310

  10. Validation of gender specific markers in plasma and surface mucus of Moronids and its utility for broodstock evaluation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sex steroids and vitellogenin (VTG) are used routinely to investigate the reproductive systems of teleost fishes. These markers are typically measured in plasma; however surface mucus samples have been shown to be an effective substitute in several species of fish. We are attempting to validate mucu...

  11. Lycopene, Lutein and Zeaxanthin May Reduce Faecal Blood, Mucus and Pus but not Abdominal Pain in Individuals with Ulcerative Colitis

    PubMed Central

    Głąbska, Dominika; Guzek, Dominika; Zakrzewska, Paulina; Włodarek, Dariusz; Lech, Gustaw

    2016-01-01

    Background: The main symptom of ulcerative colitis is diarrhoea, which is often accompanied by painful tenesmus and faecal blood and mucus. It sometimes co-occurs with abdominal pain, fever, feeling of fatigue, loss of appetite and weight loss. Some dietary factors have been indicated as important in the treatment of ulcerative colitis. The aim of the study was to analyse the association between retinoid intake (total vitamin A, retinol, β-carotene, α-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin) and ulcerative colitis symptoms (abdominal pain, faecal blood, faecal mucus, faecal pus) in individuals with ulcerative colitis in remission. Methods: Assessment of diet was based on self-reported data from each patient’s dietary records taken over a period of three typical, random days (2 weekdays and 1 day of the weekend). Results: A total of 56 individuals with ulcerative colitis in remission (19 males and 37 females) were recruited for the study. One in every four individuals with ulcerative colitis in remission was characterised as having inadequate vitamin A intake. Higher lycopene, lutein and zeaxanthin intakes in individuals with ulcerative colitis in remission were associated with lower faecal blood, mucus and pus but not with lower incidence of abdominal pain. Higher carotene intake in individuals with ulcerative colitis in remission may contribute to higher incidence of faecal mucus. Conclusions: Optimising intake of specific retinoids may enhance disease control in individuals with ulcerative colitis. Prospective studies, including patient reported and objective outcomes, are required to confirm this. PMID:27706028

  12. Growth and survival of the fish pathogenic bacterium, Flavobacterium columnare, in tilapia mucus and porcine gastric mucin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare is an economically important gram negative bacterium that infects most freshwater farmed fish worldwide. Flavobacterium columnare colonizes the skin and gills of fish in the initial steps of pathogenesis. The fish’s surface is coated with mucus made up of high molecular we...

  13. Increased neurocognitive intra-individual variability is associated with declines in medication adherence in HIV-infected adults

    PubMed Central

    Thaler, Nicholas S.; Sayegh, Philip; Arentoft, Alyssa; Thames, April D.; Castellon, Steven A.; Hinkin, Charlie H.

    2015-01-01

    There is cross-sectional evidence that neurocognitive intra-individual variability (IIV), or dispersion, is elevated in HIV disease and is associated with declines in activities of daily living, including medication adherence. This longitudinal study extends this literature by examining whether increased neurocognitive IIV in HIV+ persons over time predicts declines in medication adherence above and beyond changes in mean level of performance over a six-month observation. After controlling for drug use, declines in mean performance, and changes in depressive symptoms, results confirmed that increases in IIV were associated with overall poorer antiretroviral medication adherence. HIV+ individuals with the greatest increases in dispersion demonstrated marked reductions in adherence by the third month that exceed that observed in less variable individuals. Our results indicate that increases in dispersion are associated with poorer declines in medication adherence in HIV disease, which may have implications for the early detection and remediation of suboptimal antiretroviral adherence. PMID:25730729

  14. Adaptation of Akkermansia muciniphila to the oxic-anoxic interface of the mucus layer.

    PubMed

    Ouwerkerk, Janneke P; van der Ark, Kees C H; Davids, Mark; Claassens, Nico J; Robert Finestra, Teresa; de Vos, Willem M; Belzer, Clara

    2016-09-23

    Akkermansia muciniphila colonizes the mucus layer of the gastrointestinal tract where the organism can be exposed to the oxygen that diffuses from epithelial cells. To understand how A. muciniphila is able to survive and grow at this oxic-anoxic interface, its oxygen tolerance, response and reduction capacities were studied. A. muciniphila was found to be oxygen-tolerant. On top of this, under aerated conditions, A. muciniphila showed significant oxygen reduction capacities and its growth rate and yield were increased as compared to strict anaerobic conditions. Transcriptome analysis revealed an initial oxygen stress response upon exposure to oxygen. Hereafter, genes related to respiration were expressed, including those coding for the cytochrome bd complex, which can function as terminal oxidase. The functionality of A. muciniphila cytochrome bd genes was proven by successfully complementing the cytochrome-deficient Escherichia coli strain ECOM4. We conclude that A. muciniphila can use oxygen when present at nanomolar concentrations.

  15. Structure-Activity Relations of Myxinidin, an Antibacterial Peptide Derived from the Epidermal Mucus of Hagfish

    PubMed Central

    Cantisani, Marco; Leone, Marilisa; Mignogna, Eleonora; Kampanaraki, Katerina; Falanga, Annarita; Morelli, Giancarlo

    2013-01-01

    The structure-activity relations of myxinidin, a peptide derived from epidermal mucus of hagfish, Myxine glutinosa L., were investigated. Analysis of key residues allowed us to design new peptides with increased efficiency. Antimicrobial activity of native and modified peptides demonstrated the key role of uncharged residues in the sequence; the loss of these residues reduces almost entirely myxinidin antimicrobial activity, while insertion of arginine at charged and uncharged position increases antimicrobial activity compared with that of native myxinidin. Particularly, we designed a peptide capable of achieving a high inhibitory effect on bacterial growth. Experiments were conducted using both Gram-negative and Gram-positive bacteria. Nuclear magnetic resonance (NMR) studies showed that myxinidin is able to form an amphipathic α-helical structure at the N terminus and a random coil region at the C terminus. PMID:24002100

  16. Mucus altering agents as adjuncts for nonviral gene transfer to airway epithelium.

    PubMed

    Ferrari, S; Kitson, C; Farley, R; Steel, R; Marriott, C; Parkins, D A; Scarpa, M; Wainwright, B; Evans, M J; Colledge, W H; Geddes, D M; Alton, E W

    2001-09-01

    Nonviral vectors have been shown to be a safe and valid alternative to recombinant viruses for gene therapy of cystic fibrosis (CF). Nevertheless, gene transfer efficiency needs to be increased before clinical efficacy is likely in man. One barrier to increased efficacy is normal airway mucus. Using an ex vivo model of sheep tracheal epithelium, we show that this barrier can, in part, be overcome by treatment with the mucolytic agents, Nacystelyn or N-acetylcysteine using either a cationic lipid or a cationic polymer as the gene transfer agent. Further, in vivo application of either Nacystelyn or the anticholinergic glycopyrrolate, both clinically used agents, resulted in increased reporter gene expression in the mouse lung, but no significant correction of the bioelectric defect in CF null mice. These results, whilst unlikely to be sufficient in themselves to achieve clinically relevant gene therapy, may be a further useful step in the attainment of this goal.

  17. A novel cysteine-rich antimicrobial peptide from the mucus of the snail of Achatina fulica.

    PubMed

    Zhong, Jian; Wang, Wenhong; Yang, Xiaomei; Yan, Xiuwen; Liu, Rui

    2013-01-01

    Antimicrobial peptides (AMPs) are important components of the innate immunity. Many antimicrobial peptides have been found from marine mollusks. Little information about AMPs of mollusks living on land is available. A novel cysteine-rich antimicrobial peptide (mytimacin-AF) belonging to the peptide family of mytimacins was purified and characterized from the mucus of the snail of Achatina fulica. Its cDNA was also cloned from the cDNA library. Mytimacin-AF is composed of 80 amino acid residues including 10 cysteines. Mytimacin-AF showed potent antimicrobial activity against Gram-negative and Gram-positive bacteria and the fungus Candida albicans. Among tested microorganisms, it exerted strongest antimicrobial activity against Staphylococcus aureus with a minimal peptide concentration (MIC) of 1.9 μg/ml. Mytimacin-AF had little hemolytic activity against human blood red cells. The current work confirmed the presence of mytimacin-like antimicrobial peptide in land-living mollusks.

  18. Synthetic Mucus Nanobarriers for Identification of Glycan-Dependent Primary Influenza A Infection Inhibitors

    PubMed Central

    2016-01-01

    Current drugs against the influenza A virus (IAV) act by inhibiting viral neuraminidase (NA) enzymes responsible for the release of budding virions from sialoglycans on infected cells. Here, we describe an approach focused on a search for inhibitors that reinforce the protective functions of mucosal barriers that trap viruses en route to the target cells. We have generated mimetics of sialo-glycoproteins that insert into the viral envelope to provide a well-defined mucus-like environment encapsulating the virus. By introducing this barrier, which the virus must breach using its NA enzymes to infect a host cell, into a screening platform, we have been able to identify compounds that provide significant protection against IAV infection. This approach may facilitate the discovery of potent new IAV prophylactics among compounds with NA activities too weak to emerge from traditional drug screens. PMID:27800553

  19. Improving sensitivity of direct microscopy for detection of acid-fast bacilli in sputum: use of chitin in mucus digestion.

    PubMed

    Farnia, P; Mohammadi, F; Zarifi, Z; Tabatabee, D J; Ganavi, J; Ghazisaeedi, K; Farnia, P K; Gheydi, M; Bahadori, M; Masjedi, M R; Velayati, A A

    2002-02-01

    In order to try to improve the results of direct smear microscopy, we used the mucus-digesting quality of chitin in tuberculosis (TB) laboratories. For this purpose, a total of 430 sputum specimens were processed by the N-acetyl-L-cysteine concentration, sodium hypochlorite (NaOCl) liquefaction, chitin sedimentation, and direct microscopy methods. Then, the smear sensitivity for acid-fast bacillus detection by chitin-treated sputum was compared with the sensitivity of smears prepared by other methods. Our results showed that the chitin solution took less time to completely homogenize the mucoid sputum than did the N-acetyl-L-cysteine and NaOCl methods. The N-acetyl-L-cysteine concentration method demonstrated sensitivity and specificity levels of 83 and 97%, respectively. In comparison, the sensitivity of chitin sedimentation was 80%, with a specificity of 96.7%. The NaOCl liquefaction method showed a sensitivity of 78%, with a specificity of 96%. Finally, the sensitivity of direct microscopy was lower than those of the other tested methods and was only 46%, with a specificity of 90%. The chitin and NaOCl liquefaction methods are both easy to perform, and they do not require additional equipment (centrifuges). Also, our results demonstrated that the chitin method is less time-consuming than the NaOCl method, since only 30 min of incubation is required to bring complete sedimentation of bacilli in chitin-treated sputum whereas the NaOCl method needs 10 to 12 h to give the same results in the same sputum specimens. Therefore, the chitin liquefaction and sedimentation method may provide better results in TB laboratories of developing countries than the N-acetyl-L-cysteine concentration, NaOCl overnight sedimentation, and direct smear microscopy methods.

  20. Endometritis Increases Pro-inflammatory Cytokines in Follicular Fluid and Cervico-vaginal Mucus in the Buffalo Cow.

    PubMed

    Boby, Jones; Kumar, Harendra; Gupta, Harihar Prasad; Jan, Mustapha Hussain; Singh, Sanjay Kumar; Patra, Manas Kumar; Nandi, Sukdeb; Abraham, Asha; Krishnaswamy, Narayanan

    2016-11-17

    Emerging evidence shows that some of the pro-inflammatory cytokines are elevated not only in the endometrium but also in the follicular fluid of cows with endometritis. Developing a cervico-vaginal mucus (CVM) based test has the potential for becoming a pen-side test because of the ease of sample collection. The present study describes the results of two different experiments. The first experiment was conducted to investigate the influence of endometritis on the proinflammatory cytokines of follicular fluid based on the reproductive tracts of buffalo collected at a slaughter house Buffalo genitalia were categorized into purulent endometritis (PE), cytological endometritis (CE), and non-endometritis (NE) based on the white-side test and endometrial cytology, respectively (n = 14/group). Each group was subdivided into follicular and mid-luteal stage (n = 7/stage) and the follicular fluid was collected from the largest follicle. Second experiment was done to study the difference in the levels of proinflammatory cytokines in the CVM of repeat breeders with subclinical endometritis presented to the clinic. CVM was collected from the repeaters (n = 10) and non-repeaters (n = 10) through aseptic trans-vaginal aspiration. The pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, and TNFα were quantitated through bovine specific ELISA kits. Significantly higher concentrations of pro-inflammatory cytokines (IL-1β, IL-8, IL-6, and TNFα) along with low intra-follicular estradiol in buffaloes of PE and CE groups suggest that endometritis impedes the follicular steroidogenesis. Significantly higher concentration of IL-1β and TNF-α in the CVM of repeaters indicate their potential as a pen-side diagnostic test for CE.

  1. Colorectal mucus binds DC-SIGN and inhibits HIV-1 trans-infection of CD4+ T-lymphocytes.

    PubMed

    Stax, Martijn J; Mouser, Emily E I M; van Montfort, Thijs; Sanders, Rogier W; de Vries, Henry J C; Dekker, Henk L; Herrera, Carolina; Speijer, Dave; Pollakis, Georgios; Paxton, William A

    2015-01-01

    Bodily secretions, including breast milk and semen, contain factors that modulate HIV-1 infection. Since anal intercourse caries one of the highest risks for HIV-1 transmission, our aim was to determine whether colorectal mucus (CM) also contains factors interfering with HIV-1 infection and replication. CM from a number of individuals was collected and tested for the capacity to bind DC-SIGN and inhibit HIV-1 cis- or trans-infection of CD4+ T-lymphocytes. To this end, a DC-SIGN binding ELISA, a gp140 trimer competition ELISA and HIV-1 capture/ transfer assays were utilized. Subsequently we aimed to identify the DC-SIGN binding component through biochemical characterization and mass spectrometry analysis. CM was shown to bind DC-SIGN and competes with HIV-1 gp140 trimer for binding. Pre-incubation of Raji-DC-SIGN cells or immature dendritic cells (iDCs) with CM potently inhibits DC-SIGN mediated trans-infection of CD4+ T-lymphocytes with CCR5 and CXCR4 using HIV-1 strains, while no effect on direct infection is observed. Preliminary biochemical characterization demonstrates that the component seems to be large (>100kDa), heat and proteinase K resistant, binds in a α1-3 mannose independent manner and is highly variant between individuals. Immunoprecipitation using DC-SIGN-Fc coated agarose beads followed by mass spectrometry indicated lactoferrin (fragments) and its receptor (intelectin-1) as candidates. Using ELISA we showed that lactoferrin levels within CM correlate with DC-SIGN binding capacity. In conclusion, CM can bind the C-type lectin DC-SIGN and block HIV-1 trans-infection of both CCR5 and CXCR4 using HIV-1 strains. Furthermore, our data indicate that lactoferrin is a DC-SIGN binding component of CM. These results indicate that CM has the potential to interfere with pathogen transmission and modulate immune responses at the colorectal mucosa.

  2. Oxidative stress response in the skin mucus layer of Goodea gracilis (Hubbs and Turner, 1939) exposed to crude oil: A non-invasive approach.

    PubMed

    Dzul-Caamal, Ricardo; Salazar-Coria, Lucia; Olivares-Rubio, Hugo F; Rocha-Gómez, Maria Alejandra; Girón-Pérez, Manuel Iván; Vega-López, Armando

    2016-10-01

    The skin of the fish is the foremost target of oxidative stress due to the generation of Reactive Oxygen Species (ROS) originated in the environment and in the skin itself. In this study, a non-destructive assay was developed to evaluate the effects of crude oil (0.0001-0.1mg/L, 96h) on oxidative stress response in the Skin Mucus Layer (SML) of the dusky splitfin goodeid (Goodea gracilis). The response in the SML was compared with recognized target organs through the Integrated Biomarker Response (IBRv2) and a slight addition to the method was proposed. Crude oil was extremely toxic and elicited a clear induction of ROS in the SML, as in the brain, liver and muscle. By the exposure to crude, a significant change in the activities of Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPx) as well as on lipid peroxidation (TBARS) and carbonyl protein (RCO) levels was detected. Also, increases in the activity of EROD were found. The general IBRv2 proposed in this study (gIBRv2) showed that oil causes the higher oxidative response in the SML (60.049) under different concentrations of petroleum, which was greater in the brain (56.749), muscle (56.561) and liver (55.775). The results of the study revealed an organ-specific antioxidant defense response that was dependent on the load of petroleum. These results contributed to the understanding of the complexity of oxidative stress response in fish exposed to crude oil using the Skin Mucus Layer as a target for environmental monitoring studies.

  3. Using Computational Modeling To Optimize the Design of Antibodies That Trap Viruses in Mucus.

    PubMed

    Wessler, Timothy; Chen, Alex; McKinley, Scott A; Cone, Richard; Forest, Gregory; Lai, Samuel K

    2016-01-08

    Immunoglobulin G (IgG) antibodies that trap viruses in cervicovaginal mucus (CVM) via adhesive interactions between IgG-Fc and mucins have recently emerged as a promising strategy to block vaginally transmitted infections. The array of IgG bound to a virus particle appears to trap the virus by making multiple weak affinity bonds to the fibrous mucins that form the mucus gel. However, the antibody characteristics that maximize virus trapping and minimize viral infectivity remain poorly understood. Toward this goal, we developed a mathematical model that takes into account physiologically relevant spatial dimensions and time scales, binding, and unbinding rates between IgG and virions and between IgG and mucins, as well as the respective diffusivities of virions and IgG in semen and CVM. We then systematically explored the IgG-antigen and IgG-mucin binding and unbinding rates that minimize the flux of infectious HIV arriving at the vaginal epithelium. Surprisingly, contrary to common intuition that infectivity would drop monotonically with increasing affinities between IgG and HIV, and between IgG and mucins, our model suggests maximal trapping of HIV and minimal flux of HIV to the epithelium are achieved with IgG molecules that exhibit (i) rapid antigen binding (high kon) rather than very slow unbinding (low koff), that is, high-affinity binding to the virion, and (ii) relatively weak affinity with mucins. These results provide important insights into the design of more potent "mucotrapping" IgG for enhanced protection against vaginally transmitted infections. The model is adaptable to other pathogens, mucosal barriers, geometries, and kinetic and diffusional effects, providing a tool for hypothesis testing and producing quantitative insights into the dynamics of immune-mediated protection.

  4. Nanocomplexes for gene therapy of respiratory diseases: Targeting and overcoming the mucus barrier.

    PubMed

    Di Gioia, Sante; Trapani, Adriana; Castellani, Stefano; Carbone, Annalucia; Belgiovine, Giuliana; Craparo, Emanuela Fabiola; Puglisi, Giovanni; Cavallaro, Gennara; Trapani, Giuseppe; Conese, Massimo

    2015-10-01

    Gene therapy, i.e. the delivery and expression of therapeutic genes, holds great promise for congenital and acquired respiratory diseases. Non-viral vectors are less toxic and immunogenic than viral vectors, although they are characterized by lower efficiency. However, they have to overcome many barriers, including inflammatory and immune mediators and cells. The respiratory and airway epithelial cells, the main target of these vectors, are coated with a layer of mucus, which hampers the effective reaching of gene therapy vectors carrying either plasmid DNA or small interfering RNA. This barrier is thicker in many lung diseases, such as cystic fibrosis. This review summarizes the most important advancements in the field of non-viral vectors that have been achieved with the use of nanoparticulate (NP) systems, composed either of polymers or lipids, in the lung gene delivery. In particular, different strategies of targeting of respiratory and airway lung cells will be described. Then, we will focus on the two approaches that attempt to overcome the mucus barrier: coating of the nanoparticulate system with poly(ethylene glycol) and treatment with mucolytics. Our conclusions are: 1) Ligand and physical targeting can direct therapeutic gene expression in specific cell types in the respiratory tract; 2) Mucopenetrating NPs are endowed with promising features to be useful in treating respiratory diseases and should be now advanced in pre-clinical trials. Finally, we discuss the development of such polymer- and lipid-based NPs in the context of in vitro and in vivo disease models, such as lung cancer, as well as in clinical trials.

  5. Searching the Evolutionary Origin of Epithelial Mucus Protein Components—Mucins and FCGBP

    PubMed Central

    Lang, Tiange; Klasson, Sofia; Larsson, Erik; Johansson, Malin E. V.; Hansson, Gunnar C.; Samuelsson, Tore

    2016-01-01

    The gel-forming mucins are large glycosylated proteins that are essential components of the mucus layers covering epithelial cells. Using novel methods of identifying mucins based on profile hidden Markov models, we have found a large number of such proteins in Metazoa, aiding in their classification and allowing evolutionary studies. Most vertebrates have 5–6 gel-forming mucin genes and the genomic arrangement of these genes is well conserved throughout vertebrates. An exception is the frog Xenopus tropicalis with an expanded repertoire of at least 26 mucins of this type. Furthermore, we found that the ovomucin protein, originally identified in chicken, is characteristic of reptiles, birds, and amphibians. Muc6 is absent in teleost fish, but we now show that it is present in animals such as ghost sharks, demonstrating an early origin in vertebrate evolution. Public RNA-Seq data were analyzed with respect to mucins in zebrafish, frog, and chicken, thus allowing comparison in regard of tissue and developmental specificity. Analyses of invertebrate proteins reveal that gel-forming-mucin type of proteins is widely distributed also in this group. Their presence in Cnidaria, Porifera, and in Ctenophora (comb jellies) shows that these proteins were present early in metazoan evolution. Finally, we examined the evolution of the FCGBP protein, abundant in mucus and related to gel-forming mucins in terms of structure and localization. We demonstrate that FCGBP, ubiquitous in vertebrates, has a conserved N-terminal domain. Interestingly, this domain is also present as an N-terminal sequence in a number of bacterial proteins. PMID:27189557

  6. Acquired CFTR Dysfunction in Chronic Bronchitis and Other Diseases of Mucus Clearance

    PubMed Central

    Raju, S. Vamsee; Solomon, George M.; Dransfield, Mark T; Rowe, Steven M

    2015-01-01

    Summary Chronic obstructive pulmonary disease (COPD) is a major public health problem accounting for more than 100,000 deaths and 750,000 hospitalizations each year in the United States alone. Though bronchodilators, inhaled steroids and other anti-inflammatory drugs can improve symptoms and reduce the risk of exacerbations, no therapies alter the natural history of the disease. This is the result of a number of factors including our poor understanding of the pathobiologic processes that drive specific COPD phenotypes, which has hindered drug development. Chronic bronchitis is perhaps the most clinically troublesome phenotype as most patients with COPD complain of cough and sputum production, and yet there are no effective treatments to target the mucus hypersecretion, accumulation and poor clearance that lead to these symptoms. Though it is well known that the absence of cystic fibrosis (CF) transmembrane receptor (CFTR) is the cause of CF, the prototypical disease of impaired mucociliary clearance, emerging data strongly suggest cigarette smoke and its components can lead to acquired CFTR dysfunction. Findings in vitro, in animal models, as well smokers with and without COPD also exhibit acquired CFTR dysfunction, which is associated with chronic bronchitis. This abnormality is not only present in the airways but is also present in extrapulmonary organs, suggesting CFTR dysfunction may contribute to smoking related lung disease as well as commonly associated comorbidities in which CFTR has a role. The development of potent CFTR modulators for the treatment of CF has made these findings clinically relevant as they may also have a role in treating COPD and other diseases of mucus clearance. PMID:26857776

  7. Determinants of prognosis of COPD in the elderly: mucus hypersecretion, infections, cardiovascular comorbidity.

    PubMed

    Pistelli, R; Lange, P; Miller, D L

    2003-05-01

    In this paper, the authors update the present knowledge about three risk factors for the prognosis of chronic obstructive pulmonary disease (COPD), which may be particularly relevant in elderly people: mucus hypersecretion, respiratory infections, and cardiovascular comorbidity. Chronic mucus hypersecretion (CMH) is a common respiratory symptom in old age, the relevance of which is analysed on the basis of data collected during the first three rounds of the Copenhagen City Heart Study. In subjects aged > or = 65 yrs, CMH was a strong predictor of the incidence of respiratory infections in a 10-yr follow-up period and it was also a strong predictor of death from COPD (relative risk=2.5). However, CMH was associated with consistently lower forced expiratory volume in one second (FEV1) values, but not with an accelerated decline of FEV1 in this sample of an elderly population. Acute respiratory infections (ARI) are extremely common at all ages, mostly mild self-limiting illnesses at a young age, but severe often fatal illnesses in elderly people already affected by a chronic disease such as COPD. This paper summarises the present knowledge about aetiology, pathology, prognostic relevance, and prevention of ARI. Furthermore, the areas in which further research is needed are listed. Clinical cohort studies clearly support the relevance of cardiovascular comorbidity for the short-and long-term prognosis of elderly subjects affected by severe COPD. In this paper, the recently demonstrated association between particulate air pollution and cardiovascular events is reported to suggest the presence of an extremely susceptible cluster of elderly subjects in the population identified by the copresence of chronic obstructive pulmonary disease and cardiovascular comorbidity.

  8. Protease-Activated Receptor 2 Mediates Mucus Secretion in the Airway Submucosal Gland

    PubMed Central

    Lee, Hyun Jae; Yang, Yu-Mi; Kim, Kyubo; Shin, Dong Min; Yoon, Joo-Heon; Cho, Hyung-Ju; Choi, Jae Young

    2012-01-01

    Protease-activated receptor 2 (PAR2), a G protein-coupled receptor expressed in airway epithelia and smooth muscle, plays an important role in airway inflammation. In this study, we demonstrated that activation of PAR2 induces mucus secretion from the human airway gland and examined the underlying mechanism using the porcine and murine airway glands. The mucosa with underlying submucosal glands were dissected from the cartilage of tissues, pinned with the mucosal side up at the gas/bath solution interface of a physiological chamber, and covered with oil so that secretions from individual glands could be visualized as spherical bubbles in the oil. Secretion rates were determined by optical monitoring of the bubble diameter. The Ca2+-sensitive dye Fura2-AM was used to determine intracellular Ca2+ concentration ([Ca2+]i) by means of spectrofluorometry. Stimulation of human tracheal mucosa with PAR2-activating peptide (PAR2-AP) elevated intracellular Ca2+ and induced glandular secretion equal to approximately 30% of the carbachol response in the human airway. Porcine gland tissue was more sensitive to PAR2-AP, and this response was dependent on Ca2+ and anion secretion. When the mouse trachea were exposed to PAR2-AP, large amounts of secretion were observed in both wild type and ΔF508 cystic fibrosis transmembrane conductance regulator mutant mice but there is no secretion from PAR-2 knock out mice. In conclusion, PAR2-AP is an agonist for mucus secretion from the airway gland that is Ca2+-dependent and cystic fibrosis transmembrane conductance regulator-independent. PMID:22916223

  9. Medication adherence behaviors of Medicare beneficiaries

    PubMed Central

    Carr-Lopez, Sian M; Shek, Allen; Lastimosa, Janine; Patel, Rajul A; Woelfel, Joseph A; Galal, Suzanne M; Gundersen, Berit

    2014-01-01

    Background Medication adherence is crucial for positive outcomes in the management of chronic conditions. Comprehensive medication consultation can improve medication adherence by addressing intentional and unintentional nonadherence. The Medicare Part D prescription drug benefit has eliminated some cost barriers. We sought to examine variables that impact self-reported medication adherence behaviors in an ambulatory Medicare-beneficiary population and to identify the factors that influence what information is provided during a pharmacist consultation. Methods Medicare beneficiaries who attended health fairs in northern California were offered medication therapy management (MTM) services during which demographic, social, and health information, and responses to survey questions regarding adherence were collected. Beneficiaries were also asked which critical elements of a consultation were typically provided by their community pharmacist. Survey responses were examined as a function of demographic, socioeconomic, and health-related factors. Results Of the 586 beneficiaries who were provided MTM services, 575 (98%) completed the adherence questions. Of responders, 406 (70%) reported taking medications “all of the time”. Of the remaining 169 (30%), the following reasons for nonadherence were provided: 123 (73%) forgetfulness; 18 (11%) side effects; and 17 (10%) the medication was not needed. Lower adherence rates were associated with difficulty paying for medication, presence of a medication-related problem, and certain symptomatic chronic conditions. Of the 532 who completed survey questions regarding the content of a typical pharmacist consultation, the topics included: 378 (71%) medication name and indication; 361 (68%) administration instructions; 307 (58%) side effects; 257 (48%) missed-dose instructions; and 245 (46%) interactions. Subsidy recipients and non-English speakers were significantly less likely to be counseled on drug name, indication, and side

  10. Antiplatelet resistance in outpatients with monitored adherence.

    PubMed

    Walter, Philipp N; Tsakiris, Dimitrios A; Romanens, Michel; Arnet, Isabelle; Hersberger, Kurt E

    2014-01-01

    Antiplatelet resistance with aspirin and clopidogrel has been associated with clinical, cellular and pharmacogenetic factors; and non-adherence has been considered as a major contributor to resistance in outpatients. We aimed at assessing factors to resistance when adherence to the antiplatelet drugs and all other oral solid drugs was controlled for. In a pilot study, we tested arachidonic acid and/or ADP-induced in vitro platelet aggregation of 82 outpatients with chronic aspirin and/or clopidogrel treatment before and after a one-week period of measuring the patient's adherence with the polymedication electronic monitoring system (POEMS). Resistance was found in 20% (aspirin; n = 69) and 25% (clopidogrel; n = 32) of the patients after monitored adherence. Mean platelet aggregation was not (aspirin) or non-significantly (clopidogrel) lowered when compared to baseline. Diabetes mellitus and inflammation were consistently associated with resistance to both drugs, but CYP2C19 polymorphisms could not be confirmed as predictors of clopidogrel response. Electronically compiled multidrug dosing histories allowed the concomitant intake of high-dose lipophilic statins to be identified as a risk factor of impaired response to clopidogrel and revealed that exposure to further potential drug-drug interactions (DDIs) was too low for analysis. Multidrug adherence monitoring allowed thus dismissing non-adherence as a major contributor to resistance and inter-individual response variability in an outpatient setting. Additionally, it allowed analysing the impact of DDIs according to the actual exposure to the potentially interfering drugs. Further studies based on this methodology are essential to prevent misleading results due to incomplete adherence and gain additional insight into the impact of timing adherence on antiplatelet drug response.

  11. Socioeconomic factors in adherence to HIV therapy in low- and middle-income countries.

    PubMed

    Peltzer, Karl; Pengpid, Supa

    2013-06-01

    It is not clear what effect socioeconomic factors have on adherence to antiretroviral therapy (ART) among patients in low- and middle-income countries. We performed a systematic review of the association of socioeconomic status (SES) with adherence to treatment of patients with HIV/AIDS in low- and middle-income countries. We searched electronic databases to identify studies concerning SES and HIV/AIDS and collected data on the association between various determinants of SES (income, education, occupation) and adherence to ART in low- and middle-income countries. From 252 potentially-relevant articles initially identified, 62 original studies were reviewed in detail, which contained data evaluating the association between SES and adherence to treatment of patients with HIV/AIDS. Income, level of education, and employment/occupational status were significantly and positively associated with the level of adherence in 15 studies (41.7%), 10 studies (20.4%), and 3 studies (11.1%) respectively out of 36, 49, and 27 studies reviewed. One study for income, four studies for education, and two studies for employment found a negative and significant association with adherence to ART. However, the aforementioned SES determinants were not found to be significantly associated with adherence in relation to 20 income-related (55.6%), 35 education-related (71.4%), 23 employment/occupational status-related (81.5%), and 2 SES-related (100%) studies. The systematic review of the available evidence does not provide conclusive support for the existence of a clear association between SES and adherence to ART among adult patients infected with HIV/ AIDS in low- and middle-income countries. There seems to be a positive trend among components of SES (income, education, employment status) and adherence to antiretroviral therapy in many of the reviewed studies.

  12. Examining the interplay between depression, motivation, and antiretroviral therapy adherence: a social cognitive approach.

    PubMed

    Tatum, A K; Houston, E

    2017-03-01

    A large body of research identifies depressive symptoms as a barrier to optimal antiretroviral therapy (ART) adherence, whereas treatment motivation has been characterized as a facilitator. There is evidence, however, that these patterns may not hold for some ART patients despite the widespread use of motivational techniques aimed at promoting adherence. Little is known about how the interplay between different levels of depressive symptoms and variations in the types and levels of motivation may influence ART adherence. The purpose of this study was to examine the relationship between depressive symptoms, two types of motivation, and adherence, with self-efficacy as a mediator. The sample consisted of 121 ART patients who reported various levels of depressive symptoms (mean age = 41 years; 84% African-American; and 68% female). Path analysis revealed that self-efficacy fully mediated the relationship between the three predictor variables (depressive symptoms, intrinsic motivation, and extrinsic motivation) and adherence, χ(2)(3, N = 121) = .78, RMSEA = .00, SRMR = .02, CFI = 1.00, NNFI = 1.06. Findings suggest that interventions using motivational techniques to build adherence among patients with varying levels of depressive symptoms should address the role of treatment self-efficacy to improve their effectiveness.

  13. Transport properties and aggregation phenomena of polyoxyethylene sorbitane monooleate (polysorbate 80) in pig gastrointestinal mucin and mucus.

    PubMed

    Lafitte, G; Thuresson, K; Jarwoll, P; Nydén, M

    2007-10-23

    The aqueous environment in the gastrointestinal tract frequently requires solubilization of hydrophobic drug molecules in appropriate drug delivery vehicles. An effective uptake/absorption and systemic exposure of a drug molecule entails many processes, one being transport properties of the vehicles through the mucus layer. The mucus layer is a complex mixture of biological molecules. Among them, mucin is responsible of the gel properties of this layer. In this study, we have investigated the diffusion of polyoxyethylene sorbitane monooleate (polysorbate 80), a commonly used nonionic surfactant, in aqueous solution, in mucin solutions at 0.25 and 5 wt %, and in mucus. These measurements were done by using the pulsed field gradient spin echo nuclear magnetic resonance (PGSE-NMR) technique. We conclude that polysorbate 80 is a mixture of non-surface-active molecules that can diffuse freely through all the systems investigated and of surface-active molecules that form micellar structures with transport properties strongly dependent on the environment. Polysorbate 80 micelles do not interact with mucin even though their diffusion is hindered by obstruction of the large mucin molecules. On the other hand, the transport is slowed down in mucus due to interactions with other components such as lipids depots. In the last part of this study, a hydrophobic NMR probe molecule has been included in the systems to mimic a hydrophobic drug molecule. The measurements done in aqueous solution revealed that the probe molecules were transported in a closely similar way as the polysorbate 80 micelles, indicating that they were dissolved in the micellar core. The situation was more complex in mucus. The probe molecules seem to dissolve in the lipid depots at low concentrations of polysorbate 80, which slows down their transport. At increasing concentration of polysorbate 80, the diffusion of the probe molecules increases indicating a continuous dissolution of hexamethyldisilane in the

  14. Pallial mucus of the oyster Crassostrea virginica regulates the expression of putative virulence genes of its pathogen Perkinsus marinus.

    PubMed

    Pales Espinosa, Emmanuelle; Corre, Erwan; Allam, Bassem

    2014-04-01

    Perkinsus marinus is a pathogen responsible for severe mortalities of the eastern oyster Crassostrea virginica along the East and Gulf coasts of the United States. When cultivated, the pathogenicity of this microorganism decreases significantly, hampering the study of its virulence factors. Recent investigations have shown a significant increase of the in vivo virulence of P. marinus exposed to oyster pallial mucus. In the current study, we investigated the effect of pallial mucus on P. marinus gene expression compared with cultures supplemented with oyster digestive extracts or with un-supplemented cultures. In parallel, parasite cells cultured under these three conditions were used to challenge oysters and to assess virulence in vivo. Perkinsus marinus mRNA sequencing was performed on an Illumina GAIIX sequencer and data were analysed using the Tuxedo RNAseq suite for mapping against the draft P. marinus genome and for differential expression analysis. Results showed that exposure of P. marinus to mucus induces significant regulation of nearly 3,600 transcripts, many of which are considered as putative virulence factors. Pallial mucus is suspected to mimic internal host conditions, thereby preparing the pathogen to overcome defense factors before invasion. This hypothesis is supported by significant regulation in several antioxidant proteins, heat shock proteins, protease inhibitors and proteasome subunits. In addition, mucus exposure induced the modulation of several genes known to affect immunity and apoptosis in vertebrates and invertebrates. Several proteases (proteolysis) and merozoite surface proteins (cell recognition) were also modulated. Overall, these results provide a baseline for targeted, in depth analysis of candidate virulence factors in P. marinus.

  15. Members of native coral microbiota inhibit glycosidases and thwart colonization of coral mucus by an opportunistic pathogen

    PubMed Central

    Krediet, Cory J; Ritchie, Kim B; Alagely, Ali; Teplitski, Max

    2013-01-01

    The outcome of the interactions between native commensal microorganisms and opportunistic pathogens is crucial to the health of the coral holobiont. During the establishment within the coral surface mucus layer, opportunistic pathogens, including a white pox pathogen Serratia marcescens PDL100, compete with native bacteria for available nutrients. Both commensals and pathogens employ glycosidases and N-acetyl-glucosaminidase to utilize components of coral mucus. This study tested the hypothesis that specific glycosidases were critical for the growth of S. marcescens on mucus and that their inhibition by native coral microbiota reduces fitness of the pathogen. Consistent with this hypothesis, a S. marcescens transposon mutant with reduced glycosidase and N-acetyl-glucosaminidase activities was unable to compete with the wild type on the mucus of the host coral Acropora palmata, although it was at least as competitive as the wild type on a minimal medium with glycerol and casamino acids. Virulence of the mutant was modestly reduced in the Aiptasia model. A survey revealed that ∼8% of culturable coral commensal bacteria have the ability to inhibit glycosidases in the pathogen. A small molecular weight, ethanol-soluble substance(s) produced by the coral commensal Exiguobacterium sp. was capable of the inhibition of the induction of catabolic enzymes in S. marcescens. This inhibition was in part responsible for the 10–100-fold reduction in the ability of the pathogen to grow on coral mucus. These results provide insight into potential mechanisms of commensal interference with early colonization and infection behaviors in opportunistic pathogens and highlight an important function for the native microbiota in coral health. PMID:23254513

  16. Members of native coral microbiota inhibit glycosidases and thwart colonization of coral mucus by an opportunistic pathogen.

    PubMed

    Krediet, Cory J; Ritchie, Kim B; Alagely, Ali; Teplitski, Max

    2013-05-01

    The outcome of the interactions between native commensal microorganisms and opportunistic pathogens is crucial to the health of the coral holobiont. During the establishment within the coral surface mucus layer, opportunistic pathogens, including a white pox pathogen Serratia marcescens PDL100, compete with native bacteria for available nutrients. Both commensals and pathogens employ glycosidases and N-acetyl-glucosaminidase to utilize components of coral mucus. This study tested the hypothesis that specific glycosidases were critical for the growth of S. marcescens on mucus and that their inhibition by native coral microbiota reduces fitness of the pathogen. Consistent with this hypothesis, a S. marcescens transposon mutant with reduced glycosidase and N-acetyl-glucosaminidase activities was unable to compete with the wild type on the mucus of the host coral Acropora palmata, although it was at least as competitive as the wild type on a minimal medium with glycerol and casamino acids. Virulence of the mutant was modestly reduced in the Aiptasia model. A survey revealed that ∼8% of culturable coral commensal bacteria have the ability to inhibit glycosidases in the pathogen. A small molecular weight, ethanol-soluble substance(s) produced by the coral commensal Exiguobacterium sp. was capable of the inhibition of the induction of catabolic enzymes in S. marcescens. This inhibition was in part responsible for the 10-100-fold reduction in the ability of the pathogen to grow on coral mucus. These results provide insight into potential mechanisms of commensal interference with early colonization and infection behaviors in opportunistic pathogens and highlight an important function for the native microbiota in coral health.

  17. Therapist adherence in individual cognitive-behavioral therapy for binge-eating disorder: assessment, course, and predictors.

    PubMed

    Brauhardt, Anne; de Zwaan, Martina; Herpertz, Stephan; Zipfel, Stephan; Svaldi, Jennifer; Friederich, Hans-Christoph; Hilbert, Anja

    2014-10-01

    While cognitive-behavioral therapy (CBT) is the most well-established treatment for binge-eating disorder (BED), little is known about process factors influencing its outcome. The present study sought to explore the assessment of therapist adherence, its course over treatment, and its associations with patient and therapist characteristics, and the therapeutic alliance. In a prospective multicenter randomized-controlled trial comparing CBT to internet-based guided self-help (INTERBED-study), therapist adherence using the newly developed Adherence Control Form (ACF) was determined by trained raters in randomly selected 418 audio-taped CBT sessions of 89 patients (25% of all sessions). Observer-rated therapeutic alliance, interview-based and self-reported patient and therapist characteristics were assessed. Three-level multilevel modeling was applied. The ACF showed adequate psychometric properties. Therapist adherence was excellent. While significant between-therapist variability in therapist adherence was found, within-therapist variability was non-significant. Patient and therapist characteristics did not predict the therapist adherence. The therapist adherence positively predicted the therapeutic alliance. The ACF demonstrated its utility to assess therapist adherence in CBT for BED. The excellent levels of therapist adherence point to the internal validity of the CBT within the INTERBED-study serving as a prerequisite for empirical comparisons between treatments. Variability between therapists should be addressed in therapist trainings and dissemination trials.

  18. Tailored Information and Automated Reminding to Improve Medication Adherence in Spanish- and English-Speaking Elders Treated for Memory Impairment.

    PubMed

    Ownby, Raymond L; Hertzog, Christopher; Czaja, Sara J

    2012-05-01

    Medication adherence is recognized as an issue of critical importance within health care, as many patients do not take their medications as prescribed. This study evaluated two interventions targeted at improving adherence in elderly patients being treated for memory impairments. Twenty-seven participants were randomly assigned to control (n = 11), automated reminding (n = 8), or tailored information conditions (n = 8). Medication adherence was evaluated with an electronic pill bottle. Generalized estimating equation (GEE) models assessed the effects of the interventions on electronically monitored medication adherence after controlling for covariates. Results showed that individuals in both intervention groups had higher levels of medication adherence than those in the control group. The presence of a caregiver was associated with substantially higher levels of adherence. Verbal memory, but not general cognitive status, predicted better adherence. Mood, health literacy, and executive functions were not associated with adherence. Results thus suggest that both automated reminding and tailored information interventions may improve medication adherence in elders, even among those with memory impairments.

  19. Personalized adherence activity recognition via model-driven sensor data assessment.

    PubMed

    Hsiao, Mark; Hsueh, Pei-Yun; Ramakrishnan, Sreeram

    2012-01-01

    Creation of a personalized adherence feedback loop is crucial for initiating and sustaining health behavior change. However, self reports are not sufficient to measure actual adherence. Recording and recognizing personal activities in a ubiquitous environment has thus emerged as a promising solution. In this work, we present a model-driven sensor data assessment mechanism capable of identifying high level adherence-related activity patterns from low level signals. The proposed intelligent sensing algorithm can learn from a population-based training data set and adapt quickly to an individual's exercise patterns using the acquired personal data. Upon the recognition of each activity, the system can further provide personalized feedback such as exercise coaching, fitness planning, and abnormal event detection. The resulted system demonstrates the feasibility of a portable real-time personalized adherence feedback system that could be used for advanced healthcare services.

  20. Using the Primary Care Behavioral Health Provider Adherence Questionnaire (PPAQ) to identify practice patterns.

    PubMed

    Beehler, Gregory P; Funderburk, Jennifer S; King, Paul R; Wade, Michael; Possemato, Kyle

    2015-12-01

    Primary care-mental health integration (PC-MHI) is growing in popularity. To determine program success, it is essential to know if PC-MHI services are being delivered as intended. The investigation examines responses to the Primary Care Behavioral Health Provider Adherence Questionnaire (PPAQ) to explore PC-MHI provider practice patterns. Latent class analysis was used to identify clusters of PC-MHI providers based on their self-report of adherence on the PPAQ. Analysis revealed five provider clusters with varying levels of adherence to PC-MHI model components. Across clusters, adherence was typically lowest in relation to collaboration with other primary care staff. Clusters also differed significantly in regard to provider educational background and psychotherapy approach, level of clinic integration, and previous PC-MHI training. The PPAQ can be used to identify PC-MHI provider practice patterns that have relevance for future clinical effectiveness studies, development of provider training, and quality improvement initiatives.

  1. Microbicide clinical trial adherence: insights for introduction

    PubMed Central

    Woodsong, Cynthia; MacQueen, Kathleen; Amico, K Rivet; Friedland, Barbara; Gafos, Mitzy; Mansoor, Leila; Tolley, Elizabeth; McCormack, Sheena

    2013-01-01

    After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs. PMID:23561044

  2. Interventions to increase adherence to acne treatment

    PubMed Central

    Moradi Tuchayi, Sara; Alexander, Tiffany M; Nadkarni, Anish; Feldman, Steven R

    2016-01-01

    Background Adherence to acne medication is poor and is a major reason why treatment plans are ineffective. Recognizing solutions to nonadherence is critical. Objective The purpose of this study is to describe the hurdles associated with acne nonadherence and to provide mechanisms on how to ameliorate them. Methods PubMed database was searched. Of the 419 search results, 29 articles were reviewed to identify hurdles to adherence and corresponding solutions. Results Hurdles to primary nonadherence where the medication is not even started, include lack of knowledge, confusion about usage, weak physician–patient relationship, fear of adverse reactions, and cost. Secondary nonadherence hurdles where the medication is started but is not taken as directed include lack of results, complex regimens, side effects, busy lifestyle, forgetfulness, inconvenience, and psychiatric comorbidity. Solutions to these hurdles include treatment simplification, technology, and dynamic education. Limitations Adherence is affected by numerous factors, but available literature analyzing acne adherence and interventions to improve adherence to treatment is limited. Conclusion There are several hurdles in adhering to acne treatment. Recognition of these hurdles and finding appropriate solutions may be as important to treatment outcomes as choosing the right medication to prescribe. PMID:27784999

  3. Impact of a pharmaceutical care program on clinical evolution and antiretroviral treatment adherence: a 5-year study

    PubMed Central

    Arroyo, María Jesús Hernández; Figueroa, Salvador Enrique Cabrera; Correa, Rosa Sepúlveda; de la Paz Valverde Merino, María; Gómez, Alicia Iglesias; Hurlé, Alfonso Domínguez-Gil

    2013-01-01

    Background Antiretroviral treatments (ART) form the basis of adequate clinical control in human immunodeficiency virus-infected patients, and adherence plays a primary role in the grade and duration of the antiviral response. The objectives of this study are: (1) to determine the impact of the implementation of a pharmaceutical care program on improvement of ART adherence and on the immunovirological response of the patients; and (2) to detect possible correlations between different adherence evaluation measurements. Methods A 60-month long retrospective study was conducted. Adherence measures used were: therapeutic drug monitoring, a simplified medication adherence questionnaire, and antiretroviral dispensation records (DR). The number of interviews and interventions related to adherence made for each patient in yearly periods was related to the changes in the adherence variable (measured with DR) in these same yearly periods. The dates when the laboratory tests were drawn were grouped according to proximity with the study assessment periods (February–May, 2005–2010). Results A total of 528 patients were included in the study. A significant relationship was observed between the simplified medication adherence questionnaire and DR over the 60-month study period (P < 0.01). Improvement was observed in the mean adherence level (P < 0.001), and there was a considerable decrease in the percentage of patients with CD4+ lymphocytes less than 200 cells/mm3 (P < 0.001). A relationship was found between the number of patients with optimum adherence levels and the time that plasma viral load remained undetected. The number of interviews and interventions performed in each patient in the first 12 months from the onset of the pharmaceutical care program (month 6), was related to a significant increase in adherence during this same time period. Conclusion The results suggest that the establishment and permanence of a pharmaceutical care program may increase ART adherence

  4. Cost Effectiveness of Potential ART Adherence Monitoring Interventions in Sub-Saharan Africa

    PubMed Central

    Cambiano, Valentina; Nakagawa, Fumiyo; Bansi-Matharu, Loveleen; Sow, Papa Salif; Ehrenkranz, Peter; Ford, Deborah; Mugurungi, Owen; Apollo, Tsitsi; Murungu, Joseph; Bangsberg, David R.; Revill, Paul

    2016-01-01

    Background Interventions based around objective measurement of adherence to antiretroviral drugs for HIV have potential to improve adherence and to enable differentiation of care such that clinical visits are reduced in those with high adherence. It would be useful to understand the approximate upper limit of cost that could be considered for such interventions of a given effectiveness in order to be cost effective. Such information can guide whether to implement an intervention in the light of a trial showing a certain effectiveness and cost. Methods An individual-based model, calibrated to Zimbabwe, which incorporates effects of adherence and resistance to antiretroviral therapy, was used to model the potential impact of adherence monitoring-based interventions on viral suppression, death rates, disability adjusted life years and costs. Potential component effects of the intervention were: enhanced average adherence when on ART, reduced risk of ART discontinuation, and reduced risk of resistance acquisition. We considered a situation in which viral load monitoring is not available and one in which it is. In the former case, it was assumed that care would be differentiated based on the adherence level, with fewer clinic visits in those demonstrated to have high adherence. In the latter case, care was assumed to be primarily differentiated according to viral load level. The maximum intervention cost required to be cost effective was calculated based on a cost effectiveness threshold of $500 per DALY averted. Findings In the absence of viral load monitoring, an adherence monitoring-based intervention which results in a durable 6% increase in the proportion of ART experienced people with viral load < 1000 cps/mL was cost effective if it cost up to $50 per person-year on ART, mainly driven by the cost savings of differentiation of care. In the presence of viral load monitoring availability, an intervention with a similar effect on viral load suppression was cost

  5. The Effect of Interactive Simulations on Exercise Adherence with Overweight and Obese Adults

    DTIC Science & Technology

    2012-10-01

    Exercise Adherence with Overweight and Obese Adults PRINCIPAL INVESTIGATOR: LTC Melba C. Stetz, PhD...Simulations on Exercise Adherence with Overweight and Obese Adults 5b. GRANT NUMBER W81XWH-07-2-0010 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) LTC...exercise motivation, and self-efficacy in overweight and obese Army personnel. Although increased activity level has proven to be a critical element

  6. Factors influencing adherence to psychopharmacological medications in psychiatric patients: a structural equation modeling approach

    PubMed Central

    De las Cuevas, Carlos; de Leon, Jose; Peñate, Wenceslao; Betancort, Moisés

    2017-01-01

    Purpose To evaluate pathways through which sociodemographic, clinical, attitudinal, and perceived health control variables impact psychiatric patients’ adherence to psychopharmacological medications. Method A sample of 966 consecutive psychiatric outpatients was studied. The variables were sociodemographic (age, gender, and education), clinical (diagnoses, drug treatment, and treatment duration), attitudinal (attitudes toward psychopharmacological medication and preferences regarding participation in decision-making), perception of control over health (health locus of control, self-efficacy, and psychological reactance), and level of adherence to psychopharmacological medications. Structural equation modeling was applied to examine the nonstraightforward relationships and the interactive effects among the analyzed variables. Results Structural equation modeling demonstrated that psychiatric patients’ treatment adherence was associated: 1) negatively with cognitive psychological reactance (adherence decreased as cognitive psychological reactance increased), 2) positively with patients’ trust in their psychiatrists (doctors’ subscale), 3) negatively with patients’ belief that they are in control of their mental health and that their mental health depends on their own actions (internal subscale), and 4) positively (although weakly) with age. Self-efficacy indirectly influenced treatment adherence through internal health locus of control. Conclusion This study provides support for the hypothesis that perceived health control variables play a relevant role in psychiatric patients’ adherence to psychopharmacological medications. The findings highlight the importance of considering prospective studies of patients’ psychological reactance and health locus of control as they may be clinically relevant factors contributing to adherence to psychopharmacological medications.