Sample records for adherent human polymorphonuclear

  1. Effects of Pneumolysin on Human Polymorphonuclear Leukocytes and Platelets


    Johnson, M K; Boese-Marrazzo, D; Pierce, W. A.


    Pneumolysin was bound by human polymorphonuclear leukocytes in a reaction which occurred very rapidly at 0 degrees C. Low concentrations of pneumolysin were found to stimulate leukocyte migration and lysosomal enzyme secretion. At increasing lysin levels, inhibition of spontaneous migration and chemotaxis, cell death, and lysis were observed. Pneumolysin was also found to lyse platelets and to activate serum to become chemotactic.

  2. IFN-gamma is produced by polymorphonuclear neutrophils in human uterine endometrium and by cultured peripheral blood polymorphonuclear neutrophils. (United States)

    Yeaman, G R; Collins, J E; Currie, J K; Guyre, P M; Wira, C R; Fanger, M W


    Cytokines present in the human uterus play an important role both in modulating immune responses to infectious challenge and in the establishment and maintenance of pregnancy. In particular, successful implantation and pregnancy is thought to require the establishment of a Th2 environment, while Th1 cytokines are associated with pregnancy loss and infertility. On the other hand, a Th1 response appears to be required for the resolution of acute infection. Using novel confocal microscopic analysis of fresh sections of human tissue, we have investigated the production of IFN-gamma, a Th1 cytokine, in human endometria. Extracellular IFN-gamma, mostly associated with matrix components, was located immediately beneath the luminal epithelium and along the glandular epithelium proximal to the lumen. As evidenced by intracellular staining, IFN-gamma is produced by both stromal cells and intraepithelial lymphocytes through all stages of the menstrual cycle. Surprisingly, the stromal cell containing intracellular IFN-gamma was identified as a polymorphonuclear neutrophil on the basis of its reactivity with a panel of mAbs and its nuclear morphology. We further found that polymorphonuclear neutrophils isolated from normal donors produce IFN-gamma in response to stimulation with LPS, IL-12, and TNF-alpha. Taken together, these findings suggest that polymorphonuclear neutrophils are capable of producing IFN-gamma both in vitro and in vivo, indicating that their role in shaping immune responses may be more extensive than previously thought. Furthermore, these studies strongly suggest that polymorphonuclear neutrophils play an important role in determining immune responsiveness within the female reproductive tract.

  3. Comparison of adherent and non-adherent staphylococci in the induction of polymorphonuclear leukocyte activation in vitro

    DEFF Research Database (Denmark)

    Riber, U; Espersen, F; Kharazmi, A


    The ability to consume complement and activate neutrophils was investigated for staphylococci adherent to silicone surfaces and non-adherent staphylococci. Staphylococcus epidermidis strain ATCC 14990 and Staphylococcus aureus strain E 2371 were used in this study. The bacteria were allowed...... at 37 degrees C. The bacteria consumed complement to approximately the same extent when adherent to the catheter segments, but more slowly in comparison with planktonic bacteria. When planktonic bacteria were compared, complement was consumed more quickly by S. epidermidis than by S. aureus. Measuring...... the induction of chemiluminescence by planktonic bacteria, S. epidermidis induced a lower response than S. aureus, while when adherent to the catheter segments the bacteria induced similar responses. These responses were only 15 to 20% of those induced by planktonic bacteria and only slightly higher than...

  4. Search for CEA-like molecules in polymorphonuclear leukocytes of non-human primates using monoclonal antibodies. (United States)

    Jantscheff, P; Indzhiia, L V; Micheel, B


    The monoclonal anti-CEA antibody ZIK-A42-A/C1 which reacts with NCA of human polymorphonuclear leukocytes was found to bind also to polymorphonuclear blood leukocytes of the following non-human primates tested: hamadryas baboon (Papio hamadryas), stump-tailed monkey (Macaca arctoides), pig-tailed monkey (Macaca nemestrina), and rhesus monkey (Macaca mulata). No binding was observed to mononuclear blood leukocytes. It was concluded that non-human primates contain CEA-like substances in their polymorphonuclear leukocytes as humans do and that these substances carry some identical epitopes.

  5. Effects of Propyl Gallate on Adhesion of Polymorphonuclear Leukocytes to Human Endothelial Cells Induced by Tumor Necrosis Factor Alpha

    Institute of Scientific and Technical Information of China (English)

    JIANG Yue-rong; CHEN Ke-ji; XU Yong-gang; YANG Xiao-hong; YIN Hui-jun


    Objective: To investigate the effects of Prowl Gallate (PrG) on cellular adhesion between human umbilical vein endothelial cells (HUVEC) and polymorphonuclear leukocytes (PMN) as well as the expression of intercellular adhesion molecule-1 (ICAM-1, CD54) and E-selectin (CD62E) on the VEC surface. Methods: A human VEC inflammation model was induced by tumor necrosis factor alpha (TNF-α). VECs were pre-incubated with varying concentrations of PrG (0.001-5 mmol/L) or 1‰ DMSO (v:v) or 10 mmol/L acetylsalicylic acid (ASA) for 1 h, and then were stimulated with 10 ng/mL TNF-α for 6 h. Rose bengal vital staining method was used to measure the adherence rate of PMN to VEC, while flow cytometry was used to determine the expression of CD54 and CD62E on the VEC surface. Results: After 6 h of incubation with TNF-α, the adherence of PMN to HUVECs as well as the percentage of fluorescence-positive cells and mean fluorescence intensity (MFI) of surface CD54 and CD62E in HUVECs increased significantly (P0.05). ASA at 10 mmol/L had no obvious effect on the positive rate of CD62E and CD54. Conclusions: High concentrations of PrG (0.1-5 mmol/L) exert its inhibitory effect on cellular adherence of PMN to HUVECs, and its mechanism may be related to inhibiting surface expression of CD54 and CD62E in HUVECs. Its action concentration was lower than that of ASA.


    Directory of Open Access Journals (Sweden)

    Sudha Patil


    Full Text Available The objective of present study was to investigate Petroleum ether, ethyl acetate and hydroalcoholic extracts of B. racemosa fruits in vitro on human polymorphonuclear (PMN cells to screen their effects on phagocytosis and chemotaxis. Ethyl acetate extract of B. racemosa fruits was found to be a stimulant of PMN cell phagocytosis of Nitroblue tetrazolium (NBT dye and candida albicans. It also stimulated intracellur killing capacity of PMN cells. It was further found to increase the chemotaxis of human PMN cells. While, petroleum ether extract and hydroalcoholic extract were lesser active as far as these activities are concerned.

  7. The essential oil of bergamot stimulates reactive oxygen species production in human polymorphonuclear leukocytes. (United States)

    Cosentino, Marco; Luini, Alessandra; Bombelli, Raffaella; Corasaniti, Maria T; Bagetta, Giacinto; Marino, Franca


    Bergamot (Citrus aurantium L. subsp. bergamia) essential oil (BEO) is used in folk medicine as an antiseptic and anthelminthic and to facilitate wound healing. Evidence indicates that BEO has substantial antimicrobial activity; however its effects on immunity have never been examined. We studied the effects of BEO on reactive oxygen species (ROS) production in human polymorphonuclear leukocytes (PMN) and the role of Ca(2+) in the functional responses evoked by BEO in these cells. Results show that BEO increased intracellular ROS production in human PMN, an effect that required the contribution of extracellular (and, to a lesser extent, of intracellular) Ca(2+) . Bergamot essential oil also significantly increased ROS production induced by the chemotactic peptide N-formyl-Met-Leu-Phe and reduced the response to the protein kinase C activator phorbol myristate acetate. In conclusion, this is the first report showing the ability of BEO to increase ROS production in human PMN. This effect could both contribute to the activity of BEO in infections and in tissue healing as well as underlie an intrinsic proinflammatory potential. The relevance of these findings for the clinical uses of BEO needs careful consideration.

  8. Influence of fluoroquinolones on phagocytosis and killing of Candida albicans by human polymorphonuclear neutrophils. (United States)

    Gruger, Thomas; Morler, Caroline; Schnitzler, Norbert; Brandenburg, Kerstin; Nidermajer, Sabine; Horre, Regine; Zundorf, Josef


    Candida albicans infections often occur during or shortly after antibacterial treatment. Phagocytosis by polymorphonuclear neutrophil granulocytes (PMN) is the most important primarily defence mechanism against C. albicans. Certain antibiotics such as some fluoroquinolones (FQ) are known to influence phagocyte functions. Thus, we investigated the influence of older and newer FQ on the phagocytosis and killing of C. albicans by human PMN paying special attention to CD11b expression of these cells as an indicator of the degree of their activation. In order to obtain comprehensive and comparable results we tested 13 FQ over a wide range of concentrations and in a time dependent manner in a standardized approach. When used at therapeutic concentrations, the FQ tested did not influence to a clinically significant degree the phagocytosis or the killing of C. albicans by human PMN and also not their activation. However, at high concentrations those FQ with cyclopropyl-moiety at position N1 showed increase in CD11b expression and diminished phagocytosis and oxidative burst.

  9. Deletion of the SSK1 response regulator gene in Candida albicans contributes to enhanced killing by human polymorphonuclear neutrophils. (United States)

    Du, Chen; Calderone, Richard; Richert, John; Li, Dongmei


    The isolation and partial functional characterization of the two-component response regulator SSK1 gene of Candida albicans was previously reported. Compared to wild-type (CAF2-1) and gene-reconstituted (SSK23) strains, the ssk1 null strain (SSK21) was avirulent in a murine model of hematogenously disseminated candidiasis and less able to adhere to human esophageal cells. More recent data indicate that SSK21 is sensitive to 4 to 8 mM H(2)O(2) in vitro than CAF2-1 and SSK23. Furthermore, microarray studies indicate that the regulation of two classes of genes, those encoding cell wall functions and stress adaptation, are altered in the ssk1 mutant. In the present study, the susceptibility of strains CAF2-1, SSK21, and SSK23 to killing by human polymorphonuclear neutrophils (PMNs) was assessed. Results are also described for a newly constructed ssk1 mutant (SSK24) in which the URA3 gene is integrated into its native locus. Our results indicate that killing of SSK21 and SSK24 was significantly greater than that of CAF2-1 and SSK23 (P killing activity of human PMNs, we compared the signal transduction activity and the inflammatory response gene profiles of PMNs infected with either the wild type or the ssk1 mutant. Phosphorylation of the mitogen-activated protein kinases p42/44 and p38 from neutrophils infected with either CAF2-1 (wild type) or SSK21 (ssk1/ssk1) was similar, while expression and phosphorylation of the JNK mitogen-activated protein kinase was not observed following infection with either strain. On the other hand, we observed an upregulation of seven inflammatory response genes in PMNs infected with the SSK21 mutant only, while an increase in interleukin-10 expression was measured in PMNs infected with either strain. Downregulation of interleukin-2 was observed in PMNs infected with either strain. Verification of the transcriptional profiling was obtained by reverse transcription-PCR for three of the genes that were upregulated in neutrophils infected

  10. Characterization of the polymorphonuclear leukocyte-induced vasoconstriction in isolated human umbilical veins. (United States)

    Kerr, S W; Yu, R; Stearns, C D; Haynes, N A; Winquist, R J


    We investigated the contractile effects of both activated and unactivated polymorphonuclear leukocytes (PMNs) on human vascular tissue to characterize the influence of human PMNs on vascular tone. PMNs were added either unactivated or after f-met-leu-phe (fMLP) activation (10(-8) M), into tissue chambers containing human umbilical vein segments under either control or cytokine-treated conditions. The activation state of different PMN preparations was measured by immunofluorescence staining of the adhesion glycoproteins Mac-1 and L-selectin. Both unactivated and activated PMNs induced a cell number-dependent (1.5 x 10(5) to 2 x 10(6) cells/ml) vasoconstriction in human umbilical vein segments. This PMN-induced response was not inhibited by treatment with indomethacin (10(-5) M), superoxide dismutase (2 x 10(-7) M) or L-nitro-monomethyl arginine (10(-4) M). However, treatment of PMNs with the leukotriene biosynthesis inhibitor BIRM-270 partially inhibited (-61 +/- 19%, P <.05) the contraction induced only by unactivated PMNs. Moreover, the supernatant from unactivated, but not that from activated, PMNs elicited a contractile response comparable to that from the addition of cells. We observed a significant correlation between the Mac-1/L-selectin ratio of activated PMNs and the contractile response they generated (r = 0.77, P <.05). The activated PMN response had an endothelium-dependent component, whereas the unactivated PMN response was endothelium-independent. These results suggest that human PMNs of varying activation states have the capacity to modulate vascular smooth muscle tone via distinct mechanisms. Unactivated PMNs appear to modulate tone via a secreted product, whereas the more activated phenotype modulates vascular tone via a cognate interaction with the endothelium.

  11. Antipseudomonal agents exhibit differential pharmacodynamic interactions with human polymorphonuclear leukocytes against established biofilms of Pseudomonas aeruginosa. (United States)

    Chatzimoschou, Athanasios; Simitsopoulou, Maria; Antachopoulos, Charalampos; Walsh, Thomas J; Roilides, Emmanuel


    Pseudomonas aeruginosa is the most common pathogen infecting the lower respiratory tract of cystic fibrosis (CF) patients, where it forms tracheobronchial biofilms. Pseudomonas biofilms are refractory to antibacterials and to phagocytic cells with innate immunity, leading to refractory infection. Little is known about the interaction between antipseudomonal agents and phagocytic cells in eradication of P. aeruginosa biofilms. Herein, we investigated the capacity of three antipseudomonal agents, amikacin (AMK), ceftazidime (CAZ), and ciprofloxacin (CIP), to interact with human polymorphonuclear leukocytes (PMNs) against biofilms and planktonic cells of P. aeruginosa isolates recovered from sputa of CF patients. Three of the isolates were resistant and three were susceptible to each of these antibiotics. The concentrations studied (2, 8, and 32 mg/liter) were subinhibitory for biofilms of resistant isolates, whereas for biofilms of susceptible isolates, they ranged between sub-MIC and 2 × MIC values. The activity of each antibiotic alone or in combination with human PMNs against 48-h mature biofilms or planktonic cells was determined by XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assay. All combinations of AMK with PMNs resulted in synergistic or additive effects against planktonic cells and biofilms of P. aeruginosa isolates compared to each component alone. More than 75% of CAZ combinations exhibited additive interactions against biofilms of P. aeruginosa isolates, whereas CIP had mostly antagonistic interaction or no interaction with PMNs against biofilms of P. aeruginosa. Our findings demonstrate a greater positive interaction between AMK with PMNs than that observed for CAZ and especially CIP against isolates of P. aeruginosa from the respiratory tract of CF patients.

  12. Production of reactive oxygen species by man-made vitreous fibres in human polymorphonuclear leukocytes. (United States)

    Ruotsalainen, M; Hirvonen, M R; Luoto, K; Savolainen, K M


    Human polymorphonuclear leukocytes (PMNL) or erythrocytes, isolated from human blood, were exposed to graded doses of asbestos (chrysotile), quartz, or man-made vitreous fibres (MMVF), i.e. refractory ceramic fibres (RCF), glasswool, or rockwool fibres. None of the MMVF affected either the viability of PMNL, as measured by trypan blue exclusion test, or induced haemolysis, whereas the positive controls, quartz and chrysotile, dose-dependently induced haemolysis in PMNL. MMVF did not increase the release of lactate dehydrogenase (LDH) from the PMNL, whereas the positive controls, chrysotile and quartz, induced a marked and dose-dependent release of LDH. When PMNL were exposed to MMVF, some of the fibre types slightly increased the levels of free intracellular calcium ([Ca2+]i) within the cells in a manner similar to that induced by chrysotile or quartz. All MMVF induced a dose-dependent production of reactive oxygen species (ROS) in PMNL, with RCF-induced production of ROS being the most marked. Production of ROS by MMVF seemed to depend on the availability of extracellular calcium because it could be attenuated with a Ca2+ channel blocker, verapamil, or a Ca2+ chelating agent, EGTA. Production of ROS may be a common pathway through which PMNL respond to MMVF-induced cell activation, but alterations of levels of free intracellular Ca2+ do not seem to be an absolute prerequisite for this effect. Fibre length seemed not to be an important factor in affecting the ability of MMVF to induce ROS production in PMNL. However, the balance between different elements in the fibre seemed importantly to affect the biological activity of a fibre.

  13. Entry of Sanfetrinem into Human Polymorphonuclear Granulocytes and Its Cell-Associated Activity against Intracellular, Penicillin-Resistant Streptococcus pneumoniae (United States)

    Cuffini, Anna Maria; Tullio, Vivian; Bonino, Alessandro; Allocco, Alessandra; Palarchio, Angela Ianni; Carlone, Nicola A.


    The entry of antibiotics into phagocytes is necessary for activity against intracellular pathogens. The ability of sanfetrinem, the first member of a new class of antibiotics, to penetrate human polymorphonuclear granulocytes and its consequences upon subsequent phagocytosis and killing of ingested penicillin-resistant Streptococcus pneumoniae have been evaluated. Sanfetrinem penetrated into human polymorphonuclear leukocytes (PMNs) at all concentrations tested, with cellular concentration/extracellular concentration ratios of 6.6 to 5.03 and 4.21 when sanfetrinem was used at 0.25 to 0.5 and 1 μg/ml, respectively, within 30 min of incubation. The uptake was complete within 5 min and was not energy dependent, since it was not affected by cell viability, environmental temperature, or the addition of a metabolic inhibitor. At a concentration of one-half the MIC, sanfetrinem significantly enhanced human PMN phagocytosis and increased intracellular bactericidal activity against penicillin-resistant S. pneumoniae. Following preexposure of PMNs to a concentration of one-half the MIC of sanfetrinem, there was a significant increase in both phagocytosis and killing compared with that for the controls, indicating the ability of sanfetrinem to interact with biological membranes and remain active within PMNs. Preexposure of streptococci to sanfetrinem made penicillin-resistant S. pneumoniae more susceptible to the bactericidal mechanisms of human PMNs than untreated organisms. PMID:9661015

  14. Synergy of caspofungin with human polymorphonuclear granulocytes for killing Candida albicans


    Tullio, Vivian; Mandras, Narcisa; Scalas, Daniela; Allizond, Valeria; Banche, Giuliana; Roana, Janira; Greco, Deborah; Castagno, Franco; Cuffini, Anna Maria; Carlone, Nicola A.


    The influence of caspofungin on polymorphonuclear leukocyte (PMN) phagocytosis and intracellular killing of Candida albicans was investigated. Caspofungin, at all of the concentrations tested (2, 3.2, and 8 μg/ml), significantly increased intracellular killing by PMNs through its direct action on both yeast cells and PMNs, indicating the potential ability of caspofungin to synergize with phagocytes for candidal killing. Caspofungin may therefore constitute an effective therapeutic option for ...

  15. Inhibitory effects of N-acetylcysteine on superoxide anion generation in human polymorphonuclear leukocytes. (United States)

    Villagrasa, V; Cortijo, J; Martí-Cabrera, M; Ortiz, J L; Berto, L; Esteras, A; Bruseghini, L; Morcillo, E J


    It has been suggested that reactive oxygen species released by activated polymorphonuclear leukocytes (PMN) in man is one mechanism of tissue injury. Therapeutic action aimed at increasing antioxidant defence mechanisms is still a clinical challenge. This study examines the activity of N-acetylcysteine, a known antioxidant, in the protection of PMN exposed in-vitro to the chemoattractant peptide fMet-Leu-Phe (FMLP), the protein kinase C activator phorbol myristate acetate or the lipid peroxidation promoter t-butyl hydroperoxide. FMLP (3-300 nM) and phorbol myristate acetate (160 pm-160 nM) induced concentration-related superoxide anion generation. Pre-treatment with N-acetylcysteine (33-333 microM) resulted in concentration-related inhibition of superoxide production induced by FMLP (30 nM) or phorbol myristate acetate (16 nM);-log IC50 values were 3.97 +/- 0.07 and 3.91 +/- 0.10, respectively. Changes in intracellular calcium ion concentration ([Ca2+]i) induced by FMLP (30 nM) were studied in fura-2-loaded human PMN. FMLP produced a transient calcium response, i.e. a peak followed by decay to a residual value above baseline. N-Acetylcysteine (333 microM) did not affect either basal [Ca2+]i values or changes in [Ca2+]i values after treatment with FMLP. Activation by phorbol myristate acetate caused a reduction in glutathione levels from 5.94 +/- 0.86 (control) to 1.84 +/- 0.51 nmol/3 x 10(6) cells (P 0.05 compared with control). Exposure to t-butyl hydroperoxide (0.5 mM, 30 min) markedly increased malondialdehyde levels (from 0.03 +/- 0.02 to 0.73 +/- 0.07 nmol/10(6) cells), and index of lipid peroxidation. Malondialdehyde levels were significantly reduced in PMN treated with N-acetylcysteine (333 microM; 0.55 +/- 0.04 nmol/10(6) cells; P < 0.05 compared with untreated cells exposed to t-butyl hydroperoxide). In conclusion, N-acetylcysteine reduces superoxide generation in response to FMLP and phorbol myristate acetate and partially protects against lipid

  16. Induction of oxidative burst response in human neutrophils by adherent staphylococci. Comparison between Staphylococcus epidermidis and Staphylococcus aureus

    DEFF Research Database (Denmark)

    Riber, U; Espersen, F; Skinhøj, P


    The ability of staphylococci adherent to silicone surfaces to induce superoxide anion (O2-) production by polymorphonuclear leukocytes (PMNs) was investigated and compared with the same activity induced by planktonic bacteria. The responses to Staphylococcus aureus strain E 2371 and Staphylococcus...... epidermidis strain ATCC 14990 were compared. The staphylococci were allowed to adhere to silicone catheters for 2 h at 37 degrees C. After opsonization of adherent bacteria in 30% human AB-positive serum, the induction of superoxide anion production by PMNs was measured in a cytochrome C reduction assay. Both...... bacterial strains, when adhered to the surfaces, were able to induce superoxide anion production by PMNs to about the same extent. Comparing adherent and planktonic bacteria with these two bacterial strains, it was found that planktonic S. epidermidis induced one to three times higher superoxide anion...

  17. Effect of Legionella pneumophila sonicate on killing of Listeria monocytogenes by human polymorphonuclear neutrophils and monocytes

    DEFF Research Database (Denmark)

    Rechnitzer, C; Bangsborg, Jette Marie; Shand, G H


    polymorphonuclear neutrophils and monocytes. Preincubation of neutrophils with L. pneumophila sonicate did not affect phagocytosis of L. monocytogenes, whereas Listeria killing was significantly inhibited at sonicate concentrations of 1 and 2 mg/ml. The phenol phase of a phenol-water extraction, containing most...... of the lipopolysaccharide (LPS), had no inhibitory effect on the listericidal activity of neutrophils. Killing of Listeria by monocytes was inhibited in a similar manner. The inhibitory activity was mainly recovered in the sonicate fraction above 100 kDa, suggesting that components organized in larger molecular complexes...... are most likely to represent the inhibitory factors. The inhibitory activity of L. pneumophila sonic extract appears to be related to inhibition of killing mechanisms since uptake of Listeria was not affected by the sonicate. Our observations indicate that as Legionella infection progresses, bacterial...

  18. Modulation of polymorphonuclear leukocytes function by incubation with human serum from oxidant-challenged individuals

    Indian Academy of Sciences (India)

    E Hoffer; T Machamid; A Tabak; Y Baum; A Tamir; Y Lerman


    Polymorphonuclear leukocytes (PMN) from healthy donors were tested for stimulated release of superoxide anions after being incubated with serum of welders and of a group of unexposed individuals. These two groups were further subdivided either according to age or to smoking habits. The experiments showed that stimulated superoxide production from PMN was inhibited ( < 0.05) by serum from young smokers as compared to that of young nonsmokers, both from the unexposed group. Incubation of PMN with serum from elderly nonsmoking individuals decreased superoxide production as compared to incubation with serum from young nonsmoking individuals, both from the unexposed group. A decrease in superoxide production by incubation with serum of welders as compared to that of unexposed individuals was significant only when the comparison was carried out between the young, non-smoking subgroups. These findings suggest that age, smoking, and exposure to oxidants induce appearance in serum of factors that affect the PMN function.

  19. Possible in vivo tolerance of human polymorphonuclear neutrophil to low-grade exercise-induced endotoxaemia

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    G. Camus


    Full Text Available To address the question of whether translocation of bacterial lipopolysaccharide (LPS into the blood could be involved in the process of exercise-induced polymorphonuclear neutrophil (PMN activation, 12 healthy male subjects who took part in a sprint triathlon (1.5 km river swim, 40 km bicycle race, 10 km road race were studied. While there was no detectable amount of endotoxin in the blood samples drawn at rest, exercise was followed by the appearance of circulating endotoxin molecules at the end of competition in four subjects, and after one and 24 h recovery in three and seven athletes, respectively. The concentrations of plasma granulocyte myeloperoxidase ([MPO], were significantly higher immediately after exercise and one hour later than baseline values (P<0.001. This variable returned to pre-race levels the day after exercise, despite the presence of detectable amounts of LPS, at that time, in seven athletes. The absence of significant correlation (r=0.26;P=0.383 and temporal association between [MPO]and plasma endotoxin levels led us to conclude that endotoxaemia was not involved in the process of exercise-induced PMN degranulation observed in our subjects.

  20. [Physiology and pathology of bactericidal activity in human polymorphonuclear neutrophils (author's transl)]. (United States)

    Hakim, J


    Blood polymorphonuclear neutrophils defend man against aggressions from pathogens. Under the combined influence of granulocytic and non-granulocytic factors, the defensive process develops by steps: the neutrophil moves towards the pathogenic organism which, one reached, is engulfed and killed. The killing systems of the cell are either oxygen-dependent or independent. the oxygen-dependent system is triggered off by stimulation of the cell membrane and involves various reactions, including cyanide-resistant oxygen consumption, production of activated oxygen, oxygen peroxide and halogenisation of the pathogen membrane. Impairment of the killing activity requires quantitative assessment of its various components in the presence of autologous or control serum with the view of: determining the origin (granulocytic or non-granulocytic) of the impairment, and identifying the step in oxygen metabolism that is affected. In the vast majority of non-granulocytic insufficiencies the cause lies in defective opsonins. In granulocytic insufficiencies, global failure of the system indicates chromic granulomatous disease, a syndrome that is now being dismembered. Defective halogenisation should lead to testing for deficiency of myeloperoxidase or abnormal degranulation. The non oxygen-independent bactericidal system, although highly effective in vitro, appears to be less important in vivo than the oxygen-dependent system. Little is known of its pathology.

  1. Adherence of human basophils to cultured umbilical vein endothelial cells.



    The mechanism by which circulating human basophils adhere to vascular endothelium and migrate to sites of allergic reactions is unknown. Agents have been identified which stimulate the adherence of purified basophils to cultured human umbilical vein vascular endothelial cells (HuVEC). Treatment of HuVEC with interleukin 1, tumor necrosis factor (TNF), bacterial endotoxin, and 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in time and dose-dependent increases of adhesiveness for basophils...

  2. Oxygen-independent killing of Bacteroides fragilis by granule extracts from human polymorphonuclear leukocytes.


    Wetherall, B L; Pruul, H; McDonald, P J


    Granule proteins from human neutrophils were prepared by extraction with acetate, and their antibacterial activity against Bacteroides fragilis was determined. Activity was highly dependent on pH; greatest killing occurred at the most acid pH tested (pH 5.0). Optimum activity was observed at physiological ionic strength and low bacterial numbers. Killing was inhibited by incubation temperatures of less than 37 degrees C. Eight times more extract was required to kill 50% of stationary-phase ba...

  3. Oxygen-independent killing of Bacteroides fragilis by granule extracts from human polymorphonuclear leukocytes. (United States)

    Wetherall, B L; Pruul, H; McDonald, P J


    Granule proteins from human neutrophils were prepared by extraction with acetate, and their antibacterial activity against Bacteroides fragilis was determined. Activity was highly dependent on pH; greatest killing occurred at the most acid pH tested (pH 5.0). Optimum activity was observed at physiological ionic strength and low bacterial numbers. Killing was inhibited by incubation temperatures of less than 37 degrees C. Eight times more extract was required to kill 50% of stationary-phase bacteria, compared with those growing in logarithmic phase. The antibacterial effect of granule extract was destroyed by boiling, but some activity was retained after heating to 56 degrees C and 80 degrees C. Granule extract activity was tested under conditions in which oxygen-dependent antibacterial systems were inhibited. The rate and extent of killing was not affected by anaerobiosis, sodium azide, or cysteine hydrochloride. These results suggest that the activity of granule extract is independent of oxidative antibacterial systems, and therefore, under conditions that occur in anaerobic infections, potent leukocyte granule-associated mechanisms exist for the destruction of B. fragilis.

  4. Immunosenescence of Polymorphonuclear Neutrophils

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    Inga Wessels


    Full Text Available All immune cells are affected by aging, contributing to the high susceptibility to infections and increased mortality observed in the elderly. The effect of aging on cells of the adaptive immune system is well documented. In contrast, knowledge concerning age-related defects of polymorphonuclear neutrophils (PMN is limited. During the past decade, it has become evident that in addition to their traditional role as phagocytes, neutrophils are able to secrete a wide array of immunomodulating molecules. Their importance is underlined by the finding that genetic defects that lead to neutropenia increase susceptibility to infections. Whereas there is consistence about the constant circulating number of PMN throughout aging, the abilities of tissue infiltration, phagocytosis, and oxidative burst of PMN from aged donors are discussed controversially. Furthermore, there are numerous discrepancies between in vivo and in vitro results, as well as between results for murine and human PMN. Most of the reported functional changes can be explained by defective signaling pathways, but further research is required to get a detailed insight into the underlying molecular mechanisms. This could form the basis for drug development in order to prevent or treat age-related diseases, and thus to unburden the public health systems.

  5. Anti-Pseudomonas aeruginosa IgY Antibodies Induce Specific Bacterial Aggregation and Internalization in Human Polymorphonuclear Neutrophils

    DEFF Research Database (Denmark)

    Thomsen, K; Christophersen, L; Bjarnsholt, T;


    Polymorphonuclear neutrophils (PMNs) are essential cellular constituents in the innate host response, and their recruitment to the lungs and subsequent ubiquitous phagocytosis controls primary respiratory infection. Cystic fibrosis pulmonary disease is characterized by progressive pulmonary decline...... with P. aeruginosa by augmenting the phagocytic competence of PMNs may postpone the deteriorating chronic biofilm infection. Anti-P. aeruginosa IgY antibodies significantly increase the PMN-mediated respiratory burst and subsequent bacterial killing of P. aeruginosa in vitro. The mode of action......, which enhances bacterial killing by PMN-mediated phagocytosis and thereby may facilitate a rapid bacterial clearance in airways of people with cystic fibrosis....

  6. [Reactive oxygen species produced by the addition of sepiolite and vermiculite (expanded or not) to suspensions of human polymorphonuclear phagocytes and bovine alveolar macrophages]. (United States)

    Amati, M; Visonà, I; Valentino, M; Scancarello, G; Governa, M


    We have studied a sample of commercial sepiolite and two samples of commercial vermiculite, which are clay minerals advised to replace asbestos. We have in vitro tested their abilities to produce reacting oxygen species (ROS) after they have been added to suspension of human polymorphonuclear leukocytes and bovine alveolar macrophages. The behaviour of sepiolite and vermiculite have been compared with those of asbestos fibres given by Unione Internationale contre le Cancer (UICC) and with kaolin and illite. Sepiolite was not able to induce ROS production, while vermiculite was able to induce a relevant ROS generation, even if the values were always lower than that obtained from chrysotile. Kaolin was able to generate a high ROS production.

  7. Kinetics of staphylococcal opsonization, attachment, ingestion and killing by human polymorphonuclear leukocytes: a quantitative assay using [3H]thymidine labeled bacteria. (United States)

    Verhoef, J; Peterson, P K; Quie, P G


    A method has been developed for studying quantitatively the separate processes of bacterial opsonization, phagocytosis, and killing by human polymorphonuclear leukocytes using [3H]thymidine labeled Staphylococcus aureus. Phagocytosis is determined by assaying for leukocytes-associated radioactivity after differential centrifugation and washing the leukocytes. Opsonization is studied by incubating bacteria with an opsonic source for varying durations and then adding leukocytes. By treatment of samples with the muralytic enzyme, lysostaphin, the attachment and ingestion phases of phagocytosis can be separated. Sampling for colony forming units after disruption of the leukocytes permits the measurement of bacterial killing. Using this method, differences in the kinetics of staphylococcal opsonization by normal and C2 deficient sera were defined, opsonic influences on the attachment and ingestion phases of pH agocytosis were delineated, and the influences of different opsonins and leukocyte populations on killing were determined.

  8. Inhibition by soya isoflavones of human polymorphonuclear leukocyte function: possible relevance for the beneficial effects of soya intake. (United States)

    Rotondo, Serenella; Krauze-Brzósko, Katarzyna; Manarini, Stefano; Martelli, Nicola; Pecce, Romina; Evangelista, Virgilio; Benedetta Donati, Maria; Cerletti, Chiara


    Lower CVD incidence is reported in Asian populations consuming soya-containing food. As polymorphonuclear leukocytes (PMN) are involved in the risk of CVD, we investigated the modulatory effect of soya isoflavones on several PMN functions and their molecular mechanisms in vitro. PMN, isolated from blood from healthy subjects, were tested upon activation with 1 microm- n-formyl-methyl-leucyl-phenylalanine (fMLP) for superoxide anion production (ferric cytochrome c reduction) and released elastase (chromogenic test). PMN homotypic aggregates stimulated by fMLP or P-selectin in dynamic conditions were detected by optical microscopy. PMN, mixed with thrombin-activated, washed platelets, formed cell aggregates, measured by flow cytometry. Phosphorylation of Pyk2, a focal adhesion kinase, was studied by immunoprecipitation and immunoblotting with specific antibodies. Genistein, daidzein and equol inhibited superoxide anion production (IC50 0.25 (sem 0.1), 21.0 (sem 4.2) and 13.0 (sem 2.8) microm, respectively); the release of elastase was prevented by genistein (IC50 63 (sem 17) microm). PMN homotypic aggregates, stimulated by fMLP, were significantly reduced (24 (sem 12) and 51 (sem 14) % of control) by 100 microm genistein and equol. P-selectin-induced aggregates were reduced to 19 (sem 6), 44 (sem 10) and 28 (sem 9) % of control by 100 microm genistein, daidzein and equol, respectively. Genistein, daidzein and equol also significantly reduced mixed platelet-PMN aggregates (IC50 4.0 (sem 0.9), 57 (sem 6) and 66 (sem 23) microm, respectively). In PMN challenged by fMLP or P-selectin, activation of Pyk2 was prevented by isoflavones. The cardioprotective effect of soya-containing food might be linked to reduction of PMN activation and PMN-platelet interaction, novel targets for the biological effects of soya isoflavones.

  9. [Effect of anti-inflammatory drugs, alone and combined with ofloxacin, on the respiratory burst of human polymorphonuclear leukocytes]. (United States)

    Cabrera, E; Velert, M M; Orero, A; Martínez, P; Cantón, E


    The antibacterial activity of polymorphonuclear leukocytes (PMNs) is based on the production of superoxide anion and H(2)O(2) in the respiratory burst and can be impaired in different ways. The combination of an antibacterial agent and an antiinflammatory drug is quite common in immunodepressed patients whose respiratory burst of PMN could be impaired. In this study we examine in vitro the effect of pretreating (35 degrees C for 30 min) PMNs with the antiinflammatory drugs dexamethasone (0.4, 4 and 40 microgram/ml), methylprednisolone (0.37, 3.7 and 37 microgram/ ml), hydrocortisone (0.048, 0.48 and 4.8 microgram/ml), betamethasone (0.1, 1, 5 and 10 mg/ml), phenylbutazone (1000 microgram/ml) and acetylsalicylic acid (25, 250, 2500 microgram/ml) alone, and combined with 10 mg/ml of ofloxacin on the respiratory burst. Superoxide anion was measured by the cytochrome c reduction microtechnique and H(2)O(2) by phenol red. The antiinflammatory drugs alone decreased the production of H(2)O(2) (except dexamethasone and methylprednisolone) and superoxide anion (except betamethasone) from 15-45%, depending on the antiinflammatory drug and concentration, while ofloxacin increased the production of superoxide anion (20.2 +/- 6.7%). The combination of antiinflammatory drugs with ofloxacin neutralizes the inhibitory effect of the former on the respiratory burst of PMNs. It is therefore important to know the effect of drugs on the respiratory burst in order to choose those that have the same therapeutic effect without interfering with PMN functions.

  10. Alcohol use, antiretroviral therapy adherence, and preferences regarding an alcohol-focused adherence intervention in patients with human immunodeficiency virus

    Directory of Open Access Journals (Sweden)

    Kekwaletswe CT


    Full Text Available Connie T Kekwaletswe,1 Neo K Morojele1,21Alcohol and Drug Abuse Research Unit, Medical Research Council, Pretoria, 2School of Public Health, University of the Witwatersrand, Johannesburg, South AfricaBackground: The primary objectives of this study were to determine the association between alcohol and antiretroviral therapy (ART adherence and the perceived appropriateness and acceptability of elements of an adherence counseling program with a focus on alcohol-related ART nonadherence among a sample of ART recipients in human immunodeficiency virus (HIV clinics in Tshwane, South Africa.Methods: We conducted a cross-sectional study with purposive sampling. The sample comprised 304 male and female ART recipients at two President's Emergency Plan For AIDS Relief-supported HIV clinics. Using an interview schedule, we assessed patients' alcohol use (Alcohol Use Disorders Identification Test, other drug use, level of adherence to ART, and reasons for missing ART doses (AIDS Clinical Trials Group adherence instrument. Additionally, patients’ views were solicited on: the likely effectiveness of potential facilitators; the preferred quantity, duration, format, and setting of the sessions; the usefulness of having family members/friends attend sessions along with the patient; and potential skill sets to be imparted.Results: About half of the male drinkers’ and three quarters of the female drinkers’ Alcohol Use Disorders Identification Test scores were suggestive of hazardous or harmful drinking. Average self-reported ART adherence was 89.7%. There was a significant association between level of alcohol use and degree of ART adherence. Overall, participants perceived two clinic-based sessions, each of one hour’s duration, in a group format, and facilitated by a peer or adherence counselor, as most appropriate and acceptable. Participants also had a favorable attitude towards family and friends accompanying them to the sessions. They also favored an

  11. The quorum-sensing molecule N-3-oxododecanoyl homoserine lactone (3OC12-HSL) enhances the host defence by activating human polymorphonuclear neutrophils (PMN). (United States)

    Wagner, Christof; Zimmermann, Sabine; Brenner-Weiss, Gerald; Hug, Friederike; Prior, Birgit; Obst, Ursula; Hänsch, Gertrud Maria


    The P. aeruginosa quorum-sensing molecule N-3-oxododecanoyl homoserine lactone (3OC12-HSL) interacts not only with bacteria, but also with mammalian cells, among others with those of the immune defence system. We focussed on the possible interaction of 3OC12-HSL with human polymorphonuclear neutrophils (PMN), because these cells are the first to enter an infected site. We found that 3OC12-HSL attracts PMN, and up-regulates expression of receptors known to be involved in host defence, including the adhesion proteins CD11b/CD18 and the immunoglobulin receptors CD16 and CD64. Furthermore, the uptake of bacteria (phagocytosis), which is crucial for an efficient defence against infection, was enhanced. Thus, recognising and responding to 3OC12-HSL not only attracts the PMN to the site of a developing biofilm, but also reinforces their defence mechanisms, and hence could be a means to control the infection in an early stage and to prevent biofilm formation.

  12. Evidence of Qi-gong energy and its biological effect on the enhancement of the phagocytic activity of human polymorphonuclear leukocytes. (United States)

    Fukushima, M; Kataoka, T; Hamada, C; Matsumoto, M


    In order to test for an effect of phosphate buffered saline (PBS) treated externally with Qi energy ("Qi-treated" PBS) on the phagocytic activity of human polymorphonuclear leukocytes (PMNs), rigorously controlled experiments employing masking and randomized procedures were carried out under independent monitoring. In all experiments, Qi treatment was externally applied under monitoring to newly purchased unopened 100 ml bottles of PBS, and the PMN phagocytic activity was assayed by one experimenter in masked, randomized and monitored conditions using a highly sensitive chemiluminescence method. Phagocytic activity data were obtained in triplicate for each sample and then statistically analyzed. The PBS samples Qi-treated by the Qi-gong master and by one of the Qi-gong trainees showed clear stimulation of PMN phagocytic activity which was significant statistically, and this phenomenon was highly reproducible. Out of 10 experiments by the Qi-gong master, only twice did Qi-treatment fail to influence the PBS. The activity of Qi-treated PBS decayed over days or weeks. Furthermore, it was found that Qi-treated PBS had decreased phagocytic stimulatory activity after microwave treatment, but not after autoclave treatment. We also demonstrated that microwave irradiation and infrared laser pulse irradiation have similar effects on PBS as Qi-treatment. The results obtained in this experiment provide evidence of the existence of Qi energy, its ability to influence an electrolyte solution and its biological effect. Furthermore, microwave or infrared laser pulse treatment was found to partly mimic the Qi-treatment of PBS.

  13. Garenoxacin-induced increase of CD11b expression on human polymorphonuclear neutrophils does not affect phagocytosis and killing of Staphylococcus aureus. (United States)

    Grüger, Thomas; Reiners, Ana-Lena; Schnitzler, Norbert; Brandenburg, Kerstin; Zündorf, Josef


    Garenoxacin is considered to be the most active quinolone against Staphylococcus aureus. Quinolones are believed to alter the function of human polymorphonuclear leukocytes (PMN) and garenoxacin is known to be the only quinolone which alters the expression of the beta-chain (CD11b) of the complement receptor 3 (CR3) which is known to be important in the phagocytosis of S. aureus by PMN. Therefore, the effect of this altered CD11b expression on phagocytosis, oxidative burst, and killing of S. aureus was addressed and compared with that of standard quinolones. Phagocytosis and oxidative burst were determined by flow cytometry, and killing was measured by a colony-count method. Garenoxacin at therapeutic concentrations affected neither phagocytosis nor killing of Staphylococcus aureus NMS54. At supratherapeutic concentrations (1,500 mg/l) garenoxacin reduced and delayed phagocytosis like all other quinolones tested except norfloxacin. This decrease seems to be a result of inhibition of the oxidative burst of PMN and reduced CD11b expression at this supratherapeutic concentration. In conclusion, the alteration of CD11b expression of PMN caused by garenoxacin at 0.5, 5.0, and 100.0 mg/l is not considered to hamper the function of these first-line-defense phagocytes.

  14. New combined assay of phagocytosis and intracellular killing of Escherichia coli by polymorphonuclear leukocytes

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, P.J.; Ford, J.M. (Saint Bartholomew' s Hospital, London (UK))


    A new combined radiometric assay is described in which adherence, and phagocytosis and killing of Escherichia coli by human polymorphonuclear leucocytes (PMN) are simultaneously measured in the same sample. Pure monolayers of PMN in Petri dishes are allowed to ingest (/sup 14/C)phenylalanine labelled E. coli and excess bacteria are removed by washing. A period of incubation allows intracellular killing to occur while polymyxin-B is added to half the dishes to kill extracellular bacteria. The remaining viable bacteria in all dishes are labelled with (/sup 3/H)thymidine. The number of ingested bacteria and the percentage of intracellular organisms killed is determined from the /sup 14/C and /sup 3/H counts by a simple subtraction technique. By performing protein assays on representative monolayers, the number of PMN adhered in the monolayers and hence the mean bacterial uptake per PMN is estimated. The assay detected killing efficiencies reduced below the normal range, in monolayers treated with sodium azide, phenylbutazone, in polymorphonuclear leukocytes from patients with chronic granulomatous disease, and in immature neutrophils from the promyelocytic leukaemic cell line, HL60. The assay was adapted to measure phagocytosis and killing by cells in suspension.

  15. Study of the inhibition by polymorphonuclear leukocytes of TNF-α release from human mononuclear cells and its mechanism

    Institute of Scientific and Technical Information of China (English)


    @@ The present study was undertaken to investigate the effect of human PMNs on the production of TNF-α by the human peripheral blood mononuclear cells (PBMCs) and to elucidate its tentative mechanism.

  16. Characterization of Adherent Nonhematopoietic Cells Derived from Human Umbilical Cord Blood

    Institute of Scientific and Technical Information of China (English)

    安小惠; 蔡国平


    To confirm and characterize the adherent fibroblast-like progenitors in human umbilical cord blood, we isolated mononuclear cells from human umbilical cord blood by Ficoll-Hypaque.Two main morphologically different kinds of cells were formed by culturing the cells in collagen-coated 24-well plastic dishes and flasks.One type was the adherent fibroblast-like cells, while the other was loosely adherent clonally expanded round cells.Our experiments demonstrate that the adherent fibroblast-like cells possess multilineage potential, including the ability to differentiate into endothelial-like cells and to express the mesenchymal cell marker.

  17. Study of the inhibition by polymorphonuclear leukocytes of TNF-α release from human mononuclear cells and its mechanism

    Institute of Scientific and Technical Information of China (English)


    The present study was undertaken to investigate the effect of human PMNs on the production of TNF-α by the human peripheral blood mononuclear cells (PBMCs) and to elucidate its tentative mechanism. Human PMNs and PBMCs were isolated from the venous blood of healthy donors by dextran sedimentation and density gradient centrifugation. In the presence of lipopolysaccharide (LPS), PMNs and PBMCs were cocultured at the ratio of 2:1 for 20 h and the concentration of TNF-α in the supernatant was measured by enzyme-linked immunosorbent assay. The binding rate of monocytes with the fluorescein isothiocyanate-labeled LPS (FITC-LPS) and the mean surface fluorescence intensity of monocytes were analyzed by flow cytometry. Results showed that PMNs were capable of inhibiting the TNF-α release from PBMCs (P<0.05). PMNs suppressed the TNF-α release from PBMCs by 45% on average when PMNs and PBMCs cocultured at the ratio of 2:1. Paraformaldehyde-fixed PMNs still demonstrated the same inhibition (P<0.05),which proved that the inhibition was dependent on cell-to-cell contact and suggested that effector molecules responsible for this effect existed on the cell surface of PMNs. In the presence of PMNs, the binding rate of monocytes with the FITC-LPS and the mean surface fluorescence intensity of monocytes were not affected compared with PBMCs alone (P>0.05). As incubation time was prolonged, the binding of FITC-LPS to monocytes increased (P<0.05). Thus PMNs did not block the binding of LPS with monocytes. It was concluded that PMNs suppressed the TNF-α release from PBMCs via cell-to-cell interaction. In a cell-contact dependent manner, PMNs might interfere with the signal transduction pathway through which LPS activated PBMCs, thus attenuating the response of PBMCs to LPS and downregulating the TNF-α release.

  18. 111In)oxine labelling of polymorphonuclear leucocytes: doubts concerning elution and effects on cell behaviour

    Energy Technology Data Exchange (ETDEWEB)

    Sheehan, N.J.; Brown, K.A.; Camacho, A.; Dumonde, D.C.


    Polymorphonuclear leucocytes (PMN) from normal human subjects were labelled with (111In)oxine (20 muCi 10(8) cells). In the presence of 20% autologous serum (AS), dissociation of 111In from the cells resulted in mean losses of radioactivity of 13% at 3 h and 30% at 24 h. Adherence of 111In-labelled PMN to cultured porcine endothelial monolayers was increased by 40.7 +/- 31.6% after 60 min incubation in 20% AS at 37 degrees C when compared with unlabelled cells. Phagocytosis and intracellular killing of Candida albicans were unaltered by labelling. Elution of 111In from labelled PMN together with enhanced adhesiveness may have important implications for the study of PMN kinetics and the investigation of inflammatory disease.

  19. Increased Rate of Apoptosis and Diminished Phagocytic Ability of Human Neutrophils Infected with Afa/Dr Diffusely Adhering Escherichia coli Strains


    Brest, Patrick; Bétis, Frédéric; Çuburu, Nicolas; Selva, Eric; Herrant, Magali; Servin, Alain,; Auberger, Patrick; Hofman, Paul


    The proinflammatory effect of Afa/Dr diffusely adhering Escherichia coli (Afa/Dr DAEC) strains have been recently demonstrated in vitro by showing that polymorphonuclear leukocyte (PMN) transepithelial migration is induced after bacterial colonization of apical intestinal monolayers. The effect of Afa/Dr DAEC-PMN interaction on PMN behavior has been not investigated. Because of the putative virulence mechanism of PMN apoptosis during infectious diseases and taking into account the high level ...

  20. Adherence of clinically isolated lactobacilli to human cervical cells in competition with Neisseria gonorrhoeae. (United States)

    Vielfort, Katarina; Sjölinder, Hong; Roos, Stefan; Jonsson, Hans; Aro, Helena


    Lactobacilli are normal inhabitants of our microbiota and are known to protect against pathogens. Neisseria gonorrhoeae is a human specific pathogenic bacterium that colonises the urogenital tract where it causes gonorrhoea. In this study we analysed early interactions between lactobacilli and gonococci and investigated how they compete for adherence to human epithelial cervical cells. We show that lactobacilli adhere at various levels and that the number of adherent bacteria does not correlate to the level of protection against gonococcal infection. Protection against gonococcal adhesion varied between Lactobacillus species. Lactobacillus crispatus, Lactobacillus gasseri and Lactobacillus reuteri were capable of reducing gonococcal adherence while Lactobacillus rhamnosus was not. Lactobacillus strains of vaginal origin had the best capacity to remain attached to the host cell during gonococcal adherence. Further, we show that gonococci and lactobacilli interact with each other with resultant lactobacilli incorporation into the gonococcal microcolony. Hence, gonococci bind to colonised lactobacilli and this complex frequently detaches from the epithelial cell surface, resulting in reduced bacterial colonisation. Also, purified gonococcal pili are capable of removing adherent lactobacilli from the cell surface. Taken together, we reveal novel data regarding gonococcal and lactobacilli competition for adherence that will benefit future gonococcal prevention and treatments.

  1. ADAM9 Is a Novel Product of Polymorphonuclear Neutrophils

    DEFF Research Database (Denmark)

    Roychaudhuri, Robin; Hergrueter, Anja H; Polverino, Francesca


    A disintegrin and a metalloproteinase domain (ADAM) 9 is known to be expressed by monocytes and macrophages. In this study, we report that ADAM9 is also a product of human and murine polymorphonuclear neutrophils (PMNs). ADAM9 is not synthesized de novo by circulating PMNs. Rather, ADAM9 protein ...

  2. Enhanced adherence of methicillin-resistant Staphylococcus pseudintermedius sequence type 71 to canine and human corneocytes. (United States)

    Latronico, Francesca; Moodley, Arshnee; Nielsen, Søren Saxmose; Guardabassi, Luca


    The recent worldwide spread of methicillin-resistant Staphylococcus pseudintermedius (MRSP) in dogs is a reason for concern due to the typical multidrug resistance patterns displayed by some MRSP lineages such as sequence type (ST) 71. The objective of this study was to compare the in vitro adherence properties between MRSP and methicillin-susceptible (MSSP) strains. Four MRSP, including a human and a canine strain belonging to ST71 and two canine non-ST71 strains, and three genetically unrelated MSSP were tested on corneocytes collected from five dogs and six humans. All strains were fully characterized with respect to genetic background and cell wall-anchored protein (CWAP) gene content. Seventy-seven strain-corneocyte combinations were tested using both exponential- and stationary-phase cultures. Negative binomial regression analysis of counts of bacterial cells adhering to corneocytes revealed that adherence was significantly influenced by host and strain genotype regardless of bacterial growth phase. The two MRSP ST71 strains showed greater adherence than MRSP non-ST71 (p pseudintermedius adherence to canine corneocytes was significantly higher compared to human corneocytes (p < 0.0001), but the MRSP ST71 strain of human origin adhered equally well to canine and human corneocytes, suggesting that MRSP ST71 may be able to adapt to human skin. The genetic basis of the enhanced in vitro adherence of ST71 needs to be elucidated as this phenotypic trait may be associated to the epidemiological success and zoonotic potential of this epidemic MRSP clone.

  3. International criminal tribunals and human rights law: Adherence and contextualization

    NARCIS (Netherlands)

    Zeegers, K.J.


    Given their mandate to prosecute persons responsible for the most atrocious of human rights violations, International Criminal Tribunals (ICTs) are generally hailed as welcome enforcers of international human rights law: a new instrument in the toolkit of human rights protectors. However, ICTs inves

  4. Adherence of uropathogenic Escherichia coli to human primary epithelial cells of renal pelvis

    Institute of Scientific and Technical Information of China (English)



    Human primary epithelial cells of renal pelvis was established to investigate the adherence of uropathogenic Escherichia coli (UPEC) to this cell line, in which the primary cell culture was performed by using cultivation of the normal epithelium of renal pelvis in keratinocyte serum free medium (K-SFM)with epidermal growth factor (EGF) and bovine pituitary extract (BPE). Both UPEC132 obtained from urine specimen of patients with pyelonephritis and the pilus-free representative strain E. coli K-12p678-54 were used to study the adherence of these strains on human primary epithelial cells of renal pelvis.The UPEC adherence was performed with observation on the morphological changes of the adhered cells,while the adhesion rates and indices were calculated in different times of experiment. In addition, the virulence genes hly and cnf1 of UPEC132 were detected by multiplex PCR assay. In this study, the human primary epithelial cells of renal pelvis was found to exhibit the character of the transitional epithelial cells. Compared with the control group, the adhesion rates and indices began to increase from 15 min of the experiment time and reached its peak in 120 min. The adhesion rate and index of UPEC132 to human primary epithelial cells of renal pelvis were 74.4% and 34.0 respectively. Many microscopic changes in the primary cells adhered with UPEC132 could be detected, such as rounding or irregularity in shape,unevenness in staining and the cytoplasmic and nuclear changes. It suggests that human primary epithelial cells of renal pelvis can be used for the experiment on UPEC adhesion, thus providing a basis for the further study on the pathogenesis of UPEC.

  5. High Intracellular Concentrations of Posaconazole Do Not Impact on Functional Capacities of Human Polymorphonuclear Neutrophils and Monocyte-Derived Macrophages In Vitro. (United States)

    Farowski, Fedja; Cornely, Oliver A; Hartmann, Pia


    Posaconazole is a commonly used antifungal for the prophylaxis and treatment of invasive fungal infections. We previously demonstrated that the intracellular concentration of posaconazole in peripheral blood mononuclear cells (PBMCs) and polymorphonuclear neutrophils (PMNs) was greatly increased compared to the plasma concentration. As these professional phagocytes are crucial to combat fungal infections, we set out to investigate if and how, beneficial or deleterious, this high loading of intracellular posaconazole impacts the functional capacities of these cells. Here, we show that high intracellular concentrations of posaconazole do not significantly impact PMN and monocyte-derived macrophage function in vitro In particular, killing capacity and cytoskeletal features of PMN, such as migration, are not affected, indicating that these cells serve as vehicles for posaconazole to the site of infection. Moreover, since posaconazole as such slowed the germination of Aspergillus fumigatus conidia, infected neutrophils released less reactive oxygen species (ROS). Based on these findings, we propose that the delivery of posaconazole by neutrophils to the site of Aspergillus species infection warrants control of the pathogen and preservation of tissue integrity at the same time.

  6. Human IgA inhibits adherence of Acanthamoeba polyphaga to epithelial cells and contact lenses. (United States)

    Campos-Rodríguez, Rafael; Oliver-Aguillón, Gabriela; Vega-Pérez, Luz M; Jarillo-Luna, Adriana; Hernández-Martínez, Dolores; Rojas-Hernández, Saúl; Rodríguez-Monroy, Marco A; Rivera-Aguilar, Víctor; González-Robles, Arturo


    Specific anti-Acanthamoeba IgA antibodies have been detected in the serum and tears of patients and healthy individuals. However, the role of human secretory IgA antibodies in inhibiting the adherence of Acanthamoeba had not been previously investigated. Therefore, the purpose of this study was to purify secretory IgA from human colostrum and analyze its effect on the adherence of Acanthamoeba trophozoites to contact lenses and Madin-Darby canine kidney (MDCK) cells. IgA antibodies to Acanthamoeba polyphaga in colostrum of healthy women as well as in saliva and serum of healthy subjects were analyzed by ELISA and Western blot analysis. In serum, saliva, and colostrum, we detected IgA antibodies that recognized several antigens of A. polyphaga. In addition, colostrum and IgA antibodies purified from it inhibited adherence of A. polyphaga trophozoites to contact lenses and MDCK cells. These results suggest that IgA antibodies may participate in the resistance to the amoebic infection, probably by inhibiting the adherence of the trophozoites to contact lenses and corneal epithelial cells.

  7. Effect of respiratory syncytial virus (RSV) infection on the adherence of pathogenic bacteria to human epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Faden, H.; Hong, J.J.; Ogra, P.L.


    The effect of RSV infection on the adherence of Streptococcus pneumoniae (SP), Haemophilus influenzae (HI) and Staphylococcus aureus (SA) to human epithelial cells was determined. RSV-infected Hep-2 cell cultures at different stages of expression of surface viral antigens and bacteria labeled with /sup 3/H-thymidine were employed to examine the kinetics of bacterial adherence to virus-infected cells. RSV infection did not alter the magnitude of adherence of HI or SA to HEp-2 cells. However, adherence of SP to HEp-2 cells was significantly (P < 0.01) enhanced by prior RSV infection. The degree of adherence was directly related to the amount of viral antigen expressed on the cell surface. The adherence was temperature dependent, with maximal adherence observed at 37/sup 0/C. Heat-inactivation of SP did not alter adherence characteristics. These data suggest that RSV infection increases adherence of SP to the surface of epithelial cells in vitro. Since attachment of bacteria to mucosal surfaces is the first step in many infections, it is suggested that viral infections of epithelial cells render them more susceptible to bacterial adherence. Thus, RSV infection in vivo may predispose children to SP infections, such as in otitis media, by increasing colonization with SP.

  8. Infection with human coronavirus NL63 enhances streptococcal adherence to epithelial cells (United States)

    Golda, Anna; Malek, Natalia; Dudek, Bartosz; Zeglen, Slawomir; Wojarski, Jacek; Ochman, Marek; Kucewicz, Ewa; Zembala, Marian


    Understanding the mechanisms of augmented bacterial pathogenicity in post-viral infections is the first step in the development of an effective therapy. This study assessed the effect of human coronavirus NL63 (HCoV-NL63) on the adherence of bacterial pathogens associated with respiratory tract illnesses. It was shown that HCoV-NL63 infection resulted in an increased adherence of Streptococcus pneumoniae to virus-infected cell lines and fully differentiated primary human airway epithelium cultures. The enhanced binding of bacteria correlated with an increased expression level of the platelet-activating factor receptor (PAF-R), but detailed evaluation of the bacterium–PAF-R interaction revealed a limited relevance of this process. PMID:21325482

  9. Poly(ethylene glycol)-containing hydrogels modulate α-defensin release from polymorphonuclear leukocytes and monocyte recruitment. (United States)

    Lieberthal, Tyler Jacob; Cohen, Hannah Caitlin; Kao, W John


    Polymorphonuclear leukocytes (PMNs) release granule proteins as the first line of defense against bacteria and set up chemotactic gradients that result in monocyte infiltration to the site of injury. Although well established, the role of biomaterials in regulating adherent PMN degranulation and subsequent PMN-monocyte paracrine interactions is less clear. The aim of this study was to determine how biomaterials affect the degranulation of selected biomarkers and downstream monocyte adhesion and transendothelial migration. Poly(ethylene glycol) (PEG)-containing hydrogels (PEG and an interpenetrating network of PEG and gelatin) promote the release of the α-defensins human neutrophil peptides 1-3, but not azurocidin or monocyte chemotactic protein-1. Although human neutrophil peptides 1-3 are monocyte chemoattractants, no subsequent effects on monocyte transmigration are observed in static conditions. Under flow conditions, monocyte adhesion on human umbilical vein endothelial cells stimulated with tumor necrosis factor-α is elevated in the presence of granule proteins from PMNs adherent on polydimethylsiloxane, but not from PMNs cultured on PEG hydrogels. These results suggest that PEG promotes PMN antimicrobial capacity without enhanced monocyte recruitment.

  10. DMSO-Free Programmed Cryopreservation of Fully Dissociated and Adherent Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Igor I. Katkov


    Full Text Available Three modes for cryopreservation (CP of human iPSC cells have been compared: STD: standard CP of small clumps with 10% of CPA in cryovials, ACC: dissociation of the cells with Accutase and freezing in cryovials, and PLT: programmed freezing of adherent cells in plastic multiwell dishes in a programmable freezer using one- and multistep cooling protocols. Four CPAs were tesetd: dimethyl sulfoxide (DMSO, ethylene glycol (EG, propylene glycol (PG, and glycerol (GLY. The cells in ACC and PLT were frozen and recovered after thawing in the presence of a ROCK inhibitor Y-27632 (RI. EG was less toxic w/o CP cryopreservation than DMSO and allowed much better maintenance of pluripotency after CP than PG or GLY. The cells were cryopreserved very efficiently as adherent cultures (+RI in plates (5-6-fold higher than STD using EG and a 6-step freezing protocol. Recovery under these conditions is comparable or even higher than ACC+RI. Conclusions. Maintenance of cell-substratum adherence is a favorable environment that mitigates freezing and thawing stresses (ComfortFreeze® concept developed by CELLTRONIX. CP of cells directly in plates in ready-to-go after thawing format for HT/HC screening can be beneficial in many SC-related scientific and commercial applications such as drug discovery and toxicity tests.

  11. Assessment of factors influencing adherence to anti-retroviral therapy for human immunodeficiency virus positive mothers and their infected children

    Directory of Open Access Journals (Sweden)

    Arun Kumar De


    Full Text Available Background and Objectives: Mothers and children are biologically related and dependent. They should be considered as a single unit which is very important regarding adherence to anti-retroviral therapy (ART. Very high levels of adherence are required for effective ART. We therefore carried out this study to examine the adherence levels and different factors associated with adherence among human immunodeficiency virus (HIV-positive mothers and their HIV-positive children receiving ART. Design and Setting: A hospital-based cross-sectional study. Materials and Methods: Ninety-four HIV-positive mothers and their 94 HIV-positive children under ART attending the ART center of a tertiary care hospital were recruited in this study. Consenting mothers were asked to complete the "Case Study Form" containing socio-demographic and care-giving details. Mothers were also asked to complete the Beck′s depression inventory, State trait anxiety inventory, and Ways of coping inventory. Adherence was assessed using pill count. Criteria for good and poor adherence were defined. Current CD4 counts were retrieved from the hospital record. Results: Fifty-six percent of respondent mothers and 65.8% of respondent children showed good adherence to ART. Different factors were associated with poor adherence in both mothers and their children. Conclusion: Adherence of HIV-positive mothers and their HIV-positive children to ART is influenced by multiple factors and identification of these factors is necessary to get complete adherence to ART. There is statistically significant relationship between maternal and pediatric adherence to ART.

  12. Glia maturation factor gamma regulates the migration and adherence of human T lymphocytes

    Directory of Open Access Journals (Sweden)

    Lippert Dustin ND


    Full Text Available Abstract Background Lymphocyte migration and chemotaxis are essential for effective immune surveillance. A critical aspect of migration is cell polarization and the extension of pseudopodia in the direction of movement. However, our knowledge of the underlying molecular mechanisms responsible for these events is incomplete. Proteomic analysis of the isolated leading edges of CXCL12 stimulated human T cell lines was used to identify glia maturation factor gamma (GMFG as a component of the pseudopodia. This protein is predominantly expressed in hematopoietic cells and it has been shown to regulate cytoskeletal branching. The present studies were undertaken to examine the role of GMFG in lymphocyte migration. Results Microscopic analysis of migrating T-cells demonstrated that GMFG was distributed along the axis of movement with enrichment in the leading edge and behind the nucleus of these cells. Inhibition of GMFG expression in T cell lines and IL-2 dependent human peripheral blood T cells with shRNAmir reduced cellular basal and chemokine induced migration responses. The failure of the cells with reduced GMFG to migrate was associated with an apparent inability to detach from the substrates that they were moving on. It was also noted that these cells had an increased adherence to extracellular matrix proteins such as fibronectin. These changes in adherence were associated with altered patterns of β1 integrin expression and increased levels of activated integrins as detected with the activation specific antibody HUTS4. GMFG loss was also shown to increase the expression of the β2 integrin LFA-1 and to increase the adhesion of these cells to ICAM-1. Conclusions The present studies demonstrate that GMFG is a component of human T cell pseudopodia required for migration. The reduction in migration and increased adherence properties associated with inhibition of GMFG expression suggest that GMFG activity influences the regulation of integrin mediated

  13. Adherence to and invasion of human intestinal cells by Arcobacter species and their virulence genotypes. (United States)

    Levican, Arturo; Alkeskas, Aldukali; Günter, Claudia; Forsythe, Stephen J; Figueras, María José


    The genus Arcobacter is composed of 17 species which have been isolated from various sources. Of particular interest are A. butzleri, A. cryaerophilus, and A. skirrowii, as these have been associated with human cases of diarrhea, the probable transmission routes being through the ingestion of contaminated drinking water and food. To date, only limited studies of virulence traits in this genus have been undertaken. The present study used 60 Arcobacter strains isolated from different sources, representing 16 of the 17 species of the genus, to investigate their ability to adhere to and invade the human intestinal cell line Caco-2. In addition, the presence of five putative virulence genes (ciaB, cadF, cj1349, hecA, and irgA) was screened for in these strains by PCR. All Arcobacter species except A. bivalviorum and Arcobacter sp. strain W63 adhered to Caco-2 cells, and most species (10/16) were invasive. The most invasive species were A. skirrowii, A. cryaerophilus, A. butzleri, and A. defluvii. All invasive strains were positive for ciaB (encoding a putative invasion protein). Other putative virulence genes were present in other species, i.e., A. butzleri (cadF, cj1349, irgA, and hecA), A. trophiarum (cj1349), A. ellisii (cj1349), and A. defluvii (irgA). No virulence genes were detected in strains which showed little or no invasion of Caco-2 cells. These results indicate that many Arcobacter species are potential pathogens of humans and animals.

  14. Adhering maternal platelets can contribute to the cytokine and chemokine cocktail released by human first trimester villous placenta. (United States)

    Blaschitz, A; Siwetz, M; Schlenke, P; Gauster, M


    Placental villous explant culture has been increasingly recognized as suitable model to study secretion of inflammatory and immune modulating factors by human placenta. Most of these factors likely derive from the syncytiotrophoblast, whereas extraplacental sources such as maternal peripheral blood cells are rarely considered. Due to their small size and absence of a nucleus, platelets adhering to perivillous fibrinoid of normal placenta are frequently ignored in routine immunohistochemistry. Here we demonstrate adhering maternal platelets on first trimester placental villi after explant culture and point out that platelet-derived factors must be considered when analyzing the inflammatory secretion profile of human placenta.

  15. Human responses to Florida red tides: policy awareness and adherence to local fertilizer ordinances. (United States)

    Kirkpatrick, Barbara; Kohler, Kate; Byrne, Margaret; Fleming, Lora E; Scheller, Karen; Reich, Andrew; Hitchcock, Gary; Kirkpatrick, Gary; Ullmann, Steven; Hoagland, Porter


    To mitigate the damages of natural hazards, policy responses can be beneficial only if they are effective. Using a self-administered survey approach, this paper focuses on the adherence to local fertilizer ordinances (i.e., county or municipal rules regulating the application of fertilizer to private lawns or facilities such as golf courses) implemented in jurisdictions along the Southwest Florida coast in response to hazardous blooms of Florida red tides (Karenia brevis). These ordinances play a role in the context of evolving programs of water pollution control at federal, state, water basin, and local levels. With respect to policy effectiveness, while the strength of physical linkages is of critical importance, the extent to which humans affected are aware of and adhere to the relevant rules, is equally critical. We sought to understand the public's depth of understanding about the rationales for local fertilizer ordinances. Respondents in Sarasota, Florida, were asked about their fertilizer practices in an area that has experienced several major blooms of Florida red tides over the past two decades. A highly educated, older population of 305 residents and "snowbirds" reported relatively little knowledge about a local fertilizer ordinance, its purpose, or whether it would change the frequency, size, or duration of red tides. This finding held true even among subpopulations that were expected to have more interest in or to be more knowledgeable about harmful algal blooms. In the face of uncertain science and environmental outcomes, and with individual motivations at odds with evolving public policies, the effectiveness of local community efforts to decrease the impacts of red tides may be compromised. Targeted social-science research on human perceptions about the risks of Florida red tides and education about the rationales for potential policy responses are warranted.

  16. Highly Efficient Neural Conversion of Human Pluripotent Stem Cells in Adherent and Animal-Free Conditions. (United States)

    Lukovic, Dunja; Diez Lloret, Andrea; Stojkovic, Petra; Rodríguez-Martínez, Daniel; Perez Arago, Maria Amparo; Rodriguez-Jimenez, Francisco Javier; González-Rodríguez, Patricia; López-Barneo, José; Sykova, Eva; Jendelova, Pavla; Kostic, Jelena; Moreno-Manzano, Victoria; Stojkovic, Miodrag; Bhattacharya, Shomi S; Erceg, Slaven


    Neural differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can produce a valuable and robust source of human neural cell subtypes, holding great promise for the study of neurogenesis and development, and for treating neurological diseases. However, current hESCs and hiPSCs neural differentiation protocols require either animal factors or embryoid body formation, which decreases efficiency and yield, and strongly limits medical applications. Here we develop a simple, animal-free protocol for neural conversion of both hESCs and hiPSCs in adherent culture conditions. A simple medium formula including insulin induces the direct conversion of >98% of hESCs and hiPSCs into expandable, transplantable, and functional neural progenitors with neural rosette characteristics. Further differentiation of neural progenitors into dopaminergic and spinal motoneurons as well as astrocytes and oligodendrocytes indicates that these neural progenitors retain responsiveness to instructive cues revealing the robust applicability of the protocol in the treatment of different neurodegenerative diseases. The fact that this protocol includes animal-free medium and human extracellular matrix components avoiding embryoid bodies makes this protocol suitable for the use in clinic. Stem Cells Translational Medicine 2017;6:1217-1226.

  17. Neisseria cinerea isolates can adhere to human epithelial cells by type IV pilus-independent mechanisms. (United States)

    Wörmann, Mirka E; Horien, Corey L; Johnson, Errin; Liu, Guangyu; Aho, Ellen; Tang, Christoph M; Exley, Rachel M


    In pathogenic Neisseria species the type IV pili (Tfp) are of primary importance in host-pathogen interactions. Tfp mediate initial bacterial attachment to cell surfaces and formation of microcolonies via pilus-pilus interactions. Based on genome analysis, many non-pathogenic Neisseria species are predicted to express Tfp, but aside from studies on Neisseria elongata, relatively little is known about the formation and function of pili in these organisms. Here, we have analysed pilin expression and the role of Tfp in Neisseria cinerea. This non-pathogenic species shares a close taxonomic relationship to the pathogen Neisseria meningitidis and also colonizes the human oropharyngeal cavity. Through analysis of non-pathogenic Neisseria genomes we identified two genes with homology to pilE, which encodes the major pilin of N. meningitidis. We show which of the two genes is required for Tfp expression in N. cinerea and that Tfp in this species are required for DNA competence, similar to other Neisseria. However, in contrast to the meningococcus, deletion of the pilin gene did not impact the association of N. cinerea to human epithelial cells, demonstrating that N. cinerea isolates can adhere to human epithelial cells by Tfp-independent mechanisms.

  18. Comparative adherence of Candida albicans and Candida dubliniensis to human buccal epithelial cells and extracellular matrix proteins. (United States)

    Jordan, Rachael P C; Williams, David W; Moran, Gary P; Coleman, David C; Sullivan, Derek J


    Candida albicans and Candida dubliniensis are very closely related pathogenic yeast species. Despite their close relationship, C. albicans is a far more successful colonizer and pathogen of humans. The purpose of this study was to determine if the disparity in the virulence of the two species is attributed to differences in their ability to adhere to human buccal epithelial cells (BECs) and/or extracellular matrix proteins. When grown overnight at 30°C in yeast extract peptone dextrose, genotype 1 C. dubliniensis isolates were found to be significantly more adherent to human BECs than C. albicans or C. dubliniensis genotypes 2-4 (P albicans to human BECs was observed, and C. dubliniensis genotype 1 and C. albicans adhered to BECs in significantly greater numbers than the other C. dubliniensis genotypes (P albicans to type I and IV collagen, fibronectin, laminin, vitronectin, and proline-rich peptides. These data suggest that C. albicans is not more adherent to epithelial cells or matrix proteins than C. dubliniensis and therefore other factors must contribute to the greater levels of virulence exhibited by C. albicans.

  19. Adherence and acceptability of once daily Lamivudine and abacavir in human immunodeficiency virus type-1 infected children.

    NARCIS (Netherlands)

    LePrevost, M.; Green, H.; Flynn, J.; Head, S.; Clapson, M.; Lyall, H.; Novelli, V.; Farrelly, L.; Walker, A.S.; Burger, D.M.; Gibb, D.


    BACKGROUND: Data on adherence to and acceptability of once daily lamivudine and abacavir are few. METHODS: Twenty-four U.K. human immunodeficiency virus type-1 infected children 2-13 years of age participated in the Pediatric European Network for the Treatment of AIDS (PENTA) 13 single arm, open lab

  20. 琥珀酸对中性粒细胞的抑制作用%Succinic acid inhibits polymorphonuclear leukocyte's function

    Institute of Scientific and Technical Information of China (English)

    任利成; 黄晓元; 龙剑虹


    Objective:To examine the effect of succinic acid on the function of human polymorphonuclear(PMN)leukocyte and it's special function as a virulent factor of Bacteroides Fragilis.Methods:PMN wasseperated from the blood of healthy donors,incubated with succinic acid at the concentration of 5,10,20 and 30 mmol/L for 20 min or at the concentration of 20 mmol/L for 5,10 15 and 20 min.Tested PMN's power of adherence and deoxidizing NBT.Results:Succinic acid can inhibit PMN's power of adherence and deoxidization,the inhibitory action was related to the time of incubation and succinic acid's concentration.Conclusions:Succinic acid can inhibit PMN's function and it may be an important virulent factor to Bacteroides Fragilis.%目的探讨脆弱类杆菌代谢产物琥珀酸(succinic acid)对中性粒细胞(polymorphonuclear,PMN)功能的影响及其在脆弱类杆菌(bacteroides fragilis)发病中的作用.方法体外分离外周血PMN,以5,10,20,30 nmol/L四种浓度的琥珀酸分别孵育20 min,或以20 mmol/L浓度的琥珀酸孵育5,10,15和20 min,测定对PMN粘附率(adherencerate)及硝基蓝四氮唑(NBT)还原能力的影响.结果琥珀酸能显著抑制PMN粘附率及NBT还原能力,且呈浓度,时间依赖关系.结论琥珀酸能抑制PMN的功能,在脆弱类杆菌的发病中占有重要的作用.

  1. Cell surface and transcriptional characterization of human adipose-derived adherent stromal (hADAS) cells. (United States)

    Katz, Adam J; Tholpady, Ashok; Tholpady, Sunil S; Shang, Hulan; Ogle, Roy C


    Adult human subcutaneous adipose tissue contains cells with intriguing multilineage developmental plasticity, much like marrow-derived mesenchymal stem cells. Putative stem or progenitor cells from fat have been given many different names in the literature, reflecting an early and evolving consensus regarding their phenotypic characterization. The study reported here used microarrays to evaluate over 170 genes relating to angiogenesis and extracellular matrix in undifferentiated, early-passage human adipose-derived adherent stromal (hADAS) cells isolated from three separate donors. The hADAS populations unanimously transcribed 66% of the screened genes, and 83% were transcribed by at least two of the three populations. The most highly transcribed genes relate to functional groupings such as cell adhesion, matrix proteins, growth factors and receptors, and proteases. The transcriptome of hADAS cells demonstrated by this work reveals many similarities to published profiles of bone marrow mesenchymal stem cells (MSCs). In addition, flow analysis of over 24 hADAS cell surface proteins (n = 7 donors) both confirms and expands on the existing literature and reveals strong intergroup correlation, despite an inconsistent nomenclature and the lack of standardized protocols for cell isolation and culture. Finally, based on flow analysis and reverse transcription polymerase chain reaction studies, our results suggest that hADAS cells do not express several proteins that are implicated as markers of "stemness" in other stem cell populations, including telomerase, CD133, and the membrane transporter ABCG2.

  2. Analysis of Endothelial Adherence of Bartonella henselae and Acinetobacter baumannii Using a Dynamic Human Ex Vivo Infection Model. (United States)

    Weidensdorfer, Marko; Chae, Ju Ik; Makobe, Celestine; Stahl, Julia; Averhoff, Beate; Müller, Volker; Schürmann, Christoph; Brandes, Ralf P; Wilharm, Gottfried; Ballhorn, Wibke; Christ, Sara; Linke, Dirk; Fischer, Doris; Göttig, Stephan; Kempf, Volkhard A J


    Bacterial adherence determines the virulence of many human-pathogenic bacteria. Experimental approaches elucidating this early infection event in greater detail have been performed using mainly methods of cellular microbiology. However, in vitro infections of cell monolayers reflect the in vivo situation only partially, and animal infection models are not available for many human-pathogenic bacteria. Therefore, ex vivo infection of human organs might represent an attractive method to overcome these limitations. We infected whole human umbilical cords ex vivo with Bartonella henselae or Acinetobacter baumannii under dynamic flow conditions mimicking the in vivo infection situation of human endothelium. For this purpose, methods for quantifying endothelium-adherent wild-type and trimeric autotransporter adhesin (TAA)-deficient bacteria were set up. Data revealed that (i) A. baumannii binds in a TAA-dependent manner to endothelial cells, (ii) this organ infection model led to highly reproducible adherence rates, and furthermore, (iii) this model allowed to dissect the biological function of TAAs in the natural course of human infections. These findings indicate that infection models using ex vivo human tissue samples ("organ microbiology") might be a valuable tool in analyzing bacterial pathogenicity with the capacity to replace animal infection models at least partially.

  3. Phagocytosis and intracellular killing of Candida albicans by murine polymorphonuclear neutrophils. (United States)

    Vonk, Alieke G; Netea, Mihai G; Kullberg, Bart Jan


    Polymorphonuclear neutrophils (PMNs) are important phagocytes in the control of Candida infections. The phagocytic contribution of PMNs to host defence can by assessed by various methods, such as microbiological assays. However, assessment and definition of intracellular killing capacity can be a source of considerable confusion. A comparison of the growth of Candida in the presence of PMN with the growth of Candida in phagocyte-free suspensions may lead to an overestimation of killing capacity because PMNs can use both intracellular and extracellular killing mechanisms. Here, we describe the use of an adherent monolayer of exudate peritoneal PMNs that is used to differentiate between the process of phagocytosis and intracellular killing.

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  2. Polymorphonuclear neutrophils: an effective antimicrobial force. (United States)

    Sawyer, D W; Donowitz, G R; Mandell, G L


    The production and deployment of polymorphonuclear neutrophils (PMNs) are under close regulation. PMNs interact through cytokines with a number of cell types, including macrophages, lymphocytes, and endothelial cells. PMNs are guided by bacterial products and cytokines to target sites, where microbes are recognized and killed. Killing occurs through oxygen-dependent and oxygen-independent mechanisms. The frequent and severe infections seen in patients with defects (either congenital or acquired) in PMN function demonstrate the importance of PMNs in host defense against infection. PMNs are potent inflammatory cells and can exacerbate disease states such as myocardial ischemia, gram-negative bacterial sepsis, and the adult respiratory distress syndrome.

  3. In vitro effect of benzodiazepines on polymorphonuclear leukocyte oxidative activity. (United States)

    Goldfarb, G; Belghiti, J; Gautero, H; Boivin, P


    The effect of three benzodiazepine compounds, diazepam, flunitrazepam, and clorazepate, on oxidative activity of human polymorphonuclear leukocyte (PMN) was investigated. The oxidative activity of zymosan-stimulated PMN in the presence of three concentrations (10, 20, and 40 micrograms/ml) of these compounds was measured polarographically. In addition, zymosan-stimulated nitroblue tetrazolium (NBT) reduction was measured in the presence of various concentrations of flunitrazepam. All three compounds inhibited oxygen consumption of the PMN. The extent of inhibition was linear with respect to log-concentrations; oxygen consumption was reduced 50% for concentrations of diazepam, flunitrazepam, and clorazepate of 13 micrograms/ml, 56 micrograms/ml, and 285 micrograms/ml, respectively. In addition 30% and 100% inhibition of NBT reduction by flunitrazepam were observed at respective concentrations of 10 micrograms/ml and 60 micrograms/ml. The clinical relevance of these findings remains to be determined.

  4. Human cardiac-derived adherent proliferating cells reduce murine acute Coxsackievirus B3-induced myocarditis.

    Directory of Open Access Journals (Sweden)

    Kapka Miteva

    Full Text Available BACKGROUND: Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. We recently isolated and identified novel cardiac-derived cells from human cardiac biopsies: cardiac-derived adherent proliferating cells (CAPs. They have similarities with mesenchymal stromal cells, which are known for their anti-apoptotic and immunomodulatory properties. We explored whether CAPs application could be a novel strategy to improve acute Coxsackievirus B3 (CVB3-induced myocarditis. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the safety of our approach, we first analyzed the expression of the coxsackie- and adenovirus receptor (CAR and the co-receptor CD55 on CAPs, which are both required for effective CVB3 infectivity. We could demonstrate that CAPs only minimally express both receptors, which translates to minimal CVB3 copy numbers, and without viral particle release after CVB3 infection. Co-culture of CAPs with CVB3-infected HL-1 cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis and viral progeny release. In addition, CAPs reduced CD4 and CD8 T cell proliferation. All CAPs-mediated protective effects were nitric oxide- and interleukin-10-dependent and required interferon-γ. In an acute murine model of CVB3-induced myocarditis, application of CAPs led to a decrease of cardiac apoptosis, cardiac CVB3 viral load and improved left ventricular contractility parameters. This was associated with a decline in cardiac mononuclear cell activity, an increase in T regulatory cells and T cell apoptosis, and an increase in left ventricular interleukin-10 and interferon-γ mRNA expression. CONCLUSIONS: We conclude that CAPs are a unique type of cardiac-derived cells and promising tools to improve acute CVB3-induced myocarditis.

  5. Late Adherent Human Bone Marrow Stromal Cells Form Bone and Restore the Hematopoietic Microenvironment In Vivo

    Directory of Open Access Journals (Sweden)

    Verônica Fernandes Vianna


    Full Text Available Bone marrow stromal cells (BMSCs are a valuable resource for skeletal regenerative medicine because of their osteogenic potential. In spite of the very general term “stem cell,” this population of cells is far from homogeneous, and different BMSCs clones have greatly different phenotypic properties and, therefore, potentially different therapeutic potential. Adherence to a culture flask surface is a primary defining characteristic of BMSCs. We hypothesized that based on the adherence time we could obtain an enriched population of cells with a greater therapeutic potential. We characterized two populations of bone marrow-derived cells, those that adhered by three days (R-cells and those that did not adhere by three days but did by six days (L-cells. Clones derived from L-cells could be induced into adipogenic, chondrogenic, and osteogenic differentiation in vitro. L-cells appeared to have greater proliferative capacity, as manifested by larger colony diameter and clones with higher CD146 expression. Only clones from L-cells developed bone marrow stroma in vivo. We conclude that the use of late adherence of BMSCs is one parameter that can be used to enrich for cells that will constitute a superior final product for cell therapy in orthopedics.

  6. Modulation of Polymorphonuclear Neutrophil Response to N-formyl-l-methionyl-l-leucyl-l-phenylalanine (United States)


    to the scapular crests. The skin was closed with 4/0 chromic gut placed in a continuous subcuticular suture pattern and bandaged. These procedures...Clin. Immun. and Immunopath., 15:525, 1980. 16. Gray, G.D., Ohlmann, G.M., Morton. D.R. and Schaaub, R.G., Feline Polymorphonuclear Leukocytes Respond...Mature Human Neutrophil and Eosinophil Function, Surface Receptor Expression and Survival. J. Clin. Invest., 78:1220, 1986. Gasson, J .C., Weisbart

  7. Biphasic control of polymorphonuclear cell migration by Kupffer cells. Effect of exposure to metabolic products of ethanol

    Energy Technology Data Exchange (ETDEWEB)

    Fainsilber, Z.; Feinman, L.; Shaw, S.; Lieber, C.S.


    In order to investigate the role of the Kupffer cells in the regulation of the inflammatory reaction seen in alcoholic hepatitis, rat liver Kupffer cells were cultured and exposed to products of ethanol metabolism. The resultant supernatants were tested to study their ability to stimulate or inhibit polymorphonuclear cell chemotaxis. Kupffer cells produced increased chemokinetic activity for human polymorphonuclear leukocytes; when incubated with soluble products of microsomal peroxidation, the Kupffer cells engendered more chemokinetic activity than that produced by untreated Kupffer cells. When Kupffer cells were incubated with acetaldehyde, the chemokinetic activity that appeared in the supernatant did not differ from control. Chemotaxis of polymorphonuclear cells was not observed when the Kupffer cell supernatants were tested by checkerboard analysis.

  8. Reduced antibody-dependent cellular cytotoxicity to herpes simplex virus-infected cells of salivary polymorphonuclear leukocytes and inhibition of peripheral blood polymorphonuclear leukocyte cytotoxicity by saliva. (United States)

    Ashkenazi, M; Kohl, S


    Blood polymorphonuclear leukocytes (BPMN) have been shown to mediate antibody-dependent cellular cytotoxicity (ADCC) against HSV-infected cells. Although HSV infections are frequently found in the oral cavity, the ADCC capacity of salivary PMN (SPMN) has not been studied, mainly because methods to isolate SPMN were not available. We have recently developed a method to isolate SPMN, and in this study have evaluated their ADCC activity against HSV-infected cells. SPMN were obtained by repeated washings of the oral cavity, and separated from epithelial cells by nylon mesh filtration. ADCC was quantitatively determined by 51Cr release from HSV-infected Chang liver cells. SPMN in the presence of antibody were able to destroy HSV-infected cells, but SPMN were much less effective in mediating ADCC than BPMN (3.4% vs 40.7%, p less than 0.0001). In the presence of antiviral antibody, SPMN were able to adhere to HSV-infected cells, but less so than BPMN (34% vs 67%), and specific antibody-induced adherence was significantly lower in SPMN (p less than 0.04). The spontaneous adherence to HSV-infected cells was higher for SPMN than BPMN. SPMN demonstrated up-regulation of the adhesion glycoprotein CD18, but down-regulation of the FcRIII receptor. Incubation with saliva decreased ADCC capacity of BPMN, up-regulated CD18 expression, and down-regulated FcRIII expression.

  9. Drug resistance and adherence to human intestines of enteroaggregative Escherichia coli. (United States)

    Yamamoto, T; Echeverria, P; Yokota, T


    Clinical isolates of enteroaggregative Escherichia coli (EAggEC) were tested for their in vitro susceptibilities to 27 antimicrobial agents. Marked drug resistance was observed with sulfamethoxazole, ampicillin, and chloramphenicol in contrast to such antimicrobial agents as cefixime, sparfloxacin, and ciprofloxacin. One of the EAggEC strains carried a plasmid that conferred on its host resistance to ampicillin, tetracycline, sulfamethoxazole, streptomycin, and spectinomycin and an ability to adhere to child ileal villi or HeLa cells in the characteristic aggregative pattern. This plasmid also mediated D-mannose-resistant hemagglutinin production and bacterial clump formation (autoagglutination). The data demonstrate appearance of marked drug resistance and an intestine-adherence and drug-resistance plasmid in the newest category of diarrheagenic E. coli.

  10. Rapid necrotic killing of polymorphonuclear leukocytes is caused by quorum-sensing-controlled production of rhamnolipid by Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Jensen, Peter Ø; Bjarnsholt, Thomas; Phipps, Richard Kerry


    a QS-regulated tolerance of biofilm bacteria to the antimicrobial properties of polymorphonuclear leukocytes (PMNs). The precise QS-regulated effect on the PMNs is, however, unknown. Incubation of human PMNs with supernatants from dense P. aeruginosa cultures showed that the QS-competent P. aeruginosa...

  11. Enhanced adherence of methicillin-resistant Staphylococcus pseudintermedius sequence type 71 to canine and human corneocytes

    DEFF Research Database (Denmark)

    Latronico, Francesca; Moodley, Arshnee; Nielsen, Søren Saxmose;


    The recent worldwide spread of methicillin-resistant Staphylococcus pseudintermedius (MRSP) in dogs is a reason for concern due to the typical multidrug resistance patterns displayed by some MRSP lineages such as sequence type (ST) 71. The objective of this study was to compare the in vitro...... characterized with respect to genetic background and cell wall-anchored protein (CWAP) gene content. Seventy-seven strain-corneocyte combinations were tested using both exponential- and stationary-phase cultures. Negative binomial regression analysis of counts of bacterial cells adhering to corneocytes revealed...

  12. Human sepsis-associated Escherichia coli (SEPEC) is able to adhere to and invade kidney epithelial cells in culture

    Energy Technology Data Exchange (ETDEWEB)

    Conceição, R.A. [Departamento de Genética, Evolução e Bioagentes, Universidade Estadual de Campinas, Campinas, SP (Brazil); Ludovico, M.S. [Departamento de Microbiologia, Universidade Estadual de Londrina, Londrina, PR (Brazil); Andrade, C.G.T.J. [Departamento de Biologia Geral, Universidade Estadual de Londrina, Londrina, PR (Brazil); Yano, T. [Departamento de Genética, Evolução e Bioagentes, Universidade Estadual de Campinas, Campinas, SP (Brazil)


    The adhesins of extraintestinal pathogenic Escherichia coli are essential for mediating direct interactions between the microbes and the host cell surfaces that they infect. Using fluorescence microscopy and gentamycin protection assays, we observed that 49 sepsis-associated E. coli (SEPEC) strains isolated from human adults adhered to and invaded Vero cells in the presence of D-mannose (100%). In addition, bacteria concentrations of approximately 2 × 10{sup 7} CFU/mL were recovered from Vero cells following an invasion assay. Furthermore, PCR analysis of adhesin genes showed that 98.0% of these SEPEC strains tested positive for fimH, 69.4% for flu, 53.1% for csgA, 38.8% for mat, and 32.7% for iha. Analysis of the invasin genes showed that 16.3% of the SEPEC strains were positive for tia, 12.3% for gimB, and 10.2% for ibeA. Therefore, these data suggest that SEPEC adhesion to cell surfaces occurs through non-fimH mechanisms. Scanning electron microscopy showed the formation of microcolonies on the Vero cell surface. SEPEC invasiveness was also confirmed by the presence of intracellular bacteria, and ultrastructural analysis using electron transmission microscopy revealed bacteria inside the Vero cells. Taken together, these results demonstrate that these SEPEC strains had the ability to adhere to and invade Vero cells. Moreover, these data support the theory that renal cells may be the predominant pathway through which SEPEC enters human blood vessels.

  13. Characterization of Three-Dimensional Retinal Tissue Derived from Human Embryonic Stem Cells in Adherent Monolayer Cultures (United States)

    Singh, Ratnesh K.; Mallela, Ramya K.; Cornuet, Pamela K.; Reifler, Aaron N.; Chervenak, Andrew P.; West, Michael D.; Wong, Kwoon Y.; Nasonkin, Igor O.


    Stem cell-based therapy of retinal degenerative conditions is a promising modality to treat blindness, but requires new strategies to improve the number of functionally integrating cells. Grafting semidifferentiated retinal tissue rather than progenitors allows preservation of tissue structure and connectivity in retinal grafts, mandatory for vision restoration. Using human embryonic stem cells (hESCs), we derived retinal tissue growing in adherent conditions consisting of conjoined neural retina and retinal pigment epithelial (RPE) cells and evaluated cell fate determination and maturation in this tissue. We found that deriving such tissue in adherent conditions robustly induces all eye field genes (RX, PAX6, LHX2, SIX3, SIX6) and produces four layers of pure populations of retinal cells: RPE (expressing NHERF1, EZRIN, RPE65, DCT, TYR, TYRP, MITF, PMEL), early photoreceptors (PRs) (coexpressing CRX and RCVRN), inner nuclear layer neurons (expressing CALB2), and retinal ganglion cells [RGCs, expressing BRN3B and Neurofilament (NF) 200]. Furthermore, we found that retinal progenitors divide at the apical side of the hESC-derived retinal tissue (next to the RPE layer) and then migrate toward the basal side, similar to that found during embryonic retinogenesis. We detected synaptogenesis in hESC-derived retinal tissue, and found neurons containing many synaptophysin-positive boutons within the RGC and PR layers. We also observed long NF200-positive axons projected by RGCs toward the apical side. Whole-cell recordings demonstrated that putative amacrine and/or ganglion cells exhibited electrophysiological responses reminiscent of those in normal retinal neurons. These responses included voltage-gated Na+ and K+ currents, depolarization-induced spiking, and responses to neurotransmitter receptor agonists. Differentiation in adherent conditions allows generation of long and flexible pieces of 3D retinal tissue suitable for isolating transplantable slices of tissue for


    Institute of Scientific and Technical Information of China (English)

    李良成; 侯琦; 郭颖; 程桂芳


    目的研究美洛昔康对正常人中性粒细胞(polymorphonuclear leukocyte,PMN)与滑膜细胞(human synovial cell,HSC)粘附的抑制作用及其作用机理.方法用MTT比色法检测PMN与HSC的粘附,分别用Cell-ELISA和RT-PCR法检测粘附分子ICAM-1和VCAM-1的蛋白及基因表达,用EMSA法检测NF-κB的活性.结果美洛昔康可显著的并以剂量依赖的方式抑制TNF-α(50 u·mL-1)和IL-1β(50 u·mL-1)作用12 h诱导的PMN与HSC粘附,其IC50分别为3.38×10-7和3.56×10-6 mol·L-1.进一步研究发现美洛昔康在1×10-6~1×10-5 mol·L-1时还可在蛋白水平及mRNA水平抑制TNF-α(50 u·mL-1)诱导的HSC细胞ICAM-1的表达,但对VCAM-1蛋白及mRNA表达均未见显著影响;同时美洛昔康还可显著抑制50 u·mL-1 TNF-α诱导的NF-κB的活化.结论美洛昔康抑制NF-κB的活化,进而抑制ICAM-1的表达可能是其抑制PMN与HSC粘附的机制之一.%AIM To investigate the effect of meloxicam on human polymorphonuclear leukocyte (PMN) adhesion to human synovial cell (HSC),and to explore its mechanism.METHODS MTT colorimetry was used to determine the adhesion effect of PMN to HSC.Cell-ELISA and RT-PCR methods were used to determine the expression of ICAM-1 and VCAM-1.Nuclear transcription factor-kappa B (NF-κB) was measured by electrophoretic mobility shift assay (EMSA) method.RESULTS Meloxicam was found to effectively inhibit TNF-α (50 u·mL-1 for 12 h) and IL-1β (50 u·mL-1 for 12 h)-induced adhesion of PMN to HSC (IC50 3.38×10-7 mol·L-1 and 3.56×10-6 mol·L-1,respectively) in a concentration-dependent manner.ICAM-1 protein and mRNA expression induced by TNF-α (50 u·mL-1) were inhibited by meloxicam at 1×10-6~1×10-5 mol·L-1.The activation of NF-κB was also inhibited by meloxicam at 1×10-6~1×10-5 mol·L-1.CONCLUSION These results suggest that meloxicam inhibit TNF-α stimulated PMN-HSC adhesion and expression of ICAM-1 by suppressing the activity of NF-κB.

  15. Relationship between viral load and behavioral measures of adherence to antiretroviral therapy in children living with human immunodeficiency virus in Latin America

    Directory of Open Access Journals (Sweden)

    Horacio A. Duarte


    Full Text Available Few studies have examined antiretroviral therapy adherence in Latin American children. Standardized behavioral measures were applied to a large cohort of human immunodeficiency virus-infected children in Brazil, Mexico, and Peru to assess adherence to prescribed antiretroviral therapy doses during the three days prior to study visits, assess timing of last missed dose, and evaluate the ability of the adherence measures to predict viral suppression. Time trends in adherence were modeled using a generalized estimating equations approach to account for possible correlations in outcomes measured repeatedly in the same participants. Associations of adherence with human immunodeficiency virus viral load were examined using linear regression. Mean enrollment age of the 380 participants was 5 years; 57.6% had undetectable' viral load ( 0.3. Last time missed any antiretroviral therapy dose was reported as "never" for 52.0% at enrollment, increasing to 60.7% and 65.9% at the 6- and 12-month visits, respectively (p< 0.001 for test of trend. The proportion with undetectable viral load was higher among those who never missed a dose at enrollment and the 12-month visit (p≤ 0.005, but not at the 6-month visit (p= 0.2. While antiretroviral therapy adherence measures utilized in this study showed some association with viral load for these Latin American children, they may not be adequate for reliably identifying non-adherence and consequently children at risk for viral resistance. Other strategies are needed to improve the evaluation of adherence in this population.

  16. Macrophage Inflammatory Protein-1alpha mediates Matrix Metalloproteinase-9 enhancement in human adherent monocytes fed with malarial pigment

    Institute of Scientific and Technical Information of China (English)

    Giuliana Giribaldi; Elena Valente; Amina Khadjavi; Manuela Polimeni; Mauro Prato


    Objective:To investigate the role of macrophage inflammatory protein-1alpha (MIP-1alpha) in the detrimental enhancement of matrix metalloproteinase-9 (MMP-9)expression, release and activity induced by phagocytosis of malarial pigment (haemozoin,HZ) in human monocytes. Methods: Human adherent monocytes were unfed/fed with nativeHZ for 2 h. After 24 hours, MIP-1alpha production was evaluated by ELISA in cell supernatants. Alternatively,HZ-unfed/fed monocytes were treated in presence/absence of anti-humanMIP-1alpha blocking antibodies or recombinant humanMIP-1alpha for15 h (RNA studies) or 24 h (protein studies); therefore,MMP-9mRNA expression was evaluated in cell lysates by Real TimeRT-PCR, whereas proMMP-9and activeMMP-9protein release were measured in cell supernatants by Western blotting and gelatin zymography.Results: Phagocytosis ofHZ by human monocytes increased production ofMIP-1alpha, mRNA expression ofMMP-9and protein release of proMMP-9 and activeMMP-9. All theHZ-enhancing effects onMMP-9 were abrogated by anti-humanMIP-1alpha blocking antibodies and mimicked by recombinant humanMIP-1alpha.Conclusions:The present work suggests a role for MIP-1alpha in theHZ-dependent enhancement ofMMP-9 expression, release and activity observed in human monocytes, highlighting new detrimental effects ofHZ-triggered proinflammatory response by phagocytic cells in falciparum malaria.

  17. beta-Dystroglycan modulates the interplay between actin and microtubules in human-adhered platelets. (United States)

    Cerecedo, Doris; Cisneros, Bulmaro; Suárez-Sánchez, Rocío; Hernández-González, Enrique; Galván, Iván


    To maintain the continuity of an injured blood vessel, platelets change shape, secrete granule contents, adhere, aggregate, and retract in a haemostatic plug. Ordered arrays of microtubules, microfilaments, and associated proteins are responsible for these platelet responses. In full-spread platelets, microfilament bundles in association with other cytoskeleton proteins are anchored in focal contacts. Recent studies in migrating cells suggest that co-ordination and direct physical interaction of microtubules and actin network modulate adhesion development. In platelets, we have proposed a feasible association between these two cytoskeletal systems, as well as the participation of the dystrophin-associated protein complex, as part of the focal adhesion complex. The present study analysed the participation of microtubules and actin during the platelet adhesion process. Confocal microscopy, fluorescence resonance transfer energy and immunoprecipitation assays were used to provide evidence of a cross-talk between these two cytoskeletal systems. Interestingly, beta-dystroglycan was found to act as an interplay protein between actin and microtubules and an additional communication between these two cytoskeleton networks was maintained through proteins of focal adhesion complex. Altogether our data are indicative of a dynamic co-participation of actin filaments and microtubules in modulating focal contacts to achieve platelet function.

  18. Modulation of polymorphonuclear neutrophil functions by astrocytes

    Directory of Open Access Journals (Sweden)

    Xie Luokun


    Full Text Available Abstract Background Neuroinflammation is a complex process involving cells from the immune system and the central nerve system (CNS. Polymorphonuclear neutrophils (PMN are the most abundant class of white blood cells, and typically the first type of leukocyte recruited to sites of inflammation. In the CNS, astrocytes are the most abundant glial cell population and participate in the local innate immune response triggered by a variety of insults. In the present study, we investigated the impacts of astrocytes on PMN function. Methods Primary astrocyte cultures were derived from postnatal C57BL/6 mice and primary neutrophils were isolated from 8 to 12 weeks old C57BL/6 mice. PMNs respiratory burst was analyzed by H2DCFDA assay. For phagocytosis assay, neutrophils were incubated with FITC-labeled E. coli and the phagocytosis of E coli was determined by flow cytometer. PMNs degranulation was determined by myeloperoxidase assay. Cytokine expression was determined by real-time PCR. To determine the involvement of different signaling pathway, protein lysates were prepared and western blots were conducted to assess the activation of Akt, Erk1/2, and p38. Results Using ex vivo neutrophils and primary astrocyte cultures, our study demonstrated that astrocytes differentially regulate neutrophil functions, depending upon whether the interactions between the two cell types are direct or indirect. Upon direct cell-cell contact, astrocytes attenuate neutrophil apoptosis, respiratory bust, and degranulation, while enhancing neutrophil phagocytic capability and pro-inflammatory cytokine expression. Through indirect interaction with neutrophils, astrocytes attenuate apoptosis and enhance necrosis in neutrophils, augment neutrophil phagocytosis and respiratory burst, and inhibit neutrophil degranulation. In addition, astrocytes could augment Akt, Erk1/2, and p38 activation in neutrophils. Conclusions Astrocytes differentially regulate neutrophil functions through

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  11. Influence of light sources on the migration of polymorphonuclear leukocytes (United States)

    DellaVecchia, Michael A.; Beard, Richard B.; Dai, Xiaoyan


    In the process of inflammation, leukocytes must travel from the intraluminal space of the capillary to the interstitial space in order to reach the site of the inflammation. The two major populations of mature human leukocytes based on the morphology are the polymorphonuclear leukocytes (PMN), and mononuclear leukocytes (MNL). Previous research on PMNs and MNLs at the Biomedical Engineering and Science Institute of Drexel University have shown that their migration can be markedly enhanced by excitation with electric and magnetic fields. This presentation demonstrates that the migration of PMNs under excitation of photons is enhanced in the red light region of (lambda) equals 660 nm and inhibited in the green light region of (lambda) equals 565 nm. There is an intensity threshold at which red light enhances migration and an intensity threshold at which green light inhibits migration. In these experiments the Boyden technique was used with the distance of the cell migration through a cellulose filter measured in terms of the leading edge. The comparison of the relative value of the distance to cell migration under a light to cell migration without a light stimulus was recorded as a cytokinetic index, K.I.. K.I. is a measure of the cytokinesis which is the progress of the cell movement in which the migration is enhanced by substances in the cell environment irrespective of a concentration gradient. The cytotactic index is a measure of cytotaxis which is the directional movement along a chemical gradient formed by a chemotactic factor. A Russian pulsed commercial laser biostimulator in the near infrared wavelength above an intensity threshold enhances PMN migration. Intermittent green and red stimulators below the intensity threshold markedly influence the cytokinetic index of PMNs while above the intensity threshold, this influence is deminished.

  12. Actin filaments and microtubule dual-granule transport in human adhered platelets: the role of alpha-dystrobrevins. (United States)

    Cerecedo, Doris; Cisneros, Bulmaro; Mondragón, Ricardo; González, Sirenia; Galván, Iván J


    Upon activation with physiological stimuli, human platelets undergo morphological changes, centralizing their organelles and secreting effector molecules at the site of vascular injury. Previous studies have indicated that the actin filaments and microtubules of suspension-activated platelets play a critical role in granule movement and exocytosis; however, the participation of these cytoskeleton elements in adhered platelets remains unexplored. alpha- and beta-dystrobrevin members of the dystrophin-associated protein complex in muscle and non-muscle cells have been described as motor protein receptors that might participate in the transport of cellular components in neurons. Recently, we characterized the expression of dystrobrevins in platelets; however, their functional diversity within this cellular model had not been elucidated. The present study examined the contribution of actin filaments and microtubules in granule trafficking during the platelet adhesion process using cytoskeleton-disrupting drugs, quantification of soluble P-selectin, fluorescence resonance transfer energy analysis and immunoprecipitation assays. Likewise, we assessed the interaction of alpha-dystrobrevins with the ubiquitous kinesin heavy chain. Our results strongly suggest that microtubules and actin filaments participate in the transport of alpha and dense granules in the platelet adhesion process, during which alpha-dystrobrevins play the role of regulatory and adaptor proteins that govern trafficking events.

  13. Crohn's disease adherent-invasive Escherichia coli colonize and induce strong gut inflammation in transgenic mice expressing human CEACAM. (United States)

    Carvalho, Frédéric A; Barnich, Nicolas; Sivignon, Adeline; Darcha, Claude; Chan, Carlos H F; Stanners, Clifford P; Darfeuille-Michaud, Arlette


    Abnormal expression of CEACAM6 is observed at the apical surface of the ileal epithelium in Crohn's disease (CD) patients, and CD ileal lesions are colonized by pathogenic adherent-invasive Escherichia coli (AIEC). We investigated the ability of AIEC reference strain LF82 to colonize the intestinal mucosa and to induce inflammation in CEABAC10 transgenic mice expressing human CEACAMs. AIEC LF82 virulent bacteria, but not nonpathogenic E. coli K-12, were able to persist in the gut of CEABAC10 transgenic mice and to induce severe colitis with reduced survival rate, marked weight loss, increased rectal bleeding, presence of erosive lesions, mucosal inflammation, and increased proinflammatory cytokine expression. The colitis depended on type 1 pili expression by AIEC bacteria and on intestinal CEACAM expression because no sign of colitis was observed in transgenic mice infected with type 1 pili-negative LF82-Delta fimH isogenic mutant or in wild-type mice infected with AIEC LF82 bacteria. These findings strongly support the hypothesis that in CD patients having an abnormal intestinal expression of CEACAM6, AIEC bacteria via type 1 pili expression can colonize the intestinal mucosa and induce gut inflammation. Thus, targeting AIEC adhesion to gut mucosa represents a new strategy for clinicians to prevent and/or to treat ileal CD.

  14. Adherence to ACIP Recommendation for Human Papillomavirus Vaccine Among US Adolescent Girls. (United States)

    Rahman, Mahbubur; Hirth, Jacqueline M; Berenson, Abbey B


    The objective of this study was to examine correlates of human papillomavirus (HPV) vaccine use according to Advisory Committee on Immunization Practices (ACIP)'s recommendations among US adolescent girls. We used National Immunization Survey of Teens 2013 data. Based on provider-verified (n = 9403) information, 57.3, 39.1 and 19.0 % of adolescent girls, initiated, completed and completed the HPV vaccine according to ACIP's recommendation (by age 12), respectively. Hispanic race/ethnicity, a physician recommendation for HPV vaccine and ≥1 influenza vaccine in the past 3 years were all associated with a higher likelihood of compliance with ACIP's recommendation. Girls from a larger family and those whose immunization provider was a STD/school/teen clinic were less likely to receive the vaccine at the recommended age compared to a girl raised in a smaller sized family and received immunization from a hospital facility, respectively. Only one-fifth of 13-17 yo girls receive the HPV vaccine by age 12 as recommended by ACIP. Physician visits and influenza vaccination settings are opportunities to improve vaccine series completion at the recommended age.

  15. Biochemical changes in polymorphonuclear leucocytes in diabetic patients.



    A study on the functional ability of polymorphonuclear leucocytes (PMNL) indicates that the total lysosomal enzyme levels viz. Beta-glucuronidase, lysozyme, acid phosphatase and alkaline phosphatase were not altered in diabetics, compared to that in control subjects. However, the findings also reveal that the release of these lysosomal enzymes in response to a particulate stimulus is impaired in diabetics. This suggests that the bactericidal capacity of these cells, which are involved in phag...

  16. Mitigation of Lethal Radiation Syndrome in Mice by Intramuscular Injection of 3D Cultured Adherent Human Placental Stromal Cells.

    Directory of Open Access Journals (Sweden)

    Elena Gaberman

    Full Text Available Exposure to high lethal dose of ionizing radiation results in acute radiation syndrome with deleterious systemic effects to different organs. A primary target is the highly sensitive bone marrow and the hematopoietic system. In the current study C3H/HeN mice were total body irradiated by 7.7 Gy. Twenty four hrs and 5 days after irradiation 2×10(6 cells from different preparations of human derived 3D expanded adherent placental stromal cells (PLX were injected intramuscularly. Treatment with batches consisting of pure maternal cell preparations (PLX-Mat increased the survival of the irradiated mice from ∼27% to 68% (P<0.001, while cell preparations with a mixture of maternal and fetal derived cells (PLX-RAD increased the survival to ∼98% (P<0.0001. The dose modifying factor of this treatment for both 50% and 37% survival (DMF50 and DMF37 was∼1.23. Initiation of the more effective treatment with PLX-RAD injection could be delayed for up to 48 hrs after irradiation with similar effect. A delayed treatment by 72 hrs had lower, but still significantly effect (p<0.05. A faster recovery of the BM and improved reconstitution of all blood cell lineages in the PLX-RAD treated mice during the follow-up explains the increased survival of the cells treated irradiated mice. The number of CD45+/SCA1+ hematopoietic progenitor cells within the fast recovering population of nucleated BM cells in the irradiated mice was also elevated in the PLX-RAD treated mice. Our study suggests that IM treatment with PLX-RAD cells may serve as a highly effective "off the shelf" therapy to treat BM failure following total body exposure to high doses of radiation. The results suggest that similar treatments may be beneficial also for clinical conditions associated with severe BM aplasia and pancytopenia.

  17. Therapeutic drug monitoring of indinavir and nelfinavir to assess adherence to therapy in human immunodeficiency virus-infected children

    NARCIS (Netherlands)

    Van Rossum, AMC; Bergshoeff, AS; Fraaij, PLA; Hugen, PWH; Hartwig, NG; Geelen, SPM; Wolfs, TFW; Weemaes, CMR; De Groot, R; Burger, DM


    Introduction. Adherence to highly active anti-retroviral therapy is required to obtain an optimal long term virologic response rate of HIV-1-infected children. Plasma concentrations of protease inhibitors (PIs) outside the limits of the reference values indicate nonadherence to anti-retroviral thera

  18. Therapeutic drug monitoring of indinavir and nelfinavir to assess adherence to therapy in human immunodeficiency virus-infected children.

    NARCIS (Netherlands)

    Rossum, A.M. van; Bergshoeff, A.S.; Fraaij, P.L.; Hugen, P.W.H.; Hartwig, N.G.; Geelen, S.P.M.; Wolfs, T.F.; Weemaes, C.M.R.; Groot, R. de; Burger, D.M.


    INTRODUCTION: Adherence to highly active antiretroviral therapy is required to obtain an optimal long term virologic response rate of HIV-1-infected children. Plasma concentrations of protease inhibitors (PIs) outside the limits of the reference values indicate nonadherence to antiretroviral therapy

  19. Inhibitory effect of O-glycosylation inhibition on human intestinal epithelial cells Mucin 2 expression and bacteria adherence

    Directory of Open Access Journals (Sweden)

    Li-li SONG


    Full Text Available Objective To investigate the effect of O-glycosylation inhibition in intestinal epithelial cells on the expression of Mucin 2 (MUC2 and bacterial adherence. Methods Intestinal epithelial cells HT-29 and differentiated HT-29 cells (HT-29-Gal were treated with an inhibitor of O-glycosylation (benzyl-α-GalNAc, and then named as HT-29-OBN and HT-29-Gal-OBN, respectively. The mRNA and protein expression of MUC2 in HT-29, HT29-Gal, HT-29-OBN and HT-29-Gal-OBN were detected by real-time PCR and Western blotting. Then the four kinds of above cells were incubated with enteropathogenic Escherichia coli (EPEC or enterohemorrhagic Escherichia coli serotype O157:H7 (EHEC O157:H7. The bacteria were quantified by determining the colony forming unit (CFU following the plating of serial dilutions of the bacteria to evaluate the effect of benzyl-α-GalNAc on bacteria adherence. Results The results of real-time PCR and Western blotting showed that the mRNA and protein expression levels of MUC2 in HT-29-OBN and HT-29-Gal-OBN cells were significantly lower than those in the untreated cells HT-29 and HT-29-Gal (P<0.05. The bacterial adherence assay showed that the adherence of EPEC and EHEC O157:H7 to HT-29-OBN and HT-29-Gal-OBN cells significantly decreased compared with that to HT-29 and HT-29-Gal cells (P<0.05. Conclusion Inhibition of O-glycosylation in intestinal epithelial cells may reduce the bacteria adherence and MUC2 expression. DOI: 10.11855/j.issn.0577-7402.2013.10.009

  20. Differential effect of extracellular calcium on the Na(+)-K+ pump activity in intact polymorphonuclear leucocytes and erythrocytes

    DEFF Research Database (Denmark)

    Petersen, R H; Knudsen, T; Johansen, Torben


    The effect of extracellular calcium on the Na(+)-K+ pump activity in human polymorphonuclear leucocytes and erythrocytes was studied and compared with the activity in mixed peritoneal leucocytes from rats. While there was maximal decrease in the pump activity (25-30%) of leucocytes from both rat...... and human by calcium 0.6 mM, a concentration of 0.1 mM caused a substantial decrease indicating a high sensitivity for extracellular calcium. In contrast, calcium had no effect on the pump activity in erythrocytes. The effect of calcium on the pump activity in leucocytes may be due to regulation...

  1. Rapid Necrotic Killing of Polymorphonuclear Leukocytes Is Caused by Quorum-Sensing-Controlled Production of Rhamnolipid by Pseudomonas Aeruginosa

    DEFF Research Database (Denmark)

    Jensen, P. Ø.; Bjarnsholt, Thomas; Phipps, Richard Kerry


    a QS-regulated tolerance of biofilm bacteria to the antimicrobial properties of polymorphonuclear leukocytes (PMNs). The precise QS-regulated effect on the PMNs is, however, unknown. Incubation of human PMNs with supernatants from dense P. aeruginosa cultures showed that the QS-competent P. aeruginosa...... induced rapid necrosis of the PMNs. This mechanism was also observed in mouse lungs infected with P. aeruginosa, and in sputum obtained from P.-aeruginosa-infected patients with cystic fibrosis. Evidence is presented that the necrotic effect was caused by rhamnolipids, production of which is QS controlled...

  2. HIV Medication Adherence (United States)

    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 ...

  3. The StcE metalloprotease of enterohaemorrhagic Escherichia coli reduces the inner mucus layer and promotes adherence to human colonic epithelium ex vivo. (United States)

    Hews, Claire L; Tran, Seav-Ly; Wegmann, Udo; Brett, Bernard; Walsham, Alistair D S; Kavanaugh, Devon; Ward, Nicole J; Juge, Nathalie; Schüller, Stephanie


    Enterohaemorrhagic Escherichia coli (EHEC) is a major foodborne pathogen and tightly adheres to human colonic epithelium by forming attaching/effacing lesions. To reach the epithelial surface, EHEC must penetrate the thick mucus layer protecting the colonic epithelium. In this study, we investigated how EHEC interacts with the intestinal mucus layer using mucin-producing LS174T colon carcinoma cells and human colonic mucosal biopsies. The level of EHEC binding and attaching/effacing lesion formation in LS174T cells was higher compared to mucin-deficient colon carcinoma cell lines, and initial adherence was independent of the presence of flagellin, Escherichia coli common pilus, or long polar fimbriae. Although EHEC infection did not affect gene expression of secreted mucins, it resulted in reduced MUC2 glycoprotein levels. This effect was dependent on the catalytic activity of the secreted metalloprotease StcE, which reduced the inner mucus layer and thereby promoted EHEC access and binding to the epithelium in vitro and ex vivo. Given the lack of efficient therapies against EHEC infection, StcE may represent a suitable target for future treatment and prevention strategies.

  4. A Simple Method for Establishing Adherent Ex Vivo Explant Cultures from Human Eye Pathologies for Use in Subsequent Calcium Imaging and Inflammatory Studies

    Directory of Open Access Journals (Sweden)

    Sofija Andjelic


    Full Text Available A novel, simple, and reproducible method for cultivating pathological tissues obtained from human eyes during surgery was developed using viscoelastic material as a tissue adherent to facilitate cell attachment and expansion and calcium imaging of cultured cells challenged by mechanical and acetylcholine (ACh stimulation as well as inflammatory studies. Anterior lens capsule-lens epithelial cells (aLC-LECs from cataract surgery and proliferative diabetic retinopathy (PDR fibrovascular epiretinal membranes (fvERMs from human eyes were used in the study. We hereby show calcium signaling in aLC-LECs by mechanical and acetylcholine (ACh stimulation and indicate presence of ACh receptors in these cells. Furthermore, an ex vivo study model was established for measuring the inflammatory response in fvERMs and aLC-LECs upon TNFα treatment.

  5. First-in-Human Trial of MIV-150 and Zinc Acetate Coformulated in a Carrageenan Gel: Safety, Pharmacokinetics, Acceptability, Adherence, and Pharmacodynamics (United States)

    Hoesley, Craig J.; Plagianos, Marlena; Hoskin, Elena; Zhang, Shimin; Teleshova, Natalia; Alami, Mohcine; Novak, Lea; Kleinbeck, Kyle R.; Katzen, Lauren L.; Zydowsky, Thomas M.; Fernández-Romero, José A.; Creasy, George W.


    Objective: To evaluate the safety and pharmacokinetics of MIV-150 and zinc acetate in a carrageenan gel (PC-1005). Acceptability, adherence, and pharmacodynamics were also explored. Design: A 3-day open-label safety run-in (n = 5) preceded a placebo-controlled, double-blind trial in healthy, HIV-negative, abstinent women randomized (4:1) to vaginally apply 4 mL of PC-1005 or placebo once daily for 14 days. Methods: Assessments included physical examinations, safety labs, colposcopy, biopsies, cervicovaginal lavages (CVLs), and behavioral questionnaires. MIV-150 (plasma, CVL, tissue), zinc (plasma, CVL), and carrageenan (CVL) concentrations were determined with LC-MS/MS, ICP-MS, and ELISA, respectively. CVL antiviral activity was measured using cell-based assays. Safety, acceptability, and adherence were analyzed descriptively. Pharmacokinetic parameters were calculated using noncompartmental techniques and actual sampling times. CVL antiviral EC50 values were calculated using a dose–response inhibition analysis. Results: Participants (n = 20) ranged from 19–44 years old; 52% were black or African American. Among those completing the trial (13/17, PC-1005; 3/3, placebo), 11/17 reported liking the gel overall; 7 recommended reducing the volume. Adverse events, which were primarily mild and/or unrelated, were comparable between groups. Low systemic MIV-150 levels were observed, without accumulation. Plasma zinc levels were unchanged from baseline. Seven of seven CVLs collected 4-hour postdose demonstrated antiviral (HIV, human papillomavirus) activity. High baseline CVL anti–herpes-simplex virus type-2 (HSV-2) activity precluded assessment of postdose activity. Conclusions: PC-1005 used vaginally for 14 days was well tolerated. Low systemic levels of MIV-150 were observed. Plasma zinc levels were unchanged. Postdose CVLs had anti-HIV and anti–human papillomavirus activity. These data warrant further development of PC-1005 for HIV and sexually transmitted

  6. Contribution of phosphoglucosamine mutase to the resistance of Streptococcus gordonii DL1 to polymorphonuclear leukocyte killing. (United States)

    Yajima, Ayako; Takahashi, Yukihiro; Shimazu, Kisaki; Urano-Tashiro, Yumiko; Uchikawa, Yoshimori; Karibe, Hiroyuki; Konishi, Kiyoshi


    Phosphoglucosamine mutase (GlmM; EC catalyzes the interconversion of glucosamine-6-phosphate to glucosamine-1-phosphate, an essential step in the biosynthetic pathway leading to the formation of the peptidoglycan precursor uridine 5'-diphospho-N-acetylglucosamine. We have recently identified the gene (glmM) encoding the enzyme of Streptococcus gordonii, an early colonizer on the human tooth and an important cause of infective endocarditis, and indicated that the glmM mutation in S. gordonii appears to influence bacterial cell growth, morphology, and sensitivity to penicillins. In the present study, we assessed whether the glmM mutation also affects escape from polymorphonuclear leukocyte (PMN)-dependent killing. Although no differences in attachment to human PMNs were observed between the glmM mutant and the wild-type S. gordonii, the glmM mutation resulted in increased sensitivity to PMN-dependent killing. Compared with the wild type, the glmM mutant induced increased superoxide anion production and lysozyme release by PMNs. Moreover, the glmM mutant is more sensitive to lysozyme, indicating that the GlmM may be required for synthesis of firm peptidoglycans for resistance to bacterial cell lysis. These findings suggest that the GlmM contributes to the resistance of S. gordonii to PMN-dependent killing. Enzymes such as GlmM could be novel drug targets for this organism.

  7. EDU pretreatment decreases polymorphonuclear leukocyte migration into rat lung airways. (United States)

    Bassett, D J; Elbon, C L; Ishii, Y; Yang, H; Otterbein, L; Boswell, G A; Kerr, J S


    Pretreatment with the heterocyclic compound EDU (N-[2-(2-oxo-1-imidazolindinyl)ethyl]-N'-phenylurea) has previously been shown to reduce polymorphonuclear leukocyte (PMN) infiltration into the airways of ozone-exposed rats. The present study further examined the effects of 1 and 2 days EDU pretreatment on rat lung inflammatory responses by determining PMN infiltration in response to intratracheal instillation with the chemoattractant formyl-norleucine-leucine-phenylalanine (fNLP). Maximal recovery of PMNs by bronchoalveolar lavage was observed 4 hr after fNLP instillation with no alteration in the numbers of recoverable macrophages and lymphocytes. Although 1-day pretreatment with EDU did not affect PMN recovery from fNLP-instilled rat lungs, 2 days of EDU pretreatment prevented PMN infiltration as indicated by PMN recoveries that were similar to those obtained from saline-instilled lungs. Measurements of lung-marginated and interstitial pools of inflammatory cells using collagenase tissue digestion demonstrated no effect of 2 days EDU pretreatment. Although 2 days EDU pretreatment alone did not alter blood PMN content, lung permeability, and the lavage recoveries of inflammatory cells, blood PMN responses to chemotactic stimuli in vitro were impaired. In addition, EDU was shown to directly inhibit PMN chemotaxis and superoxide anion generation in vitro. These data demonstrated that EDU acts by interfering with PMN activation and migration rather than by decreasing PMN availability. EDU, by modulating the inflammatory response, represents a useful compound for preventing PMN-associated amplification of acute lung injuries.

  8. Adherence to antidepressants

    Directory of Open Access Journals (Sweden)

    Abimbola Farinde


    Full Text Available While major depression is considered a frequent mental illness there are ongoing reports of high non-adherence to antidepressant medications which places suffers at high risk for relapse, recurrence, or greater impairment,. The World Health Organization (WHO defines adherence as the extent to which a person′s behavior (e.g. taking medications can align with the agreed recommendations of a health care provider. Unfortunately while patient may recognize the importance of adherence to antidepressant medications the majority of patients do not adhere to their prescribed antidepressants. Some of the factors that may contribute to or lead to non-adherence include knowingly or unknowingly missing doses, taking extra doses, delaying administration times, or taking drug holidays. Pharmacists have the unique ability to deter non-adherence through the performance of continuous assessment and monitoring of adherence in this population given these accessibility. Additionally, pharmacists are able to develop therapeutic alliances with patients that can help to increase the likelihood of achieving positive patient outcomes. Antidepressant non-adherence can be viewed as a significant public health concern so it is important for patients to be educated about the importance of adherence, and health care professionals should be aware of factors or patient characteristics that can serve as barriers to non-adherence.

  9. 78 FR 34109 - ``Script Your Future'' Medication Adherence Campaign (United States)


    ... HUMAN SERVICES Food and Drug Administration ``Script Your Future'' Medication Adherence Campaign AGENCY... importance of medication adherence to enhance the health of Americans. Medication adherence is taking... each patient. Nearly three out of four Americans report that they do not take their medication...

  10. Afa/Dr diffusely adhering Escherichia coli strain C1845 induces neutrophil extracellular traps that kill bacteria and damage human enterocyte-like cells. (United States)

    Marin-Esteban, Viviana; Turbica, Isabelle; Dufour, Guillaume; Semiramoth, Nicolas; Gleizes, Aude; Gorges, Roseline; Beau, Isabelle; Servin, Alain L; Lievin-Le Moal, Vanessa; Sandré, Catherine; Chollet-Martin, Sylvie


    We recently documented the neutrophil response to enterovirulent diffusely adherent Escherichia coli expressing Afa/Dr fimbriae (Afa/Dr DAEC), using the human myeloid cell line PLB-985 differentiated into fully mature neutrophils. Upon activation, particularly during infections, neutrophils release neutrophil extracellular traps (NETs), composed of a nuclear DNA backbone associated with antimicrobial peptides, histones, and proteases, which entrap and kill pathogens. Here, using fluorescence microscopy and field emission scanning electron microscopy, we observed NET production by PLB-985 cells infected with the Afa/Dr wild-type (WT) E. coli strain C1845. We found that these NETs were able to capture, immobilize, and kill WT C1845 bacteria. We also developed a coculture model of human enterocyte-like Caco-2/TC7 cells and PLB-985 cells previously treated with WT C1845 and found, for the first time, that the F-actin cytoskeleton of enterocyte-like cells is damaged in the presence of bacterium-induced NETs and that this deleterious effect is prevented by inhibition of protease release. These findings provide new insights into the neutrophil response to bacterial infection via the production of bactericidal NETs and suggest that NETs may damage the intestinal epithelium, particularly in situations such as inflammatory bowel diseases.

  11. Effect of telithromycin (HMR 3647) on polymorphonuclear neutrophil killing of Staphylococcus aureus in comparison with roxithromycin. (United States)

    Vazifeh, D; Abdelghaffar, H; Labro, M T


    HMR 3647 (telithromycin), a new ketolide, is active on intracellular pathogens. It was previously demonstrated that it inhibits superoxide anion production in a time- and concentration-dependent manner, at concentrations which inhibit 50% of the control response of about 55 microg/ml (5 min) to 30 microg/ml (30 min); these values are similar to those obtained with roxithromycin, a classical erythromycin A derivative. Here we investigated whether these drugs modified the bactericidal activity of human polymorphonuclear neutrophils (PMN) on four strains of Staphylococcus aureus with different profiles of susceptibility to macrolides and ketolides. We found that the main factor involved in killing was the antibacterial potency of the drugs, although combinations of antibiotics with PMN were slightly more active than each component used alone against two of the four strains. In addition, high concentrations of the drugs, which impaired the PMN oxidative burst, did not impair PMN bactericidal activity. Likewise, some cytokines which enhance PMN oxidative metabolism did not modify PMN bactericidal activity in the presence or absence of macrolides or ketolides. These data suggest that oxygen-independent mechanisms contribute to the bactericidal activity of PMN on these strains of S. aureus. Both live and/or heat-killed bacteria impaired the uptake of telithromycin and roxithromycin (but not that of levofloxacin, a quinolone) in a concentration-dependent manner, owing to a modulation of PMN transductional systems involved in the activation of the macrolide carrier.

  12. 金葡菌P-V杀白细胞毒素的原核表达及对人多形核白细胞的杀伤效应%Prokaryotie expression of Staphylococcus aureus Panton-Valentine leukocidin and its cytolytic activities to human polymorphonuclear neutrophils'

    Institute of Scientific and Technical Information of China (English)

    黄静; 张天托; 吴本权; 朱家馨; 刘慧; 周宇麒


    AIM:Panton-Valentine leukocidin(PVL)is a pore-forming toxin secreted by Staphylococcus aureus epidemiologieally associated with the often-lethal necrotizing pneumonia.Until now,the mechanisms of pathogene-sis of PVL leading to the fatal pulmonia remains undefined and also acquired plenty of the toxins is difficult.In the present study,we obtain recombinant staphylococcal F and S components of the Panton-Valentine leukocidin by gene engineering and evaluate its biological activity in vitro,which provides an experimental basis for the further studies of its biological func-tion and its toxicity in pneumonia.METHODS:The full-length of F and S components of PVL gene amplified from the strain of Staphylococcus aureus DNA by hiSh-fidelity PCR was cloned into prokaryotic expression vector pET22b(+),and the vector was transformed into BL21(DE3)plysS to construct a prokaryotie expression system.The integrity of the opening-reading frame of each construct was verified by DNA sequencing.The recombinant PVL(rPVL)was induced by1.0 mmol/L IPTG.The expressed products were identified by SDS-PAGE and the fusion proteins(6His-LukS-PV and 6His-LukF-PV)were purified from lysates of transfeeted E.coli cells by affinity chromatography on nitrilotriacetic acid columns.The eytolytie activity was tested by incubation of rPVL with human polymorphonuclear neutrophils(PMNs)in vitro.RESULTS:The nueleotide sequence of the cloned PVL gene was the same as that of reported in GenBank.E coli BL21(DE3)plysS containing recombinant vectors grow at 37℃causes some proteins to accumulate as inclusion bodies.while incubation at 30℃led to a significant amount of soluble active proteins which accounted for about 31.7% of the total bacterial protein.The relative molecular weight showed on SDS-PAGE profile was consistent with the expected value which the LukS-PV protein was about 34 kD.and the LukF-PV protein was about 35 kD.The purified rPVL was obtained and its cytolytic activity to PMNs was

  13. Harvesting the noncirculating pool of polymorphonuclear leukocytes in rats by hetastarch exchange transfusion (HET): yield and functional assessment

    Energy Technology Data Exchange (ETDEWEB)

    Williams, J.H. Jr.; Moser, K.M.; Ulich, T.; Cairo, M.S.


    Isolation of polymorphonuclear leukocytes (PMN) provides an opportunity to study PMN activity in vitro and to label PMN for study of in vivo kinetics. However, simple phlebotomy (SP) of a small animal frequently yields too few PMN for in vitro handling, while PMN harvested from an induced-peritonitis may not accurately reflect PMN in a less stimulated state. We report a novel method of harvesting PMN from the circulation of rats, using hetastarch exchange transfusion (HET), which is both time and animal sparing. HET harvested 8-fold more PMN than SP. In vitro cell function was examined with assays of adherence, chemotaxis, bacterial killing, and superoxide generation. No significant (p less than 0.05) difference was found between PMN obtained by HET and pooled-PMN obtained by SP. In vivo function was examined following labeling with indium 111-oxine. The kinetics pattern described suggested normal migratory activity when compared to previous reports. The data demonstrate that rats possess a relatively large, noncirculating pool of PMN which is readily accessible by HET.

  14. Mechanisms of innate immunity: cytoplasmic granules of polymorphonuclear neutrophilic granulocytes, antimicrobial action, translocation, role, and fate in antimicrobial phagocytosis. Progress report, March 1976--June 30, 1977

    Energy Technology Data Exchange (ETDEWEB)

    Spitznagel, J.K.


    Progress is reported on the following research projects: characterization of the III f granules of human neutrophil polymorphonuclear granulocytes (PMN); studies on glycosidases using methylumbelliferyl derivatives of the sugars with spectrofluorometry; distribution of proteinases and cationic proteins in human PMN; comparison of granules of eosinophils with those of other PMN; identification of a cyanide-resistant NADPH oxidase in PMN; subcellular localization of superoxide dismutase in PMN; oxygen-independent antimicrobial activities of each granule class; the phagocytic and intraleukocytic killing capacity of PMN deprived of their specific granules with phorbol myristate acetate; and studies on the PMN of an infant with the Chediak Higashi syndrome. (HLW)

  15. An Adherence Semigroup

    Institute of Scientific and Technical Information of China (English)


    By a dynamical system we mean a pair of (X,T), where X is compact Hausdorff space. In this paper we define an adherence semigroup A(X,T)∈XX, which is the set of all pointwise limit of subnets of (Tn)n∈N. We will prove some commonness between adherence semigroup and Ellis semigroup.

  16. The Collagen-Binding Protein Cnm Is Required for Streptococcus mutans Adherence to and Intracellular Invasion of Human Coronary Artery Endothelial Cells ▿ (United States)

    Abranches, Jacqueline; Miller, James H.; Martinez, Alaina R.; Simpson-Haidaris, Patricia J.; Burne, Robert A.; Lemos, José A.


    Streptococcus mutans is considered the primary etiologic agent of dental caries, a global health problem that affects 60 to 90% of the population, and a leading causative agent of infective endocarditis. It can be divided into four different serotypes (c, e, f, and k), with serotype c strains being the most common in the oral cavity. In this study, we demonstrate that in addition to OMZ175 and B14, three other strains (NCTC11060, LM7, and OM50E) of the less prevalent serotypes e and f are able to invade primary human coronary artery endothelial cells (HCAEC). Invasive strains were also significantly more virulent than noninvasive strains in the Galleria mellonella (greater wax worm) model of systemic disease. Interestingly, the invasive strains carried an additional gene, cnm, which was previously shown to bind to collagen and laminin in vitro. Inactivation of cnm rendered the organisms unable to invade HCAEC and attenuated their virulence in G. mellonella. Notably, the cnm knockout strains did not adhere to HCAEC as efficiently as the parental strains did, indicating that the loss of the invasion phenotype observed for the mutants was linked to an adhesion defect. Comparisons of the invasive strains and their respective cnm mutants did not support a correlation between biofilm formation and invasion. Thus, Cnm is required for S. mutans invasion of endothelial cells and possibly represents an important virulence factor of S. mutans that may contribute to cardiovascular infections and pathologies. PMID:21422186

  17. The collagen-binding protein Cnm is required for Streptococcus mutans adherence to and intracellular invasion of human coronary artery endothelial cells. (United States)

    Abranches, Jacqueline; Miller, James H; Martinez, Alaina R; Simpson-Haidaris, Patricia J; Burne, Robert A; Lemos, José A


    Streptococcus mutans is considered the primary etiologic agent of dental caries, a global health problem that affects 60 to 90% of the population, and a leading causative agent of infective endocarditis. It can be divided into four different serotypes (c, e, f, and k), with serotype c strains being the most common in the oral cavity. In this study, we demonstrate that in addition to OMZ175 and B14, three other strains (NCTC11060, LM7, and OM50E) of the less prevalent serotypes e and f are able to invade primary human coronary artery endothelial cells (HCAEC). Invasive strains were also significantly more virulent than noninvasive strains in the Galleria mellonella (greater wax worm) model of systemic disease. Interestingly, the invasive strains carried an additional gene, cnm, which was previously shown to bind to collagen and laminin in vitro. Inactivation of cnm rendered the organisms unable to invade HCAEC and attenuated their virulence in G. mellonella. Notably, the cnm knockout strains did not adhere to HCAEC as efficiently as the parental strains did, indicating that the loss of the invasion phenotype observed for the mutants was linked to an adhesion defect. Comparisons of the invasive strains and their respective cnm mutants did not support a correlation between biofilm formation and invasion. Thus, Cnm is required for S. mutans invasion of endothelial cells and possibly represents an important virulence factor of S. mutans that may contribute to cardiovascular infections and pathologies.

  18. Characterization of a distinct population of circulating human non-adherent endothelial forming cells and their recruitment via intercellular adhesion molecule-3.

    Directory of Open Access Journals (Sweden)

    Sarah L Appleby

    Full Text Available Circulating vascular progenitor cells contribute to the pathological vasculogenesis of cancer whilst on the other hand offer much promise in therapeutic revascularization in post-occlusion intervention in cardiovascular disease. However, their characterization has been hampered by the many variables to produce them as well as their described phenotypic and functional heterogeneity. Herein we have isolated, enriched for and then characterized a human umbilical cord blood derived CD133(+ population of non-adherent endothelial forming cells (naEFCs which expressed the hematopoietic progenitor cell markers (CD133, CD34, CD117, CD90 and CD38 together with mature endothelial cell markers (VEGFR2, CD144 and CD31. These cells also expressed low levels of CD45 but did not express the lymphoid markers (CD3, CD4, CD8 or myeloid markers (CD11b and CD14 which distinguishes them from 'early' endothelial progenitor cells (EPCs. Functional studies demonstrated that these naEFCs (i bound Ulex europaeus lectin, (ii demonstrated acetylated-low density lipoprotein uptake, (iii increased vascular cell adhesion molecule (VCAM-1 surface expression in response to tumor necrosis factor and (iv in co-culture with mature endothelial cells increased the number of tubes, tubule branching and loops in a 3-dimensional in vitro matrix. More importantly, naEFCs placed in vivo generated new lumen containing vasculature lined by CD144 expressing human endothelial cells (ECs. Extensive genomic and proteomic analyses of the naEFCs showed that intercellular adhesion molecule (ICAM-3 is expressed on their cell surface but not on mature endothelial cells. Furthermore, functional analysis demonstrated that ICAM-3 mediated the rolling and adhesive events of the naEFCs under shear stress. We suggest that the distinct population of naEFCs identified and characterized here represents a new valuable therapeutic target to control aberrant vasculogenesis.

  19. Characterization of a distinct population of circulating human non-adherent endothelial forming cells and their recruitment via intercellular adhesion molecule-3. (United States)

    Appleby, Sarah L; Cockshell, Michaelia P; Pippal, Jyotsna B; Thompson, Emma J; Barrett, Jeffrey M; Tooley, Katie; Sen, Shaundeep; Sun, Wai Yan; Grose, Randall; Nicholson, Ian; Levina, Vitalina; Cooke, Ira; Talbo, Gert; Lopez, Angel F; Bonder, Claudine S


    Circulating vascular progenitor cells contribute to the pathological vasculogenesis of cancer whilst on the other hand offer much promise in therapeutic revascularization in post-occlusion intervention in cardiovascular disease. However, their characterization has been hampered by the many variables to produce them as well as their described phenotypic and functional heterogeneity. Herein we have isolated, enriched for and then characterized a human umbilical cord blood derived CD133(+) population of non-adherent endothelial forming cells (naEFCs) which expressed the hematopoietic progenitor cell markers (CD133, CD34, CD117, CD90 and CD38) together with mature endothelial cell markers (VEGFR2, CD144 and CD31). These cells also expressed low levels of CD45 but did not express the lymphoid markers (CD3, CD4, CD8) or myeloid markers (CD11b and CD14) which distinguishes them from 'early' endothelial progenitor cells (EPCs). Functional studies demonstrated that these naEFCs (i) bound Ulex europaeus lectin, (ii) demonstrated acetylated-low density lipoprotein uptake, (iii) increased vascular cell adhesion molecule (VCAM-1) surface expression in response to tumor necrosis factor and (iv) in co-culture with mature endothelial cells increased the number of tubes, tubule branching and loops in a 3-dimensional in vitro matrix. More importantly, naEFCs placed in vivo generated new lumen containing vasculature lined by CD144 expressing human endothelial cells (ECs). Extensive genomic and proteomic analyses of the naEFCs showed that intercellular adhesion molecule (ICAM)-3 is expressed on their cell surface but not on mature endothelial cells. Furthermore, functional analysis demonstrated that ICAM-3 mediated the rolling and adhesive events of the naEFCs under shear stress. We suggest that the distinct population of naEFCs identified and characterized here represents a new valuable therapeutic target to control aberrant vasculogenesis.

  20. Killing of gram-negative bacteria by polymorphonuclear leukocytes: role of an O2-independent bactericidal system. (United States)

    Weiss, J; Victor, M; Stendhal, O; Elsbach, P


    Previous studies have suggested that a cationic bactericidal/permeability-increasing protein (BPI) present in both rabbit and human polymorphonuclear leukocytes is the principal O2-independent bactericidal agent of these cells toward several strains of Escherichia coli and Salmonella typhimurium (1978. J. Biol. Chem. 253: 2664--2672; 1979. J. Biol. Chem. 254: 11000--11009). To further evaluate the possible role of this protein in the killing of gram-negative bacteria by polymorphonuclear leukocytes, we have measured the bactericidal activity of intact rabbit peritoneal exudate leukocytes under aerobic or anaerobic conditions and of intact human leukocytes from a patient with chronic granulomatous disease. Anaerobic conditions were created by flushing the cells under a nitrogen stream. Effective removal of oxygen was demonstrated by the inability of nitrogen-flushed leukocytes to mount a respiratory burst (measured as increased conversion of 1-[14C]glucose leads to 14CO2 or by superoxide production) during bacterial ingestion. At a bacteria/leukocyte ratio of 10:1, killing of gram-positive, BPI-resistant, Staphylococcus epidermidis is markedly impaired in the absence of oxygen (76.4 +/- 3.3% killing in room air, 29.2 +/- 8.2% killing in nitrogen). Essentially all increased bacterial survival is intracellular. In contrast, both a nonopsonized rough strain (MR-10) and an opsonized smooth strain (MS) of S. typhimurium 395 are killed equally well in room air and nitrogen. A maximum of 70--80 MR-10 and 30--40 MS are killed per leukocyte either in the presence or absence of oxygen. There is no intracellular bacterial survival in either condition indicating that intracellular O2-independent bactericidal system(s) of rabbit polymorphonuclear leukocytes can at least match the leukocyte's ingestive capacity. Whole homogenates and crude acid extracts manifest similar bactericidal capacity toward S. typhimurium 395. This activity can be accounted for by the BPI content of these

  1. 76 FR 12969 - Campaign To Improve Poor Medication Adherence (U18) (United States)


    ... HUMAN SERVICES Food and Drug Administration Campaign To Improve Poor Medication Adherence (U18) AGENCY... ] importance of good medication adherence, a vital first step toward improved adherence behavior and better...' awareness of the importance of good medication adherence and provide tools to prescribers to help...

  2. HIV Treatment Adherence (United States)

    ... Viral Suppression Doctor, Clinical & Dental Visits Treatment Adherence Mental Health Substance Abuse Issues Sexual Health Nutrition & Food Safety Exercise Immunizations Aging with HIV/AIDS Women’s Health Housing ...

  3. Ormocomp-modified glass increases collagen binding and promotes the adherence and maturation of human embryonic stem cell-derived retinal pigment epithelial cells. (United States)

    Käpylä, Elli; Sorkio, Anni; Teymouri, Shokoufeh; Lahtonen, Kimmo; Vuori, Leena; Valden, Mika; Skottman, Heli; Kellomäki, Minna; Juuti-Uusitalo, Kati


    In in vitro live-cell imaging, it would be beneficial to grow and assess human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells on thin, transparent, rigid surfaces such as cover glasses. In this study, we assessed how the silanization of glass with 3-aminopropyltriethoxysilane (APTES), 3-(trimethoxysilyl)propyl methacrylate (MAPTMS), or polymer-ceramic material Ormocomp affects the surface properties, protein binding, and maturation of hESC-RPE cells. The surface properties were studied by contact angle measurements, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and a protein binding assay. The cell adherence and proliferation were evaluated by culturing hESCRPE cells on collagen IV-coated untreated or silanized surfaces for 42 days. The Ormocomp treatment significantly increased the hydrophobicity and roughness of glass surfaces compared to the APTES and MAPTMS treatments. The XPS results indicated that the Ormocomp treatment changes the chemical composition of the glass surface by increasing the carbon content and the number of C-O/═O bonds. The protein-binding test confirmed that the Ormocomp-treated surfaces bound more collagen IV than did APTES- or MAPTMS-treated surfaces. All of the silane treatments increased the number of cells: after 42 days of culture, Ormocomp had 0.38, APTES had 0.16, MAPTMS had 0.19, and untreated glass had only 0.062, all presented as million cells cm(-2). There were no differences in cell numbers compared to smoother to rougher Ormocomp surfaces, suggesting that the surface chemistry and, more specifically, the collagen binding in combination with Ormocomp are beneficial to hESC-RPE cell culture. This study clearly demonstrates that Ormocomp treatment combined with collagen coating significantly increases hESC-RPE cell attachment compared to commonly used silanizing agents APTES and MAPTMS. Ormocomp silanization could thus enable the use of microscopic live cell imaging methods for h

  4. Vero cytotoxin binding to polymorphonuclear leukocytes among households with children with hemolytic uremic syndrome.

    NARCIS (Netherlands)

    Loo, D.M.W.M. te; Heuvelink, A.E.; Boer, E. de; Nauta, J.; Walle, J. van der; Schröder, C.H.; Hinsbergh, V.W.H. van; Chart, H.; Kar, N.C.A.J. van de; Heuvel, L.P.W.J. van den


    Hemolytic uremic syndrome (HUS), the leading cause of acute renal failure in childhood, can be caused by different serotypes of vero cytotoxin (VT; i.e., Shiga toxin)-producing Escherichia coli (VTEC). Recently, VT was shown to bind to polymorphonuclear leukocytes (PMNL) in the systemic circulation

  5. Phagocytosis and intracellular killing of Candida albicans by murine polymorphonuclear neutrophils.

    NARCIS (Netherlands)

    Vonk, A.G.; Netea, M.G.; Kullberg, B.J.


    Polymorphonuclear neutrophils (PMNs) are important phagocytes in the control of Candida infections. The phagocytic contribution of PMNs to host defence can by assessed by various methods, such as microbiological assays. However, assessment and definition of intracellular killing capacity can be a so

  6. Human placenta-derived adherent cell treatment of experimental stroke promotes functional recovery after stroke in young adult and older rats.

    Directory of Open Access Journals (Sweden)

    Amjad Shehadah

    Full Text Available BACKGROUND: Human Placenta-Derived Adherent Cells (PDAC® are a novel mesenchymal-like cell population derived from normal human placental tissue. PDA-001 is a clinical formulation of PDAC® developed for intravenous administration. In this study, we investigated the efficacy of PDA-001 treatment in a rat model of transient middle cerebral artery occlusion (MCAo in young adult (2-3 month old and older rats (10-12 months old. METHODS: To evaluate efficacy and determine the optimal number of transplanted cells, young adult Wistar rats were subjected to MCAo and treated 1 day post MCAo with 1×10(6, 4×10(6 or 8×10(6 PDA-001 cells (i.v., vehicle or cell control. 4×10(6 or 8×10(6 PDA-001 cells were also tested in older rats after MCAo. Treatment response was evaluated using a battery of functional outcome tests, consisting of adhesive-removal test, modified Neurological Severity Score (mNSS and foot-fault test. Young adult rats were sacrificed 56 days after MCAo, older rats were sacrificed 29 days after MCAo, and lesion volumes were measured using H&E. Immunohistochemical stainings for bromodeoxyuridine (BrdU and von Willebrand Factor (vWF, and synaptophysin were performed. RESULTS: In young adult rats, treatment with 4×10(6 PDA-001 cells significantly improved functional outcome after stroke (p<0.05. In older rats, significant functional improvement was observed with PDA-001 cell therapy in both of the 4×10(6 and 8×10(6 treatment groups. Functional benefits in young adult and older rats were associated with significant increases in the number of BrdU immunoreactive endothelial cells, vascular density and perimeter in the ischemic brain, as well as significantly increased synaptophysin expression in the ischemic border zone (p<0.05. CONCLUSION: PDA-001 treatment significantly improved functional outcome after stroke in both young adult and older rats. The neurorestorative effects induced by PDA-001 treatment may be related to increased

  7. Milk digesta and milk protein fractions influence the adherence of Lactobacillus gasseri R and Lactobacillus casei FMP to human cultured cells. (United States)

    Volstatova, Tereza; Havlik, Jaroslav; Potuckova, Miroslava; Geigerova, Martina


    Adhesion to the intestinal epithelium is considered an important feature of probiotic bacteria, which may increase their persistence in the intestine, allowing them to exert their beneficial health effect or promote the colonisation process. However, this feature might be largely dependent on the host specificity or diet. In the present study, we investigated the effect of selected milks and milk protein fractions on the ability of selected lactobacilli to adhere to the cells of an intestinal model based on co-culture Caco-2/HT29-MTX cell lines. Most milk digesta did not significantly affect bacterial adhesion except for UHT-treated milk and sheep milk. The presence of UHT-treated milk digesta reduced the adhesion of Lactobacillus gasseri R by 61% but not that of Lactobacillus casei FMP. However, sheep milk significantly increased the adherence of L. casei FMP (P < 0.05) but not of L. gasseri R. Among the protein fractions, rennet casein (RCN) and bovine serum albumin (BSA) showed reproducible patterns and strain-specific effects on bacterial adherence. While RCN reduced the adherence of L. gasseri R to <50% compared to the control, it did not have a significant effect on L. casei FMP. In contrast, BSA reduced L. casei FMP adherence to a higher extent than that of L. gasseri R. Whey protein (WH) tended to increase the adherence of both strains by 130%-180%. Recently, interactions between the host diet and its microbiota have attracted considerable interest. Our results may explain one of the aspects of the role of milk in the development of microbiota or support of probiotic supplements. Based on our data, we conclude that the persistence of probiotic strains supplemented as part of dairy food or constitutional microbiota in the gut might be affected negatively or positively by the food matrix through complex strain or concentration dependent effects.

  8. Dendritic cells take up and present antigens from viable and apoptotic polymorphonuclear leukocytes.

    Directory of Open Access Journals (Sweden)

    Carlos Alfaro

    Full Text Available Dendritic cells (DC are endowed with the ability to cross-present antigens from other cell types to cognate T cells. DC are poised to meet polymorphonuclear leukocytes (PMNs as a result of being co-attracted by interleukin-8 (IL-8, for instance as produced by tumor cells or infected tissue. Human monocyte-derived and mouse bone marrow-derived DC can readily internalize viable or UV-irradiated PMNs. Such internalization was abrogated at 4°C and partly inhibited by anti-CD18 mAb. In mice, DC which had internalized PMNs containing electroporated ovalbumin (OVA protein, were able to cross-present the antigen to CD8 (OT-1 and CD4 (OT-2 TCR-transgenic T cells. Moreover, in humans, tumor cell debris is internalized by PMNs and the tumor-cell material can be subsequently taken up from the immunomagnetically re-isolated PMNs by DC. Importantly, if human neutrophils had endocytosed bacteria, they were able to trigger the maturation program of the DC. Moreover, when mouse PMNs with E. coli in their interior are co-injected in the foot pad with DC, many DC loaded with fluorescent material from the PMNs reach draining lymph nodes. Using CT26 (H-2(d mouse tumor cells, it was observed that if tumor cells are intracellularly loaded with OVA protein and UV-irradiated, they become phagocytic prey of H-2(d PMNs. If such PMNs, that cannot present antigens to OT-1 T cells, are immunomagnetically re-isolated and phagocytosed by H-2(b DC, such DC productively cross-present OVA antigen determinants to OT-1 T cells. Cross-presentation to adoptively transferred OT-1 lymphocytes at draining lymph nodes also take place when OVA-loaded PMNs (H-2(d are coinjected in the footpad of mice with autologous DC (H-2(b. In summary, our results indicate that antigens phagocytosed by short-lived PMNs can be in turn internalized and productively cross-presented by DC.

  9. The Effect of Hypertonic Saline on mRNA of Proinflammatory Cytokines in Lipopolysaccharide-Stimulated Polymorphonuclear Cells

    Directory of Open Access Journals (Sweden)

    Sung-Hyuk Choi, MD, PhD


    Conclusions: Hypertonic saline has an immunomodulatory effect on polymorphonuclear cells through the TLR-4 pathway, and the interleukin–1β-associated pathway is influenced more by hypertonic saline than is the tumor necrosis factor–α-associated pathway.

  10. Polymorphonuclear leucocyte dysfunction during short term metabolic changes from normo- to hyperglycemia in type 1 (insulin dependent) diabetic patients

    DEFF Research Database (Denmark)

    Kjersem, H; Hilsted, J; Madsbad, S


    Polymorphonuclear leucocyte (PMN) ingestion of particles coated with lipopolysaccharide (LPS) from Escherichia coli was compared to other PMN functions in seven patients with insulin dependent diabetes mellitus (IDDM) during short-term controlled metabolic changes from normo- to hyperglycemia wit...

  11. A large mobility of hydrophilic molecules at the outmost layer controls the protein adsorption and adhering behavior with the actin fiber orientation of human umbilical vein endothelial cells (HUVEC). (United States)

    Kakinoki, Sachiro; Seo, Ji-Hun; Inoue, Yuuki; Ishihara, Kazuhiko; Yui, Nobuhiko; Yamaoka, Tetsuji


    Adhesion behaviors of human umbilical vein endothelial cells (HUVECs) are interestingly affected by the mobility of hydrophilic chains on the material surfaces. Surfaces with different molecular mobilities were prepared using ABA-type block copolymers consisting polyrotaxane (PRX) or poly(ethylene glycol) (PEG) central block (A block), and amphiphilic anchoring B blocks of poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB). Two different molecular mobilities of the PRX chains were designed by using normal α-cyclodextrin (α-CD) or α-CD whose hydroxyl groups were converted to methoxy groups in a given ratio to improve its molecular mobility (PRX-PMB and OMe-PRX-PMB). The surface mobility of these materials was assessed as the mobility factor (Mf), which is measured by quartz crystal microbalance with dissipation monitoring system. HUVECs adhered on OMe-PRX-PMB surface much more than PRX-PMB and PMB-block-PEG-block-PMB (PEG-PMB) surfaces. These different HUVEC adhesions were correlated with the density of cell-binding site of adsorbed fibronectin. In addition, the alignment of the actin cytoskeleton of adhered HUVECs was strongly suppressed on the PEG-PMB, PRX-PMB, and OMe-PRX-PMB in response to the increased Mf value. Remarkably, the HUVECs adhered on the OMe-PRX-PMB surface with much less actin organization. We concluded that not only the cell adhesion but also the cellular function are regulated by the molecular mobility of the outmost material surfaces.

  12. Thermal injury induces impaired function in polymorphonuclear neutrophil granulocytes and reduced control of burn wound infection

    DEFF Research Database (Denmark)

    Calum, H.; Moser, C.; Jensen, P. O.;


    with infected burn wound. Furthermore, the oxidative burst and the phagocytic capacity of the PMNs were reduced in the group of mice with burn wound. Using this novel mouse model of thermal injury a decline of peripheral leucocytes was observed, whereas the increased local inflammatory response at the site...... of mice with burn wound. The reduction was ascribed to the decline in concentration of polymorphonuclear neutrophil leucocytes and monocytes. When infecting the skin with Pseudomonas aeruginosa, a dissemination of bacteria was observed only in the burn wound group. Histological characterization...... of the skin showed a more polymorphonuclear neutrophil granulocytes (PMNs)-dominated inflammation in the group of mice with infected burn wound compared with the with burn wound group. In contrast, a higher degree of inflammation was observed in the burn wound group compared with the group of mice...

  13. Adherence to antiretroviral therapy among people living with HIV

    Directory of Open Access Journals (Sweden)

    Basavaprabhu Achappa


    Full Text Available Background: Acquired immune deficiency syndrome (AIDS is now considered as a manageable chronic illness. There has been a dramatic reduction in human immunodeficiency virus (HIV related morbidity and mortality due to antiretroviral therapy. A high level of adherence (>95% is required for antiretroviral therapy to be effective. There are many barriers to adherence in both developed and developing countries. Aim: The aim of our study was to determine adherence levels and factors influencing adherence to antiretroviral therapy among people living with HIV. Materials and Methods: Using a cross-sectional study design, 116 HIV positive patients receiving antiretroviral therapy for at least 1 year were interviewed using a semi structured questionnaire. The collected data was analyzed using Statistical Product and Service Solutions (SPSS version 11.5. Chi-square test was done. A P value of < 0.05 was considered statistically significant. Results: Of 116 participants, 63.7% reported adherence ≥ 95%. Mean adherence index was 91.25%. Financial constraints, forgetting to take medication, lack of family care, depression, alcohol use, social stigma and side effects to antiretroviral therapy were barriers for adherence in our study. Conclusion: Adherence to antiretroviral therapy in south India is suboptimal. Intensive adherence counseling should be provided to all patients before initiation ofantiretroviral therapy. Health care providers must identify possible barriers to adherence at the earliest and provide appropriate solutions.

  14. Therapeutic relevance of penicillin-induced hypersensitivity of Staphylococcus aureus to killing by polymorphonuclear leukocytes.


    Lam, C; Georgopoulos, A.; Laber, G.; Schütze, E


    There is an overwhelming body of evidence that certain Staphylococcus aureus strains become more sensitive to killing by polymorphonuclear leukocytes after their growth in media containing subinhibitory concentrations of penicillin. However, it is not clear to what extent this phenomenon contributes to the curative effect of penicillin in vivo. To explore its therapeutic relevance, we evaluated the interaction of staphylococci pretreated with penicillin in vitro with leukocytes in cell-proof ...

  15. Phagocytosis of Pseudomonas aeruginosa by polymorphonuclear leukocytes and monocytes: effect of cystic fibrosis serum.


    Thomassen, M J; Demko, C A; Wood, R.E.; Sherman, J. M.


    It has been shown previously that serum from chronically infected patients with cystic fibrosis inhibits the phagocytosis of Pseudomonas aeruginosa by both normal and cystic fibrosis alveolar macrophages. In the present study, the ability of peripheral monocytes and polymorphonuclear leukocytes from normal volunteers and cystic fibrosis patients to phagocytize P. aeruginosa was shown not to be inhibited in the presence of serum from cystic fibrosis patients.

  16. Pseudomonas aeruginosa recognizes and responds aggressively to the presence of polymorphonuclear leukocytes

    DEFF Research Database (Denmark)

    Alhede, Morten; Bjarnsholt, T.; Jensen, P.O.;


    Polymorphonuclear neutrophilic leukocytes (PMNs) play a central role in innate immunity, where they dominate the response to infections, in particular in the cystic fibrosis lung. PMNs are phagocytic cells that produce a wide range of antimicrobial agents aimed at killing invading bacteria. Howev...... rhamnolipids surround the biofilm bacteria and on contact eliminate incoming PMNs. Our data strengthen the view that cross-kingdom communication plays a key role in P. aeruginosa recognition and evasion of the host defence....

  17. Blood Level of Polymorphonuclear Neutrophil Leukocytes and Bronchial Hyperreactivity in Chronic Obstructive Pulmonary Disease


    Cukic, Vesna


    Introduction: Polymorphonuclear neutrophil leukocytes (PMNL) have an important defensive role against various microorganisms and other agents, but by liberating various substances, first of all the superoxide anion (O 2¯), they can damage the bronchial mucosa and influence the development of bronchial inflammation which is the fundamental of bronchial hyperreactivity (BHR). Objective: to show the role of the PMNL for development and level of BHR in patients with chronic obstructive pulmonary ...

  18. 77 FR 20637 - Request for Information on Prescription Medication Adherence (United States)


    ... HUMAN SERVICES Request for Information on Prescription Medication Adherence AGENCY: Department of Health... potential solutions associated with the public health problem of prescription medication non-adherence in..., health care providers, and industry and private organizations in efforts to improve medication...

  19. Genetic factors in exercise adoption, adherence and obesity. (United States)

    Herring, M P; Sailors, M H; Bray, M S


    Physical activity and exercise play critical roles in energy balance. While many interventions targeted at increasing physical activity have demonstrated efficacy in promoting weight loss or maintenance in the short term, long term adherence to such programmes is not frequently observed. Numerous factors have been examined for their ability to predict and/or influence physical activity and exercise adherence. Although physical activity has been demonstrated to have a strong genetic component in both animals and humans, few studies have examined the association between genetic variation and exercise adherence. In this review, we provide a detailed overview of the non-genetic and genetic predictors of physical activity and adherence to exercise. In addition, we report the results of analysis of 26 single nucleotide polymorphisms in six candidate genes examined for association to exercise adherence, duration, intensity and total exercise dose in young adults from the Training Interventions and Genetics of Exercise Response (TIGER) Study. Based on both animal and human research, neural signalling and pleasure/reward systems in the brain may drive in large part the propensity to be physically active and to adhere to an exercise programme. Adherence/compliance research in other fields may inform future investigation of the genetics of exercise adherence.

  20. Adherence of Pseudomonas aeruginosa to tracheal cells injured by influenza infection or by endotracheal intubation. (United States)

    Ramphal, R; Small, P M; Shands, J W; Fischlschweiger, W; Small, P A


    Adherence of Pseudomonas aeruginosa to normal, injured, and regenerating tracheal mucosa was examined by scanning electron microscopy. Uninfected and influenza-infected murine tracheas were exposed to six strains of P. aeruginosa isolated from human sources and one strain of platn origin. All of the strains tested adhered to desquamating cells of the infected tracheas, but not to normal mucosa, the basal cell layer, or the regenerating epithelium. Adherence increased when the incubation time of the bacteria with the trachea was prolonged. Strains isolated from human tracheas appeared to adhere better than strains derived from the urinary tract. After endotracheal intubation of ferrets, P. aeruginosa adhered only to the injured cells and to areas of exposed basement membrane. We call this phenomenon "opportunistic adherence" and propose that alteration of the cell surfaces or cell injury facilitates the adherence of this bacterium and that adherence to injured cells may be a key to the pathogenesis of opportunistic Pseudomonas infections.

  1. The Adherent/Invasive Escherichia coli Strain LF82 Invades and Persists in Human Prostate Cell Line RWPE-1, Activating a Strong Inflammatory Response (United States)

    Aleandri, Marta; Marazzato, Massimiliano; Conte, Antonietta L.; Ambrosi, Cecilia; Nicoletti, Mauro; Zagaglia, Carlo; Gambara, Guido; Palombi, Fioretta; De Cesaris, Paola; Ziparo, Elio; Palamara, Anna T.; Riccioli, Anna


    Adherent/invasive Escherichia coli (AIEC) strains have recently been receiving increased attention because they are more prevalent and persistent in the intestine of Crohn's disease (CD) patients than in healthy subjects. Since AIEC strains show a high percentage of similarity to extraintestinal pathogenic E. coli (ExPEC), neonatal meningitis-associated E. coli (NMEC), and uropathogenic E. coli (UPEC) strains, here we compared AIEC strain LF82 with a UPEC isolate (strain EC73) to assess whether LF82 would be able to infect prostate cells as an extraintestinal target. The virulence phenotypes of both strains were determined by using the RWPE-1 prostate cell line. The results obtained indicated that LF82 and EC73 are able to adhere to, invade, and survive within prostate epithelial cells. Invasion was confirmed by immunofluorescence and electron microscopy. Moreover, cytochalasin D and colchicine strongly inhibited bacterial uptake of both strains, indicating the involvement of actin microfilaments and microtubules in host cell invasion. Moreover, both strains belong to phylogenetic group B2 and are strong biofilm producers. In silico analysis reveals that LF82 shares with UPEC strains several virulence factors: namely, type 1 pili, the group II capsule, the vacuolating autotransporter toxin, four iron uptake systems, and the pathogenic island (PAI). Furthermore, compared to EC73, LF82 induces in RWPE-1 cells a marked increase of phosphorylation of mitogen-activated protein kinases (MAPKs) and of NF-κB already by 5 min postinfection, thus inducing a strong inflammatory response. Our in vitro data support the hypothesis that AIEC strains might play a role in prostatitis, and, by exploiting host-cell signaling pathways controlling the innate immune response, likely facilitate bacterial multiplication and dissemination within the male genitourinary tract. PMID:27600504

  2. Production of high-titer human influenza A virus with adherent and suspension MDCK cells cultured in a single-use hollow fiber bioreactor. (United States)

    Tapia, Felipe; Vogel, Thomas; Genzel, Yvonne; Behrendt, Ilona; Hirschel, Mark; Gangemi, J David; Reichl, Udo


    Hollow fiber bioreactors (HFBRs) have been widely described as capable of supporting the production of highly concentrated monoclonal antibodies and recombinant proteins. Only recently HFBRs have been proposed as new single-use platforms for production of high-titer influenza A virus. These bioreactors contain multiple hollow fiber capillary tubes that separate the bioreactor in an intra- and an extra-capillary space. Cells are usually cultured in the extra-capillary space and can grow to a very high cell concentration. This work describes the evaluation of the single-use hollow fiber bioreactor PRIMER HF (Biovest International Inc., USA) for production of influenza A virus. The process was setup, characterized and optimized by running a total of 15 cultivations. The HFBRs were seeded with either adherent or suspension MDCK cells, and infected with influenza virus A/PR/8/34 (H1N1), and the pandemic strain A/Mexico/4108/2009 (H1N1). High HA titers and TCID₅₀ of up to 3.87 log₁₀(HA units/100 μL) and 1.8 × 10(10)virions/mL, respectively, were obtained for A/PR/8/34 influenza strain. Influenza virus was collected by performing multiple harvests of the extra-capillary space during a virus production time of up to 12 days. Cell-specific virus yields between 2,000 and 8,000 virions/cell were estimated for adherent MDCK cells, and between 11,000 and 19,000 virions/cell for suspension MDCK.SUS2 cells. These results do not only coincide with the cell-specific virus yields obtained with cultivations in stirred tank bioreactors and other high cell density systems, but also demonstrate that HFBRs are promising and competitive single-use platforms that can be considered for commercial production of influenza virus.

  3. Interactions between polymorphonuclear leukocytes and Pseudomonas aeruginosa biofilms on silicone implants in vivo

    DEFF Research Database (Denmark)

    van Gennip, Maria; Hultqvist, Louise Dahl; Alhede, Morten;


    Chronic infections with Pseudomonas aeruginosa persist because the bacterium forms biofilms that are tolerant to antibiotic treatment and the host immune response. Scanning electron microscopy and confocal laser scanning microscopy were used to visualize biofilm development in vivo following...... intraperitoneal inoculation of mice with bacteria growing on hollow silicone tubes, as well as to examine the interaction between these bacteria and the host innate immune response. Wild-type P. aeruginosa developed biofilms within 1 day that trapped and caused visible cavities in polymorphonuclear leukocytes...

  4. Killing of Pseudomonas pseudomallei by polymorphonuclear leukocytes and peritoneal macrophages from chicken, sheep, swine and rabbits. (United States)

    Markova, N; Kussovski, V; Radoucheva, T


    Differences in the kinetics of Pseudomonas pseudomallei killing by peritoneal macrophages (PM) and polymorphonuclear leucocytes (PMNL) from chickens, sheep, swine and rabbits were found. P. pseudomallei was rapidly killed by porcine PM and PMNL. However the bacterial killing by ovine and lapine PM and PMNL proceeded at a slower rate. In contrast, chicken PM and PMNL ingested and killed the lowest number of P. pseudomallei bacteria. The differences in the bactericidal activity of PM and PMNL from different animal species correlated with the level of their acid phosphatase and glycolytic activity.

  5. Impaired metabolic function of polymorphonuclear leukocytes in glycogen storage disease Ib. (United States)

    Gahr, M; Heyne, K


    To elucidate the basis for the recurrent infections in patients with glycogen storage disease (GSD) Ib we tested polymorphonuclear leukocyte (PMN) function in one patient. Bactericidal capacity and phagocytosis-induced O2 consumption were reduced. Also, phorbol myristate acetate-stimulated superoxide production and glucose oxidation through the hexose monophosphate shunt were diminished compared to control subjects. Therefore it could be speculated that in PMN of patients with GSD Ib, glucose-6-phosphate has no access to the enzymes of the hexose monophosphate shunt due to a transport-related defect as shown for glucogenesis in hepatocytes.

  6. Multiple roles of Activin/Nodal, bone morphogenetic protein, fibroblast growth factor and Wnt/β-catenin signalling in the anterior neural patterning of adherent human embryonic stem cell cultures (United States)

    Lupo, Giuseppe; Novorol, Claire; Smith, Joseph R.; Vallier, Ludovic; Miranda, Elena; Alexander, Morgan; Biagioni, Stefano; Pedersen, Roger A.; Harris, William A.


    Several studies have successfully produced a variety of neural cell types from human embryonic stem cells (hESCs), but there has been limited systematic analysis of how different regional identities are established using well-defined differentiation conditions. We have used adherent, chemically defined cultures to analyse the roles of Activin/Nodal, bone morphogenetic protein (BMP), fibroblast growth factor (FGF) and Wnt/β-catenin signalling in neural induction, anteroposterior patterning and eye field specification in hESCs. We show that either BMP inhibition or activation of FGF signalling is required for effective neural induction, but these two pathways have distinct outcomes on rostrocaudal patterning. While BMP inhibition leads to specification of forebrain/midbrain positional identities, FGF-dependent neural induction is associated with strong posteriorization towards hindbrain/spinal cord fates. We also demonstrate that Wnt/β-catenin signalling is activated during neural induction and promotes acquisition of neural fates posterior to forebrain. Therefore, inhibition of this pathway is needed for efficient forebrain specification. Finally, we provide evidence that the levels of Activin/Nodal and BMP signalling have a marked influence on further forebrain patterning and that constitutive inhibition of these pathways represses expression of eye field genes. These results show that the key mechanisms controlling neural patterning in model vertebrate species are preserved in adherent, chemically defined hESC cultures and reveal new insights into the signals regulating eye field specification. PMID:23576785

  7. Adherence as a language game. (United States)

    Kolberg, Espen Skarstein


    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.

  8. [Adherence to psychopharmacological treatment: Psychotherapeutic strategies to enhance adherence]. (United States)

    Lencer, R; Korn, D


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

  9. Biologic Influences on Exercise Adherence. (United States)

    Dishman, Rod K.


    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…

  10. Pathogenesis of human diffusely adhering Escherichia coli expressing Afa/Dr adhesins (Afa/Dr DAEC): current insights and future challenges. (United States)

    Servin, Alain L


    The pathogenicity and clinical pertinence of diffusely adhering Escherichia coli expressing the Afa/Dr adhesins (Afa/Dr DAEC) in urinary tract infections (UTIs) and pregnancy complications are well established. In contrast, the implication of intestinal Afa/Dr DAEC in diarrhea is still under debate. These strains are age dependently involved in diarrhea in children, are apparently not involved in diarrhea in adults, and can also be asymptomatic intestinal microbiota strains in children and adult. This comprehensive review analyzes the epidemiology and diagnosis and highlights recent progress which has improved the understanding of Afa/Dr DAEC pathogenesis. Here, I summarize the roles of Afa/Dr DAEC virulence factors, including Afa/Dr adhesins, flagella, Sat toxin, and pks island products, in the development of specific mechanisms of pathogenicity. In intestinal epithelial polarized cells, the Afa/Dr adhesins trigger cell membrane receptor clustering and activation of the linked cell signaling pathways, promote structural and functional cell lesions and injuries in intestinal barrier, induce proinflammatory responses, create angiogenesis, instigate epithelial-mesenchymal transition-like events, and lead to pks-dependent DNA damage. UTI-associated Afa/Dr DAEC strains, following adhesin-membrane receptor cell interactions and activation of associated lipid raft-dependent cell signaling pathways, internalize in a microtubule-dependent manner within urinary tract epithelial cells, develop a particular intracellular lifestyle, and trigger a toxin-dependent cell detachment. In response to Afa/Dr DAEC infection, the host epithelial cells generate antibacterial defense responses. Finally, I discuss a hypothetical role of intestinal Afa/Dr DAEC strains that can act as "silent pathogens" with the capacity to emerge as "pathobionts" for the development of inflammatory bowel disease and intestinal carcinogenesis.

  11. Kruppel-Like Factor 4 Overexpression Initiates a Mesenchymal-to-Epithelial Transition and Redifferentiation of Human Pancreatic Cells following Expansion in Long Term Adherent Culture.

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    Kenneth R Muir

    Full Text Available A replenishable source of insulin-producing cells has the potential to cure type 1 diabetes. Attempts to culture and expand pancreatic β-cells in vitro have resulted in their transition from insulin-producing epithelial cells to mesenchymal stromal cells (MSCs with high proliferative capacity but devoid of any hormone production. The aim of this study was to determine whether the transcription factor Krüppel-like factor 4 (KLF4, could induce a mesenchymal-to-epithelial transition (MET of the cultured cells. Islet-enriched pancreatic cells, allowed to dedifferentiate and expand in adherent cell culture, were transduced with an adenovirus containing KLF4 (Ad-Klf4. Cells were subsequently analysed for changes in cell morphology by light microscopy, and for the presence of epithelial and pancreatic markers by immunocytochemistry and quantitative RT/PCR. Infection with Ad-Klf4 resulted in morphological changes, down-regulation of mesenchymal markers, and re-expression of both epithelial and pancreatic cell markers including insulin and transcription factors specific to β-cells. This effect was further enhanced by culturing cells in suspension. However, the effects of Ad-KLf4 were transient and this was shown to be due to increased apoptosis in Klf4-expressing cells. Klf4 has been recently identified as a pioneer factor with the ability to modulate the structure of chromatin and enhance reprogramming/transdifferentiation. Our results show that Klf4 may have a role in the redifferentiation of expanded pancreatic cells in culture, but before this can be achieved the off-target effects that result in increased apoptosis would need to be overcome.

  12. Pro-apoptotic role of NF-κB pathway inhibition in lipopolysaccharide-stimulated polymorphonuclear neutrophils

    Institute of Scientific and Technical Information of China (English)

    刘艳梅; 张君岚; 赵占胜; 凌亦凌


    Objective To investigate the role of nuclear factor kappa B (NF-κB) pathway inhibition in lipopolysaccharide (LPS)-stimulated apoptosis of polymorphonuclear neutrophils (PMNs).Methods Rats with acute lung injury induced by LPS intratracheal instillation and cultured human venous PMNs were studied. Pyrrolidine dithiocarbamate (PDTC) and gliotoxin were used as NF-κB inhibitors. Additionally, to explore the role of extracellularly regulated protein kinase as an upstream signal in NF-κB pathway on regulating LPS-stimulated PMN apoptosis, PD098059, the specific inhibitor of extracellularly regulated protein kinase, was also applied. The lung injury was determined by protein content and PMN numbers in bronchoalveolar lavage fluid. PMN apoptosis was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) end labeling and DNA fragmentation. IκBα degradation was analyzed by Western blot. NF-κB DNA binding activity was detected by an electrophoretic mobility shift assay.Results (1) The increase of protein content and PMN numbers in bronchoalveolar lavage fluid induced by LPS (100 μg per rat) intratracheal instillation were alleviated by PDTC (50, 100, or 200 mg/kg, I.p.) in a dose-dependent manner. (2) PMNs apoptosis in vivo or in vitro was delayed by LPS, and accelerated by PDTC, gliotoxin or PD098059 pretreatment. (3) IκBα degradation and increased NF-κB DNA binding activity mediated by LPS were inhibited by PDTC, gliotoxin or PD098059 pretreatment.Conclusion Inhibition of either NF-κB itself or the upstream signals in NF-κB pathway such as extracellularly regulated protein kinases has therapeutic effect on LPS-induced acute lung injury, in which the dysregulation of PMN apoptosis plays an important role.

  13. Interaction of bovine peripheral blood polymorphonuclear cells and Leptospira species; innate responses in the natural bovine reservoir host.

    Directory of Open Access Journals (Sweden)

    Jennifer H Wilson-Welder


    Full Text Available Cattle are the reservoir hosts of Leptospira borgpetersenii serovar Hardjo, and can also be reservoir hosts of other Leptospira species such as L. kirschneri, and L. interrogans. As a reservoir host, cattle shed Leptospira, infecting other animals, including humans. Previous studies with human and murine neutrophils have shown activation of neutrophil extracellular trap or NET formation, and upregulation of inflammatory mediators by neutrophils in the presence of Leptospira. Humans, companion animals and most widely studied models of Leptospirosis are of acute infection, hallmarked by systemic inflammatory response, neutrophilia and septicemia. In contrast, cattle exhibit chronic infection with few outward clinical signs aside from reproductive failure. Taking into consideration that there is host species variation in innate immunity, especially in pathogen recognition and response, the interaction of bovine peripheral blood polymorphonuclear cells (PMNs and several Leptospira strains was evaluated. Studies including bovine-adapted strains, human pathogen strains, a saprophyte and inactivated organisms. Incubation of PMNs with Leptospira did induce slight activation of neutrophil NETs, greater than unstimulated cells but less than the quantity from E. coli P4 stimulated PMNs. Very low but significant from non-stimulated, levels of reactive oxygen peroxides were produced in the presence of all Leptospira strains and E. coli P4. Similarly, significant levels of reactive nitrogen intermediaries (NO2 was produced from PMNs when incubated with the Leptospira strains and greater quantities in the presence of E. coli P4. PMNs incubated with Leptospira induced RNA transcripts of IL-1β, MIP-1α, and TNF-α, with greater amounts induced by live organisms when compared to heat-inactivated leptospires. Transcript for inflammatory cytokine IL-8 was also induced, at similar levels regardless of Leptospira strain or viability. However, incubation of

  14. Improving Trend of Adhering to Ethical Measures in Iranian Research in Human Genetics: A Survey from 2005 to 2009; and the Road Ahead.

    Directory of Open Access Journals (Sweden)

    Seyed Hasan Saadat


    Full Text Available The overwhelming rate of progress in biotechnological research especially in human genetics, as well as the high levels of power these researches provide us to intervene in human lives, brings serious concerns on the ethical problems that may rise from these research endeavors. To address this critical issue in Iran, we conducted a study issuing publishing authors of studies in human genetics from Iran, between years 2005 to 2011.We contacted 116 corresponding authors of articles issuing genetics research on human subjects, asking them that whether they have gotten either informed consent from their study subjects or ethical approval from their institutional ethics committee.Only 13% of the authors presented both documents; 52% had not gotten any of the documents; 19% of authors felt no need for getting the mentioned documents; 13% declared that they only gotten oral consent and 3% of authors did not remember whether they have gotten any documentation or not.The trend for informed consent taking was improving over time, from 5% in year 2006 to 24% in 2009. The result was not satisfactory but showed good trend towards improvement, recommending more serious follow up concerning ethical aspects of articles published in human genetics.

  15. Impairment of polymorphonuclear leucocyte function in patients with acquired immunodeficiency syndrome and with lymphadenopathy syndrome. (United States)

    Lazzarin, A; Uberti Foppa, C; Galli, M; Mantovani, A; Poli, G; Franzetti, F; Nóvati, R


    Granulocyte functions were studied in 20 patients with acquired immunodeficiency syndrome (AIDS), 20 subjects with lymphadenopathy syndrome (LAS) and 15 symptom-free drug addicts (SFDA). Polymorphonuclear leucocyte (PMNL) phagocytosis and killing of C. albicans appeared normal in homosexual men with AIDS, while drug addicts with AIDS or LAS and SFDA showed a significant defect of these functions as compared to healthy controls. Migration of PMNL in response to a chemoattractant was normal in SFDA, but markedly defective both in LAS and in AIDS patients. In the AIDS group no significant differences were evident between homosexual men and drug addicts. We conclude that defective PMNL phagocytosis and killing, unlike defective migration, are somehow related to drug abuse rather than to infection with the causative agent of the immunodeficiency. PMID:3791696

  16. Dammarane triterpene saponin from Bacopa monniera as the superoxide inhibitor in polymorphonuclear cells. (United States)

    Pawar, R; Gopalakrishnan, C; Bhutani, K K


    The hydroalcoholic extract of the whole plant of Bacopa monniera Wettst. (Scrophulariaceae), exhibited an inhibitory effect on superoxide released from polymorphonuclear (PMN) cells in the nitroblue tetrazolium (NBT) assay. The major saponin bacoside A(3) was found to be responsible for this effect in the herb. This compound showed 85, 91.66, 91.66, and 83 % inhibitions of NBT reduction at the concentrations of 200, 100, 50, and 25 microg/ml, respectively, with an IC(50) value of 10.22 microg/ml. These inhibitory effects were compared with those of the standard positive controls, quercetin and ascorbic acid with IC(50) of 111 and 14.16 microg/ml, respectively. Another major saponin bacopasaponin C was found to be much less potent as compared to bacoside A(3) whereas the remaining two mixtures of saponins were found to be inactive.

  17. Effect of donkey seminal plasma on sperm movement and sperm-polymorphonuclear neutrophils attachment in vitro. (United States)

    Miró, Jordi; Vilés, Karina; García, Wilber; Jordana, Jordi; Yeste, Marc


    To evaluate the effect of seminal plasma in endometrial inflammation in donkeys, samples from fresh pure, fresh diluted and frozen-thawed semen of three different jackasses were co-incubated in water bath at 37°C with uterine Jennie's secretions collected 6h after artificial insemination with frozen-thawed donkey semen. Individual sperm movement parameters using the computerised sperm analysis system (CASA) and sperm-polymorphonuclear neutrophils (sperm-PMN) attachment observed in Diff-Quick stained smears were evaluated at 0, 1, 2, 3 and 4h of co-incubation. Controls consisted of incubating diluted or frozen-thawed sperm in the absence of uterine secretions. For data analyses, a repeated measures ANOVA was performed with incubation time as intra-subject factor and with treatment and donkey as inter-subject factor, followed by a post-hoc Bonferroni's test. Greater values (Pdonkey semen. As a result, spermatozoa with the greater motility characteristics are selected.

  18. High affinity capture and concentration of quinacrine in polymorphonuclear neutrophils via vacuolar ATPase-mediated ion trapping: Comparison with other peripheral blood leukocytes and implications for the distribution of cationic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Roy, Caroline; Gagné, Valérie; Fernandes, Maria J.G.; Marceau, François, E-mail:


    trapping. • Human peripheral blood leukocytes capture and concentrate quinacrine. • Polymorphonuclear leukocytes do so with higher apparent affinity. • Polymorphonuclear are also more competent than lymphocytes for pinocytosis.

  19. Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells (United States)

    Starost, Laura Julia; Karassek, Sascha; Sano, Yasuteru; Kanda, Takashi; Kim, Kwang Sik; Dobrindt, Ulrich; Rüter, Christian; Schmidt, Marcus Alexander


    Pertussis toxin (PTx), the major virulence factor of the whooping cough-causing bacterial pathogen Bordetella pertussis, permeabilizes the blood–brain barrier (BBB) in vitro and in vivo. Breaking barriers might promote translocation of meningitis-causing bacteria across the BBB, thereby facilitating infection. PTx activates several host cell signaling pathways exploited by the neonatal meningitis-causing Escherichia coli K1-RS218 for invasion and translocation across the BBB. Here, we investigated whether PTx and E. coli K1-RS218 exert similar effects on MAPK p38, NF-κB activation and transcription of downstream targets in human cerebral endothelial TY10 cells using qRT-PCR, Western blotting, and ELISA in combination with specific inhibitors. PTx and E. coli K1-RS218 activate MAPK p38, but only E. coli K1-RS218 activates the NF-κB pathway. mRNA and protein levels of p38 and NF-κB downstream targets including IL-6, IL-8, CxCL-1, CxCL-2 and ICAM-1 were increased. The p38 specific inhibitor SB203590 blocked PTx-enhanced activity, whereas E. coli K1-RS218’s effects were inhibited by the NF-κB inhibitor Bay 11-7082. Further, we found that PTx enhances the adherence of human monocytic THP-1 cells to human cerebral endothelial TY10 cells, thereby contributing to enhanced translocation. These modulations of host cell signaling pathways by PTx and meningitis-causing E. coli support their contributions to pathogen and monocytic THP-1 cells translocation across the BBB. PMID:27754355

  20. Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Laura Julia Starost


    Full Text Available Pertussis toxin (PTx, the major virulence factor of the whooping cough-causing bacterial pathogen Bordetella pertussis, permeabilizes the blood–brain barrier (BBB in vitro and in vivo. Breaking barriers might promote translocation of meningitis-causing bacteria across the BBB, thereby facilitating infection. PTx activates several host cell signaling pathways exploited by the neonatal meningitis-causing Escherichia coli K1-RS218 for invasion and translocation across the BBB. Here, we investigated whether PTx and E. coli K1-RS218 exert similar effects on MAPK p38, NF-κB activation and transcription of downstream targets in human cerebral endothelial TY10 cells using qRT-PCR, Western blotting, and ELISA in combination with specific inhibitors. PTx and E. coli K1-RS218 activate MAPK p38, but only E. coli K1-RS218 activates the NF-κB pathway. mRNA and protein levels of p38 and NF-κB downstream targets including IL-6, IL-8, CxCL-1, CxCL-2 and ICAM-1 were increased. The p38 specific inhibitor SB203590 blocked PTx-enhanced activity, whereas E. coli K1-RS218’s effects were inhibited by the NF-κB inhibitor Bay 11-7082. Further, we found that PTx enhances the adherence of human monocytic THP-1 cells to human cerebral endothelial TY10 cells, thereby contributing to enhanced translocation. These modulations of host cell signaling pathways by PTx and meningitis-causing E. coli support their contributions to pathogen and monocytic THP-1 cells translocation across the BBB.

  1. Mechanisms and target sites of damage in killing of Candida albicans hyphae by human polymorphonuclear neutrophils. (United States)

    Christin, L; Wysong, D R; Meshulam, T; Wang, S; Diamond, R D


    Target sites of fungal cell damage were studied to define mechanisms of neutrophil-mediated killing of Candida albicans hyphae. Neutrophils induced hyphal cell wall damage, as evidenced by release of cell wall glycoproteins and confocal microscopic changes. Damage occurred in the presence of neutrophil granule extracts and did not require oxidants. However, oxidation of hyphal surface glycoproteins correlated strongly with parallel increments in fungicidal activity, suggesting that oxidants did contribute to maximal cell wall damage. Neutrophil oxidants also induced hyphal DNA fragmentation, primarily single-strand breakage, as shown by increased electrophoretic migration after nuclease-S1 DNA digestion at single-strand break sites. The onset of damage to hyphal cell walls and DNA preceded detectable neutrophil-mediated fungicidal effects. Likewise, hyphal amino acid and nucleotide turnover as well as ATP initially rose, then declined as lethal effects became detectable. Thus, preceding detectable fungal cell death, neutrophil oxidative and oxygen-independent mechanisms damaged defined targets.

  2. Phagocytosis of haemozoin (malarial pigment enhances metalloproteinase-9 activity in human adherent monocytes: Role of IL-1beta and 15-HETE

    Directory of Open Access Journals (Sweden)

    Giribaldi Giuliana


    Full Text Available Abstract Background It has been shown previously that human monocytes fed with haemozoin (HZ or trophozoite-parasitized RBCs displayed increased matrix metalloproteinase-9 (MMP-9 enzyme activity and protein/mRNA expression and increased TNF production, and showed higher matrix invasion ability. The present study utilized the same experimental model to analyse the effect of phagocytosis of: HZ, delipidized HZ, beta-haematin (lipid-free synthetic HZ and trophozoites on production of IL-1beta and MMP-9 activity and expression. The second aim was to find out which component of HZ was responsible for the effects. Methods Native HZ freshly isolated from Plasmodium falciparum (Palo Alto strain, Mycoplasma-free, delipidized HZ, beta-haematin (lipid-free synthetic HZ, trophozoites and control meals such as opsonized non-parasitized RBCs and inert latex particles, were fed to human monocytes. The production of IL-1beta by differently fed monocytes, in presence or absence of specific MMP-9 inhibitor or anti-hIL-1beta antibodies, was quantified in supernatants by ELISA. Expression of IL-1beta was analysed by quantitative real-time RT-PCR. MMP-9 activity and protein expression were quantified by gelatin zymography and Western blotting. Results Monocytes fed with HZ or trophozoite-parasitized RBCs generated increased amounts of IL-1beta and enhanced enzyme activity (in cell supernatants and protein/mRNA expression (in cell lysates of monocyte MMP-9. The latter appears to be causally related to enhanced IL-1beta production, as enhancement of both expression and enzyme activity were abrogated by anti-hIL-1beta Abs. Upregulation of IL-1beta and MMP-9 were absent in monocytes fed with beta-haematin or delipidized HZ, indicating a role for HZ-attached or HZ-generated lipid components. 15-HETE (15(S,R-hydroxy-6,8,11,13-eicosatetraenoic acid a potent lipoperoxidation derivative generated by HZ from arachidonic acid via haem-catalysis was identified as one mediator

  3. Glycogen synthase kinase 3 (GSK3)-inhibitor SB216763 promotes the conversion of human umbilical cord mesenchymal stem cells into neural precursors in adherent culture. (United States)

    Gao, Liyang; Zhao, Mingyan; Li, Peng; Kong, Junchao; Liu, Zhijun; Chen, Yonghua; Huang, Rui; Chu, Jiaqi; Quan, Juanhua; Zeng, Rong


    The ability to generate neural progenitor cells from human umbilical cord mesenchymal stem cells (hUC-MSCs) has provided an option to treat neurodegenerative diseases. To establish a method for this purpose, we characterized the early neural markers of hUC-MSCs-derived cells under different conditions. We found that neither the elimination of signals for alternative fate nor N2 supplement was sufficient to differentiate hUC-MSCs into neural precursor cells, but the GSK3 inhibitor SB216763 could promote an efficient neural commitment of hUC-MSCs. The results indicated that Wnt/β-catenin might play an important role during the early neural differentiation of hUC-MSCs. Here, we report a method for hUC-MSCs to commit efficiently into a neural fate within a short period of time. This protocol provides an efficient method for hUC-MSCs-based neural regeneration.

  4. The development of the ProMAS: a Probabilistic Medication Adherence Scale

    Directory of Open Access Journals (Sweden)

    Kleppe M


    Full Text Available Mieke Kleppe,1,2 Joyca Lacroix,2 Jaap Ham,1 Cees Midden1 1Human Technology Interaction, Eindhoven University of Technology, Eindhoven, the Netherlands; 2Behavior, Cognition and Perception, Philips Research, Eindhoven, the Netherlands Abstract: Current self-report medication adherence measures often provide heavily skewed results with limited variance, suggesting that most participants are highly adherent. This contrasts with findings from objective adherence measures. We argue that one of the main limitations of these self-report measures is the limited range covered by the behaviors assessed. That is, the items do not match the adherence behaviors that people perform, resulting in a ceiling effect. In this paper, we present a new self-reported medication adherence scale based on the Rasch model approach (the ProMAS, which covers a wide range of adherence behaviors. The ProMAS was tested with 370 elderly receiving medication for chronic conditions. The results indicated that the ProMAS provided adherence scores with sufficient fit to the Rasch model. Furthermore, the ProMAS covered a wider range of adherence behaviors compared to the widely used Medication Adherence Report Scale (MARS instrument, resulting in more variance and less skewness in adherence scores. We conclude that the ProMAS is more capable of discriminating between people with different adherence rates than the MARS. Keywords: questionnaire design, probabilistic models, methodology

  5. Adherence to Treatment of Phenylketonuria

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    Tatiane Alves Vieira


    Full Text Available Introduction: Phenylketonuria (PKU is caused by the deficient activity of phenylalanine hydroxylase. Aim: To identify the factors associated with treatment adherence among patients with PKU seen at a southern Brazil reference center. Methodology: A cross-sectional, outpatient-based study including 56 patients with PKU (median age, 12 years for whom a Phe-restrict diet plus specific metabolic formula have been prescribed. Patients were considered adherent or nonadherent depending on the median phenylalanine concentration for the 12 months prior to study and target levels of phenylalanine for each age range (<13 years = ≤360 µmol/L; ≥13 years = ≤900 µmol/L. Data were collected through a review of patient’s medical records and a set of interviews with patients and their relatives. Results: Eighteen patients (32.1%; ≥13 years, 11 were classified as treatment adherent. Among all factors analyzed, only mental retardation, living with parents, and level of maternal education were associated with adherence to treatment. Conclusion: Our findings reinforce the importance of the family as promoting factor for treatment adherence.

  6. Myocellular enzyme leakage, polymorphonuclear neutrophil activation and delayed onset muscle soreness induced by isokinetic eccentric exercise. (United States)

    Croisier, J L; Camus, G; Deby-Dupont, G; Bertrand, F; Lhermerout, C; Crielaard, J M; Juchmès-Ferir, A; Deby, C; Albert, A; Lamy, M


    To address the question of whether delayed onset muscular soreness (DOMS) following intense eccentric muscle contraction could be due to increased production of the arachidonic acid derived product prostaglandin E2 (PGE2). 10 healthy male subjects were submitted to eccentric and concentric isokinetic exercises on a Kin Trex device at 60 degrees/s angular velocity. Exercise consisted of 8 stages of 5 maximal contractions of the knee extensor and flexor muscle groups of both legs separated by 1 min rest phases. There was an interval of at least 30 days between eccentric and concentric testing, and the order of the two exercise sessions was randomly assigned. The subjective presence and intensity of DOMS was evaluated using a visual analogue scale, immediately, following 24 h and 48 h after each test. Five blood samples were drawn from an antecubital vein: at rest before exercise, immediately after, after 30 min recovery, 24 h and 48 h after the tests. The magnitude of the acute inflammatory response to exercise was assessed by measuring plasma levels of polymorphonuclear elastase ([EL]), myeloperoxidase ([MPO]) and PGE2 ([PGE2]). Using two way analysis of variance, it appeared that only eccentric exercise significantly increased [EL] and DOMS, especially of the hamstring muscles. Furthermore, a significant decrease in eccentric peak torque of this muscle group only was observed on day 2 after eccentric work (- 21%; P < 0.002). Serum activity of creatine kinase and serum concentration of myoglobin increased significantly 24 and 48 h after both exercise tests. However, these variables reached significantly higher values following eccentric contractions 48 h after exercise. Mean [PGE2] in the two exercise modes remained unchanged over time and were practically equal at each time point. On the basis of these findings, we conclude that the magnitude of polymorphonuclear (PMN) activation, muscle damage, and DOMS are greater after eccentric than after concentric muscle

  7. Increased secretion of pro-inflammatory cytokines by circulating polymorphonuclear neutrophils and regulation by interleukin 10 during intestinal inflammation


    Nikolaus, S; Bauditz, J; Gionchetti, P; Witt, C; Lochs, H; Schreiber, S.


    Background—Concentrations of pro-inflammatory cytokines are increased in the intestinal mucosa of patients with active inflammatory bowel disease (IBD). Polymorphonuclear neutrophil granulocytes (PMN) are the most abundant cell type in intestinal lesions in IBD. Interleukin 10 (IL-10) is an important contra-inflammatory cytokine which induces downregulation of pro-inflammatory cytokines. 
Aims—To investigate whether PMN from patients with IBD or infectious colitis, respec...

  8. Opsonisation and phagocytosis of group B meningococci by polymorphonuclear leucocytes: comparison of sulphonamide sensitive and resistant strains.


    Ward, K N; Fleer, A; Verhoef, J; Jones, D M


    A large proportion of disease caused by sulphonamide resistant strains of group B type 15 meningococci affects patients 10-24 years. In contrast, disease caused by sulphonamide sensitive strains conforms to the usual pattern, and most infection occurs in early childhood. In an attempt to explain this phenomenon possible differences in susceptibility of resistant and sensitive strains to phagocytosis by polymorphonuclear leucocytes were investigated, using radioactively labelled bacteria. In i...

  9. Polymorphonuclear leukocytes restrict growth of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients

    DEFF Research Database (Denmark)

    Kragh, Kasper Nørskov; Alhede, Morten; Jensen, Peter Ø.;


    in a mouse model. The growth rate of P. aeruginosa within CF lungs did not correlate with the dimensions of bacterial aggregates but showed an inverse correlation to the concentration of polymorphonuclear leukocytes (PMNs) surrounding the bacteria. A growth-limiting effect on P. aeruginosa by PMNs was also...... PMNs slow the growth of the bacteria and render them less susceptible to antibiotic treatment while enabling them to persist by anaerobic respiration....

  10. First step in using molecular data for microbial food safety risk assessment; hazard identification of Escherichia coli O157:H7 by coupling genomic data with in vitro adherence to human epithelial cells. (United States)

    Pielaat, Annemarie; Boer, Martin P; Wijnands, Lucas M; van Hoek, Angela H A M; Bouw, El; Barker, Gary C; Teunis, Peter F M; Aarts, Henk J M; Franz, Eelco


    The potential for using whole genome sequencing (WGS) data in microbiological risk assessment (MRA) has been discussed on several occasions since the beginning of this century. Still, the proposed heuristic approaches have never been applied in a practical framework. This is due to the non-trivial problem of mapping microbial information consisting of thousands of loci onto a probabilistic scale for risks. The paradigm change for MRA involves translation of multidimensional microbial genotypic information to much reduced (integrated) phenotypic information and onwards to a single measure of human risk (i.e. probability of illness). In this paper a first approach in methodology development is described for the application of WGS data in MRA; this is supported by a practical example. That is, combining genetic data (single nucleotide polymorphisms; SNPs) for Shiga toxin-producing Escherichia coli (STEC) O157 with phenotypic data (in vitro adherence to epithelial cells as a proxy for virulence) leads to hazard identification in a Genome Wide Association Study (GWAS). This application revealed practical implications when using SNP data for MRA. These can be summarized by considering the following main issues: optimum sample size for valid inference on population level, correction for population structure, quantification and calibration of results, reproducibility of the analysis, links with epidemiological data, anchoring and integration of results into a systems biology approach for the translation of molecular studies to human health risk. Future developments in genetic data analysis for MRA should aim at resolving the mapping problem of processing genetic sequences to come to a quantitative description of risk. The development of a clustering scheme focusing on biologically relevant information of the microbe involved would be a useful approach in molecular data reduction for risk assessment.

  11. Piracy of decay-accelerating factor (CD55) signal transduction by the diffusely adhering strain Escherichia coli C1845 promotes cytoskeletal F-actin rearrangements in cultured human intestinal INT407 cells. (United States)

    Peiffer, I; Servin, A L; Bernet-Camard, M F


    Diffusely adhering Escherichia coli (DAEC) C1845 (clinical isolate) harboring the fimbrial adhesin F1845 can infect cultured human differentiated intestinal epithelial cells; this process is followed by the disassembly of the actin network in the apical domain. The aim of this study was to examine the mechanism by which DAEC C1845 promotes F-actin rearrangements. For this purpose, we used a human embryonic intestinal cell line (INT407) expressing the membrane-associated glycosylphosphatidylinositol (GPI) protein-anchored decay-accelerating factor (DAF), the receptor of the F1845 adhesin. We show here that infection of INT407 cells by DAEC C1845 can provoke dramatic F-actin rearrangements without cell entry. Clustering of phosphotyrosines was observed, revealing that the DAEC C1845-DAF interaction involves the recruitment of signal transduction molecules. A pharmacological approach with a subset of inhibitors of signal transduction molecules was used to identify the cascade of signal transduction molecules that are coupled to the DAF, that are activated upon infection, and that promote the F-actin rearrangements. DAEC C1845-induced F-actin rearrangements can be blocked dose dependently by protein tyrosine kinase, phospholipase Cgamma, phosphatidylinositol 3-kinase, protein kinase C, and Ca2+ inhibitors. F-actin rearrangements and blocking by inhibitors were observed after infection of the cells with two E. coli recombinants carrying the plasmids containing the fimbrial adhesin F1845 or the fimbrial hemagglutinin Dr, belonging to the same family of adhesins. These findings show that the DAEC Dr family of pathogens promotes alterations in the intestinal cell cytoskeleton by piracy of the DAF-GPI signal cascade without bacterial cell entry.

  12. Study of Adherent Oxide Scales (United States)


    The bond between alumina and NiCrAl substrate is intrinsically strong. The segregation of sulfur to the interface reduces bond strength, sulfur is...which laser-processing and minor element additions improve oxide scale adherence of a NiCrAl turbine coating composition. However, it was shown at the...adherence. However, significant observations were made with respect to the morphology of the oxide scale that forms on NiCrAl and NiCrAlY and these are

  13. Adherence with Preventive Medication in Childhood Asthma

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    Scott Burgess


    Full Text Available Suboptimal adherence with preventive medication is common and often unrecognised as a cause of poor asthma control. A number of risk factors for nonadherence have emerged from well-conducted studies. Unfortunately, patient report a physician's estimation of adherence and knowledge of these risk factors may not assist in determining whether non-adherence is a significant factor. Electronic monitoring devices are likely to be more frequently used to remind patients to take medication, as a strategy to motivate patients to maintain adherence, and a tool to evaluate adherence in subjects with poor disease control. The aim of this paper is to review non-adherence with preventive medication in childhood asthma, its impact on asthma control, methods of evaluating non-adherence, risk factors for suboptimal adherence, and strategies to enhance adherence.

  14. Impaired bactericidal but not fungicidal activity of polymorphonuclear neutrophils in patients with chronic lymphocytic leukemia. (United States)

    Kontoyiannis, Dimitrios P; Georgiadou, Sarah P; Wierda, William G; Wright, Susan; Albert, Nathaniel D; Ferrajoli, Alessandra; Keating, Michael; Lewis, Russell E


    We examined the qualitative polymorphonuclear neutrophil (PMN)-associated immune impairment in patients with chronic lymphocytic leukemia (CLL) by characterizing phagocytic killing of key non-opsonized bacterial (Staphylococcus aureus and Pseudomonas aeruginosa) and fungal (Candida albicans and Aspergillus fumigatus) pathogens. Neutrophils were collected from 47 non-neutropenic patients with CLL (PMN count > 1000/mm(3)) and age-matched and young healthy controls (five each). A subset of patients (13%) had prior or subsequent infections. We found that the patients with CLL had diminished PMN microbicidal response against bacteria but not against fungi compared with the controls. Compared to patients with effective PMN responses, we did not identify differences of basal PMN pathogen-associated molecular pattern receptor gene expression, soluble pathogen-associated molecular pattern gene expression or inflammatory cytokine signatures in patients with impaired PMN responses when PMNs were analyzed in multiplex real-time polymerase chain reaction assays. However, differences in PMN microbicidal response against A. fumigatus in patients with CLL were associated with the degree of hypogammaglobulinemia.

  15. Differential effects of acute morphine administrations on polymorphonuclear cell metabolism in various mouse strains. (United States)

    Di Francesco, P; Tavazzi, B; Gaziano, R; Lazzarino, G; Casalinuovo, I A; Di Pierro, D; Garaci, E


    This paper shows that an acute morphine treatment dose-dependently alters the energetic and oxidative metabolism of polymorphonuclear leukocytes obtained from BALB/c and DBA/2 mice, while phagocytic cells from C57BL/6 were not affected. In sensitive mouse strains, i.e. BALB/c and DBA/2, morphine decreased both ATP concentration and energy charge potential. At the same time, ATP catabolic products, i.e. nucleosides (inosine+adenosine) and oxypurines (hypoxanthine+xanthine+uric acid), significantly increased, indicating an imbalance between energy production and consumption. Morphine treatment also induced malondialdehyde and superoxide anions production in leukocyte cells from sensitive mice. The opiate antagonist naloxone blocked morphine-induced modifications by the lower morphine dose. The same parameters in cells from C57BL/6 mice were not affected. These findings confirm that: i) the phagocytic cells are an important target for the in vivo effects of morphine, and ii) the genotype-dependent variation influences the immunological responsiveness to opiates.

  16. Macrophage inflammatory protein-2 is a mediator of polymorphonuclear neutrophil influx in ocular bacterial infection. (United States)

    Kernacki, K A; Barrett, R P; Hobden, J A; Hazlett, L D


    Polymorphonuclear neutrophils (PMN) in Pseudomonas aeruginosa-infected cornea are required to clear bacteria from affected tissue, yet their persistence may contribute to irreversible tissue destruction. This study examined the role of C-X-C chemokines in PMN infiltration into P. aeruginosa-infected cornea and the contribution of these mediators to disease pathology. After P. aeruginosa challenge, corneal PMN number and macrophage inflammatory protein-2 (MIP-2) and KC levels were compared in mice that are susceptible (cornea perforates) or resistant (cornea heals) to P. aeruginosa infection. While corneal PMN myeloperoxidase activity (indicator of PMN number) was similar in both groups of mice at 1 and 3 days postinfection, by 5-7 days postinfection corneas of susceptible mice contained a significantly greater number of inflammatory cells. Corneal MIP-2, but not KC, levels correlated with persistence of PMN in the cornea of susceptible mice. To test the biological relevance of these data, resistant mice were treated systemically with rMIP-2. This treatment resulted in increased corneal PMN number and significantly exacerbated corneal disease. Conversely, administration of neutralizing MIP-2 pAb to susceptible mice reduced both PMN infiltration and corneal destruction. Collectively, these findings support an important role for MIP-2 in recruitment of PMN to P. aeruginosa-infected cornea. These data also strongly suggest that a timely down-regulation of the host inflammatory response is critical for resolution of infection.

  17. Polymorphonuclear neutrophil granulocyte chemotactic hyperresponsiveness in a case of canine acromegaly. (United States)

    Jensen, A L; Thomsen, M K; Aaes, H; Andreasen, M; Søndergaard, J


    Growth hormone (GH) has recently been shown to affect polymorphonuclear neutrophil granulocyte (PMN) function and to be secreted by mononuclear cells, indicating that the hormone may be active in an immunophysiologic network, acting as an endo- or paracrine priming agent. The purpose of the present study was to evaluate the chemotactic responsiveness of canine peripheral PMN in a dog with acromegaly, caused by spontaneous, progesterone-induced hypersecretion of GH and, secondary to this, a seven-fold increase in insulin-like growth factor I (IGF-I). The chemotactic responsiveness towards zymosan-activated serum (ZAS) and leukotriene B4 (LTB4) was evaluated at a time when the dog suffered from acromegaly and again 57 days after corrective surgery (ovariohysterectomy). The experiments showed that PMN from the patient exhibited enhanced chemotactic migration that appeared to be associated with the hypersomatotropic condition as judged from the reversibility of the phenomenon. The glucose intolerance and elevated serum alkaline phosphatase that were observed in the acromegalic dog were also shown to be reversible following surgery.

  18. CCL2 Promotes Colorectal Carcinogenesis by Enhancing Polymorphonuclear Myeloid-Derived Suppressor Cell Population and Function

    Directory of Open Access Journals (Sweden)

    Eunyoung Chun


    Full Text Available Our study reveals a non-canonical role for CCL2 in modulating non-macrophage, myeloid-derived suppressor cells (MDSCs and shaping a tumor-permissive microenvironment during colon cancer development. We found that intratumoral CCL2 levels increased in patients with colitis-associated colorectal cancer (CRC, adenocarcinomas, and adenomas. Deletion of CCL2 blocked progression from dysplasia to adenocarcinoma and reduced the number of colonic MDSCs in a spontaneous mouse model of colitis-associated CRC. In a transplantable mouse model of adenocarcinoma and an APC-driven adenoma model, CCL2 fostered MDSC accumulation in evolving colonic tumors and enhanced polymorphonuclear (PMN-MDSC immunosuppressive features. Mechanistically, CCL2 regulated T cell suppression of PMN-MDSCs in a STAT3-mediated manner. Furthermore, CCL2 neutralization decreased tumor numbers and MDSC accumulation and function. Collectively, our experiments support that perturbing CCL2 and targeting MDSCs may afford therapeutic opportunities for colon cancer interception and prevention.

  19. Do indium 111-labeled polymorphonuclear leukocytes detect neutrophil-prominent, fibrosing lung disease in rats

    Energy Technology Data Exchange (ETDEWEB)

    Williams, J.H. Jr.; Hartman, T.M.; Lichter, J.; Moser, K.M.


    The role of polymorphonuclear leukocytes (PMNs) in fibrotic lung disease remains poorly defined, but PMN prominence may predict a poor response to therapy in some patients. The bleomycin injury to rats represents a model of PMN-prominent alveolitis leading to fibrosis. We examined a method of identifying the alveolitis during its PMN-prominent phase with indium 111-labeled homologous PMNs (In-PMNs). When pairs of injured and uninjured rats were compared, greater activity was consistently found persisting in the lung images of the injured rats, both several hours (early) and a day (late) after injection of In-PMNs. Differences could likewise be identified when lung activity was normalized to activity of the injectate, the spleen, and variably the liver, as determined from organ images. These differences in gamma camera images were supported by direct measurement of activity in organs obtained by killing the animals after scanning. When groups of animals were compared, lung/spleen ratios appeared to most consistently differentiate the group of normal animals from those with alveolitis. These methods may provide a noninvasive means of identifying PMN prominence in the lung, which occurs in some fibrotic processes.

  20. Different Modulating Effects of Adenosine on Neonatal and Adult Polymorphonuclear Leukocytes

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    Pei-Chen Hou


    Full Text Available Polymorphonuclear leukocytes (PMNs are the major leukocytes in the circulation and play an important role in host defense. Intact PMN functions include adhesion, migration, phagocytosis, and reactive oxygen species (ROS release. It has been known for a long time that adenosine can function as a modulator of adult PMN functions. Neonatal plasma has a higher adenosine level than that of adults; however, little is known about the modulating effects of adenosine on neonatal PMNs. The aim of this study was to investigate the effects of adenosine on neonatal PMN functions. We found that neonatal PMNs had impaired adhesion, chemotaxis, and ROS production abilities, but not phagocytosis compared to adult PMNs. As with adult PMNs, adenosine could suppress the CD11b expressions of neonatal PMNs, but had no significant suppressive effect on phagocytosis. In contrast to adult PMNs, adenosine did not significantly suppress chemotaxis and ROS production of neonatal PMNs. This may be due to impaired phagocyte reactions and a poor neonatal PMN response to adenosine. Adenosine may not be a good strategy for the treatment of neonatal sepsis because of impaired phagocyte reactions and poor response.

  1. Polymorphonuclear cells stimulate the migration and metastatic potential of rat sarcoma cells. (United States)

    Remedi, María Mónica; Donadio, Ana Carolina; Chiabrando, Gustavo Alberto


    The tumour microenvironment, which is largely composed of inflammatory cells, is a crucial participant in the neoplastic process through the promotion of cell proliferation, survival and migration. Neutrophil polymorphonuclear cells (PMNs) induce inflammatory reactions that can be either cytotoxic for tumour cells or can promote tumour growth and metastasis. Previously, we have reported a spontaneous metastasis tumour model that has tumour PMNs infiltration, and metastasis, to liver and spleen. The aim of this study was to evaluate the PMNs influences on the tumour cell invasion and metastatic properties. We analysed intercellular adhesion molecule-1 (ICAM-1), urokinase-type plasminogen activator receptor (uPAR), MT1-MMP (membrane type 1-matrix metalloproteinase) and MMP2 protein expression in TuE-t cells cultured with PMNs or PMNs-conditioned medium isolated from tumour bearing and normal rats. The interaction between tumour cells and PMNs induced a decrease in ICAM-1 expression in tumour cells as well as an increase in MMP2 and tumour cell motility. Besides, conserved expression of uPAR and MT1-MMP in tumour cells was also demonstrated. The up-regulation in MMP2 associated with uPAR and MT1-MMP conserved expression may be related to an increased extracellular matrix proteolysis. These results showed that the interaction of tumour cells with PMNs could favour tumour cell spreading through the promotion of a tumour invasive phenotype.

  2. Differential inhibition of polymorphonuclear leukocyte recruitment in vivo by dextran sulphate and fucoidan

    Directory of Open Access Journals (Sweden)

    N. Van Osselaer


    Full Text Available The selectin-mediated rolling of leukocytes along the endothelial cells is a prerequisite step followed by firm adhesion and extravasation into the inflamed tissue. This initial contact can be suppressed by sulphated polysaccharides. We have studied the effect of sulphated polysaccharides on the ultimate polymorphonuclear leukocyte (PMN recruitment and plasma leakage in rabbit skin in response to intradermal injection of various inflammatory mediators. PMN infiltration evoked by various PMN chemoattractants (FMLP, C5a desArg, LTB4 and IL-8 was significantly inhibited after intravenous injection of dextran sulphate (25 mg/kg, heparin (2 × 90 mg/kg or fucoidan (1 mg/kg. PMN-dependent plasma leakage was equally well reduced by the different sulphated polymers. Vascular permeability induced by histamine or thrombin acting via a PMN-independent mechanism was not reduced. Fucoidan was the only polysaccharide able to suppress IL-1-induced PMN infiltration for 60–70%. Local administration of dextran sulphate had no effect on PMN-dependent plasma leakage. Differential inhibition of PMN recruitment was determined after injection of dextran sulphate or fucoidan depending on the type of insult. Therefore, these results suggest that different adhesion pathways are utilized during PMN recruitment in vivo in response to chemoattractants and IL-1.

  3. An antagonist of the platelet-activating factor receptor inhibits adherence of both nontypeable Haemophilus influenzae and Streptococcus pneumoniae to cultured human bronchial epithelial cells exposed to cigarette smoke

    Directory of Open Access Journals (Sweden)

    Shukla SD


    Full Text Available Shakti D Shukla,1,* Rory L Fairbairn,1,* David A Gell,1 Roger D Latham,1 Sukhwinder S Sohal,1,2 Eugene H Walters,1 Ronan F O’Toole11Breathe Well Centre, School of Medicine, Faculty of Health, University of Tasmania, Hobart, TAS, Australia; 2School of Health Sciences, Faculty of Health, University of Tasmania, Launceston, TAS, Australia*These authors contributed equally to this workBackground: COPD is emerging as the third largest cause of human mortality worldwide after heart disease and stroke. Tobacco smoking, the primary risk factor for the development of COPD, induces increased expression of platelet-activating factor receptor (PAFr in the lung epithelium. Nontypeable Haemophilus influenzae (NTHi and Streptococcus pneumoniae adhere to PAFr on the luminal surface of human respiratory tract epithelial cells.Objective: To investigate PAFr as a potential drug target for the prevention of infections caused by the main bacterial drivers of acute exacerbations in COPD patients, NTHi and S. pneumoniae.Methods: Human bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract (CSE. PAFr expression levels were determined using immunocytochemistry and quantitative polymerase chain reaction. The epithelial cells were challenged with either NTHi or S. pneumoniae labeled with fluorescein isothiocyanate, and bacterial adhesion was measured using immunofluorescence. The effect of a well-evaluated antagonist of PAFr, WEB-2086, on binding of the bacterial pathogens to BEAS-2B cells was then assessed. In silico studies of the tertiary structure of PAFr and the binding pocket for PAF and its antagonist WEB-2086 were undertaken.Results: PAFr expression by bronchial epithelial cells was upregulated by CSE, and significantly associated with increased bacterial adhesion. WEB-2086 reduced the epithelial adhesion by both NTHi and S. pneumoniae to levels observed for non-CSE-exposed cells. Furthermore, it was nontoxic toward the bronchial epithelial

  4. On World Religion Adherence Distribution Evolution (United States)

    Ausloos, Marcel; Petroni, Filippo

    Religious adherence can be considered as a degree of freedom, in a statistical physics sense, for a human agent belonging to a population. The distribution, performance and life time of religions can thus be studied having in mind heterogeneous interacting agent modeling. We present a comprehensive analysis of 58 so-called religions (to be better defined in the main text) as measured through their number of adherents evolutions, between 1900 and 2000, - data taken from the World Christian Trends (Barrett and Johnson, "World Christian Trends AD 30 - AD 2200: Interpreting the Annual Christian Megacensus", William Carey Library, 2001): 40 are considered to be "presently growing" cases, including 11 turn overs in the twentieth century; 18 are "presently decaying", among which 12 are found to have had a recent maximum, in the nineteenth or the twentieth century. The Avrami-Kolmogorov differential equation which usually describes solid state transformations, like crystal growth, is used in each case in order to obtain the preferential attachment parameter introduced previously (Europhys Lett 77:38002, 2007). It is not often found close to unity, though often corresponding to a smooth evolution. However large values suggest the occurrence of extreme cases which we conjecture are controlled by so-called external fields. A few cases indicate the likeliness of a detachment process. We discuss a few growing and decaying religions, and illustrate various fits. Some cases seem to indicate the lack of reliability of the data, but others some marked departure from Avrami law. Whence the Avrami evolution equation might be surely improved, in particular, and somewhat obviously, for the decaying religion cases. We point out two major difficulties in such an analysis: (1) the "precise" original time of apparition of a religion, (2) the time at which there is a maximum number of adherents, both information being necessary for integrating reliably any evolution equation.

  5. Tuberculin skin test and interferon-gamma release assay values are associated with antimicrobial peptides expression in  polymorphonuclear cells during latent tuberculous infection

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    Julio E Castañeda-Delgado


    Full Text Available It has been reported that patients with progressive tuberculosis (TB express abundant amounts of the antimicrobial peptides (AMPs cathelicidin (LL-37 and human neutrophil peptide-1 (HNP-1 in circulating cells, whereas latent TB infected donors showed no differences when compared with purified protein derivative (PPD and QuantiFERON®-TB Gold (QFT-healthy individuals. The aim of this study was to determine whether LL-37 and HNP-1 production correlates with higher tuberculin skin test (TST and QFT values in TB household contacts. Twenty-six TB household contact individuals between 26-58 years old TST and QFT positive with at last two years of latent TB infection were recruited. AMPs production by polymorphonuclear cells was determined by flow cytometry and correlation between TST and QFT values was analysed. Our results showed that there is a positive correlation between levels of HNP-1 and LL-37 production with reactivity to TST and/or QFT levels. This preliminary study suggests the potential use of the expression levels of these peptides as biomarkers for progression in latent infected individuals.

  6. Impact of an exercise program on adherence and fitness indicators. (United States)

    Carpenter, Roger; Gilleland, Diana


    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 body fat. Twenty-four subjects continued into Phase II, with only eight completing Phase II. Of those eight, only one subject visited the HPL at least 8 times/month. Health history data including co-morbidities, symptoms, habits, perceived tension, job stress, and fitness level were not associated with adherence. Symptoms of swollen, stiff, painful joints, and swollen ankles and legs were associated with decreased adherence to exercise. Supervised exercise was positively related to adherence and improved fitness indicators. Adults with joint symptoms may require more support. Based on these pilot data, designing a study with a larger sample and the inclusion of barriers and facilitators for adherence to self-directed exercise would allow additional analysis. Innovative interventions are needed that mimic the supervised environment, shifting responsibility for the exercise plan from the supervisor to those exercising.

  7. Adherence to the Treatment in Psychiatric Patients

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    Mehmet Emin Demirkol


    Conclusion: Although medical treatments and drug industry develop day by day, there have been no changes in the treatment adherence ratios in the past years. To generate possible solutions, treatment adherence should be assessed in all clinical interviews and if patient is non-adherent this issue should be handled seriously. [Cukurova Med J 2015; 40(3.000: 555-568

  8. Blood Level of Polymorphonuclear Neutrophil Leukocytes and Bronchial Hyperreactivity in Chronic Obstructive Pulmonary Disease (United States)

    Cukic, Vesna


    Introduction: Polymorphonuclear neutrophil leukocytes (PMNL) have an important defensive role against various microorganisms and other agents, but by liberating various substances, first of all the superoxide anion (O 2¯), they can damage the bronchial mucosa and influence the development of bronchial inflammation which is the fundamental of bronchial hyperreactivity (BHR). Objective: to show the role of the PMNL for development and level of BHR in patients with chronic obstructive pulmonary disease (COPD). Material and methods: We observed 160 patients with COPD treated in Clinic for Pulmonary Diseases and TB “Podhrastovi” Sarajevo during three years :from 2012 to 2014. They were divided into groups and subgroups according to the first registration of BHR in the course of illness and to the number of exacerbations of the disease in one year. The number of blood PMNL was measured in a stable state of disease at the begging and at the end of investigation. Results: The number of blood PMNL was significantly greater in patients with 3 or more exacerbations per one year (p <0.01). Patients with BHR had significantly greater number blood PMNL than patients without BHR (p< 0.05). Patients with 3 exacerbations per year had a statistically significant increase of number of PMNL between first and last examination (p<0.01). Conclusion: There is statistically significant correlation between the number of blood PMNL and the level of BHR in COPD, but future examination need to be done to determine real role and mode of action of PMNL for these processes. PMID:26543311

  9. Adherence and health care costs

    Directory of Open Access Journals (Sweden)

    Iuga AO


    Full Text Available Aurel O Iuga,1,2 Maura J McGuire3,4 1Johns Hopkins Bloomberg School of Public Health, 2Johns Hopkins University, 3Johns Hopkins Community Physicians, 4Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: Medication nonadherence is an important public health consideration, affecting health outcomes and overall health care costs. This review considers the most recent developments in adherence research with a focus on the impact of medication adherence on health care costs in the US health system. We describe the magnitude of the nonadherence problem and related costs, with an extensive discussion of the mechanisms underlying the impact of nonadherence on costs. Specifically, we summarize the impact of nonadherence on health care costs in several chronic diseases, such as diabetes and asthma. A brief analysis of existing research study designs, along with suggestions for future research focus, is provided. Finally, given the ongoing changes in the US health care system, we also address some of the most relevant and current trends in health care, including pharmacist-led medication therapy management and electronic (e-prescribing. Keywords: patient, medication, adherence, compliance, nonadherence, noncompliance, cost

  10. Cryopreservation of adherent neuronal networks. (United States)

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


    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.

  11. Physiology of polymorphonuclear neutrophils Fisiología de los polimorfonucleares neutrófilos


    Diana García de Olarte; Pablo Javier Patiño Grajales


    Phagocytic cells. particularly neutrophils. are a fundamental part of the host response against aggression by infectious as well as non-infectious agents. and they are Involved In the generation of tissue damage during Inflammatory response. Cell responses of neutrophils depend on a series of closely related events like adherence to and diapedesis through endothelial cells. migration toward the sites of inflamma...

  12. Anti-Pseudomonas aeruginosa IgY antibodies promote bacterial opsonization and augment the phagocytic activity of polymorphonuclear neutrophils

    DEFF Research Database (Denmark)

    Thomsen, Kim; Christophersen, Lars; Jensen, Peter Østrup


    Moderation of polymorphonuclear neutrophils (PMNs) as part of a critical defense against invading pathogens may offer a promising therapeutic approach to supplement the antibiotic eradication of Pseudomonas aeruginosa infection in non-chronically infected cystic fibrosis (CF) patients. We have...... observed that egg yolk antibodies (IgY) harvested from White leghorn chickens that target P. aeruginosa opsonize the pathogen and enhance the PMN-mediated respiratory burst and subsequent bacterial killing in vitro. The effects on PMN phagocytic activity were observed in different Pseudomonas aeruginosa...

  13. Nano-layered magnesium fluoride reservoirs on biomaterial surfaces strengthen polymorphonuclear leukocyte resistance to bacterial pathogens. (United States)

    Guo, Geyong; Zhou, Huaijuan; Wang, Qiaojie; Wang, Jiaxing; Tan, Jiaqi; Li, Jinhua; Jin, Ping; Shen, Hao


    Biomaterial-related bacterial infections cause patient suffering, mortality and extended periods of hospitalization, imposing a substantial burden on medical systems. In this context, understanding of nanomaterials-bacteria-cells interactions is of both fundamental and clinical significance. Herein, nano-MgF2 films were deposited on titanium substrate via magnetron sputtering. Using this platform, the antibacterial behavior and mechanism of the nano-MgF2 films were investigated in vitro and in vivo. It was found that, for S. aureus (CA-MRSA, USA300) and S. epidermidis (RP62A), the nano-MgF2 films possessed excellent anti-biofilm activity, but poor anti-planktonic bacteria activity in vitro. Nevertheless, both the traditional SD rat osteomyelitis model and the novel stably luminescent mouse infection model demonstrated that nano-MgF2 films exerted superior anti-infection effect in vivo, which cannot be completely explained by the antibacterial activity of the nanomaterial itself. Further, using polymorphonuclear leukocytes (PMNs), the critical immune cells of innate immunity, a complementary investigation of MgF2-bacteria-PMNs co-culturing revealed that the nano-MgF2 films improved the antibacterial effect of PMNs through enhancing their phagocytosis and stability. To our knowledge, this is the first time of exploring the antimicrobial mechanism of nano-MgF2 from the perspective of innate immunity both in vitro and in vivo. Based on the research results, a plausible mechanism is put forward for the predominant antibacterial effect of nano-MgF2in vivo, which may originate from the indirect immune enhancement effect of nano-MgF2 films. In summary, this study of surface antibacterial design using MgF2 nanolayer is a meaningful attempt, which can promote the host innate immune response to bacterial pathogens. This may give us a new understanding towards the antibacterial behavior and mechanism of nano-MgF2 films and pave the way towards their clinical applications.

  14. MicroRNA-941 Expression in Polymorphonuclear Granulocytes Is Not Related to Granulomatosis with Polyangiitis (United States)

    Svendsen, Jesper Brink; Baslund, Bo; Cramer, Elisabeth Præstekjær; Rapin, Nicolas; Borregaard, Niels


    Jumonji Domain-Containing Protein 3 (JMJD3)/lysine demethylase 6B (KDM6B) is an epigenetic modulator that removes repressive histone marks on genes. Expression of KDM6B mRNA is elevated in leukocytes from patients with ANCA-associated vasculitis (AAV) and has been suggested to be the reason for higher proteinase 3 (PR3) mRNA expression in these cells due to derepression of PRTN3 gene transcription. MicroRNA-941 (miR-941) has been shown to target KDM6B mRNA and inhibit JMJD3 production. We therefore investigated whether polymorphonuclear granulocytes (PMNs) from patients suffering from granulomatosis with polyangiitis (GPA) have lower expression of miR-941 than healthy control donors as a biological cause for higher JMJD3 levels. We found no significant difference in the degree of maturation of PMNs from GPA patients (n = 8) and healthy controls (n = 11) as determined from cell surface expression of the neutrophil maturation marker CD16 and gene expression profile of FCGR3B. The expression of PRTN3 and KDM6B mRNAs and miR-941 was not significantly different in GPA patients and healthy controls. Transfection of pre-miR-941 into the neutrophil promyelocyte cell line PLB-985 cells did not result in reduction of the KDM6B mRNA level as shown previously in a hepatocellular carcinoma cell line. The amount of PR3 in PMNs from GPA patients and healthy controls was comparable. In conclusion, we found that PRTN3 mRNA, KDM6B mRNA, and miR-941 expression levels in PMNs do not differ between GPA patients and healthy controls, and that miR-941 does not uniformly regulate KDM6B mRNA levels by inducing degradation of the transcript. Thus, decreased miR-941 expression in PMNs cannot be part of the pathogenesis of GPA. PMID:27755585

  15. Sulfur dioxide attenuates LPS-induced acute lung injury via enhancing polymorphonuclear neutrophil apoptosis

    Institute of Scientific and Technical Information of China (English)

    Hui-jie MA; Xin-li HUANG; Yan LIU; Ya-min FAN


    Aim:We speculated that the enhanced apoptosis of polymorphonuclear neutrophil (PMN) might be responsible for the inhibition of PMN infiltration in the lung.This study was designed to investigate the effects of sulfur dioxide (SO2) on PMN apoptosis in vivo and in vitro,which may mediate the protective action of SO2 on pulmonary diseases.Methods:Acute lung injury (ALI) was induced by intratracheally instillation of lipopolysaccharide (LPS,100 μg/100 200 μL saline) in adult male SD rats.SO2 solution (25 μmol/kg) was administered intraperitoneally 30 min before LPS treatment.The rats were killed 6 h after LPS treatment.Lung tissues were collected for histopathologic study and SO2 concentration assay.Bronchoalveolar lavage fluid (BALF) was collected for the measurement of PMN apoptosis.For in vitro experiments,rat peripheral blood PMNs were cultured and treated with LPS (30 mg/L) and S02 (10,20 and 30 μmol/L) for 6 h,and apoptosis-related protein expression was detected by Western blotting,and apoptosis rate was measured with flow cytometry.Results:LPS treatment significantly reduced the SO2 concentrations in the lung tissue and peripheral blood,as compared with the control group.Pretreatment with SO2 prevented LPS-induced reduction of the SO2 concentration in the lung tissue and peripheral blood.LPS treatment significantly reduced PMN apoptosis both in vivo and in vitro,which could be prevented by the pretreatment with SO2.The protein levels of caspase-3 and Bax was significantly increased,but Bcl-2 was decreased by the pretreatment with SO2,as compared with LPS administration alone.Conclusion:SO2 plays an important role as the modulator of PMN apoptosis during LPS-induced ALl,which might be one of the mechanisms underlying the protective action of SO2 on pulmonary diseases.

  16. In vitro adherence patterns of Shigella serogroups to bovine recto-anal junction squamous epithelial (RSE) cells are similar to those of Escherichia coli O157 (United States)

    The aim of this study was to determine whether Shigella species, which are human gastrointestinal pathogens, can adhere to cattle recto-anal junction squamous epithelial (RSE) cells using a recently standardized adherence assay, and to compare their adherence patterns to that of Escherichia coli O15...

  17. Human colostral cells. I. Separation and characterization. (United States)

    Crago, S S; Prince, S J; Pretlow, T G; McGhee, J R; Mestecky, J


    Analyses of the cells present in human colostrum obtained from fifty-four healthy donors during the first four days of lactation revealed that there were 3.3 x 10(6) (range 1.1 x 10(5)--1.2 x 10(7)) cells per ml of colostrum. Based on histochemical examinations, it was found that this population consisted of 30--47% macrophages, 40--60% polymorphonuclear leucocytes, 5.2--8.9% lymphocytes, and 1.3--2.8% colostral corpuscles; epithelial cells were rarely encountered. The identity of various cell types was confirmed by Wright's stain and by a series of histochemical techniques which disclosed the presence of non-specific esterase, peroxidase, and lipids. For further characterization, the different types of cells were separated by various methods, such as Ficoll-Hypaque density centrifugation, isokinetic centrifugation on a linear Ficoll gradient, adherence to glass or plastic, and phagocytosis of carbonyl iron. Immunohistochemical staining with FITC- and/or TRITC-labelled reagents to IgA, IgM, IgG, K- and lambda-chains, secretory component, lactoferrin, and alpha-lactalbumin were applied to unseparated as well as separated colostral cells. Polymorphonuclear leucocytes (staining for peroxidase) as well as macrophages and colostral corpuscles (staining for non-specific esterase) exhibited numerous intracellular vesicles that contained lipids as well as various combinations of milk proteins. Lymphoid cells did not stain with any of these reagents and plasma cells were not detected among the colostral cells. Individual phagocytic cells contained immunoglobulins of the IgA and IgM classes, both K and lambda light chains, secretory component, lactoferrin, and alpha-lactalbumin. The coincidental appearance of these proteins in single, phagocytic cells but not in lymphoid cells indicate that the cells acquired these proteins by ingestion from the environment. Markers commonly used for the identification of B lymphocytes (surface immunoglobulins) and T lymphocytes (receptors

  18. Factors influencing adherence to antiretroviral treatment in Nepal: a mixed-methods study.

    Directory of Open Access Journals (Sweden)

    Sharada P Wasti

    Full Text Available BACKGROUND: Antiretroviral therapy (ART is a lifesaver for individual patients treated for Human Immunodeficiency Virus (HIV and Acquired Immune Deficiency Syndrome (AIDS. Maintaining optimal adherence to antiretroviral drugs is essential for HIV infection management. This study aimed to understand the factors influencing adherence amongst ART-prescribed patients and care providers in Nepal. METHODS: A cross-sectional mixed-methods study surveying 330 ART-prescribed patients and 34 in-depth interviews with three different types of stakeholders: patients, care providers, and key people at policy level. Adherence was assessed through survey self-reporting and during the interviews. A multivariate logistic regression model was used to identify factors associated with adherence, supplemented with a thematic analysis of the interview transcripts. RESULTS: A total of 282 (85.5% respondents reported complete adherence, i.e. no missed doses in the four-weeks prior to interview. Major factors influencing adherence were: non-disclosure of HIV status (OR = 17.99, p = 0.014; alcohol use (OR = 12.89, p = 1 hour (OR = 2.84, p = 0.035. Similarly, lack of knowledge and negative perception towards ART medications also significantly affected non-adherence. Transport costs (for repeat prescription, followed by pills running out, not wanting others to notice, side-effects, and being busy were the most common reasons for non-adherence. The interviews also revealed religious or ritual obstacles, stigma and discrimination, ART-associated costs, transport problems, lack of support, and side-effects as contributing to non-adherence. CONCLUSION: Improving adherence requires a supportive environment; accessible treatment; clear instructions about regimens; and regimens tailored to individual patients' lifestyles. Healthcare workers should address some of the practical and cultural issues around ART medicine whilst policy-makers should develop

  19. Natural variability of in vitro adherence to fibrinogen and fibronectin does not correlate with in vivo infectivity of Staphylococcus aureus. (United States)

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


    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.

  20. Intent-to-adhere and adherence to malaria prevention recommendations in two travel clinics. (United States)

    Goldstein, Irit; Grefat, Rami; Ephros, Moshe; Rishpon, Shmuel


    Malaria infects 30,000 travelers annually worldwide. At greatest risk are those who travel for long duration. Prevention of malaria includes chemoprophylaxis. This prospective study on 121 travelers who visited two travel clinics shows that adherence to prophylactic treatment was low, especially in long duration trips, and that adherence rate could be predicted by the much more available intent-to-adhere rate.

  1. Leakage of protein into lungs of preterm ventilated rabbits is correlated with activation of clotting, complement, and polymorphonuclear leukocytes in plasma

    NARCIS (Netherlands)

    Brus, F; vanOeveren, W; Heikamp, A; Okken, A; Oetomo, SB


    We investigated whether leakage of protein in lungs of pre term ventilated rabbits of 28- and 29-d gestational age is correlated with activation of clotting, complement, and polymorphonuclear leukocytes (PMN) in plasma. We found signs of systemic activation of clotting, complement, and PMN in ventil

  2. Combination of autoantibodies against different histone proteins influences complement-dependent phagocytosis of necrotic cell material by polymorphonuclear leukocytes in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Gullstrand, Birgitta; Lefort, Malin H; Tydén, Helena


    Polymorphonuclear leukocytes (PMN) with autoantibody-coated engulfed necrotic cell material (NC) are frequently seen in systemic lupus erythematosus (SLE). We evaluated the roles of complement, different antihistone antibodies (anti-H ab), and oxidative burst in the phagocytosis of NC by PMN...

  3. Measurement of oxide adherence to PFM alloys. (United States)

    Mackert, J R; Parry, E E; Hashinger, D T; Fairhurst, C W


    A method has been reported for evaluating adherence of an oxide to its substrate metal to a maximum value of about 40 MPa. Oxidized alloy plates were cemented between two aluminum cylinders with a high-strength cyanoacrylate cement and loaded in tension until failure occurred either at the oxide/metal interface, within the oxide layer, or in the cement itself. Significant differences were found among the oxide adherence values obtained from different PFM alloys. The oxides formed on five of the alloys exhibited adherence strengths in excess of the published value for cohesive strength of dental opaque porcelain, indicating that they possess sufficient adherence to act as the transition zone between the porcelain and the alloy. In addition, a correspondence was found between the quality of porcelain bond for a given alloy and its oxide adherence strength. These results remove the principal objection to the oxide-layer theory of porcelain bonding in dental alloy systems and emphasize the importance of oxide adherence in the establishment of a bond. It is therefore suggested that future work devoted to porcelain-metal bonding should seek to elucidate the mechanism of oxide adherence to PFM alloys and explore the development of new alloys which form adherent oxides.

  4. Asthma and Adherence to Inhaled Corticosteroids

    DEFF Research Database (Denmark)

    Bårnes, Camilla Boslev; Ulrik, Charlotte Suppli


    Inhaled corticosteroids (ICS) are the cornerstone of maintenance asthma therapy. However, in spite of this, adherence to ICS remains low. The aim of this systematic literature review was to provide an overview of the current knowledge of adherence to ICS, effects of poor adherence, and means...... was found to be between 22 and 63%, with improvement up to and after an exacerbation. Poor adherence was associated with youth, being African-American, having mild asthma, ... prescribed fixed-combination therapy (ICS and long-acting β2 agonists). Good adherence was associated with higher FEV1, a lower percentage of eosinophils in sputum, reduction in hospitalizations, less use of oral corticosteroids, and lower mortality rate. Overall, 24% of exacerbations and 60% of asthma...

  5. Dietary Fiber Intake is Associated with Increased Colonic Mucosal GPR43+ Polymorphonuclear Infiltration in Active Crohn's Disease. (United States)

    Zhao, Mingli; Zhu, Weiming; Gong, Jianfeng; Zuo, Lugen; Zhao, Jie; Sun, Jing; Li, Ning; Li, Jieshou


    G protein-coupled receptor 43/free fatty acid receptor 2 (GPR43/FFAR2) is essential for polymorphonuclear (PMN) recruitment. We investigated the expression of GPR43/FFAR2 in the colon from Crohn's disease patients and whether dietary fiber in enteral nutrition increases GPR43+ polymorphonuclear infiltration in mucosa. Segments of ascending colon and white blood cells from peripheral blood were obtained from 46 Crohn's disease patients and 10 colon cancer patients. The Crohn's disease patients were grouped by the activity of disease (active or remission) and enteral nutrition with or without dietary fiber. Histological feature, expression and location of GPR43/FFAR2 and level of tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6) and myeloperoxidase were assessed. The results of hematoxylin-eosin and immunohistochemistry staining revealed that the infiltration of immune cells, including GPR43+ PMN, was more severe in active Crohn's disease patients who consumed normal food or enteral nutrition with dietary fiber than in remission patients and colon cancer patients. This finding was supported by the results of GPR43 and myeloperoxidase expression. Active Crohn's disease (CD) patients who consumed enteral nutrition without dietary fiber exhibited severe immune cell infiltration similar to the other active CD patients, but GPR43+ PMNs were rarely observed. The level of TNF-α mRNA in active Crohn's disease patients was higher than those of the other patients. In conclusion, the use of dietary fiber in enteral nutrition by active Crohn's disease patients might increase GPR43+ PMNs infiltration in colon mucosa. This effect was not observed in Crohn's disease patients in remission.

  6. Transient improvement of urticaria induces poor adherence as assessed by Morisky Medication Adherence Scale-8. (United States)

    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


    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.

  7. Comparison of invasiveness among surface-adherent variants of Listeria monocytogenes in Caco-2 cell culture assays. (United States)

    Kushwaha, Kalpana; Muriana, Peter M


    The persistence of Listeria monocytogenes in meat processing plants is believed to be partly linked with their adherence properties to abiotic surfaces that may allow contamination of ready-to-eat (RTE) foods. Isolates of raw meats, RTE meats and environmental samples from RTE meat processing facilities that demonstrated differences in adherence to abiotic surfaces (glass, plastic, stainless steel, and rubber) were tested for cellular adherence and invasion in the Caco-2 human cell line. Strains of L. monocytogenes were classified into strong (CW50, 99-38, CW77, SM5 and CW62) and weakly adherent (CW34, CW35, CW72, SM3, J7 and J126) based on a microplate adherence assay using the fluorescing substrate, 5,6-CFDA. These strains were tested for adherence and invasion in cell culture assays with Caco-2 cells. At long incubation time (2h) and high multiplicity of infection (MOI, 100:1) we observed equivalent cellular adherence and invasiveness. After optimizing conditions for time of infection (15-, 30-, 60-, 90-, and 120-min) and MOI (100:1, 10:1, 1:1, and 0.1:1), we found that under the conditions of 15-min infection time at an MOI of 10:1 (Listeria:Caco-2 cells), we again observed equivalent cellular adherence by the two distinct surface-adherent groups, but we only recovered invading Listeria from the group that was strongly adherent to environmental surfaces. The data indicate that a surface factor that provides for strong environmental surface adherence may also be involved with internal cellular virulence and survival and implicates strongly adherent strains as possibly being of greater invasiveness than weakly adherent strains.

  8. Improving adherence with inhaler therapy in COPD

    Directory of Open Access Journals (Sweden)

    Suzanne C Lareau


    Full Text Available Suzanne C Lareau1, Barbara P Yawn21College of Nursing, University of Colorado Denver, Aurora, Colorado; 2Department of Research, Olmsted Medical Center, Rochester, Minnesota, USAAbstract: Chronic obstructive pulmonary disease (COPD is a major public health problem, associated with considerable morbidity and health care costs. The global burden of COPD morbidity is predicted to rise substantially in the coming decade, but could be moderated by better use of existing management strategies. Smoking cessation, medication therapy, and pulmonary rehabilitation have all been shown to diminish morbidity and improve patient outcomes. But each of these strategies requires adherence. Adherence is crucial for optimizing clinical outcomes in COPD, with nonadherence resulting in a significant health and economic burden. Suboptimal medication adherence is common among COPD patients, due to a number of factors that involve the medication, the delivery device, the patient, and the health professionals caring for the patient. Lack of medication adherence needs to be identified and addressed by using simplified treatment regimens, increasing patient knowledge about self-management, and enhancing provider skills in patient education, communication, and adherence counseling. This article reports some of the challenges of medication nonadherence faced by the clinician in the management of COPD, and suggests ways to evaluate and improve adherence effectively in primary care.Keywords: chronic obstructive pulmonary disease, adherence, clinician

  9. Adherence to Antihypertensive Medications in Iranian Patients

    Directory of Open Access Journals (Sweden)

    Azin Behnood-Rod


    Full Text Available 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.

  10. Patient Adherence to Biologic Agents in Psoriasis

    DEFF Research Database (Denmark)

    Hsu, Der Yi; Gniadecki, Robert


    BACKGROUND: Low adherence to therapies in psoriasis decreases treatment outcomes and increases the total health care costs. In spite of the wide use of biologic agents, patients' adherence to these drugs has not been extensively investigated. OBJECTIVE: The aim of this study is to measure adherence...... adverse effects, and positive attitudes to the treatment. CONCLUSION: Adherence to biologic therapies is very high in patients with psoriasis, which is consistent with a positive attitude to the treatment....... to the biologic drugs in a population of patients treated for psoriasis vulgaris using the medication possession ratio (MPR) index and to survey patients' attitudes to the treatment. METHODS: This is a single-center study on 247 patients with psoriasis vulgaris treated with adalimumab (n = 113), etanercept (n...

  11. Adherence to anti-depressant medication

    DEFF Research Database (Denmark)

    Buus, Niels


    The study of medicine taking is controversial as it often reveals a discrepancy between healthcare professionals' advice and patients' actual behaviour. Qualitative researchers have examined depressed people's adherence to prescriptions of antidepressants by exploring the meaning they impute to t...

  12. Mobile Applications to Improve Medication Adherence. (United States)

    Haase, Jamie; Farris, Karen B; Dorsch, Michael P


    Background and Introduction: Mobile applications are useful tools to improve medication adherence. As developers continue to improve the features of existing mobile applications, pharmacists should be aware of the current features that are available to patients. There are limited studies available that discuss which applications have the most desirable features. The aim of this study was to compare available mobile applications and identify ideal application features used to improve medication adherence.

  13. Microbicide clinical trial adherence: insights for introduction

    Directory of Open Access Journals (Sweden)

    Cynthia Woodsong


    Full Text Available 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.

  14. Dirty Money: A Matter of Bacterial Survival, Adherence, and Toxicity. (United States)

    Vriesekoop, Frank; Chen, Jing; Oldaker, Jenna; Besnard, Flavien; Smith, Reece; Leversha, William; Smith-Arnold, Cheralee; Worrall, Julie; Rufray, Emily; Yuan, Qipeng; Liang, Hao; Scannell, Amalia; Russell, Cryn


    In this study we report the underlying reasons to why bacteria are present on banknotes and coins. Despite the use of credit cards, mobile phone apps, near-field-communication systems, and cryptocurrencies such as bitcoins which are replacing the use of hard currencies, cash exchanges still make up a significant means of exchange for a wide range of purchases. The literature is awash with data that highlights that both coins and banknotes are frequently identified as fomites for a wide range of microorganisms. However, most of these publications fail to provide any insight into the extent to which bacteria adhere and persist on money. We treated the various currencies used in this study as microcosms, and the bacterial loading from human hands as the corresponding microbiome. We show that the substrate from which banknotes are produced have a significant influence on both the survival and adherence of bacteria to banknotes. Smooth, polymer surfaces provide a poor means of adherence and survival, while coarser and more fibrous surfaces provide strong bacterial adherence and an environment to survive on. Coins were found to be strongly inhibitory to bacteria with a relatively rapid decline in survival on almost all coin surfaces tested. The inhibitory influence of coins was demonstrated through the use of antimicrobial disks made from coins. Despite the toxic effects of coins on many bacteria, bacteria do have the ability to adapt to the presence of coins in their environment which goes some way to explain the persistent presence of low levels of bacteria on coins in circulation.

  15. Physiology of polymorphonuclear neutrophils Fisiología de los polimorfonucleares neutrófilos

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    Diana García de Olarte


    Full Text Available

    Phagocytic cells. particularly neutrophils. are a fundamental part of the host response against aggression by infectious as well as non-infectious agents. and they are Involved In the generation of tissue damage during Inflammatory response. Cell responses of neutrophils depend on a series of closely related events like adherence to and diapedesis through endothelial cells. migration toward the sites of inflammation. phagocytósis and destruction of opsonized particles. All these actions are performed through the perfect integration between the systems of cellular activation and microbicidal mechanisms. Both oxygen-dependent and independent. A large portion of the biochemical. molecular and genetic mechanisms that lead to the physiologic response of neutrophils has been elucidated which permits the identification and understanding of the pathogenesis of disorders affecting these cells.

    Las células fagocíticas, en particular los neutrófilos son una pieza fundamental en la respuesta del huésped contra la agresión por diversos agentes, Infecciosos O no y están Involucradas en la generación de daño tisular durante la inflamación. Las respuestas celulares de los PMN dependen de una serie de hechos íntimamente relacionados, como la adherencia al endotelio vascular, la diapedesis a través de las células endoteliales, la migración hacia los sitios de Inflamación y la fagocitosis y ulterior destrucción de las partículas opsonizadas. Todo esto se logra mediante la integración perfecta entre los sistemas de activación celular y los mecanismos microbicidas, dependientes O no del oxígeno. Se ha esclarecido una gran parte de los mecanismos bioquímicos, moleculares y genéticos que llevan a la respuesta fisiológica de los neutrófilos lo cual ha permitido Identificar y entender la patogénesis de

  16. Adherence in patients with chronic treatment: data of “adherence day 2013”

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    Olatz Ibarra Barrueta


    Full Text Available Objetive: The primary objective of this study was to evaluate the adherence level in chronic conditions patients during “The Adherence Day” celebrated on November 15, 2013. Methods: We performed a transversal, observational and multicenter study at 43 Spanish hospitals, in order to estimate adherence in chronic treatments. We used the validated questionnaires Haynes- Sackett and Morisky- Green to measure medication adherence; but also a visual analogue scale and questions related with treatment complexity and selective adherence were applied. We performed a descriptive analysis and the closeness of agreement between questionnaires results. Results: A total of 723 surveys were collected especially among outpatients. 43% of the participants were women, with a median age of 51 and taking 3 drugs per day. 10.8% of the patients reported to have difficulty taking their pills according to Haynes- Sackett test. However, depending on Morisky- Green questionnaire, 56.4% of the participants were totally compliant; but considering only the question about forgetfulness, more were adherents (77%. 71% of the patients considered their compliance level as good (more than 8 according to visual analogue scale. And 11% presented a selective adherence, no taking equally well all the medications. The closeness of agreement between questionnaires and Morisky- Green test, as gold standard, was poor for Haynes- Sackett and weak for visual analogue scale. Conclusions: In our study only 56% of the patients with chronic treatment had a perfect adherence

  17. Assessing adherence factors in patients under topical treatment: development of the Topical Therapy Adherence Questionnaire (TTAQ). (United States)

    Zschocke, Ina; Mrowietz, Ulrich; Lotzin, Annett; Karakasili, Eleni; Reich, Kristian


    Medication adherence rates strongly depend on favorable disease outcomes. It is known that medication adherence rates are lower for topical treatment than for systemic treatment. However, to date no validated instrument for the assessment of adherence factors in topical treatment is available. The aim of this study was to develop a new questionnaire to assess adherence risk factors in topical treatment. The development of the Topical Therapy Adherence Questionnaire (TTAQ) and Patient Preference Questionnaire (PPQ) was based on a systematic literature review, and qualitative patient focus interviews and expert focus groups' input. The psychometric properties and comprehensibility of the TTAQ and PPQ were assessed in a feasibility study with 59 psoriasis patients. Our first preliminary results indicate that the TTAQ and PPQ are psychometrically sound and reliable measures for the assessment of factors influencing topical treatment adherence. The questionnaires are currently being further developed and various parameters (e.g., time point of assessment) are currently being tested in an exploratory pilot study with ca. 2,000 psoriasis patients receiving topical treatment in a European clinical trial. The use of the final versions of TTAQ and PPQ in clinical practice may facilitate the early identification of specific non-adherence factors in patients under topical treatment, which could enable designing and applying adherence-enhancing interventions according to the patient's individual needs.

  18. Effects of methylprednisolone on exercise-induced increases of plasma levels of polymorphonuclear elastase and myeloperoxidase in man. Preliminary results

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    G. Camus


    Full Text Available The aim of the present study was to verify whether a single oral dose of methylprednisolone could modulate the exercise-induced release of polymorphonuclear neutrophil (PMN elastase and myeloperoxidase. Four healthy, male subjects were submitted to a 20 min downhill run (−20% at 60% VO2 max, 3 h after oral absorption of a placebo or a single dose of 32 mg methylprednisolone. A marked neutrophilia (+103% of basal PMN count; p < 0.02 was observed 3 h after methylprednisolone ingestion. During both exercise trials, placebo and methylprednisolone, PMN counts were increased by 46% and 19% (p < 0.05, respectively. The running test caused marked and significant (p < 0.05 increases in plasma myeloperoxidase concentration (MPO. The magnitude of MPO changes was the same in the two trials (+110%. Exercise also resulted in significant changes in plasma elastase concentration (EL in both experimental conditions (placebo: +104%, p < 0.05; methylprednisolone: +338%, p < 0.005. Plasma elastase levels reached at the end of exercise on methylprednisolone were significantly higher than after placebo (p < 0.05. A significant relationship was found between EL and PMN in methylprednisolone trial only (r = 0.72; l0 < 0.005. These results showed that the transient exercise-induced release of elastase and myeloperoxidase were not decreased by methylprednisolone.

  19. Effects of Acer okamotoanum sap on the function of polymorphonuclear neutrophilic leukocytes in vitro and in vivo. (United States)

    An, Beum-Soo; Kang, Ji-Houn; Yang, Hyun; Yang, Mhan-Pyo; Jeung, Eui-Bae


    Sap is a plant fluid that primarily consists of water and small amounts of mineral elements, sugars, hormones and other nutrients. Acer mono (A. mono) is an endemic Korean mono maple which was recently suggested to have health benefits due to its abundant calcium and magnesium ion content. In the present study, we examined the effects of sap from Acer okamotoanum (A. okamotoanum) on the phagocytic response of mouse neutrophils in vivo and rat and canine neutrophils in vitro. We tested the regulation of phagocytic activity, oxidative burst activity (OBA) and the levels of filamentous polymeric actin (F-actin) in the absence and presence of dexamethasone (DEX) in vitro and in vivo. Our results showed that DEX primarily reduced OBA in the mouse neutrophils, and that this was reversed in the presence of the sap. By contrast, the phagocytic activity of the mouse cells was not regulated by either DEX or the sap. Rat and canine polymorphonuclear neutrophilic leukocytes (PMNs) responded in vitro to the sap in a similar manner by increasing OBA. However, regulation of phagocytic activity by the sap was different between the species. In canine PMNs, phagocytic activity was enhanced by the sap at a high dose, while it did not significantly modulate this activity in rat PMNs. These findings suggest that the sap of A. okamotoanum stimulates neutrophil activity in the mouse, rat and canine by increasing OBA in vivo and in vitro, and thus may have a potential antimicrobial effect in the PMNs of patients with infections.

  20. Polymorphonuclear leukocyte integrin pattern, at baseline and after activation, in type 2 diabetic subjects with macrovascular complications. (United States)

    Caimi, G; Montana, M; Ferrara, F; Porretto, F; Musso, M; Canino, B; Lo Presti, R


    In vascular atherosclerotic disease and in diabetes mellitus few studies have evaluated the polymorphonuclear leukocyte (PMN) adhesion molecule pattern. In this study we examined the PMN integrin expression at baseline and after activation in controls and type 2 diabetic subjects with macrovascular complications (MVC). We enrolled 21 subjects with type 2 diabetes mellitus and macrovascular complications, localized in peripheral, coronary and cerebral sites. The patients had peripheral occlusive arterial disease, chronic cerebrovascular disease or coronary heart disease. We evaluated the expression of some PMN integrins (CD11a, CD11b, CD11c, CD18), using flow cytofluorimetry, at baseline and after in vitro activation with 4-phorbol-12-myristate-13 acetate. Type 2 diabetic subjects with MVC showed, compared to normals, an increase of CD11a and CD18 and a decrease of CD11b and CD11c. After activation, in PMN(s) of normal subjects, we found an increase in the expression of all adhesion molecules, while in PMNS of type 2 diabetic subjects with MVC we observed an increase of CD11b and CD11c and a decrease of CD11a. In type 2 diabetic patients with MVC the basal upregulation of CD11a and CD18 may be related to the PMN spontaneous activation, while the behavior of CD11b may depend on its self-consumption. After activation the CD11a modification may be due to its cleavage or to an altered integrin phosphorylation/dephosphorylation balance.

  1. Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Jensen, Peter Østrup; Burmølle, Mette;


    The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis (CF) patients. P. aeruginosa colonizes the CF lungs by forming biofilm structures in the alveoli. In the biofilm mode of growth the bacteria are highly tolerant...

  2. The Respiratory Pathogen Moraxella catarrhalis Targets Collagen for Maximal Adherence to Host Tissues (United States)

    Singh, Birendra; Alvarado-Kristensson, Maria; Johansson, Martin; Hallgren, Oskar; Westergren-Thorsson, Gunilla; Mörgelin, Matthias


    ABSTRACT Moraxella catarrhalis is a human respiratory pathogen that causes acute otitis media in children and is associated with exacerbations in patients suffering from chronic obstructive pulmonary disease (COPD). The first step in M. catarrhalis colonization is adherence to the mucosa, epithelial cells, and extracellular matrix (ECM). The objective of this study was to evaluate the role of M. catarrhalis interactions with collagens from various angles. Clinical isolates (n = 43) were tested for collagen binding, followed by a detailed analysis of protein-protein interactions using recombinantly expressed proteins. M. catarrhalis-dependent interactions with collagen produced by human lung fibroblasts and tracheal tissues were studied by utilizing confocal immunohistochemistry and high-resolution scanning electron microscopy. A mouse smoke-induced chronic obstructive pulmonary disease (COPD) model was used to estimate the adherence of M. catarrhalis in vivo. We found that all M. catarrhalis clinical isolates tested adhered to fibrillar collagen types I, II, and III and network-forming collagens IV and VI. The trimeric autotransporter adhesins ubiquitous surface protein A2 (UspA2) and UspA2H were identified as major collagen-binding receptors. M. catarrhalis wild type adhered to human tracheal tissue and collagen-producing lung fibroblasts, whereas UspA2 and UspA2H deletion mutants did not. Moreover, in the COPD mouse model, bacteria devoid of UspA2 and UspA2H had a reduced level of adherence to the respiratory tract compared to the adherence of wild-type bacteria. Our data therefore suggest that the M. catarrhalis UspA2 and UspA2H-dependent interaction with collagens is highly critical for adherence in the host and, furthermore, may play an important role in the establishment of disease. PMID:27006460

  3. The Respiratory Pathogen Moraxella catarrhalis Targets Collagen for Maximal Adherence to Host Tissues

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    Birendra Singh


    Full Text Available Moraxella catarrhalis is a human respiratory pathogen that causes acute otitis media in children and is associated with exacerbations in patients suffering from chronic obstructive pulmonary disease (COPD. The first step in M. catarrhalis colonization is adherence to the mucosa, epithelial cells, and extracellular matrix (ECM. The objective of this study was to evaluate the role of M. catarrhalis interactions with collagens from various angles. Clinical isolates (n = 43 were tested for collagen binding, followed by a detailed analysis of protein-protein interactions using recombinantly expressed proteins. M. catarrhalis-dependent interactions with collagen produced by human lung fibroblasts and tracheal tissues were studied by utilizing confocal immunohistochemistry and high-resolution scanning electron microscopy. A mouse smoke-induced chronic obstructive pulmonary disease (COPD model was used to estimate the adherence of M. catarrhalis in vivo. We found that all M. catarrhalis clinical isolates tested adhered to fibrillar collagen types I, II, and III and network-forming collagens IV and VI. The trimeric autotransporter adhesins ubiquitous surface protein A2 (UspA2 and UspA2H were identified as major collagen-binding receptors. M. catarrhalis wild type adhered to human tracheal tissue and collagen-producing lung fibroblasts, whereas UspA2 and UspA2H deletion mutants did not. Moreover, in the COPD mouse model, bacteria devoid of UspA2 and UspA2H had a reduced level of adherence to the respiratory tract compared to the adherence of wild-type bacteria. Our data therefore suggest that the M. catarrhalis UspA2 and UspA2H-dependent interaction with collagens is highly critical for adherence in the host and, furthermore, may play an important role in the establishment of disease.

  4. Protective Effect of Distillate and Redistillate of Cow's Urine in Human Polymorphonuclear Leukocytes Challenged With Established Genotoxic Chemicals

    Institute of Scientific and Technical Information of China (English)



    From the ancient period cow's urine has been used as a medicine. In Veda, cow's urine was compared to the nectar. In Susrut, several medicinal properties of cow's urine have been mentioned and are known to cause weight loss, reversal of certain cardiac and kidney problems, indigestion, stomach ache, edema, etc. However, the literature and scripture did not mention the antigenotoxic properties of cow's urine. Methods In the present investigation, the antigenotoxic/ antioxidant properties of cow's urine distillate and redistillate were studied in vitro. The antioxidant status and volatile fatty acid levels were determined. Actinomycin-D (0.1 μmol/L) and hydrogen peroxide (150 μmol/L) were used for inducing DNA strand break with 0.1% DMSO as negative control. Dose for the antigenotoxic effect of cow's urine was chosen from the dose response study carried out earlier. Results Both actinomycin-D and H2O2 caused statistically significant DNA unwinding of 80% & 75% respectively (P<0.001) as revealed by fluorimetric analysis of DNA unwinding (FADU), and the damage could be protected with the redistilled cow's urine distillate (1, 50 & 100 μL) in simultaneous treatment with genotoxic chemicals. Conclusion The redistillate of cow's urine was found to possess total antioxidant status of around 2.6 mmol, contributed mainly by volatile fatty acids (1500 mg/L) as revealed by the GC-MS studies. These fatty acids and other antioxidants might cause the observed protective effects.

  5. In vitro adherence patterns of Shigella serogroups to bovine recto-anal junction squamous epithelial (RSE) cells are similar to those of Escherichia coli O157. (United States)

    Kudva, Indira T


    The aims of this study were to determine whether Shigella species, which are human gastrointestinal pathogens, can adhere to cattle recto-anal junction squamous epithelial (RSE) cells using a recently standardized in vitro adherence assay, and to compare their adherence patterns with that of Escherichia coli O157. Shigella dysenteriae (serogroup A), S. flexneri (serogroup B), S. boydii (serogroup C), and S. sonnei (serogroup D) were tested in adherence assays using both RSE and HEp-2 cells, in the presence or absence of D+mannose. Escherichia coli O157, which adheres to RSE cells in a Type I fimbriae-independent manner, was used as a positive control. Shigella serogroups A, B, D, but not C adhered to RSE cells with distinct adherence patterns in the presence of D+mannose. No such distinction could be made between the four Shigella serogroups based on the HEp-2 cell adherence patterns. Thus, this study provides evidence that certain Shigella serogroups adhere to RSE cells in a manner that is similar to the adherence pattern of E. coli O157. These unexpected observations of in vitro binding of these foodborne human pathogens to cells of the bovine gastrointestinal tract warrant evaluation of Shigella carriage by cattle using both experimental and observational studies, especially for serogroups B and D. Such studies are currently underway.

  6. Antiretroviral Treatment Adherence: Knowledge and Experiences among Adolescents and Young Adults in Soweto, South Africa

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    Stefanie Hornschuh


    Full Text Available Human immunodeficiency virus (HIV management of adolescents and young adults (AYAs is particularly pertinent to sub-Saharan Africa, where the pediatric HIV burden is marked. Antiretroviral treatment (ART adherence is a major challenge for AYAs. This qualitative study explored knowledge and experiences of adherence amongst AYAs attending treatment at the Perinatal HIV Research Unit (PHRU, Soweto, South Africa. Four focus group discussions (FGDs and eight in-depth interviews (IDIs were conducted with HIV-infected 15–25-year-old ART recipients. Transcripts were coded thematically. Participants (n=26 were aged median 18.5 years, 59.1% female and 69.2% virally suppressed <400 cp/ml. Three main themes emerged during FGDs and IDIs: (i correct knowledge about how to be adherent, benefits, and nonadherence consequences, (ii social, personal, and medication-related barriers to adherence, and (iii reminder, concealment, and motivational strategies to optimize adherence. Interventions to improve AYA adherence could focus on practical strategies, including status disclosure and medication concealment.

  7. Photosensitizer Adhered to Cell Culture Microplates Induces Phototoxicity in Carcinoma Cells

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    Verena Ziegler


    Full Text Available In vitro experiments in plastic receptacles are the basis of characterization of new photosensitizers (PSs for the photodynamic therapy. We recently reported that lipophilic PSs adhere to cell culture microplates in a kinetic-like manner (Engelhardt et al., 2011. In the current study, we examined the interaction and phototoxic effects of the microplate-adhered PS in cancer cells. Therefore, we preloaded microplates with hypericin, Foscan, PVP-hypericin, or aluminum (III phthalocyanine tetrasulfonate chloride (AlPCS4 for 24 hours and measured the PS distribution after addition of A431 human carcinoma cells: following another 24 hours up to 68% of hypericin were detected in the cell fraction. The hydrophilic PVP-hypericin and AlPCS4 also diffused into the cells, but the quantities of PS adherence were considerably lower. Microplate-adhered Foscan appeared not to be redistributed. In contrast to the hydrophilic PSs, the cellular phototoxicity of microplate-adhered lipophilic PS was high, independent of whether the PS (i was pre-loaded onto microplates or (ii added simultaneously with the cells or (iii one day after cell seeding. Based on these results, we suggest testing lipophilic PS dyes for their adherence to microplates. Furthermore, the ability of plastic materials to (reversibly store PSs might represent a new approach for the PS delivery or the development of antimicrobial coatings.

  8. Improving medication adherence in patients with hypertension

    DEFF Research Database (Denmark)

    Hedegaard, Ulla; Kjeldsen, Lene Juel; Pottegård, Anton


    BACKGROUND: and Purpose: In patients with hypertension, medication adherence is often suboptimal, thereby increasing the risk of ischemic heart disease and stroke. In a randomized trial, we investigated the effectiveness of a multifaceted pharmacist intervention in a hospital setting to improve...... medication adherence in hypertensive patients. Motivational interviewing was a key element of the intervention. METHODS: Patients (N=532) were recruited from 3 hospital outpatient clinics and randomized to usual care or a 6-month pharmacist intervention comprising collaborative care, medication review......, tailored adherence counselling including motivational interviewing and telephone follow-ups. The primary outcome was composite medication possession ratio (MPR) to antihypertensive and lipid-lowering agents, at one-year follow-up, assessed by analyzing pharmacy records. Secondary outcomes at 12 months...

  9. Efficacy of a brief multifactorial adherence-based intervention on reducing the blood pressure of patients with poor adherence: protocol for a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Llobera Joan


    Full Text Available Abstract Background Lowering of blood pressure by antihypertensive drugs reduces the risks of cardiovascular events, stroke, and total mortality. However, poor adherence to antihypertensive medications reduces their effectiveness and increases the risk of adverse events. In terms of relative risk reduction, an improvement in medication adherence could be as effective as the development of a new drug. Methods/Design The proposed randomized controlled trial will include patients with a low adherence to medication and uncontrolled blood pressure. The intervention group will receive a multifactorial intervention during the first, third, and ninth months, to improve adherence. This intervention will include motivational interviews, pill reminders, family support, blood pressure self-recording, and simplification of the dosing regimen. Measurement The primary outcome is systolic blood pressure. The secondary outcomes are diastolic blood pressure, proportion of patients with adequately controlled blood pressure, and total cost. Discussion The trial will evaluate the impact of a multifactorial adherence intervention in routine clinical practice. Ethical approval was given by the Ethical Committee on Human Research of Balearic islands, Spain (approval number IB 969/08 PI. Trial registration Current controlled trials ISRCTN21229328

  10. Adherence to diabetes medication in individuals with schizophrenia:a systematic review of rates and determinants of adherence


    Gorczynski, Paul; Patel, Hiren; Ganguli, Rohan


    Introduction: Despite the importance of medication adherence for the effective treatment of type II diabetes mellitus (T2DM), little research has examined adherence with diabetes medication treatment in schizophrenia. The purpose of this systematic review was to 1) evaluate rates of adherence and determinants of adherence with medication for T2DM in individuals with schizophrenia, and, where possible, 2) examine the relationship between medication adherence and glycemic control. Methods: Stud...

  11. Current strategies for improving access and adherence to antiretroviral therapies in resource-limited settings

    Directory of Open Access Journals (Sweden)

    Scanlon ML


    Full Text Available Michael L Scanlon,1,2 Rachel C Vreeman1,21Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA; 2USAID, Academic Model Providing Access to Healthcare (AMPATH Partnership, Eldoret, KenyaAbstract: The rollout of antiretroviral therapy (ART significantly reduced human immunodeficiency virus (HIV-related morbidity and mortality, but good clinical outcomes depend on access and adherence to treatment. In resource-limited settings, where over 90% of the world’s HIV-infected population resides, data on barriers to treatment are emerging that contribute to low rates of uptake in HIV testing, linkage to and retention in HIV care systems, and suboptimal adherence rates to therapy. A review of the literature reveals limited evidence to inform strategies to improve access and adherence with the majority of studies from sub-Saharan Africa. Data from observational studies and randomized controlled trials support home-based, mobile and antenatal care HIV testing, task-shifting from doctor-based to nurse-based and lower level provider care, and adherence support through education, counseling and mobile phone messaging services. Strategies with more limited evidence include targeted HIV testing for couples and family members of ART patients, decentralization of HIV care, including through home- and community-based ART programs, and adherence promotion through peer health workers, treatment supporters, and directly observed therapy. There is little evidence for improving access and adherence among vulnerable groups such as women, children and adolescents, and other high-risk populations and for addressing major barriers. Overall, studies are few in number and suffer from methodological issues. Recommendations for further research include health information technology, social-level factors like HIV stigma, and new research directions in cost-effectiveness, operations, and implementation. Findings from this review make a

  12. Neutrophil bactericidal activity against Staphylococcus aureus adherent on biological surfaces. Surface-bound extracellular matrix proteins activate intracellular killing by oxygen-dependent and -independent mechanisms.


    Hermann, M.; Jaconi, M E; Dahlgren, C; Waldvogel, F A; Stendahl, O; Lew, D P


    The activation patterns of surface adherent neutrophils are modulated via interaction of extracellular matrix proteins with neutrophil integrins. To evaluate neutrophil bactericidal activity, Staphylococcus aureus adherent to biological surfaces were incubated with neutrophils and serum, and the survival of surface bacteria was determined. When compared to albumin-coated surfaces, the bactericidal activity of neutrophils adherent to purified human extracellular matrix was markedly enhanced (m...

  13. Factors affecting medication adherence in elderly people

    Directory of Open Access Journals (Sweden)

    Jin HK


    Full Text Available Hyekyung Jin,1 Yeonhee Kim,2 Sandy Jeong Rhie1,3 1College of Pharmacy, 2Center for Excellence in Teaching & Learning, 3Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea 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

  14. Adherence to methotrexate in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Bliddal, Henning; Eriksen, Stine A; Christensen, Robin;


    Objectives. To study adherence to methotrexate (MTX) and factors of importance thereof in patients with rheumatoid arthritis (RA). Methods. Patients with a hospital diagnosis of RA (ICD10 codes M05.X or M06.X) after January 1, 1997, and aged ≥18 years at the date of first diagnosis/contact, with ......Objectives. To study adherence to methotrexate (MTX) and factors of importance thereof in patients with rheumatoid arthritis (RA). Methods. Patients with a hospital diagnosis of RA (ICD10 codes M05.X or M06.X) after January 1, 1997, and aged ≥18 years at the date of first diagnosis...

  15. Introducing the Adherence Strategy Engineering Framework (ASEF)

    DEFF Research Database (Denmark)

    Wagner, Stefan Rahr; Toftegaard, Thomas Skjødeberg; Bertelsen, Olav W.


    Background: Patients performing self-care in the unsupervised setting do not always adhere to the instructions they were initially provided with. As a consequence, a patient’s ability to successfully comply with the treatment plan cannot be verified by the treating healthcare professional, possib...

  16. Community health workers adherence to referral guidelines

    DEFF Research Database (Denmark)

    Lal, Sham; Ndyomugenyi, Richard; Paintain, Lucy


    Background Many malaria-endemic countries have implemented national community health worker (CHW) programmes to serve remote populations that have poor access to malaria diagnosis and treatment. Despite mounting evidence of CHWs’ ability to adhere to malaria rapid diagnostic tests (RDTs) and trea......Background Many malaria-endemic countries have implemented national community health worker (CHW) programmes to serve remote populations that have poor access to malaria diagnosis and treatment. Despite mounting evidence of CHWs’ ability to adhere to malaria rapid diagnostic tests (RDTs......) and treatment guidelines, there is limited evidence whether CHWs adhere to the referral guidelines and refer severely ill children for further management. In southwest Uganda, this study examined whether CHWs referred children according to training guidelines and described factors associated with adherence...... to the referral guideline. Methods A secondary analysis was undertaken of data collected during two cluster-randomized trials conducted between January 2010 and July 2011, one in a moderate-to-high malaria transmission setting and the other in a low malaria transmission setting. All CHWs were trained to prescribe...

  17. Barriers to adherence in cystic fibrosis

    DEFF Research Database (Denmark)

    Bregnballe, Vibeke; Schiøtz, Peter Oluf


    Danish patients with cystic fibrosis aged 14 to 25 years and their parents. Conclusions: The present study showed that the majority of adolescents with CF and their parents experienced barriers to treatment adherence. Patients and parents agreed that the three most common barriers encountered lack...


    Directory of Open Access Journals (Sweden)



    Full Text Available ABSTRACT: BACKGROUND: In spite of any number of medicines will not be of use unless patient takes’ them. After diagnosing the disease, the next most i mportant step is to follow the instructions of physician in terms of treatment. The doctor’s respons ibility does not end with writing prescription, assuming patient will adhere to it. He/ she should cross check the behavior of patient for drug compliance and see that patient follo ws it and get the benefit. Non compliance is the main barrier for the effective delivery of the medical care. This will have greater implications on the economic burde n on the country in terms of frequent hospitalization, use of expensive medicines in case o f relapse due to non adherence.Though the terms compliance and adherence are used synonymously , they differ in the delivery of quality of the medicare as the former implicates the passive fol lowing of the physician instruction, while in the later, patient actively participates in the dev elopment of the treatment plan, which will improves outcome of the treatment. Adherence is the preferred term over compliance by WHO.

  19. Psoriasis: improving adherence to topical therapy.

    NARCIS (Netherlands)

    Feldman, S.R.; Horn, E.J.; Balkrishnan, R.; Basra, M.K.; Finlay, A.Y.; McCoy, D.; Menter, A.; Kerkhof, P.C.M. van de


    Topical therapy has an important role in psoriasis treatment. It is efficacious and has a favorable safety profile as demonstrated in clinical trials. However, poor treatment outcomes from topical therapy regimens likely result from poor adherence and ineffective use of the medication. The Internati

  20. Adherence to Exercise and Physical Activity: Preface. (United States)

    Morgan, William P.; Dishman, Rod K.


    Introduces a collection of papers on adherence to exercise programs and physical activity from the 2000 American Academy of Kinesiology and Physical Education conference, which included research on middle school boys and girls, college men and women, and men and women in the later years, as well as on the more traditional subject of middle aged…

  1. Non-adherence in difficult asthma and advances in detection. (United States)

    Lindsay, John T; Heaney, Liam G


    Non-adherence to anti-inflammatory therapies is common in patients referred for specialist assessment at difficult-to-treat asthma services. In the difficult asthma setting, non-adherence to treatment is associated with poor baseline asthma control, increased frequency of exacerbations and asthma-related hospitalizations, as well as increased risk of death. Here, we present a review of the current literature surrounding the prevalence and risks of non-adherence in difficult asthma and we report on current methods of measuring treatment adherence and advances in the detection of non-adherence. We will also explore methods by which non-adherence in difficult asthma can be addressed.

  2. Spermadhesin PSP-I/PSP-II heterodimer induces migration of polymorphonuclear neutrophils into the uterine cavity of the sow. (United States)

    Rodriguez-Martinez, H; Saravia, F; Wallgren, M; Martinez, E A; Sanz, L; Roca, J; Vazquez, J M; Calvete, J J


    Seminal plasma (SP) is a complex fluid which exerts biological actions in the female reproductive tract. In pigs, SP elicits endometrial inflammation and consequent immune changes after mating. This study tested whether heparin-binding spermadhesins (HBPs) and the heterodimer of porcine sperm adhesions I and II (PSP-I/PSP-II) in SP recruit different lymphocyte subsets (CD2(+), CD4(+) and CD8(+) T cells) or polymorphonuclear leukocytes (PMNs) to the superficial endometrium or luminal epithelium and lumen, respectively, of oestrous sows. In Experiment 1, endometrial biopsies were taken between 2 and 120 min after infusion of uterine horns with HBPs, PSP-I/PSP-II or saline and evaluated by immunohistochemistry or histology. In Experiment 2, the uterus of oestrous sows was infused with PSP-I/PSP-II or saline to assess PMN numbers in the uterine lumen 3h later. PSP-I/PSP-II elicited CD2+ T cell recruitment from 10 min, and CD8(+) T cells from 60 min after infusion, while HBPs increased CD4(+) T cell recruitment by 120 min. PSP-I/PSP-II but not HBPs induced PMN migration to the surface epithelium by 10 min. PMN numbers were elevated 5-fold by 30 min and 7-fold from 60 min, with PMNs detectable in the lumen from 30 min after infusion. Six-fold more PMNs were collected from the uterine lumen of PSP-I/PSP-II-infused sows compared to controls at 3h after infusion. These data show that PSP-I/PSP-II heterodimer in seminal plasma has a predominant role in triggering the recruitment of uterine PMNs and T cells after mating, initiating a cascade of transient and long-lasting immunological events.

  3. Oral polymorphonuclear neutrophil characteristics in relation to oral health:a cross-sectional, observational clinical study

    Institute of Scientific and Technical Information of China (English)

    Patrick Rijkschroeff; Ineke DC Jansen; Fridus A van der Weijden; Bart JF Keijser; Bruno G Loos; Elena A Nicu


    Polymorphonuclear neutrophils (PMNs) have a major role in the innate immune system. However, little is known about PMN contribution in relation to oral health. The objective of this study was to investigate the numbers and functional characteristics of oral PMNs (oPMNs) compared with circulatory PMNs (cPMNs). Oral rinse and venous blood samples were obtained from 268 systemically and orally healthy volunteers in a cross-sectional observational study. PMN counts, cell cycle analysis and cellular activation state were investigated. Also, reactive oxygen species (ROS) production was analyzed, with and without bacterial stimulation (Fusobacterium nucleatum). In males, 1.2 × 106 ± 1.0 × 106 oPMNs were collected, and showed a tendency to correlate with the levels of gingival bleeding (r=0.215, P=0.008). Comparable oPMNs counts were found among females (1.0 × 106 ± 0.7 × 106). More late-stage apoptotic/necrotic cells were found among the oPMNs (53.1%) compared with the cPMNs (8.5%;Po0.001). Without additional stimulation, oPMNs were more activated than cPMNs, as indicated by higher expression of CD11b, CD63 and CD66b, and higher constitutive ROS levels (Po0.001). Notably, in response to bacterial stimulation, oPMNs released comparable ROS levels as cPMNs (P=0.042). In conclusion, this study provides data on viable oPMNs showing high levels of activation in orally and systemically healthy individuals, free of apparent caries lesions and periodontal disease. These data suggests that although the oPMNs are in a more mature stage of their life cycle compared with the cPMNs, oPMNs are still responsive to stimulation, which indicates their functional potential and possible contribution to a healthy oral ecosystem.

  4. Comparative proteomics of uropathogenic Escherichia coli during growth in human urine identify UCA-like (UCL) fimbriae as an adherence factor involved in biofilm formation and binding to uroepithelial cells. (United States)

    Wurpel, Daniël J; Totsika, Makrina; Allsopp, Luke P; Webb, Richard I; Moriel, Danilo G; Schembri, Mark A


    Uropathogenic Escherichia coli (UPEC) are the primary cause of urinary tract infection (UTI) in humans. For the successful colonisation of the human urinary tract, UPEC employ a diverse collection of secreted or surface-exposed virulence factors including toxins, iron acquisition systems and adhesins. In this study, a comparative proteomic approach was utilised to define the UPEC pan and core surface proteome following growth in pooled human urine. Identified proteins were investigated for subcellular origin, prevalence and homology to characterised virulence factors. Fourteen core surface proteins were identified, as well as eleven iron uptake receptor proteins and four distinct fimbrial types, including type 1, P, F1C/S and a previously uncharacterised fimbrial type, designated UCA-like (UCL) fimbriae in this study. These pathogenicity island (PAI)-associated fimbriae are related to UCA fimbriae of Proteus mirabilis, associated with UPEC and exclusively found in members of the E. coli B2 and D phylogroup. We further demonstrated that UCL fimbriae promote significant biofilm formation on abiotic surfaces and mediate specific attachment to exfoliated human uroepithelial cells. Combined, this study has defined the surface proteomic profiles and core surface proteome of UPEC during growth in human urine and identified a new type of fimbriae that may contribute to UTI.

  5. Bacterial adherence to anodized titanium alloy

    Energy Technology Data Exchange (ETDEWEB)

    Peremarch, C Perez-Jorge; Tanoira, R Perez; Arenas, M A; Matykina, E; Conde, A; De Damborenea, J J; Gomez Barrena, E; Esteban, J, E-mail:


    The aim of this study was to evaluate Staphylococcus sp adhesion to modified surfaces of anodized titanium alloy (Ti-6Al-4V). Surface modification involved generation of fluoride-containing titanium oxide nanotube films. Specimens of Ti-6Al-4V alloy 6-4 ELI-grade 23- meets the requirements of ASTM F136 2002A (AMS 2631B class A1) were anodized in a mixture of sulphuric/hydrofluoric acid at 20 V for 5 and 60 min to form a 100 nm-thick porous film of 20 nm pore diameter and 230 nm-thick nanotube films of 100 nm in diameter. The amount of fluorine in the oxide films was of 6% and of 4%, respectively. Collection strains and six clinical strains each of Staphylococcus aureus and Staphylococcus epidermidis were studied. The adherence study was performed using a previously published protocol by Kinnari et al. The experiments were performed in triplicates. As a result, lower adherence was detected for collection strains in modified materials than in unmodified controls. Differences between clinical strains were detected for both species (p<0.0001, Kruskal-Wallis test), although global data showed similar results to that of collection strains (p<0.0001, Kruskal-Wallis test). Adherence of bacteria to modified surfaces was decreased for both species. The results also reflect a difference in the adherence between S. aureus and S. epidermidis to the modified material. As a conclusion, not only we were able to confirm the decrease of adherence in the modified surface, but also the need to test multiple clinical strains to obtain more realistic microbiological results due to intraspecies differences.

  6. Standard Care Impact on Effects of Highly Active Antiretroviral Therapy Adherence Interventions

    NARCIS (Netherlands)

    Bruin, de M.; Viechtbauer, W.; Schaalma, H.P.; Kok, G.; Abraham, C.; Hospers, H.J.


    BACKGROUND: Poor adherence to medication limits the effectiveness of treatment for human immunodeficiency virus. Systematic reviews can identify practical and effective interventions. Meta-analyses that control for variability in standard care provided to control groups may produce more accurate est

  7. Experiencing antiretroviral adherence: helping healthcare staff better understand adherence to paediatric antiretrovirals

    Directory of Open Access Journals (Sweden)

    Phelps Benjamin R


    Full Text Available Abstract Background Lack of adherence to antiretroviral medications is one of the key challenges for paediatric HIV care and treatment programmes. There are few hands-on opportunities for healthcare workers to gain awareness of the psychosocial and logistic challenges that caregivers face when administering daily antiretroviral therapy to children. This article describes an educational activity that allows healthcare workers to simulate this caregiver role. Methods Paediatric formulations of several antiretroviral medications were dispensed to a convenience sample of staff at the Baylor College of Medicine-Bristol-Myers Squibb Children's Clinical Center of Excellence in Mbabane, Swaziland. The amounts of the medications remaining were collected and measured one week later. Adherence rates were calculated. Following the exercise, a brief questionnaire was administered to all staff participants. Results The 27 clinic staff involved in the exercise had varying and low adherence rates over the week during which the exercise was conducted. Leading perceived barriers to adherence included: "family friends don't help me remember/tell me I shouldn't take it" and "forgot". Participants reported that the exercise was useful as it allowed them to better address the challenges faced by paediatric patients and caregivers. Conclusions Promoting good adherence practices among caregivers of children on antiretrovirals is challenging but essential in the treatment of paediatric HIV. Participants in this exercise achieved poor adherence rates, but identified with many of the barriers commonly reported by caregivers. Simulations such as this have the potential to promote awareness of paediatric ARV adherence issues among healthcare staff and ultimately improve adherence support and patient outcomes.

  8. Ensuring medication adherence with direct oral anticoagulant drugs: lessons from adherence with vitamin K antagonists (VKAs). (United States)

    Di Minno, Alessandro; Spadarella, Gaia; Tufano, Antonella; Prisco, Domenico; Di Minno, Giovanni


    Medication adherence (taking drugs properly) is uncommon among patients on warfarin. Poor adherence to warfarin leads to an increase in adverse medical events, including stroke in atrial fibrillation (AF). Factors related to patients, physicians and the health system account for poor adherence. Direct oral anticoagulants (DOACs) are easier to use than warfarin, with fewer drug and food interactions and no need for routine blood monitoring. A proper use of DOACs may reduce the risk of stroke in AF. However, in clinical settings where no laboratory monitoring is needed, a poor medication adherence is common and may impact clinical outcomes. In the management of chronic disorders, careful knowledge of the individual patient's attitudes and behaviors is a pre-requisite for a successful doctor-patient communication. To increase patient's awareness of the risks and benefits of DOACs and, in turn, increase medication adherence, at each follow-up visit physicians should screen for priorities and motivational problems; check for the lack of understanding and/or knowledge; assess any health system or personal barriers to medication adherence; identify appropriate interventions and provide tailored support to patient needs. Dissemination of guidelines to the health care chain (prescribing physician, general practitioners, caregivers, nurses, pharmacists) further encourages medication adherence. However, the long-term effect of some of these strategies is unknown; one tool may not fit all patients, and the prescribing physician should consider individualization of these aids to ensure medication adherence and persistence (continuing to take drugs properly in long-term treatments) for DOACs in every day practice.

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

    Directory of Open Access Journals (Sweden)

    Hernández Arroyo MJ


    Full Text Available María Jesús Hernández Arroyo,1 Salvador Enrique Cabrera Figueroa,2 Rosa Sepúlveda Correa,3 María de la Paz Valverde Merino,1 Alicia Iglesias Gómez,4 Alfonso Domínguez-Gil Hurlé5 On behalf of the Tormes Team 1Pharmacy Service, University Hospital of Salamanca, Salamanca, Spain; 2Pharmacy Institute, University Austral of Chile, Valdivia, Chile; 3Department of Statistics, University of Salamanca, Salamanca, Spain; 4Infectious Disease Service, University Hospital of Salamanca, Salamanca, Spain; 5Department of Pharmacy and Pharmaceutical Technology, University of Salamanca, Salamanca, Spain 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

  10. Drug effects on platelet adherence to collagen and damaged vessel walls. (United States)

    Packham, M A; Cazenave, J P; Kinlough-Rathbone, R L; Mustard, J F


    The interaction of platelets with damaged vessel walls leads to the formation of platelet-fibrin thrombi and may also contribute to the development of atherosclerotic lesions because platelets adherent to exposed collagen release a mitogen that stimulates smooth muscle cell proliferation. The first step in thrombus formation, platelet adherence to an injured vessel wall, can be studied quantitatively by the use of platelets labeled with 51chromium. In these investigations, rabbit aortas were damaged by passage of a balloon catheter and segments of the aortas were everted on probes that were rotated in platelet suspensions. Collagen-coated glass cylinders were also used. Adherence was measured in a medium containing approximately physiologic concentrations of calcium, magnesium, protein and red blood cells. Conditions of testing influence the effect of non-steroidal anti-inflammatory drugs, sulfinpyrazone, and dipyridamole on platelet adherence. Aspirin and sulfinpyrazone were not inhibitory when tested in a medium with a 40% hematocrit; this indicates that products formed by platelets from arachidonate probably do not play a major part in the adherence of the first layer of platelets to the surface, although they may be involved in thrombus formation. Indomethacin, dipyridamole, prostaglandin E1, methylprednisolone and penicillin G and related antibiotics did inhibit platelet adherence although the concentrations required were higher than would likely be achieved in vivo upon administration to human patients. None of the non-steroidal anti-inflammatory drugs inhibited the release of granule contents from adherent platelets. Pretreatment of the damaged vessel wall with aspirin increased platelet adherence, presumably because it prevented the formation of PGI2 by the vessel wall. Platelet adherence to undamaged or damaged vessel walls was enhanced by prior exposure of the wall to thrombin. Platelet reactions with aggregating agents and platelet survival can be

  11. Adherence in children with growth hormone deficiency treated with r-hGH and the easypod™ device


    S. Loche; Salerno, M.; Garofalo, P; Cardinale, G. M.; Licenziati, MR; Citro, G.; Caruso Nicoletti, M.; Cappa, M.; Longobardi, S.; Maghnie, M; Perrone, R


    Purpose Poor adherence to recombinant human growth hormone (r-hGH) therapy is associated with reduced growth velocity in children with growth hormone deficiency (GHD). This twelve-month observational study was to assess adherence in r-hGH patients treated with the easypod™, an electronic, fully automated injection device designed to track the time, date and dose administered. Methods Ninety-seven prepubertal patients receiving r-hGH therapy were included in the study from ten Italian clinical...

  12. Adherence of Moraxella bovis to cell cultures of bovine origin. (United States)

    Annuar, B O; Wilcox, G E


    The adherence of five strains of Moraxella bovis to cell cultures was investigated. M bovis adhered to cultures of bovine corneal epithelial and Madin-Darby bovine kidney cells but not to cell types of non-bovine origin. Both piliated and unpiliated strains adhered but piliated strains adhered to a greater extent than unpiliated strains. Antiserum against pili of one strain inhibited adherence of piliated strains but caused only slight inhibition of adherence to the unpiliated strains. Treatment of bacteria with magnesium chloride caused detachment of pili from the bacterial cell and markedly inhibited adherence of piliated strains but caused only slight inhibition of adherence by the unpiliated strains. The results suggested that adhesion of piliated strains to cell cultures was mediated via pili but that adhesins other than pili may be involved in the attachment of unpiliated strains of M bovis to cells.

  13. Adherence inhibition of Streptococcus mutans on dental enamel surface using silver nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Espinosa-Cristóbal, L.F. [Doctorado Institucional en Ingeniería y Ciencia de Materiales, Universidad Autónoma de San Luis Potosí, Av. Salvador Nava S/N, Zona Universitaria, C.P. 78290 San Luis Potosí, S.L.P. (Mexico); Maestría en Ciencias Odontológicas en el Área de Odontología Integral Avanzada, Universidad Autónoma de San Luis Potosí, Av. Salvador Nava S/N, Zona Universitaria, C.P. 78290 San Luis Potosí, S.L.P. (Mexico); Martínez-Castañón, G.A., E-mail: [Doctorado Institucional en Ingeniería y Ciencia de Materiales, Universidad Autónoma de San Luis Potosí, Av. Salvador Nava S/N, Zona Universitaria, C.P. 78290 San Luis Potosí, S.L.P. (Mexico); Maestría en Ciencias Odontológicas en el Área de Odontología Integral Avanzada, Universidad Autónoma de San Luis Potosí, Av. Salvador Nava S/N, Zona Universitaria, C.P. 78290 San Luis Potosí, S.L.P. (Mexico); Téllez-Déctor, E.J. [Facultad de Odontología de la Universidad Veracruzana campus Río Blanco, Mariano Abasolo S/N. Col. Centro. Río Blanco, Veracruz (Mexico); and others


    The aim of this ex vivo study was to evaluate the adherence capacity of Streptococcus mutans after being exposed to three different sizes of silver nanoparticles on healthy human dental enamel. Three different sizes of silver nanoparticles (9.3, 21.3 and 98 nm) were prepared, characterized and an adherence testing was performed to evaluate their anti-adherence activity on a reference strain of S. mutans on healthy dental enamel surfaces. Colony-Forming Unit count was made for adherence test and light microscopy, atomic force microscopy and scanning electron microscopy were used to compare qualitative characteristics of S. mutans. 9.3 nm and 21.3 nm groups did not show differences between them but statistical differences were found when 9.3 nm and 21.3 nm groups were compared with 98 nm and negative control groups (p < 0.05). Microscopy analysis shows a better inhibition of S. mutans adherence in 9.3 nm and 21.3 nm groups than the 98 nm group when compared with control group. Silver nanoparticles showed an adherence inhibition on S. mutans and the anti-adherence capacity was better when silver nanoparticles were smaller. Highlights: ► We examined how SNP can affect cellular adhesion from S. mutans. ► Several techniques were applied to analyzed S. mutans biofilm on enamel. ► All SNP sizes had an adhesion inhibition of S. mutans. ► Smaller SNP showed a better adhesion inhibition than larger SNP. ► Inhibition effect of SNP could be related with adhesion inhibition from S. mutans.

  14. Improving adherence to medical regimens for juvenile rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Lindsley Carol B


    Full Text Available Abstract Poor adherence to medical regimens can compromise the efficacy of treatments for children and adolescents with juvenile rheumatoid arthritis (JRA. The purpose of this review is to describe medical regimens for the treatment of JRA and the rates of adherence to these regimens. We also summarize and critically the few research studies aimed at improving adherence to regimens for JRA. Finally, we summarize strategies for enhancing adherence in clinical practice.

  15. Iron Chelation Adherence to Deferoxamine and Deferasirox in Thalassemia


    Trachtenberg, Felicia; Vichinsky, Elliott; Haines, Dru; Pakbaz, Zahra; Mednick, Lauren; Sobota, Amy; Kwiatkowski, Janet; Thompson, Alexis A.; Porter, John; Coates, Thomas; Giardina, Patricia J.; Olivieri, Nancy; Yamashita, Robert; Neufeld, Ellis J.


    The Thalassemia Clinical Research Network collected adherence information from 79 patients on deferoxamine and 186 on deferasirox from 2007 to 2009. Chelation adherence was defined as percent of doses administered in the last 4 weeks (patient report) out of those prescribed (chart review). Chelation history since 2002 was available for 97 patients currently on deferoxamine and 217 on deferasirox, with crude estimates of adherence from chart review. Self-reported adherence to both deferoxamine...

  16. Medication adherence among transgender women living with HIV



    Medication adherence is linked to health outcomes among adults with HIV infection. Transgender women living with HIV (TWLWH) in the U.S. report suboptimal adherence to medications and are found to have difficulty integrating HIV medication into their daily routine, but few studies explore factors associated with medication adherence among transgender women. Thus, the purpose of this paper is to examine demographic and clinical factors related to self-reported medication adherence among transg...

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

    Directory of Open Access Journals (Sweden)

    Jones Gareth


    Full Text Available Abstract 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

  18. Medication Adherence and Growth in Children with CKD (United States)

    Schneider, Michael F.; Mulqueen, Lucy; Brooks, Ellen R.; Langman, Craig B.; Greenbaum, Larry A.; Furth, Susan L.; Moxey-Mims, Marva; Warady, Bradley A.; Kaskel, Frederick J.; Skversky, Amy L.


    Background and objectives Poor growth is a consequence of CKD, but can often be partially or fully prevented or corrected with the use of a number of medications. The extent of nonadherence with medications used to treat or mitigate growth failure in CKD has not been examined prospectively in children with CKD. Design, setting, participants, & measurements The prevalence of both prescription of and nonadherence to recombinant human growth hormone (rhGH), phosphate binders, alkali, active vitamin D, nutritional vitamin D, iron, and erythrocyte-stimulating agents was summarized over the first seven visits of the Chronic Kidney Disease in Children cohort study. The association between self-reported nonadherence to each medication group and the mean annual change in age- and sex-specific height z score was quantified using seven separate linear regression models with generalized estimating equations. Results Of 834 participants, 597 reported use of at least one of these medication groups and had adherence data available. Nonadherence ranged from 4% over all visits for erythrocyte-stimulating agents to 22% over all visits for nutritional vitamin D. Of the study participants, 451 contributed data to at least one of the analyses of adherence and changes in height z score. Children nonadherent to rhGH had no change in height z score, whereas those adherent to rhGH had a significant improvement of 0.16 SDs (95% confidence interval, 0.05 to 0.27); the effect size was slightly larger and remained significant after adjustment. Among participants with height≤3rd percentile and after adjustment, adherence to rhGH was associated with a 0.33 SD (95% confidence interval, 0.10 to 0.56) greater change in height z score. Nonadherence with other medication groups was not significantly associated with a change in height z score. Conclusions Self-reported nonadherence to rhGH was associated with poorer growth velocity in children with CKD, suggesting an opportunity for intervention and

  19. Medication Adherence in Psychopharmacologically Treated Adults with ADHD (United States)

    Safren, Steven A.; Duran, Petra; Yovel, Iftah; Perlman, Carol A.; Sprich, Susan


    Objective: One of the potential causes of residual symptoms of ADHD in adults can be difficulties with consistent adherence to medications. Method: This formative study examined self-reported medication adherence in adults with ADHD with clinically significant symptoms despite medication treatment. Results: Mean adherence for the two-week period…

  20. Adhesion Forces and Composition of Planktonic and Adhering Oral Microbiomes

    NARCIS (Netherlands)

    Wessel, S. W.; Chen, Y.; Maitra, A.; van den Heuvel, E. R.; Slomp, A. M.; Busscher, H. J.; van der Mei, H. C.


    The oral microbiome consists of a planktonic microbiome residing in saliva and an adhering microbiome (the biofilm adhering to oral hard and soft tissues). Here we hypothesized that possible differences in microbial composition of the planktonic and adhering oral microbiome on teeth can be related t

  1. Measuring adherence to treatment of paediatric HIV/AIDS. (United States)

    Naar-King, S; Frey, M; Harris, M; Arfken, C


    Parent, child, physician report and pill counts were used to measure adherence in paediatric HIV. Relationships to viral load were assessed. Pill counts were considered invalid. Adherence measures did not correlate with one another. Physicians reported lower adherence than parents, but parent and physician report correlated with viral load. The clinical and research utility of the various measures are discussed.

  2. A Matter of Trust: Patient Barriers to Primary Medication Adherence (United States)

    Polinski, J. M.; Kesselheim, A. S.; Frolkis, J. P.; Wescott, P.; Allen-Coleman, C.; Fischer, M. A.


    Primary medication adherence occurs when a patient properly fills the first prescription for a new medication. Primary adherence only occurs about three-quarters of the time for antihypertensive medications. We assessed patients' barriers to primary adherence and attributes of patient-provider discussions that might improve primary adherence…

  3. Medication adherence among older adults with schizophrenia. (United States)

    Leutwyler, Heather C; Fox, Patrick J; Wallhagen, Margaret


    Older adults with schizophrenia are a growing segment of the population, yet their physical and mental health status is extremely poor. This article presents findings from a qualitative study that explored the understanding older adults with schizophrenia have of their physical health status. The study was conducted among 28 older adults with schizophrenia from a variety of settings using semi-structured interviews and participant observation. Self-management of psychiatric and non-psychiatric medications and its effect on participants' health status was one of the central themes that emerged from the study. Different styles of medication adherence were identified and factors associated with each style are presented. The findings provide insights into the design of clinical interventions aimed at promoting medication adherence among older adults with schizophrenia.

  4. Expert Involvement and Adherence to Medical Evidence in Medical Mobile Phone Apps

    DEFF Research Database (Denmark)

    Subhi, Yousif; Bube, Sarah Hjartbro; Rolskov Bojsen, Signe


    BACKGROUND: Both clinicians and patients use medical mobile phone apps. Anyone can publish medical apps, which leads to contents with variable quality that may have a serious impact on human lives. We herein provide an overview of the prevalence of expert involvement in app development and whether...... or not app contents adhere to current medical evidence. OBJECTIVE: To systematically review studies evaluating expert involvement or adherence of app content to medical evidence in medical mobile phone apps. METHODS: We systematically searched 3 databases (PubMed, The Cochrane Library, and EMBASE......), and included studies evaluating expert involvement or adherence of app content to medical evidence in medical mobile phone apps. Two authors performed data extraction independently. Qualitative analysis of the included studies was performed. RESULTS: Based on inclusion criteria, 52 studies were included...

  5. Identification of Corynebacterium diphtheriae gene involved in adherence to epithelial cells. (United States)

    Kolodkina, Valentina; Denisevich, Tatyana; Titov, Leonid


    Corynebacterium diphtheriae the causative pathogen of human diphtheria infects the nasopharynx or skin. Although diphtheria has been extensively studied, little is known about the two key aspects of C. diphtheriae invasiveness: colonization and invasion. The role of adhesive properties in establishing the infection of C. diphtheriae strains, independent of toxin production, still needs to be clarified. In this study, we describe a novel gene involved in adherence to epithelial cells. Transformation of C. diphtheriae 225, biotype gravis, ribotype St-Petersburg by EZ:TN(KAN-2)Tnp Transposome was undertaken. A C. diphtheriae 225 Tn5 insertion library of 2800 mutants was created. Five hundred and eighty five transformants were qualitatively screened for reduced adherence to HEp-2 cells by an adherence assay. One mutant strain consistently exhibiting 15.2% of the wild-type adherence was isolated. The DNA flanking the transposon was identified by inverse PCR and subsequent sequencing. The disrupted gene was 94% identical to the C. diphtheriae DIP1621 gene that belongs to unclassified genes. In conclusion, the disruption of the C. diphtheriae DIP1621 gene led to decreased adherence to epithelial cells; its exact function remains to be established.

  6. Optimization and inhibition of the adherent ability of Plasmodium falciparum-infected erythrocytes

    Directory of Open Access Journals (Sweden)

    Heidi Smith


    Full Text Available The vast majority of the 1-2 million malaria associated deaths that occur each year are due to anemia and cerebral malaria (the attachment of erythrocytes containing mature forms of Plasmodium falciparum to the endothelial cells that line the vascular beds of the brain. A "model" system"for the study of cerebral malaria employs amelanotic melanoma cells as the "target"cells in an vitro cytoadherence assay. Using this model system we determined that the optimum pH for adherence is 6.6 to 6.8, that high concentrations of Ca²* (50mM result in increased levels of binding, and that the type of buffer used influences adherence (Bis Tris > MOPS > HEPES > PIPES. We also observed that the ability of infected erythrocytes to cytoadhere varied from (erythrocyte donor to donor. We have produced murine monoclonal antibodies against P. falciparum-infected red cells which recognized modified forms of human band 3; these inhibit the adherence of infected erythrocytes to melanoma cells in a doso responsive fashion. Antimalarials (chloroquine, quinacrine, mefloquine, artemisinin, on the other hand, affected adherence in an indirect fashion i.e. since cytoadherence is due, in part to the presence of knobs on the surface of the infected erythrocyte, and knob formation is dependent on intracellular parasite growth, when plasmodial development is inhibited so is knob production, and consequently adherence is ablated.

  7. Improving diabetes medication adherence: successful, scalable interventions

    Directory of Open Access Journals (Sweden)

    Zullig LL


    Full Text Available Leah L Zullig,1,2 Walid F Gellad,3,4 Jivan Moaddeb,2,5 Matthew J Crowley,1,2 William Shrank,6 Bradi B Granger,7 Christopher B Granger,8 Troy Trygstad,9 Larry Z Liu,10 Hayden B Bosworth1,2,7,11 1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center, Durham, NC, USA; 2Department of Medicine, Duke University, Durham, NC, USA; 3Center for Health Equity Research and Promotion, Pittsburgh Veterans Affairs Medical Center, Pittsburgh, PA, USA; 4Division of General Internal Medicine, University of Pittsburgh, Pittsburgh, PA, USA; 5Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA; 6CVS Caremark Corporation; 7School of Nursing, Duke University, Durham, NC, USA; 8Department of Medicine, Division of Cardiology, Duke University School of Medicine, Durham, NC, USA; 9North Carolina Community Care Networks, Raleigh, NC, USA; 10Pfizer, Inc., and Weill Medical College of Cornell University, New York, NY, USA; 11Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA Abstract: Effective medications are a cornerstone of prevention and disease treatment, yet only about half of patients take their medications as prescribed, resulting in a common and costly public health challenge for the US healthcare system. Since poor medication adherence is a complex problem with many contributing causes, there is no one universal solution. This paper describes interventions that were not only effective in improving medication adherence among patients with diabetes, but were also potentially scalable (ie, easy to implement to a large population. We identify key characteristics that make these interventions effective and scalable. This information is intended to inform healthcare systems seeking proven, low resource, cost-effective solutions to improve medication adherence. Keywords: medication adherence, diabetes mellitus, chronic disease, dissemination research

  8. A Study of Adherent Oxide Formation (United States)


    improve oxide scale adherence to NiCrAl were investigated. Laser-processed materials were isothermally and cyclically oxidized and oxide scale...modified NiCrAl altered the morphology of the alumina scale and promoted the formation of a thinner, dense protective layer. • Thin aluminum oxide films...6 A. Materials. ........................... 6 B. Oxidation Studies. ....................... 7 1. NiCrAl .. .......................... 7a2

  9. Pharmacy Adherence Measures to Assess Adherence to Antiretroviral Therapy: Review of the Literature and Implications for Treatment Monitoring


    Mayer, Kenneth H.; McMahon, James H.; Jordan, Michael R.; Kelley, Karen; Bertagnolio, Silvia; Hong, Steven Y.; Wanke, Christine A.; Sharon R Lewin; Elliott, Julian H.


    Prescription or pill-based methods for estimating adherence to antiretroviral therapy (ART), pharmacy adherence measures (PAMs), are objective estimates calculated from routinely collected pharmacy data. We conducted a literature review to evaluate PAMs, including their association with virological and other clinical outcomes, their efficacy compared with other adherence measures, and factors to consider when selecting a PAM to monitor adherence. PAMs were classified into 3 categories: medica...

  10. Concordance of adherence measurement using self-reported adherence questionnaires and medication monitoring devices. (United States)

    Shi, Lizheng; Liu, Jinan; Koleva, Yordanka; Fonseca, Vivian; Kalsekar, Anupama; Pawaskar, Manjiri


    The primary objective of this review was to identify and examine the literature on the association between medication adherence self-reported questionnaires (SRQs) and medication monitoring devices. The primary literature search was performed for 1980-2009 using PubMed, PubMed In Process and Non-Indexed, Ovid MEDLINE, Ovid MEDLINE In-Process, PsycINFO (EBSCO), CINAHL (EBSCO), Ovid HealthStar, EMBASE (Elsevier) and Cochrane Databases and using the following search terms: 'patient compliance', 'medication adherence', 'treatment compliance', 'drug monitoring', 'drug therapy', 'electronic', 'digital', 'computer', 'monitor', 'monitoring', 'drug', 'drugs', 'pharmaceutical preparations', 'compliance' and 'medications'. We identified studies that included SRQs and electronic monitoring devices to measure adherence and focused on the SRQs that were found to be moderately to highly correlated with the monitoring devices. Of the 1679 citations found via the primary search, 41 full-text articles were reviewed for correlation between monitoring devices and SRQs. A majority (68%) of articles reported high (27%), moderate (29%) or significant (12%) correlation between monitoring devices (37 using Medication Event Monitoring System [MEMS®] and four using other devices) and SRQs (11 identified and numerous other unnamed SRQs). The most commonly used SRQs were the Adult/Pediatric AIDS Clinical Trial Group (AACTG/PACTG; 24.4%, 10/41) followed by the 4-item Morisky (9.8%, 4/41), Brief Medication Questionnaire (9.8%, 4/41) and visual analogue scale (VAS; 7.3%, 3/41). Although study designs differed across the articles, SRQs appeared to report a higher rate of medication adherence (+14.9%) than monitoring devices. In conclusion, several medication adherence SRQs were validated using electronic monitoring devices. A majority of them showed high or moderate correlation with medication adherence measured using monitoring devices, and could be considered for measuring patient

  11. Can adherence to antihypertensive therapy be used to promote adherence to statin therapy?

    Directory of Open Access Journals (Sweden)

    Richard H Chapman


    Full Text Available Richard H Chapman1, Elise M Pelletier1, Paula J Smith1, Craig S Roberts21US Health Economics and Outcomes Research, IMS Health, Falls Church, VA, USA; 2Global Outcomes Research, Pfizer Inc, New York, NY, USAObjective: To compare adherence with statin therapy in patients switching to single-pill amlodipine besylate/atorvastatin calcium with patients adding a separate statin to their amlodipine regimen.Methods: We identified hypertensive patients prescribed amlodipine who switched to amlodipine/atorvastatin (switch or added a statin to their amlodipine regimen (add-on from July 2004 to June 2007. Propensity score matching (1 switch:3 add-on was applied based on ‘nearest neighbor’ approach. The primary adherence measure was patients with proportion of days covered (PDC ≥0.80 at 180 days; secondary measures included mean PDC and persistence. A sensitivity analysis was performed, accounting for total statin/amlodipine exposure.Results: Among 4556 matched patients (n = 1139 switch; n = 3417 add-on, mean age was 53.9 years and 52.1% were male. After 180 days, adherence with statin therapy was higher for the switch vs add-on cohort (50.8% vs 44.3%; P < 0.001. After adjusting for pre-index amlodipine adherence, the switch cohort was more likely to be adherent than the add-on cohort (odds ratio: 1.64 [95% confidence interval: 1.42 to 1.89]. Persistence was higher in the switch than the add-on cohort (127.6 vs 117 days; P < 0.001.Conclusion: Hypertensive patients taking amlodipine who initiated statin therapy via single-pill amlodipine/atorvastatin were more likely to remain adherent to their statin than patients adding a separate statin to their antihypertensive regimen.Keywords: adherence, amlodipine, atorvastatin, cardiovascular disease, persistence, single-pill

  12. Adherence to asthma guidelines in general practices. (United States)

    Roghmann, M C; Sexton, M


    Adherence to asthma practice guidelines is low. Improved compliance could potentially improve care of patients with asthma. The purpose of this study was to determine if patients managed in a general practice with an associated asthma clinic are more likely to use asthma medications according to clinical practice guidelines than patients managed in the general surgery of the practice. A cross-sectional study of adult asthmatics, aged 18-55 years, was conducted in six British general practices. Prescription data on all asthma medication was collected for a 6-month period. Information on asthma clinic attendance, age, sex, employment status, other medical illness, and how patients used their inhaled beta2-agonist was collected through questionnaire. The prescription data for asthma medication and patient use of inhaled beta2-agonist were compared to the British Thoracic Society's (BTS) Guidelines for Management of Asthma in Adults to determine if the patient's asthma medication regimen was appropriate. There was no significant association found between appropriate asthma medication and asthma clinic attendance or other patient characteristics. Adherence to the BTS guidelines was low. Fifty-eight percent of the asthma patients used asthma medication regimens that were not consistent with the BTS guidelines published 1 year earlier. Adherence to the BTS guidelines was low regardless of patient characteristics, including asthma clinic attendance, age, sex, employment status, other medical illness, or individual practice. These findings underscore the need to document the utility of clinical practice guidelines which may improve physician compliance.

  13. Characterization of early and terminal complement proteins associated with polymorphonuclear leukocytes in vitro and in vivo after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Galvan Manuel D


    Full Text Available Abstract Background The complement system has been suggested to affect injury or disease of the central nervous system (CNS by regulating numerous physiological events and pathways. The activation of complement following traumatic CNS injury can also result in the formation and deposition of C5b-9 membrane attack complex (C5b-9/MAC, causing cell lysis or sublytic effects on vital CNS cells. Although complement proteins derived from serum/blood-brain barrier breakdown can contribute to injury or disease, infiltrating immune cells may represent an important local source of complement after injury. As the first immune cells to infiltrate the CNS within hours post-injury, polymorphonuclear leukocytes (PMNs may affect injury through mechanisms associated with complement-mediated events. However, the expression/association of both early and terminal complement proteins by PMNs has not been fully characterized in vitro, and has not observed previously in vivo after traumatic spinal cord injury (SCI. Method We investigated the expression of complement mRNAs using rt-PCR and the presence of complement proteins associated with PMNs using immunofluroescence and quantitative flow cytometry. Results Stimulated or unstimulated PMNs expressed mRNAs encoding for C1q, C3, and C4, but not C5, C6, C7 or C9 in culture. Complement protein C1q or C3 was also detected in less than 30% of cultured PMNs. In contrast, over 70% of PMNs that infiltrated the injured spinal cord were associated with C1q, C3, C7 and C5b-9/MAC 3 days post-SCI. The localization/association of C7 or C5b-9/MAC with infiltrating PMNs in the injured spinal cord suggests the incorporation or internalization of C7 or C5b-9/MAC bound cellular debris by infiltrating PMNs because C7 and C5b-9/MAC were mostly localized to granular vesicles within PMNs at the spinal cord epicenter region. Furthermore, PMN presence in the injured spinal cord was observed for many weeks post-SCI, suggesting that this

  14. Adherence to physical and mental activity interventions: Coping plans as a mediator and prior adherence as a moderator.

    NARCIS (Netherlands)

    Evers, A.W.M.; Klusmann, V.; Schwarzer, R.; Heuser, I.


    Objective. Adherence to behavioural intervention programmes is a necessary condition for beneficial outcomes to be achieved. This study tested whether social cognitive variables and coping plans predict adherence. Design and methods. Adherence was examined in a randomized controlled trial with healt

  15. Adherence of Helicobacter pylori to the Gastric Mucosa

    Directory of Open Access Journals (Sweden)

    Marguerite Clyne


    Full Text Available Bacterial adhesion to the intestinal epithelium is a critical initial step in the pathogenesis of many enteric diseases. Helicobacter pylori is a duodenal pathogen that adheres to the gastric epithelium and causes gastritis and peptic ulceration. The mechanism by which H pylori causes disease has not yet been elucidated but adherence to the gastric mucosa is thought to be an important virulence determinant of the organism. What is known about adherence of H pylori to the gastric mucosa is summarized. Topics discussed are the mechanism of H pylori adherence; in vitro and in vivo models of H pylori infection; and adherence and potential adhesins and receptors for H pylori.

  16. Adherence Characteristics of Cement Clinker on Basic Bricks

    Institute of Scientific and Technical Information of China (English)

    GUO Zongqi; Michel Rigaud


    Based on the sandwich test, adherence mechanisms of cement clinker on various basic bricks were tackled by microstructural observations with help of cathodoluminescence technique. Doloma based bricks offer sufficient lime to react with clinker, forming C3 S rich layer and initializing superior adherence. However, clinker with low silica ratio leads to MgO agglomeration at the interface of doloma bricks, which reduces adherence strength. On magnesia spinel bricks, fine, crystalline spinel easily reacts with lime containing phases from clinker to form lowmelting phases and belite zone, which shows high adherence performance. Lack of fine spinel in magnesia spinel bricks results in poor adherence.

  17. Sharia Adherence Mosque Survey: Correlations between Sharia Adherence and Violent Dogma in U.S. Mosques

    Directory of Open Access Journals (Sweden)

    Mordechai Kedar


    Full Text Available A random survey of 100 representative mosques in the U.S. was conducted to measure the correlation between Sharia adherence and dogma calling for violence against non-believers.  Of the 100 mosques surveyed, 51% had texts on site rated as severely advocating violence; 30% had texts rated as moderately advocating violence; and 19% had no violent texts at all.  Mosques that presented as Sharia adherent were more likely to feature violence-positive texts on site than were their non-Sharia-adherent counterparts.  In 84.5% of the mosques, the imam recommended studying violence-positive texts.  The leadership at Sharia-adherent mosques was more likely to recommend that a worshipper study violence-positive texts than leadership at non-Sharia-adherent mosques.  Fifty-eight percent of the mosques invited guest imams known to promote violent jihad.  The leadership of mosques that featured violence-positive literature was more likely to invite guest imams who were known to promote violent jihad than was the leadership of mosques that did not feature violence-positive literature on mosque premises.  

  18. Iron Chelation Adherence to Deferoxamine and Deferasirox in Thalassemia (United States)

    Trachtenberg, Felicia; Vichinsky, Elliott; Haines, Dru; Pakbaz, Zahra; Mednick, Lauren; Sobota, Amy; Kwiatkowski, Janet; Thompson, Alexis A.; Porter, John; Coates, Thomas; Giardina, Patricia J.; Olivieri, Nancy; Yamashita, Robert; Neufeld, Ellis J.


    The Thalassemia Clinical Research Network collected adherence information from 79 patients on deferoxamine and 186 on deferasirox from 2007 to 2009. Chelation adherence was defined as percent of doses administered in the last 4 weeks (patient report) out of those prescribed (chart review). Chelation history since 2002 was available for 97 patients currently on deferoxamine and 217 on deferasirox, with crude estimates of adherence from chart review. Self-reported adherence to both deferoxamine and deferasirox were quite high, with slightly higher adherence to the oral chelator (97 vs. 92%). Ninety percent of patients on deferasirox reported at least 90% adherence, compared with 75% of patients on deferoxamine. Adherence to both chelators was highest in children, followed by adolescents and older adults. Predictors of lower deferoxamine adherence were smoking in the past year, problems sticking themselves (adults only), problems wearing their pump, and fewer transfusions in the past year. Predictors of lower deferasirox adherence were bodily pain and depression. Switching chelators resulted in increased adherence, regardless of the direction of the switch, although switching from deferoxamine to deferasirox was far more common. As adherence to deferoxamine is higher than previously reported, it appears beneficial for patients to have a choice in chelators. PMID:21523808

  19. Iron chelation adherence to deferoxamine and deferasirox in thalassemia. (United States)

    Trachtenberg, Felicia; Vichinsky, Elliott; Haines, Dru; Pakbaz, Zahra; Mednick, Lauren; Sobota, Amy; Kwiatkowski, Janet; Thompson, Alexis A; Porter, John; Coates, Thomas; Giardina, Patricia J; Olivieri, Nancy; Yamashita, Robert; Neufeld, Ellis J


    The Thalassemia Clinical Research Network collected adherence information from 79 patients on deferoxamine and 186 on deferasirox from 2007 to 2009. Chelation adherence was defined as percent of doses administered in the last 4 weeks (patient report) out of those prescribed(chart review). Chelation history since 2002 was available for 97 patients currently on deferoxamine and 217 on deferasirox, with crude estimates of adherence from chart review. Self-reported adherence to both deferoxamine and deferasirox were quite high, with slightly higher adherence to the oral chelator (97 vs. 92%). Ninety percent of patients on deferasirox reported at least 90% adherence, compared with 75% of patients on deferoxamine. Adherence to both chelators was highest in children, followed by adolescents and older adults.Predictors of lower deferoxamine adherence were smoking in the past year, problems sticking themselves (adults only), problems wearing their pump, and fewer transfusions in the past year. Predictors of lower deferasirox adherence were bodily pain and depression. Switching chelators resulted in increased adherence, regardless of the direction of the switch, although switching from deferoxamine to deferasirox was far more common. As adherence to deferoxamine is higher than previously reported, it appears beneficial for patients to have a choice in chelators.

  20. Unsupervised explorative data analysis of normal human leukocytes and BCR/ABL positive leukemic cells mid-infrared spectra

    NARCIS (Netherlands)

    Bellisola, G.; Bolomini-Vittori, M.; Cinque, G.; Dumas, P.; Fiorini, Z.; Laudanna, C.; Mirenda, M.; Sandt, C.; Silvestri, G.; Tomasello, L.; Vezzalini, M.; Wehbe, K.; Sorio, C.


    We proved the ability of Fourier Transform Infrared microspectroscopy (microFTIR) complemented by Principal Component Analysis (PCA) to detect protein phosphorylation/de-phosphorylation in mammalian cells. We analyzed by microFTIR human polymorphonuclear neutrophil (PMNs) leukocytes, mouse-derived p

  1. A simple method for measuring thickness of the mucus gel layer adherent to rat, frog and human gastric mucosa: influence of feeding, prostaglandin, N-acetylcysteine and other agents. (United States)

    Kerss, S; Allen, A; Garner, A


    1. A technique has been developed for measuring thickness of the gastric surface mucus gel layer. Mucosal sections (1.6 mm) were cut from frog and rat stomach and human antrum, mounted transversely and viewed by an inverse microscope (x 200 magnification) under dark field illumination or phase contrast. The mucus layer was readily distinguishable and its dimensions could be recorded by means of an eyepiece graticule. 2. Mean mucus gel thickness in rat, frog was 73, 76, 55 and 192 micrometer respectively. However, there was variation in the average thickness of the gel layer between individual mucosae from the same species (up to twofold). Mucus thickness between adjacent regions of the same mucosal section also varied markedly (up to tenfold). 3. Topical administration of 16,16-dimethylprostaglandin E2 by oral intubation caused a significant increase in thickness in both rat and frog at doses of 5 microgram/ml and 0.5 microgram/ml respectively. Feeding and exposure of the mucosa to N-acetylcysteine (10-20%, w/v) produced variable effects whereas pepsin (1 mg/ml) caused a marked reduction in thickness of the surface gel layer in both rat and frog. 4. The technique provides a rapid and simple method for determining gastrointestinal mucus thickness in relation to mucosal morphology. It is ideally suited for studying the control of mucus secretion and effect of drugs.

  2. Pharmacy adherence measures to assess adherence to antiretroviral therapy: review of the literature and implications for treatment monitoring. (United States)

    McMahon, James H; Jordan, Michael R; Kelley, Karen; Bertagnolio, Silvia; Hong, Steven Y; Wanke, Christine A; Lewin, Sharon R; Elliott, Julian H


    Prescription or pill-based methods for estimating adherence to antiretroviral therapy (ART), pharmacy adherence measures (PAMs), are objective estimates calculated from routinely collected pharmacy data. We conducted a literature review to evaluate PAMs, including their association with virological and other clinical outcomes, their efficacy compared with other adherence measures, and factors to consider when selecting a PAM to monitor adherence. PAMs were classified into 3 categories: medication possession ratio (MPR), pill count (PC), and pill pick-up (PPU). Data exist to recommend PAMs over self-reported adherence. PAMs consistently predicted patient outcomes, but additional studies are needed to determine the most predictive PAM parameters. Current evidence suggests that shorter duration of adherence assessment (≤ 6 months) and use of PAMs to predict future outcomes may be less accurate. PAMs which incorporate the number of days for which ART was prescribed without the counting of remnant pills, are reasonable minimum-resource methods to assess adherence to ART.

  3. Adherence to Mediterranean diet and bone health

    Directory of Open Access Journals (Sweden)

    Antonio Romero Pérez


    Full Text Available Introduction: Several studies have concluded that incidences of osteoporosis and osteoporosis-related fractures vary across the European Union, the lowest incidence being reported in the Mediterranean area. The beneficial effect is mainly attributed to a specific eating pattern. The Mediterranean diet contain a complex array of naturally occurring bioactive molecules with antioxidant, anti-inflammatory and alkalinising properties that may contribute to the bone-sparing effect of the Mediterranean diet. Objective: The purpose of this review is to examine the evidence to date on the effects of Mediterranean diet on bone health. Methods: The search for articles came from extensive research in the following databases: PubMed, Scopus and Web of Science. We used the search terms "Mediterranean diet", "adherence", "fruit and vegetable", "olive oil", "fish" "legume", "cereal" "alcohol", "bone", "osteoporosis", "fracture", and combinations, such as "Mediterranean diet and bone" or "Mediterranean diet and fracture". Results: A limited number of studies have examined the relationship between Mediterranean Diet and bone health, and they have reported conflicting results. On the one hand, adherence to a traditional MeDi has been associated with higher bone mineral density and lower fracture risk. The results of these studies could be attributed to the combined beneficial effects of individual components of the Mediterranean diet. On the contrary, several studies failed to show any association between adherence to the MeDi and indices of bone mass. Conclusions: Further large-scale studies are required to clarify the effect of Mediterranean diet on bone health, in order to establish the role of this diet in the prevention of osteoporosis.

  4. Community health workers adherence to referral guidelines

    DEFF Research Database (Denmark)

    Lal, Sham; Ndyomugenyi, Richard; Paintain, Lucy;


    Background Many malaria-endemic countries have implemented national community health worker (CHW) programmes to serve remote populations that have poor access to malaria diagnosis and treatment. Despite mounting evidence of CHWs’ ability to adhere to malaria rapid diagnostic tests (RDTs...... artemisinin-based combination therapy (ACT) and recognize symptoms in children that required immediate referral to the nearest health centre. Intervention arm CHWs had additional training on how to conduct an RDT; CHWs in the control arm used a presumptive diagnosis for malaria using clinical signs...

  5. Patient adherence to medical treatment: a review of reviews

    Directory of Open Access Journals (Sweden)

    Heerdink Rob


    Full Text Available Abstract Background Patients' non-adherence to medical treatment remains a persistent problem. Many interventions to improve patient adherence are unsuccessful and sound theoretical foundations are lacking. Innovations in theory and practice are badly needed. A new and promising way could be to review the existing reviews of adherence to interventions and identify the underlying theories for effective interventions. That is the aim of our study. Methods The study is a review of 38 systematic reviews of the effectiveness of adherence interventions published between 1990 and 2005. Electronic literature searches were conducted in Medline, Psychinfo, Embase and the Cochrane Library. Explicit inclusion and exclusion criteria were applied. The scope of the study is patient adherence to medical treatment in the cure and care sector. Results Significant differences in the effectiveness of adherence interventions were found in 23 of the 38 systematic reviews. Effective interventions were found in each of four theoretical approaches to adherence interventions: technical, behavioural, educational and multi-faceted or complex interventions. Technical solutions, such as a simplification of the regimen, were often found to be effective, although that does not count for every therapeutic regimen. Overall, our results show that, firstly, there are effective adherence interventions without an explicit theoretical explanation of the operating mechanisms, for example technical solutions. Secondly, there are effective adherence interventions, which clearly stem from the behavioural theories, for example incentives and reminders. Thirdly, there are other theoretical models that seem plausible for explaining non-adherence, but not very effective in improving adherence behaviour. Fourthly, effective components within promising theories could not be identified because of the complexity of many adherence interventions and the lack of studies that explicitly compare

  6. Curli Temper Adherence of Escherichia coli O157:H7 to Squamous Epithelial Cells from the Bovine Recto-Anal Junction in a Strain-Dependent Manner. (United States)

    Kudva, Indira T; Carter, Michelle Q; Sharma, Vijay K; Stasko, Judith A; Giron, Jorge A


    Our recent studies have shown that intimin and the locus of enterocyte effacement-encoded proteins do not play a role in Escherichia coli O157:H7 (O157) adherence to the bovine recto-anal junction squamous epithelial (RSE) cells. To define factors that play a contributory role, we investigated the role of curli, fimbrial adhesins commonly implicated in adherence to various fomites and plant and human epithelial cells, in O157 adherence to RSE cells. Specifically, we examined (i) wild-type strains of O157; (ii) curli variants of O157 strains; (iii) isogenic curli deletion mutants of O157; and (iv) adherence inhibition of O157 using anti-curlin sera. Results of these experiments conducted under stringent conditions suggest that curli do not solely contribute to O157 adherence to RSE cells and in fact demonstrate a modulating effect on O157 adherence to RSE cells in contrast to HEp-2 cells (human epidermoid carcinoma of the larynx cells with HeLa contamination). The absence of curli and presence of blocking anti-curli antibodies enhanced O157-RSE cell interactions among some strains, thus alluding to a spatial, tempering effect of curli on O157 adherence to RSE cells when present. At the same time, the presence or absence of curli did not alter RSE cell adherence patterns of another O157 strain. These observations are at variance with the reported role of curli in O157 adherence to human cell lines such as HEp-2 and need to be factored in when developing anti-adherence modalities for preharvest control of O157 in cattle.

  7. IL-6 acts on endothelial cells to preferentially increase their adherence for lymphocytes. (United States)

    Watson, C; Whittaker, S; Smith, N; Vora, A J; Dumonde, D C; Brown, K A


    Using a quantitative monolayer adhesion assay, the current report shows that treatment of human umbilical vein endothelial cells (HUVEC) with IL-6 increases their adhesiveness for blood lymphocytes, particularly CD4+ cells, but not for polymorphonuclear cells and monocytes. This effect, which was most pronounced when using low concentrations of the cytokine (0.1-1.0 U/ml) and a short incubation period (4h), was also apparent with microvascular endothelial cells and a hybrid endothelial cell line. Skin lesions from patients with mycosis fungoides contain high levels of IL-6, and blood lymphocytes from patients with this disorder also exhibited an enhanced adhesion to IL-6-treated HUVEC. The cytokine enhanced intercellular adhesion molecule-1 (ICAM-1) expression and induced the expression of vascular cell adhesion molecule-1 (VCAM-1) and E-selectin on endothelial cells. Antibody blocking studies demonstrated that the vascular adhesion molecules ICAM-1, VCAM-1 and E-selectin and the leucocyte integrin LFA-1 all contributed to lymphocyte binding to endothelium activated by IL-6. It is proposed that IL-6 may be involved in the recruitment of lymphocytes into non-lymphoid tissue.

  8. Using communication skills to improve adherence in children with chronic disease : The adherence equation

    NARCIS (Netherlands)

    Brand, Paul L. P.; Klok, Ted; Kaptein, Adrian A.


    Nonadherence to maintenance medication is common in paediatric chronic conditions. Despite the common belief that nonadherence is therapy-resistant, and the apparent lack of evidence for successful interventions to improve adherence, there is, in fact, a considerable body of evidence suggesting that

  9. Accurate reporting of adherence to inhaled therapies in adults with cystic fibrosis: methods to calculate normative adherence

    Directory of Open Access Journals (Sweden)

    Hoo ZH


    Full Text Available Zhe Hui Hoo,1,2 Rachael Curley,1,2 Michael J Campbell,1 Stephen J Walters,1 Daniel Hind,3 Martin J Wildman1,2 1School of Health and Related Research (ScHARR, University of Sheffield, 2Sheffield Adult Cystic Fibrosis Centre, Northern General Hospital, 3Sheffield Clinical Trials Research Unit, University of Sheffield, Sheffield, UK 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

  10. Statistical Dynamics of Religions and Adherents

    CERN Document Server

    Ausloos, M; Ausloos, Marcel; Petroni, Filippo


    Religiosity is one of the most important sociological aspects of populations. All religions may evolve in their beliefs and adapt to the society developments. A religion is a social variable, like a language or wealth, to be studied like any other organizational parameter. Several questions can be raised, as considered in this study: e.g. (i) from a ``macroscopic'' point of view : How many religions exist at a given time? (ii) from a ``microscopic'' view point: How many adherents belong to one religion? Does the number of adherents increase or not, and how? No need to say that if quantitative answers and mathematical laws are found, agent based models can be imagined to describe such non-equilibrium processes. It is found that empirical laws can be deduced and related to preferential attachment processes, like on evolving network; we propose two different algorithmic models reproducing as well the data. Moreover, a population growth-death equation is shown to be a plausible modeling of evolution dynamics in a...

  11. Automated microinjection system for adherent cells (United States)

    Youoku, Sachihiro; Suto, Yoshinori; Ando, Moritoshi; Ito, Akio


    We have developed an automated microinjection system that can handle more than 500 cells an hour. Microinjection injects foreign agents directly into cells using a micro-capillary. It can randomly introduce agents such as DNA, proteins and drugs into various types of cells. However, conventional methods require a skilled operator and suffer from low throughput. The new automated microinjection techniques we have developed consist of a Petri dish height measuring method and a capillary apex position measuring method. The dish surface height is measured by analyzing the images of cells that adhere to the dish surface. The contrast between the cell images is minimized when the focus plane of an object lens coincides with the dish surface. We have developed an optimized focus searching method with a height accuracy of +/-0.2 um. The capillary apex position detection method consists of three steps: rough, middle, and precise. These steps are employed sequentially to cover capillary displacements of up to +/-2 mm, and to ultimately accomplish an alignment accuracy of less than one micron. Experimental results using this system we developed show that it can introduce fluorescent material (Alexa488) into adherent cells, HEK293, with a success rate of 88.5%.

  12. Statistical dynamics of religions and adherents (United States)

    Ausloos, M.; Petroni, F.


    Religiosity is one of the most important sociological aspects of populations. All religions may evolve in their beliefs and adapt to the society developments. A religion is a social variable, like a language or wealth, to be studied like any other organizational parameter. Several questions can be raised, as considered in this study; e.g.: i) From a "macroscopic" point of view: How many religions exist at a given time? ii) From a "microscopic" viewpoint: How many adherents belong to one religion? Does the number of adherents increase or not, and how? No need to say that if quantitative answers and mathematical laws are found, agent-based models can be imagined to describe such non-equilibrium processes. It is found that empirical laws can be deduced and related to preferential attachment processes, like on an evolving network; we propose two different algorithmic models reproducing as well the data. Moreover, a population growth-death equation is shown to be a plausible modeling of evolution dynamics in a continuous-time framework. Differences with language dynamic competition are emphasized.

  13. LL-37, HNP-1, and HBD2/3 modulate the secretion of cytokines TNF-α, IL-6, IFN-γ, IL-10 and MMP1 in human primary cell cultures. (United States)

    Medina Santos, Carlos Erik; López Hurtado, Carmen Nathaly; Rivas Santiago, Bruno; Gonzalez-Amaro, Roberto; Cataño Cañizales, Yolanda Guadalupe; Martínez Fierro, Margarita de la Luz; Enciso-Moreno, José Antonio; García Hernández, Mariana Haydee


    The aim of this study was to evaluate the effects of the LL-37, HNP-1 and HBD2/3 peptides on cytokine and MMP production in human polymorphonuclear cells, mononuclear cells and chondrocytes. The levels of cytokines in supernatants from mononuclear and polymorphonuclear cell cultures were measured with a cytometric bead array by flow cytometry. Likewise, the levels of metalloproteinase/MMP-1, 3, and 13 were measured in supernatants from chondrocyte cultures using an ELISA. The expression of RANKL on lymphocytes was analyzed by flow cytometry. We observed increased levels of TNF-α, IL-6 and IL-10 in mononuclear and polymorphonuclear cell cultures stimulated with HBD-2/3. We also observed increased levels of IFN-γ, IL-10, and IL-6 in mononuclear cell cultures stimulated with HNP-1, and increased IL-6 levels were observed in polymorphonuclear cell cultures exposed to HNP-1. We also found that the MMP-1 level increased in the chondrocyte cultures stimulated with HBD-3, whereas the MMP-1 level was decreased in cultures exposed to LL-37. The present report is the first study to determine that HNP-1and HBD2/3 promote the secretion of pro-inflammatory cytokines by polymorphonuclear and mononuclear cells and the secretion of MMP by chondrocytes, whereas LL-37 diminishes MMP1 secretion. Our results suggest that HBD-2/3 and HNP1 might play a pathological role in rheumatoid arthritis, while LL-37 might have a protective role.

  14. Side effects, adherence self-efficacy, and adherence to antiretroviral treatment: a mediation analysis in a Chinese sample. (United States)

    Zhang, Liying; Li, Xiaoming; Lin, Zhenping; Jacques-Tiura, Angela J; Xu, Jinping; Zhou, Yuejiao; Qiao, Shan; Shen, Zhiyong; Stanton, Bonita


    Antiretroviral therapy (ART) is a lifelong treatment. To date, ART adherence is suboptimal for most patients in resource-poor settings. Previous research indicates that medication side effects are perceived to be a significant barrier of high ART adherence. Data regarding the role of adherence self-efficacy in mediating the relationship between side effects from ART and adherence to ART are limited; thus, this study examines this potential mediational role of self-efficacy. A cross-sectional survey of 2987 people living with HIV aged ≥18 years was conducted in 2012-2013 in Guangxi Autonomous Region (Guangxi) which has one of the fastest-growing HIV rates in China. Of the total sample, 2146 (72.1%) participants had initiated ART. Participants reported the number of days of completing the daily dose of ART in the past month; adherence was defined as completing the daily dose at least 28 days in the last month (≥90%). Side effects were significantly negatively related to adherence to ART. Mediation analyses indicated that adherence self-efficacy significantly mediated the side effects-adherence relationship. Future interventions to increase adherence self-efficacy and effective coping with side effects among HIV patients are needed in order to improve their ART adherence.

  15. Stability of adherence to highly active antiretroviral therapy over time among clients enrolled in the treatment adherence demonstration project. (United States)

    Tesoriero, James; French, Tyler; Weiss, Linda; Waters, Mark; Finkelstein, Ruth; Agins, Bruce


    Adherence to antiretroviral medications is essential to therapeutic success. Many published studies have investigated the degree of adherence or nonadherence, but sample sizes have generally been small, and adherence has seldom been viewed as a longitudinal process. This paper investigates the stability of adherence over time among HIV-infected individuals attending adherence support programs in New York State. The study cohort consists of 435 clients who were on HAART at baseline and who completed at least 2 follow-up interviews. Although cross-sectional nonadherence did not exceed 35%, nonadherence reached 54% when considered across all 3 interviews. Analysis of transition matricies revealed moderate stability in adherence over time (e.g., first follow-up adherence was 81.0% for clients adherent at baseline, compared with 58.3% for clients nonadherent at baseline). Second-order transition matricies offered additional predictive utility. Multivariate results indicated that, for some, it was the transition from a desirable to an undesirable state (e.g., from no illicit drug use to illicit drug use) that increased the likelihood of nonadherence, rather than the presence of these characteristics over time. Findings illustrate the importance of multiple, periodic assessments of adherence and the need to consider strategies to increase stability in the factors affecting adherence to HAART.

  16. High throughput RNAi assay optimization using adherent cell cytometry

    Directory of Open Access Journals (Sweden)

    Pradhan Leena


    Full Text Available Abstract Background siRNA technology is a promising tool for gene therapy of vascular disease. Due to the multitude of reagents and cell types, RNAi experiment optimization can be time-consuming. In this study adherent cell cytometry was used to rapidly optimize siRNA transfection in human aortic vascular smooth muscle cells (AoSMC. Methods AoSMC were seeded at a density of 3000-8000 cells/well of a 96well plate. 24 hours later AoSMC were transfected with either non-targeting unlabeled siRNA (50 nM, or non-targeting labeled siRNA, siGLO Red (5 or 50 nM using no transfection reagent, HiPerfect or Lipofectamine RNAiMax. For counting cells, Hoechst nuclei stain or Cell Tracker green were used. For data analysis an adherent cell cytometer, Celigo® was used. Data was normalized to the transfection reagent alone group and expressed as red pixel count/cell. Results After 24 hours, none of the transfection conditions led to cell loss. Red fluorescence counts were normalized to the AoSMC count. RNAiMax was more potent compared to HiPerfect or no transfection reagent at 5 nM siGLO Red (4.12 +/-1.04 vs. 0.70 +/-0.26 vs. 0.15 +/-0.13 red pixel/cell and 50 nM siGLO Red (6.49 +/-1.81 vs. 2.52 +/-0.67 vs. 0.34 +/-0.19. Fluorescence expression results supported gene knockdown achieved by using MARCKS targeting siRNA in AoSMCs. Conclusion This study underscores that RNAi delivery depends heavily on the choice of delivery method. Adherent cell cytometry can be used as a high throughput-screening tool for the optimization of RNAi assays. This technology can accelerate in vitro cell assays and thus save costs.

  17. [e-Health interventions and improvement in treatment adherence]. (United States)

    Sieben, Angelien; Bredie, S J H Bas; van Laarhoven, C J H M Kees; Schoonhoven, Lisette; Burger, David M; van Onzenoort, Hein A W


    Poor adherence to medication is one of the most important determinants in the treatment of patients with chronic disorders. e-Health-based interventions may be able to improve treatment adherence. This article gives an overview of the available e-Health interventions and the extent to which they can improve adherence. We searched in the PubMed, Cinahl, PsycInfo, and Embase databases for e-Health interventions that aimed at improving adherence to treatment. Of the 16 included studies, 15 used a website and one used an app. Ten studies showed a significant improvement in treatment adherence by using the intervention. e-Health interventions were generally complex. Simple interventions were the most successful in improving treatment adherence.

  18. Measuring insulin adherence among adults with type 2 diabetes. (United States)

    Osborn, Chandra Y; Gonzalez, Jeffery S


    Non-adherence to insulin is common and associated with suboptimal health. We adapted the Morisky Medication Adherence Scale to specify insulin adherence (MIAS) and compared it to the Adherence to Refills and Medication Scale for Diabetes (ARMS-D) and the Summary of Diabetes Self-Care Activities medications subscale (SDSCA-MS) and an insulin-specific (SDSCA-IS) version. A sample of 144 insulin-treated adults (58 % African American/Black, 34 % Caucasian/White, 8 % Other/Mixed race; 6.9 % Hispanic) completed these measures along with a HbA1C test. The internal consistency and factor structure of the MIAS were adequate; 59 % of participants forgot to take insulin and 46 % reported non-adherence. The MIAS was associated with the ARMS-D, SDSCA-MS, and SDSCA-IS (p insulin adherence assessment tool for practice and research applications.

  19. What strategies do ulcerative colitis patients employ to facilitate adherence? (United States)

    Kawakami, Aki; Tanaka, Makoto; Naganuma, Makoto; Maeda, Shin; Kunisaki, Reiko; Yamamoto-Mitani, Noriko


    Background Overall, 30%–45% of patients with ulcerative colitis (UC) are non-adherent and have difficulties taking their medications; this non-adherence increases the risk of clinical relapse 1.4- to 5.5-fold. This study aimed to clarify the strategies patients employ to facilitate adherence and determine whether the strategies had an impact on good adherence. Methods This was a cross-sectional survey using a self-administered questionnaire and review of medical records. Patients diagnosed as having UC and attending one of the outpatient clinics of four urban hospitals from June 2009 to December 2012 were enrolled. A questionnaire was developed to identify the strategies patients employ to facilitate adherence and then administered to patients with UC. Adherence to 5-aminosalicylic acid was calculated, and univariate and multiple logistic regression analyses were performed to determine the strategies that were associated with good adherence. Results The final analyses included 671 participants (mean age 40.2 years; 54.3% males). The valid response rate was 96.9%; 186 (27.7%) participants were classified as non-adherent, the mean adherence rate being 86.1% (standard deviation [SD] 17.9). Seven strategies that patients employ to facilitate adherence were identified, the following two being significantly associated with good adherence: “I keep my medicines where I eat meals” and “I keep each day’s medicine in a pill case or something similar to make sure I have taken them”. Conclusion The identified strategies might be used to develop a program to improve medication adherence in patients with UC. PMID:28203059

  20. Concern between medication non-adherence and diabetes associated depression


    Krishnan Vengadaragava Chary; Porchelvan Swaminathan


    Background: Diabetes mellitus is one of the health disorders that acquire mankind immensely. An ominous twin of diabetes mellitus is diabetes associated depression which is often unrecognised in routine diabetic care. The objective of this study was to find the prevalence and correlation between medication adherence and diabetes associated depression. Methods: It is a conducted as cross sectional study using Morisky medication adherence scale to evaluate treatment adherence of type II diab...

  1. Marginal Microleakage of Conventional Fissure Sealants and Self-Adhering Flowable Composite as Fissure Sealant in Permanent Teeth

    Directory of Open Access Journals (Sweden)

    Sara Rahimian-Imam


    Full Text Available Objectives: Application of sealants is a safe and effective way to prevent occlusal caries in the posterior teeth. A successful sealant therapy depends on good isolation. Decreased steps of adhesive application may enable proper isolation and use of self-adhering flowable composites for sealant therapy. This study sought to compare the marginal microleakage of fissure sealants and self-adhering flowable composites in permanent teeth.Materials and Methods: This in vitro, experimental study was conducted on 60 extracted human premolar teeth. The teeth were divided randomly into two groups of 30. In the first group, fissure sealant (Clinpro, 3M ESPE, USA was placed on the teeth. In the second group, self-adhering flowable composite (Vertise Flow, Kerr, USA was applied as the sealant. Then, both groups were immersed in 0.5% fuchsin dye solution for 24 hours. Sectioned samples were observed with a stereomicroscope for the extent of dye penetration. Data were analyzed using SPSS 21 and the Mann-Whitney test (P<0.05.Results: Microleakage in the fissure sealant group was significantly higher than that in the self-adhering flowable composite group (P<0.001.Conclusion: Microleakage was less using self-adhering flowable composite compared to conventional fissure sealant; therefore, self-adhering flowable composite can be used as a suitable fissure sealant in permanent teeth.

  2. The role of family caregivers in HIV medication adherence. (United States)

    Beals, K P; Wight, R G; Aneshensel, C S; Murphy, D A; Miller-Martinez, D


    This study examines the role that mid-life and older wives and mothers play in promoting medication adherence among their HIV-infected husbands or adult sons who require daily living assistance. Interviews were conducted with 112 caregiving dyads, with caregivers reporting on their own behaviours and attitudes towards medications, and care-recipients (persons living with HIV [PLH]) providing information about their own adherence practices. By examining how caregiver characteristics, behaviours, and attitudes may influence PLH adherence it is explicitly recognized that caregivers and PLH are linked within a caregiving dyad. Findings indicate that caregivers often remind PLH to take medications, but these reminders are not significantly associated with adherence. Caregivers also report strong attitudes about medication hassles, concerns over treatment failure and general concerns about adherence. Controlling for background characteristics, high perceived adherence hassles on the part of the caregiver were associated with low PLH adherence, providing evidence of shared influence within the caregiving dyad. Adherence interventions may maximize their effectiveness if they consider the role of the family caregiver because these data suggest that caregiver attitudes are linked with PLH adherence behaviours.

  3. Factors influencing adherence among older people with osteoarthritis. (United States)

    Loew, Laurianne; Brosseau, Lucie; Kenny, Glen P; Durand-Bush, Natalie; Poitras, Stéphane; De Angelis, Gino; Wells, George A


    This study aims to identify potential factors that could affect adherence and influence the implementation of an evidence-based structured walking program, among older adults diagnosed with knee osteoarthritis. A total of 69 participants with mild to moderate osteoarthritis of the knee fulfilled an online survey on potential factors that could affect their adherence to an evidence-based structured walking program. Adherence with regard to the influencing factors was explored using a logistic regression model. Results tend to show higher odds of adhering to the evidence-based walking program if the participants were supervised (more than 2.9 times as high), supported by family/friends (more than 3.7 times as high), and not influenced by emotional involvement (more than 11 times as high). The odds of adhering were 3.6 times lower for participants who indicated a change in their medication intake and 3.1 times lower for individuals who considered themselves as less physically active (95 % confidence interval (CI)). Our exploratory findings identified and defined potential adherence factors that could guide health professionals in their practice to better identify positive influences and obstacles to treatment adherence, which would lead to the adoption of a more patient-centered approach. A large-scale study is required to clearly delineate the key factors that would influence adherence. We addressed a new knowledge gap by identifying the main strategies to promote the long-term adherence of community-based walking program.

  4. The effect of reminder systems on patients' adherence to treatment

    Directory of Open Access Journals (Sweden)

    Fenerty SD


    Full Text Available Sarah D Fenerty1, Cameron West1, Scott A Davis1, Sebastian G Kaplan3, Steven R Feldman1,2,41Center for Dermatology Research, Department of Dermatology, 2Department of Pathology, 3Department of Psychiatry and Behavioral Medicine, 4Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USABackground: Patient adherence is an important component of the treatment of chronic disease. An understanding of patient adherence and its modulating factors is necessary to correctly interpret treatment efficacy and barriers to therapeutic success.Purpose: This meta-analysis aims to systematically review published randomized controlled trials of reminder interventions to assist patient adherence to prescribed medications.Methods: A Medline search was performed for randomized controlled trials published between 1968 and June 2011, which studied the effect of reminder-based interventions on adherence to self-administered daily medications.Results: Eleven published randomized controlled trials were found between 1999 and 2009 which measured adherence to a daily medication in a group receiving reminder interventions compared to controls receiving no reminders. Medication adherence was measured as the number of doses taken compared to the number prescribed within a set period of time. Meta-analysis showed a statistically significant increase in adherence in groups receiving a reminder intervention compared to controls (66.61% versus 54.71%, 95% CI for mean: 0.8% to 22.4%. Self-reported and electronically monitored adherence rates did not significantly differ (68.04% versus 63.67%, P = 1.0. Eight of eleven studies showed a statistically significant increase in adherence for at least one of the reminder group arms compared to the control groups receiving no reminder intervention.Limitations: The data are limited by imperfect measures of adherence due to variability in data collection methods. It is also likely

  5. Impact of prescription size on statin adherence and cholesterol levels

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    Mehler Phillip S


    Full Text Available Abstract Background Therapy with 3-Hydroxy-3-methylglutaryl Co-enzyme A reductase inhibitors (statins improve outcomes in a broad spectrum of patients with hyperlipidemia. However, effective therapy requires ongoing medication adherence; restrictive pharmacy policies may represent a barrier to successful adherence, particularly among vulnerable patients. In this study we sought to assess the relationship between the quantity of statin dispensed by the pharmacy with patient adherence and total cholesterol. Methods We analyzed a cohort of 3,386 patients receiving more than one fill of statin medications through an integrated, inner-city health care system between January 1, 2000 and December 31, 2002. Our measure of adherence was days of drug acquisition divided by days in the study for each patient, with adequate adherence defined as ≥ 80%. Log-binomial regression was used to determine the relative risk of various factors, including prescription size, on adherence. We also assessed the relationship between adherence and total cholesterol using multiple linear regression. Results After controlling for age, gender, race, co-payment, comorbidities, and insurance status, patients who obtained a majority of fills as 60-day supply compared with 30-day supply were more likely to be adherent to their statin medications (RR 1.41, 95% CI 1.28–1.55, P Conclusion In a healthcare system serving predominantly indigent patients, the provision of a greater quantity of statin medication at each prescription fill contributes to improved adherence and greater drug effectiveness.

  6. Health system barriers and facilitators to medication adherence for the secondary prevention of cardiovascular disease: a systematic review (United States)

    Banerjee, Amitava; Khandelwal, Shweta; Nambiar, Lavanya; Saxena, Malvika; Peck, Victoria; Moniruzzaman, Mohammed; Faria Neto, Jose Rocha; Quinto, Katherine Curi; Smyth, Andrew; Leong, Darryl; Werba, José Pablo


    Background Secondary prevention is cost-effective for cardiovascular disease (CVD), but uptake is suboptimal. Understanding barriers and facilitators to adherence to secondary prevention for CVD at multiple health system levels may inform policy. Objectives To conduct a systematic review of barriers and facilitators to adherence/persistence to secondary CVD prevention medications at health system level. Methods Included studies reported effects of health system level factors on adherence/persistence to secondary prevention medications for CVD (coronary artery or cerebrovascular disease). Studies considered at least one of β blockers, statins, angiotensin–renin system blockers and aspirin. Relevant databases were searched from 1 January 1966 until 1 October 2015. Full texts were screened for inclusion by 2 independent reviewers. Results Of 2246 screened articles, 25 studies were included (12 trials, 11 cohort studies, 1 cross-sectional study and 1 case–control study) with 132 140 individuals overall (smallest n=30, largest n=63 301). 3 studies included upper middle-income countries, 1 included a low middle-income country and 21 (84%) included high-income countries (9 in the USA). Studies concerned established CVD (n=4), cerebrovascular disease (n=7) and coronary heart disease (n=14). Three studies considered persistence and adherence. Quantity and quality of evidence was limited for adherence, persistence and across drug classes. Studies were concerned with governance and delivery (n=19, including 4 trials of fixed-dose combination therapy, FDC), intellectual resources (n=1), human resources (n=1) and health system financing (n=4). Full prescription coverage, reduced copayments, FDC and counselling were facilitators associated with higher adherence. Conclusions High-quality evidence on health system barriers and facilitators to adherence to secondary prevention medications for CVD is lacking, especially for low-income settings. Full prescription coverage

  7. Tuberculosis treatment adherence and fatality in Spain

    Directory of Open Access Journals (Sweden)

    Vidal Rafael


    Full Text Available Abstract Background The adherence to long tuberculosis (TB treatment is a key factor in TB control programs. Always some patients abandon the treatment or die. The objective of this study is to identify factors associated with defaulting from or dying during antituberculosis treatment. Methods Prospective study of a large cohort of TB cases diagnosed during 2006-2007 by 61 members of the Spanish Society of Pneumology and Thoracic Surgery (SEPAR. Predictive factors of completion outcome (cured plus completed treatment vs. defaulters plus lost to follow-up and fatality (died vs. the rest of patients were based on logistic regression, calculating odds ratios (OR and 95% confidence intervals (CI. Results Of the 1490 patients included, 29.7% were foreign-born. The treatment outcomes were: cured 792 (53.2%, completed treatment 540 (36.2%, failure 2 (0.1%, transfer-out 33 (2.2%, default 27 (1.8%, death 27 (1.8%, lost to follow-up 65 (4.4%, other 4 (0.3%. Completion outcome reached 93.5% and poor adherence was associated with: being an immigrant (OR = 2.03; CI:1.06-3.88, living alone (OR = 2.35; CI:1.05-5.26, residents of confined institutions (OR = 4.79; CI:1.74-13.14, previous treatment (OR = 2.93; CI:1.44-5.98, being an injecting drug user (IDU (OR = 9.51; CI:2.70-33.47 and treatment comprehension difficulties (OR = 2.93; CI:1.44-5.98. Case fatality was 1.8% and it was associated with the following variables: age 50 or over (OR = 10.88; CI:1.12-105.01, retired (OR = 12.26;CI:1.74-86.04, HIV-infected (OR = 9.93; CI:1.48-66.34, comprehension difficulties (OR = 4.07; CI:1.24-13.29, IDU (OR = 23.59; CI:2.46-225.99 and Directly Observed Therapy (DOT (OR = 3.54; CI:1.07-11.77. Conclusion Immigrants, those living alone, residents of confined institutions, patients treated previously, those with treatment comprehension difficulties, and IDU patients have poor adherence and should be targeted for DOT. To reduce fatality rates, stricter monitoring is required

  8. Activation of toll-like receptor 4 is necessary for trauma hemorrhagic shock-induced gut injury and polymorphonuclear neutrophil priming. (United States)

    Reino, Diego C; Palange, David; Feketeova, Elenora; Bonitz, Robert P; Xu, Da Zhong; Lu, Qi; Sheth, Sharvil U; Peña, Geber; Ulloa, Luis; De Maio, Antonio; Feinman, Rena; Deitch, Edwin A


    Interactions of toll-like receptors (TLRs) with nonmicrobial factors play a major role in the pathogenesis of early trauma-hemorrhagic shock (T/HS)-induced organ injury and inflammation. Thus, we tested the hypothesis that TLR4 mutant (TLR4 mut) mice would be more resistant to T/HS-induced gut injury and polymorphonuclear neutrophil (PMN) priming than their wild-type littermates and found that both were significantly reduced in the TLR4 mut mice. In addition, the in vivo and ex vivo PMN priming effect of T/HS intestinal lymph observed in the wild-type mice was abrogated in TLR4 mut mice as well the TRIF mut-deficient mice and partially attenuated in Myd88 mice, suggesting that TRIF activation played a more predominant role than MyD88 in T/HS lymph-induced PMN priming. Polymorphonuclear neutrophil depletion studies showed that T/HS lymph-induced acute lung injury was PMN dependent, because lung injury was totally abrogated in PMN-depleted animals. Because the lymph samples were sterile and devoid of endotoxin or bacterial DNA, we investigated whether the effects of T/HS lymph was related to endogenous nonmicrobial TLR4 ligands. High-mobility group box 1 protein 1, heat shock protein 70, heat shock protein 27, and hyaluronic acid all have been implicated in ischemia-reperfusion-induced tissue injury. None of these "danger" proteins appeared to be involved, because their levels were similar between the sham and shock lymph samples. In conclusion, TLR4 activation is important in T/HS-induced gut injury and in T/HS lymph-induced PMN priming and lung injury. However, the T/HS-associated effects of TLR4 on gut barrier dysfunction can be uncoupled from the T/HS lymph-associated effects of TLR4 on PMN priming.

  9. Alexithymia, Assertiveness and Psychosocial Functioning in HIV: Implications for Medication Adherence and Disease Severity. (United States)

    McIntosh, Roger C; Ironson, Gail; Antoni, Michael; Fletcher, Mary Ann; Schneiderman, Neil


    Psychosocial function and adherence to antiretroviral regimen are key factors in human immunodeficiency virus (HIV) disease management. Alexithymia (AL) is a trait deficit in the ability to identify and describe feelings, emotions and bodily sensations. A structural equation model was used to test whether high levels of AL indirectly relate to greater non-adherent behavior and HIV disease severity via psychosocial dysfunction. Blood draws for HIV-1 viral load and CD4 T-lymphocyte, along with psychosocial surveys were collected from 439 HIV positive adults aged 18-73 years. The structural model supports significant paths from: (1) AL to non-active patient involvement, psychological distress, and lower social support, (2) psychological distress and non-active involvement to non-adherent behavior, and (3) non-adherence to greater HIV disease severity (CFI = .97, RMSEA = .04, SRMR = .05). A second model confirmed the intermediary effect of greater patient assertiveness on the path from AL to social support and non-active patient involvement (CFI = .94, RMSEA = .04, SRMR = .05). Altogether, AL is indirectly linked with HIV disease management through it's association with poor psychosocial function, however greater patient assertiveness buffers the negative impact of AL on relationship quality with healthcare providers and members of one's social support network.

  10. Distinct mechanical behavior of HEK293 cells in adherent and suspended states. (United States)

    Haghparast, Seyed Mohammad Ali; Kihara, Takanori; Miyake, Jun


    The mechanical features of individual animal cells have been regarded as indicators of cell type and state. Previously, we investigated the surface mechanics of cancer and normal stromal cells in adherent and suspended states using atomic force microscopy. Cancer cells possessed specific mechanical and actin cytoskeleton features that were distinct from normal stromal cells in adherent and suspended states. In this paper, we report the unique mechanical and actin cytoskeletal features of human embryonic kidney HEK293 cells. Unlike normal stromal and cancer cells, the surface stiffness of adherent HEK293 cells was very low, but increased after cell detachment from the culture surface. Induced actin filament depolymerization revealed that the actin cytoskeleton was the underlying source of the stiffness in suspended HEK293 cells. The exclusive mechanical response of HEK293 cells to perturbation of the actin cytoskeleton resembled that of adherent cancer cells and suspended normal stromal cells. Thus, with respect to their special cell-surface mechanical features, HEK293 cells could be categorized into a new class distinct from normal stromal and cancer cells.

  11. Adherence to COPD guidelines in general practice

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; Sørensen, Tina Brandt; Højmark, Torben Brunse


    BACKGROUND: The general practitioner (GP) is often the first healthcare contact for patients with chronic obstructive pulmonary disease (COPD). AIMS: To determine whether participating in a standardised educational programme delivered in the GP's own practice is associated with adherence to COPD...... guidelines. METHODS: A nationwide register-based observational before and after study was undertaken with a control group of propensity-matched practices (follow-up period 6 months). COPD was defined as age 40+ years and at least two prescriptions for inhaled medication. The educational programme consisted...... were used to compare the rate of spirometry testing, preventive consultations, and influenza vaccinations provided to COPD patients and the rate of spirometry testing in non-COPD individuals, assumed to reflect diagnostic activity. RESULTS: Data for 102 participating GP practices were analysed...

  12. Sister Carrie, an Adherent of Desires

    Institute of Scientific and Technical Information of China (English)



    Sister Carrie is one of the most controversial characters in American literature.Thought as a "fallen woman" firstly,she was defined as a "new woman" by some critics later. However, by digging into the motivaton behind the whole process of Carrie's "success", the relationship between Carrie and her creator (the author), the social conditions of then American, it can be found that Carrie has never been free-standing on her thought and she has never found her real-sdf even after becoming a famous actress. In a society dominated by mass consumerism Carrie is only an adherent of her own desires. She also is a representative of all those country girls flooded into cities, a symbol and a sacrifice of the urbanization of America in a time countryside was overcome by cities.

  13. The Role of Helicobacter pylori Outer Membrane Proteins in Adherence and Pathogenesis

    Directory of Open Access Journals (Sweden)

    Armelle Ménard


    Full Text Available Helicobacter pylori is one of the most successful human pathogens, which colonizes the mucus layer of the gastric epithelium of more than 50% of the world’s population. This curved, microaerophilic, Gram-negative bacterium induces a chronic active gastritis, often asymptomatic, in all infected individuals. In some cases, this gastritis evolves to more severe diseases such as peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. H. pylori has developed a unique set of factors, actively supporting its successful survival and persistence in its natural hostile ecological niche, the human stomach, throughout the individual’s life, unless treated. In the human stomach, the vast majority of H. pylori cells are motile in the mucus layer lining, but a small percentage adheres to the epithelial cell surfaces. Adherence to the gastric epithelium is important for the ability of H. pylori to cause disease because this intimate attachment facilitates: (1 colonization and persistence, by preventing the bacteria from being eliminated from the stomach, by mucus turnover and gastric peristalsis; (2 evasion from the human immune system and (3 efficient delivery of proteins into the gastric cell, such as the CagA oncoprotein. Therefore, bacteria with better adherence properties colonize the host at higher densities. H. pylori is one of the most genetically diverse bacterial species known and is equipped with an extraordinarily large set of outer membrane proteins, whose role in the infection and persistence process will be discussed in this review, as well as the different receptor structures that have been so far described for mucosal adherence.

  14. Cloning of Humanα-defensin-1(HNP-1) Gene and Construction of Its Eukaryotic Expression Vector

    Institute of Scientific and Technical Information of China (English)


    1 IntroductionDefensins are small cationic antimicrobial peptides that function in the host's innate immune system. The human defensin family includes three small peptides from the azurophil granules of polymorphonuclear cells named human neutrophil peptide (HNP)-1, HNP-2, HNP-3, which consist 5%-7% of the protein of human neutrophil. HNP-4 is approximately one hundred times less abundant. They demonstrate antibacterial, antifungal and antiviral properties in vitro. HNPs are important component of nonoxidat...

  15. Associations between patients' adherence and GPs' attitudes towards risk, statin therapy and management of non-adherence

    DEFF Research Database (Denmark)

    Barfoed, Benedicte L; Paulsen, Maja S; Christensen, Palle M;


    BACKGROUND: Previous studies suggest that doctors' personal lifestyle, risk taking personality and beliefs about risk reducing therapies may affect their clinical decision-making. Whether such factors are further associated with patients' adherence with medication is largely unknown. OBJECTIVE......: To estimate associations between GPs' attitudes towards risk, statin therapy and management of non-adherence and their patients' adherence, and to identify subgroups of GPs with poor patient adherence. METHODS: All Danish GPs were invited to participate in an online survey. We asked whether they regarded...

  16. Modelling imperfect adherence to HIV induction therapy

    Directory of Open Access Journals (Sweden)

    Smith? Robert J


    Full Text Available Abstract Background Induction-maintenance therapy is a treatment regime where patients are prescribed an intense course of treatment for a short period of time (the induction phase, followed by a simplified long-term regimen (maintenance. Since induction therapy has a significantly higher chance of pill fatigue than maintenance therapy, patients might take drug holidays during this period. Without guidance, patients who choose to stop therapy will each be making individual decisions, with no scientific basis. Methods We use mathematical modelling to investigate the effect of imperfect adherence during the inductive phase. We address the following research questions: 1. Can we theoretically determine the maximal length of a possible drug holiday and the minimal number of doses that must subsequently be taken while still avoiding resistance? 2. How many drug holidays can be taken during the induction phase? Results For a 180 day therapeutic program, a patient can take several drug holidays, but then has to follow each drug holiday with a strict, but fairly straightforward, drug-taking regimen. Since the results are dependent upon the drug regimen, we calculated the length and number of drug holidays for all fifteen protease-sparing triple-drug cocktails that have been approved by the US Food and Drug Administration. Conclusions Induction therapy with partial adherence is tolerable, but the outcome depends on the drug cocktail. Our theoretical predictions are in line with recent results from pilot studies of short-cycle treatment interruption strategies and may be useful in guiding the design of future clinical trials.

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

    Directory of Open Access Journals (Sweden)

    Decoo D


    Full Text Available Danny Decoo,1 Mathieu Vokaer2 1Department of Neurology and Neurorehab, AZ Alma, Sijsele, Belgium; 2Multiple Sclerosis Clinic, Edith Cavell Hospital, CHIREC group, Brussels, Belgium 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. Keywords: multiple sclerosis, treatment adherence, physician survey

  18. Non-adherence to topical treatments for actinic keratosis (United States)

    Shergill, Bav; Zokaie, Simon; Carr, Alison J


    Background There is limited information on the patterns of use, adherence rates, and factors that impact adherence with topical treatments for actinic keratosis (AK). Objectives To establish patterns of use and adherence with topical treatments for AK and to identify treatment-related factors that impact on adherence. Methods A community-based, cross-sectional study was performed using a standardized questionnaire completed online or via telephone interview. Patients were stratified according to the presence of AK lesions on the scalp and/or other extremities; and presence of scarring resulting from treatment. Results This study included 305 patients with AK who were currently using a patient-applied topical therapy for AK or had used one within the previous 12 months. In total, 88% (n = 268/305) of patients were either non-adherent, non-persistent or both non-adherent and non-persistent to topical therapy. Duration of treatment was associated with increasing rates of non-adherence (adjusted odds ratio [OR]; for treatment durations greater than 4 weeks, 2.2, P < 0.01): 52% of patients were non-adherent with 3–4 week treatment duration; 69% of patients with 4–8 week treatment duration; and 71% of patients with 6–12 week treatment duration. There were similar increases in non-persistence with increasing treatment duration (adjusted OR; for treatment durations greater than 4 weeks, 2.1, P < 0.05). Conclusion This study found high rates of non-adherence and non-persistence in patients with AK. Duration of treatment was a significant factor contributing to non-adherence and non-persistence to topical treatments. Patient-applied topical therapies that require less frequent application and have shorter treatment duration may be associated with improved adherence rates. PMID:24379656

  19. Social Support and the Mediating Roles of Alcohol Use and Adherence Self-Efficacy on Antiretroviral Therapy (ART) Adherence Among ART Recipients in Gauteng, South Africa. (United States)

    Kekwaletswe, Connie T; Jordaan, Esmé; Nkosi, Sebenzile; Morojele, Neo K


    We sought to (a) replicate and (b) extend (via the addition of alcohol use) Cha et al.'s cross-sectional multi-component model of ART adherence on the relationship between social support, depression, self-efficacy beliefs, and antiretroviral therapy (ART) adherence, among HIV patients in Tshwane, South Africa. Using purposive sampling, 304 male and female ART recipients were recruited. ART adherence was assessed using three manifest indicators: total adherence ratio, the CASE adherence index and 1-month adherence measure. Data were analysed using structural equation modeling. In our replicated model, social support had both direct and indirect relationships with ART adherence, and inclusion of alcohol use improved prediction of ART adherence. Direct and indirect effects of alcohol use on ART adherence emerged: adherence self-efficacy beliefs partially mediated the latter path. Findings highlight the importance of integrating into ART promotion interventions, the reduction of alcohol use, provision of social support, and enhancement of adherence self-efficacy beliefs.

  20. Pinpointing differences in cisplatin-induced apoptosis in adherent and non-adherent cancer cells

    DEFF Research Database (Denmark)

    Tastesen, Hanne Sørup; Holm, Jacob Bak; Poulsen, Kristian Arild


    Platinum compounds are used in the treatment of cancer. We demonstrate that cisplatin-induced (10 µM) apoptosis (caspase-3 activity) is pronounced within 18 hours in non-adherent Ehrlich ascites tumour cells (EATC), whereas there is no increase in caspase-3 activity in the adherent Ehrlich Lettré...... ascites tumour cells (ELA). Loss of KCl and cell shrinkage are hallmarks in apoptosis and has been shown in EATC. However, we find no reduction in cell volume and only a minor loss of K(+) which is accompanied by net uptake of Na(+) following 18 hours cisplatin exposure in ELA. Glutathione and taurine...... have previously been demonstrated to protect cells from apoptosis. We find, however, that increase or decrease in the cellular content of glutathione and taurine has no effect on cisplatin-induced cell death in EATC and ELA. Nevertheless, knock-down of the taurine transporter TauT leads...

  1. 14 CFR 1260.72 - Adherence to original budget estimates. (United States)


    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Adherence to original budget estimates. 1260.72 Section 1260.72 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Post-Award Requirements § 1260.72 Adherence to original budget estimates....

  2. Concern between medication non-adherence and diabetes associated depression

    Directory of Open Access Journals (Sweden)

    Krishnan Vengadaragava Chary


    Conclusions: Unnoticed depression among diabetic individuals reduces treatment adherence and must be addressed in any patient showing poor response to the treatment. Improving treatment adherence helps to combat diabetes as well as depression. [Int J Basic Clin Pharmacol 2016; 5(2.000: 523-527

  3. Treatment Adherence among Latina Female Adolescent Suicide Attempters. (United States)

    Rotheram-Borus, Mary Jane; Piacentini, John; Van Rossem, Ronan; Graae, Flemming; Cantwell, Coleen; Castro-Blanco, David; Feldman, Julie


    Disenfranchised Latina adolescents (N=140) and their mothers presenting at a large urban emergency room after a suicide attempt by the adolescent were assessed to examine treatment adherence. Predictor variables for treatment adherence were established. Results are discussed in relation to treatment session attendance. Implications for the…

  4. Improving Adherence to Hand Hygiene among Health Care Workers (United States)

    Maskerine, Courtney; Loeb, Mark


    Increased adherence to hand hygiene is widely acknowledged to be the most important way of reducing infections in health care facilities. Despite evidence of benefit, adherence to hand hygiene among health care professionals remains low. Several behavioral and organizational theories have been proposed to explain this. As a whole, the success of…

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

    Directory of Open Access Journals (Sweden)

    Basheti IA


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

  6. Method for preventing micromechanical structures from adhering to another object (United States)

    Smith, J.H.; Ricco, A.J.


    A method for preventing micromechanical structures from adhering to another object includes the step of immersing a micromechanical structure and its associated substrate in a chemical species that does not stick to itself. The method can be employed during the manufacture of micromechanical structures to prevent micromechanical parts from sticking or adhering to one another and their associated substrate surface. 3 figs.

  7. Reliability of assessment of adherence to an antimicrobial treatment guideline

    NARCIS (Netherlands)

    Mol, PGM; Gans, ROB; Panday, PVN; Degener, JE; Laseur, M; Haaijer-Ruskamp, FM


    Assessment procedures for adherence to a guideline must be reliable and credible. The aim of this study was to explore the reliability of assessment of adherence, taking account of the professional backgrounds of the observers. A secondary analysis explored the impact of case characteristics on asse

  8. Unravelling adherence to prophylaxis in haemophilia : A patients' perspective

    NARCIS (Netherlands)

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


    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 proph

  9. 42 CFR 447.304 - Adherence to upper limits; FFP. (United States)


    ... 42 Public Health 4 2010-10-01 2010-10-01 false Adherence to upper limits; FFP. 447.304 Section 447... Noninstitutional Services § 447.304 Adherence to upper limits; FFP. (a) The Medicaid agency must not pay more than... payments may be made only up to the reasonable charge under Medicare. (c) FFP is not available for a...

  10. Cognitive-Behavioral Therapy for HIV Medication Adherence and Depression (United States)

    Safren, Steven A.; Hendriksen, Ellen S.; Mayer, Kenneth H.; Mimiaga, Matthew J.; Pickard, Robert; Otto, Michael W.


    For patients with HIV, depression is a common, distressing condition that can interfere with a critical self-care behavior--adherence to antiretroviral therapy. The present study describes a cognitive-behavioral treatment designed to integrate cognitive-behavioral therapy for depression with our previously tested approach to improving adherence to…

  11. Adherence to Pharmacological Treatment for Juvenile Bipolar Disorder (United States)

    Drotar, Dennis; Greenley, Rachel Neff; Demeter, Christine A.; McNamara, Nora K.; Stansbrey, Robert J.; Calabrese, Joseph R.; Stange, Jonathan; Vijay, Priya; Findling, Robert L.


    Objective: The objective of this study was to describe the prevalence and correlates of adherence to divalproex sodium (DVPX) and lithium carbonate (Li) combination treatment during the initial stabilization treatment phase. Method: Adherence to Li/DVPX combination therapy was measured by the presence or absence of minimum serum concentrations of…

  12. Psychosocial factors and treatment adherence in paediatric HIV/AIDS. (United States)

    Naar-King, S; Arfken, C; Frey, M; Harris, M; Secord, E; Ellis, D


    A social ecological model provides a promising framework for understanding the individual, family, and societal factors contributing to non-adherence to treatment of paediatric HIV. This study explored which factors relevant to this model are associated with caregivers' adherence and child health outcomes. A cross-sectional design was utilized to assess relationships among current individual, familial, extra-familial factors, caregiver adherence, and viral load. Data were collected from 43 caregivers, and viral load data were obtained from the medical records of their HIV+ children. Caregiver drug and alcohol use and HIV+ status were associated with non-adherence and elevated viral load. Negative outcome expectancy was associated with lower adherence but was not significant in the multivariate analyses. Family factors were not significant, but these measures had low reliability in this sample. Extra-familial factors such as dissatisfaction with medical specialty care and more stressful life events were not directly associated with adherence but were related to increased caregiver substance use. Results of this first study to explore multiple predictors of adherence and health outcomes in paediatric HIV require replication with larger samples, but findings suggest caregiver characteristics that place children at risk for disease progression due to poor adherence to treatment.

  13. Towards tailored and targeted adherence assessment to optimise asthma management

    NARCIS (Netherlands)

    van Boven, Job F. M.; Trappenburg, Jaap C. A.; van der Molen, Thys; Chavannes, Niels H.


    In this paper, we aim to emphasise the need for a more comprehensive and tailored approach to manage the broad nature of non-adherence, to personalise current asthma management. Although currently several methods are available to measure the extent of asthma patients' adherence, the vast majority do

  14. Medication Adherence in Older Adults: A Qualitative Study (United States)

    Holt, Elizabeth W.; Rung, Ariane L.; Leon, Kyla A.; Firestein, Catherine; Krousel-Wood, Marie


    To effectively address medication adherence and improve cardiovascular health among older adults, a deeper understanding is needed of the barriers that this age group faces and of approaches that would be most effective and feasible for improving adherence. We conducted a focus group study (n = 25) in a diverse population of older adults with…

  15. Medication Adherence in a Comparative Effectiveness Trial for Bipolar Disorder (United States)

    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.


    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

  16. Patient adherence to medical treatment. A review of reviews.

    NARCIS (Netherlands)

    Dulmen, S. van; Sluijs, E.; Dijk, L. van; Ridder, D. de; Heerdink, R.; Bensing, J.


    BACKGROUND: Patients' non-adherence to medical treatment remains a persistent problem. Many interventions to improve patient adherence are unsuccessful and sound theoretical foundations are lacking. Innovations in theory and practice are badly needed. A new and promising way could be to review the e

  17. Factors related to adherence to treatment for systemic hypertension

    Directory of Open Access Journals (Sweden)

    Silvana Maria Coelho Leite Fava


    Full Text Available This study aimed to seek the evidence available in the literature regarding the factors related to adherence to treatment for systemic hypertension. It used the method of integrative review in the databases MEDLINE, CINAHL, and LILACS, using the keywords: hypertension, compliance, non-compliance, adherence, non-adherence, patient compliance, in the period 2004 – 2008, and articles in Portuguese, English and Spanish, with the use of a validated instrument and content analysis. 28 studies were selected, 64.3% of which had level of evidence VI. The following were identified as factors related to adherence to treatment: treatment costs, educational activities, sex, physician-patient relationship, physiological and behavioral aspects, drug therapy, attending checkups and lifestyle. The use of combined strategies is suggested in order to increase the individuals’ adherence to the treatment. Gaps point to the valorization of dialogic relationships for integrated and more efficacious health practices.

  18. Interventional tools to improve medication adherence: review of literature (United States)

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


    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

  19. Quantification of the Forgiveness of Drugs to Imperfect Adherence. (United States)

    Assawasuwannakit, P; Braund, R; Duffull, S B


    The circumstance of how sensitive therapeutic success is under imperfect adherence is driven by the property known as forgiveness. To date, no studies have considered variability in the pharmacokinetic-pharmacodynamic process in conjunction with imperfect adherence patterns in order to develop a comparative criterion to determine the forgiveness of a drug. In this study, we have proposed a criterion to quantify forgiveness; illustrated the criterion for a theoretical example and evaluated the forgiveness of a motivating example, namely warfarin. A forgiveness criterion, relative forgiveness, is defined as the number of times more likely that a target is successfully attained under perfect adherence compared to imperfect adherence; or when comparing two drugs under a standard setting of imperfect adherence. The relative forgiveness criterion may have important implications for both drug development and clinical practice since the choice of drug can account for the likely influence of its forgiveness.

  20. Forgiveness of non-adherence to HIV-1 antiretroviral therapy. (United States)

    Shuter, Jonathan


    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.

  1. Update on denosumab in the management of postmenopausal osteoporosis: patient preference and adherence

    Directory of Open Access Journals (Sweden)

    Cairoli E


    Full Text Available Elisa Cairoli,1,2 Cristina Eller-Vainicher,1 Iacopo Chiodini1,2 1Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, Padiglione Granelli, Milan, Italy; 2Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy Abstract: Patient adherence to many osteoporosis treatments, primarily bisphosphonates, is generally poor, thus leading to a significant reduction in antifracture efficacy. Patient perceptions about the necessity of the prescribed medication to treat osteoporosis and the concerns about the potential adverse effects are important and potentially modifiable determinants of adherence, in addition to other factors, such as difficult dosing regimens and high dosing frequency. Denosumab (Dmab is a fully human monoclonal antibody against the receptor activator of nuclear factor-κB ligand (RANKL, which, through the prevention of the RANKL/RANK interaction, inhibits osteoclast-mediated bone resorption and significantly reduces the risk of vertebral, nonvertebral, and hip fractures. It is administered subcutaneously every 6 months for the treatment of postmenopausal osteoporosis. Preference and adherence to Dmab treatment were assessed in various clinical trials. Although with some limitations, available data suggest that Dmab is preferred to bisphosphonates, produces greater satisfaction than bisphosphonates, and would be preferentially chosen for long-term treatment. Moreover, patient perceptions about the necessity of Dmab treatment clearly outweigh the concerns about the injections, and positive beliefs about treatment positively influence medication-taking behavior. According to these data, Dmab may represent a reasonable alternative to bisphosphonates, particularly for osteoporotic women in whom a suboptimal or even poor adherence to oral treatments is expected. Keywords: denosumab, RANKL, osteoporosis treatment, preference, satisfaction, adherence

  2. A Selective and Purification-Free Strategy for Labeling Adherent Cells with Inorganic Nanoparticles. (United States)

    Gao, Yu; Lim, Jing; Yeo, David Chen Loong; Liao, Shanshan; Lans, Malin; Wang, Yaqi; Teoh, Swee-Hin; Goh, Bee Tin; Xu, Chenjie


    Cellular labeling with inorganic nanoparticles such as magnetic iron oxide nanoparticles, quantum dots, and fluorescent silica nanoparticles is an important method for the noninvasive visualization of cells using various imaging modalities. Currently, this is mainly achieved through the incubation of cultured cells with the nanoparticles that eventually reach the intracellular compartment through specific or nonspecific internalization. This classic method is advantageous in terms of simplicity and convenience, but it suffers from issues such as difficulties in fully removing free nanoparticles (suspended in solution) and the lack of selectivity on cell types. This article reports an innovative strategy for the specific labeling of adherent cells without the concern of freely suspended nanoparticles. This method relies on a nanocomposite film that is prepared by homogeneously dispersing nanoparticles within a biodegradable polymeric film. When adherent cells are seeded on the film, they adhere, spread, and filtrate into the film through the micropores formed during the film fabrication. The pre-embedded nanoparticles are thus internalized by the cells during this infiltration process. As an example, fluorescent silica nanoparticles were homogeneously distributed within a polycaprolactone film by utilizing cryomilling and heat pressing. Upon incubation within physiological buffer, no silica nanoparticles were released from the nanocomposite film even after 20 d of incubation. However, when adherent cells (e.g., human mesenchymal stem cells) were grown on the film, they became fluorescent after 3 d, which suggests internalization of silica nanoparticles by cells. In comparison, the suspension cells (e.g., monocytes) in the medium remained nonfluorescent no matter whether there was the presence of adherent cells or not. This strategy eventually allowed the selective and concomitant labeling of mesenchymal stem cells during their harvest from bone marrow aspiration.

  3. ESPACOMP Medication Adherence Reporting Guidelines (EMERGE): a reactive-Delphi study protocol (United States)

    Helmy, R; Zullig, L L; Dunbar-Jacob, J; Hughes, D A; Vrijens, B; Wilson, I B; De Geest, S


    Introduction Medication adherence is fundamental to achieving optimal patient outcomes. Reporting research on medication adherence suffers from some issues—including conceptualisation, measurement and data analysis—that thwart its advancement. Using the ABC taxonomy for medication adherence as the conceptual basis, a steering committee of members of the European Society for Patient Adherence, COMpliance, and Persistence (ESPACOMP) launched an initiative to develop ESPACOMP Medication Adherence Reporting Guidelines (EMERGE). This paper is a protocol for a Delphi study that aims to build consensus among a group of topic experts regarding an item list that will support developing EMERGE. Methods and analysis This study uses a reactive-Delphi design where a group of topic experts will be asked to rate the relevance and clarity of an initial list of items, in addition to suggesting further items and/or modifications of the initial items. The initial item list, generated by the EMERGE steering committee through a structured process, consists of 26 items distributed in 2 sections: 4 items representing the taxonomy-based minimum reporting criteria, and 22 items organised according to the common reporting sections. A purposive sample of experts will be selected from relevant disciplines and diverse geographical locations. Consensus will be achieved through predefined decision rules to keep, delete or modify the items. An iterative process of online survey rounds will be carried out until consensus is reached. Ethics and dissemination An ethics approval was not required for the study according to the Swiss federal act on research involving human beings. The participating experts will be asked to give an informed consent. The results of this Delphi study will feed into EMERGE, which will be disseminated through peer-reviewed publications and presentations at conferences. Additionally, the steering committee will encourage their endorsement by registering the guidelines at

  4. Treatment adherence with the easypod™ growth hormone electronic auto-injector and patient acceptance: survey results from 824 children and their parents

    Directory of Open Access Journals (Sweden)

    Larroque Sylvain


    Full Text Available Abstract Background Accurately monitoring adherence to treatment with recombinant human growth hormone (r-hGH enables appropriate intervention in cases of poor adherence. The electronic r-hGH auto-injector, easypod™, automatically records the patient's adherence to treatment. This study evaluated adherence to treatment of children who started using the auto-injector and assessed opinions about the device. Methods A multicentre, multinational, observational 3-month survey in which children received r-hGH as part of their normal care. Physicians reviewed the recorded dose history and children (with or without parental assistance completed a questionnaire-based survey. Children missing ≤2 injections per month (92% of injections given were considered adherent to treatment. Adherence was compared between GH treatment-naïve and treatment-experienced children. Results Of 834 recruited participants, 824 were evaluated. The median (range age was 11 (1-18 years. From the recorded dose history, 87.5% of children were adherent to treatment over the 3-month period. Recorded adherence was higher in treatment-naïve (89.7%, n = 445/496 than in treatment-experienced children (81.7%, n = 152/186 [Fisher's exact test FI(X = 7.577; p = 0.0062]. According to self-reported data, 90.2% (607/673 of children were adherent over 3 months; 51.5% (421/817 missed ≥1 injection over this period (mainly due to forgetfulness. Concordance between reported and recorded adherence was 84.3%, with a trend towards self-reported adherence being higher than recorded adherence. Most children liked the auto-injector: over 80% gave the top two responses from five options for ease of use (720/779, speed (684/805 and comfort (716/804. Although 38.5% (300/780 of children reported pain on injection, over half of children (210/363 considered the pain to be less or much less than expected. Given the choice, 91.8% (732/797 of children/parents would continue using the device. Conclusions

  5. Inactivation of the rhlA gene in Pseudomonas aeruginosa prevents rhamnolipid production, disabling the protection against polymorphonuclear leukocytes

    DEFF Research Database (Denmark)

    van Gennip, Maria; Christensen, Louise Dahl; Alhede, Morten;


    Many of the virulence factors produced by the opportunistic human pathogen Pseudomonas aeruginosa are quorum-sensing (QS) regulated. Among these are rhamnolipids, which have been shown to cause lysis of several cellular components of the human immune system, e.g. monocyte-derived macrophages and ...

  6. Flow-induced detachment of red blood cells adhering to surfaces by specific antigen-antibody bonds.


    Xia, Z; Goldsmith, H L; van de Ven, T G


    Fixed spherical swollen human red blood cells of blood type B adhering on a glass surface through antigen-antibody bonds to monoclonal mouse antihuman IgM, adsorbed or covalently linked on the surface, were detached by known hydrodynamic forces created in an impinging jet. The dynamic process of detachment of the specifically bound cells was recorded and analyzed. The fraction of adherent cells remaining on the surface decreased with increasing hydrodynamic force. For an IgM coverage of 0.26%...

  7. Viral suppression and adherence among HIV-infected children and adolescents on antiretroviral therapy: results of a multicenter study

    Directory of Open Access Journals (Sweden)

    Maria L.S. Cruz


    Full Text Available OBJECTIVE: To evaluate treatment adherence among perinatally-infected pediatric human immunodeficiency virus (HIV patients followed in pediatric centers in Brazil. METHODS: This was a cross-sectional multicenter study. Medical records were reviewed and adherence scale, assessment of caregivers' quality of life (WHOQOL-BREF, anxiety, depression, and alcohol/substances use/abuse were assessed. Outcomes included self-reported 100% adherence in the last three days and HIV viral load (VL < 50 copies/mL. Statistical analyses included contingency tables and respective statistics, and multivariable logistic regression. RESULTS: 260 subjects were enrolled: 78% children and 22% adolescents; 93% of caregivers for the children and 77% of adolescents reported 100% adherence; 57% of children and 49% of adolescents had VL < 50 copies/mL. In the univariate analyses, HIV diagnosis for screening due to maternal infection, lower caregiver scores for anxiety, and higher scores in physical and psychological domains of WHOQOL-BREF were associated with 100% adherence. Shorter intervals between pharmacy visits were associated with VL < 50 copies/mL (p ≤ 0.01. Multivariable regression demonstrated that caregivers who did not abuse alcohol/other drugs (OR = 0.49; 95% CI: 0.27-0.89 and median interval between pharmacy visits < 33 days (OR = 0.97; 95% CI: 0.95-0.98 were independently associated with VL < 50 copies/mL; whereas lower caregiver scores for anxiety (OR = 2.57; 95% CI: 1.27-5.19 and children's HIV diagnosis for screening due to maternal infection (OR = 2.25; 95% CI: 1.12-4.50 were found to be independently associated with 100% adherence. CONCLUSIONS: Pediatric HIV programs should perform routine assessment of caregivers' quality of life, and anxiety and depression symptoms. In this setting, pharmacy records are essential to help identify less-than-optimal adherence.

  8. Cloning of Human α-defensin-1 (HNP-1) Gene and Construction of Its Eukaryotic Expression Vector

    Institute of Scientific and Technical Information of China (English)

    Hua-Hua CHEN; Jing-Ping Ou YANG; Bao-Hua WANG; Yue Yang; Han-Qiao ZHENG


    @@ 1 Introduction Defensins are small cationic antimicrobial peptides that function in the host's innate immune system. The human defensin family includes three small peptides from the azurophil granules of polymorphonuclear cells named human neutrophil peptide (HNP)-1, HNP-2, HNP-3,which consist 5%-7% of the protein of human neutrophil. HNP-4 is approximately one hundred times less abundant. They demonstrate antibacterial, antifungal and antiviral properties in vitro. HNPs are important component of nonoxidative mechanism in macrophages, and can direct inactivate the enveloped viruses. Because only special cells express defensins. And it is hard to extract them naturally and the production is few. So researcher expect to obtain defensins highly through heterogenous expression by gene engineering technology. In order to express HNP-1, we cloned the cDNA of HNP-1 from human polymorphonuclear cells in peripheral blood, and constructed its eukaryotic expression vector, which provided a base for the further study on its mechanism of antimicrobial effect.

  9. Unravelling adherence to prophylaxis in haemophilia: a patients' perspective. (United States)

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


    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.

  10. Factors affecting adherence to a raw vegan diet. (United States)

    Link, Lilli B; Jacobson, Judith S


    The purpose of this study was to evaluate adherence and identify predictors of adherence to a raw vegan diet (i.e., uncooked plant foods) following a stay at a raw vegan institute. In this cohort study of guests at a raw vegan institute, subjects completed written questionnaires upon arrival and 12 weeks later. Of 107 eligible guests, 84 participated. Mean age was 54 years, 23 were male, and 73 white. Fifty-one completed the 12-week follow-up. Eight (16%) reported their diet to be 80% raw vegan at baseline and 14 (28%) at follow-up. Based on a raw vegan dietary adherence score (range 0-42) created for this study, mean adherence (SD) increased from 15.1 (5.4) to 17.0 (5.8) over 12 weeks (p=0.03). Baseline predictors of adherence included: education (beta=0.95), severity of disease (beta=0.98), and self-efficacy to adhere (beta=0.72). Future interventions that evaluate this diet should address self-efficacy, an important, potentially remediable predictor of adherence.

  11. A fully automated system for adherent cells microinjection. (United States)

    Becattini, Gabriele; Mattos, Leonardo S; Caldwell, Darwin G


    This paper proposes an automated robotic system to perform cell microinjections to relieve human operators from this highly difficult and tedious manual procedure. The system, which uses commercial equipment currently found on most biomanipulation laboratories, consists of a multitask software framework combining computer vision and robotic control elements. The vision part features an injection pipette tracker and an automatic cell targeting system that is responsible for defining injection points within the contours of adherent cells in culture. The main challenge is the use of bright-field microscopy only, without the need for chemical markers normally employed to highlight the cells. Here, cells are identified and segmented using a threshold-based image processing technique working on defocused images. Fast and precise microinjection pipette positioning over the automatically defined targets is performed by a two-stage robotic system which achieves an average injection rate of 7.6 cells/min with a pipette positioning precision of 0.23 μm. The consistency of these microinjections and the performance of the visual targeting framework were experimentally evaluated using two cell lines (CHO-K1 and HEK) and over 500 cells. In these trials, the cells were automatically targeted and injected with a fluorescent marker, resulting in a correct cell detection rate of 87% and a successful marker delivery rate of 67.5%. These results demonstrate that the new system is capable of better performances than expert operators, highlighting its benefits and potential for large-scale application.

  12. Spillover adherence effects of fixed-dose combination HIV therapy

    Directory of Open Access Journals (Sweden)

    Kauf TL


    Full Text Available Teresa L Kauf1, Keith L Davis2, Stephanie R Earnshaw2, E Anne Davis31Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, 2RTI Health Solutions, Research Triangle Park, NC, 3Independent consultant, Pittsboro, NC, USAAbstract: The impact of fixed-dose combination (FDC products on adherence to other, non-fixed regimen components has not been examined. We compared adherence to a third antiretroviral (ART component among patients receiving a nucleoside reverse transcriptase inhibitor (NRTI backbone consisting of the FDC Epzicom®, GlaxoSmithKline Inc, Research Triangle Park, NC (abacavir sulfate 600 mg + lamivudine 300 mg; FDC group versus NRTI combinations taken as two separate pills (NRTI Combo group using data from a national sample of 30 health plans covering approximately 38 million lives from 1997 to 2005. Adherence was measured as the medication possession ratio (MPR. Multivariate logistic regression compared treatment groups based on the likelihood of achieving ≥95% adherence, with sensitivity analyses using alternative thresholds. MPR was assessed as a continuous variable using multivariate linear regression. Covariates included age, gender, insurance payer type, year of study drug initiation, presence of mental health and substance abuse disorders, and third agent class. The study sample consisted of 650 FDC and 1947 NRTI Combo patients. Unadjusted mean adherence to the third agent was higher in the FDC group than the NRTI Combo group (0.92 vs 0.85; P < 0.0001. In regression analyses, FDC patients were 48% and 39% more likely to achieve 95% and 90% third agent adherence, respectively (P ≤ 0.03. None of the other MPR specifications achieved comparable results. Among managed care patients, use of an FDC appears to substantially improve adherence to a third regimen component and thus the likelihood of achieving the accepted standard for adherence to HIV therapy of 95%.Keywords

  13. Aspergillus galactosaminogalactan mediates adherence to host constituents and conceals hyphal β-glucan from the immune system.

    Directory of Open Access Journals (Sweden)

    Fabrice N Gravelat

    Full Text Available Aspergillus fumigatus is the most common cause of invasive mold disease in humans. The mechanisms underlying the adherence of this mold to host cells and macromolecules have remained elusive. Using mutants with different adhesive properties and comparative transcriptomics, we discovered that the gene uge3, encoding a fungal epimerase, is required for adherence through mediating the synthesis of galactosaminogalactan. Galactosaminogalactan functions as the dominant adhesin of A. fumigatus and mediates adherence to plastic, fibronectin, and epithelial cells. In addition, galactosaminogalactan suppresses host inflammatory responses in vitro and in vivo, in part through masking cell wall β-glucans from recognition by dectin-1. Finally, galactosaminogalactan is essential for full virulence in two murine models of invasive aspergillosis. Collectively these data establish a role for galactosaminogalactan as a pivotal bifunctional virulence factor in the pathogenesis of invasive aspergillosis.

  14. Adherence to diabetes regimens: empirical status and clinical applications. (United States)

    Kurtz, S M


    Adherence to diabetes treatment regimens has proved to be a conceptual and empirical enigma. Consequently, reliable and valid applications to the clinical practice of diabetes care and education have been wanting. Rates of nonadherence are staggeringly high, regardless of the methodology employed, and verification of self-reports is complicated by social desirability to appear compliant. Low intertask correlations further complicate our understanding of adherence-metabolic control relationships. Studies relating to the Health Belief Model, social learning theory, and the psychology of interpersonal relationships that have sought to identify determinants of adherence behaviors have specific relevance to the clinical practice of diabetes education.

  15. Primary non-adherence to prescribed medication in general practice

    DEFF Research Database (Denmark)

    Linnet, Kristján; Halldórsson, Matthías; Thengilsdóttir, Gudrún


    prescriptions issued electronically by 140 physicians at 16 primary health care centres in the Reykjavik capital area during two periods before and after increases in copayment were matched with those dispensed in pharmacies, the difference constituting primary non-adherence (population: 200&emsp14......;000; patients: 21 571; prescriptions: 22 991). Eight drug classes were selected to reflect symptom relief and degree of copayment. Two-tailed chi-square test and odds ratios for non-adherence by patient copayment groups were calculated. RESULTS: The rate of primary non-adherence was 6...

  16. Oxidative DNA damage of peripheral blood polymorphonuclear leukocytes, selectively induced by chronic arsenic exposure, is associated with extent of arsenic-related skin lesions

    Energy Technology Data Exchange (ETDEWEB)

    Pei, Qiuling, E-mail: [Department of Toxicology, Public Health College, Shanxi Medical University, No 56 Xin Jian Nan Lu, Taiyuan (030001) (China); Ma, Ning [Faculty of Health Science, Suzuka University of Medical Science, Suzuka, 510-0293 (Japan); Zhang, Jing; Xu, Wenchao; Li, Yong; Ma, Zhifeng; Li, Yunyun; Tian, Fengjie; Zhang, Wenping [Department of Toxicology, Public Health College, Shanxi Medical University, No 56 Xin Jian Nan Lu, Taiyuan (030001) (China); Mu, Jinjun [The Second Hospital, Shanxi Medical University, Taiyuan (030001) (China); Li, Yuanfei [The First Hospital, Shanxi Medical University, Taiyuan (030001) (China); Wang, Dongxing; Liu, Haifang; Yang, Mimi; Ma, Caifeng; Yun, Fen [Department of Toxicology, Public Health College, Shanxi Medical University, No 56 Xin Jian Nan Lu, Taiyuan (030001) (China)


    There is increasing evidence that oxidative stress is an important risk factor for arsenic-related diseases. Peripheral blood leukocytes constitute an important defense against microorganisms or pathogens, while the research on the impact of chronic arsenic exposure on peripheral blood leukocytes is much more limited, especially at low level arsenic exposure. The purpose of the present study was to explore whether chronic arsenic exposure affects oxidative stress of peripheral blood leukocytes and possible linkages between oxidative stress and arsenic-induced skin lesions. 75 male inhabitants recruited from an As-endemic region of China were investigated in the present study. The classification of arsenicosis was based on the degree of skin lesions. Arsenic levels were measured in drinking water and urine by Atomic Fluorescence Spectroscopy. Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) was tested by Enzyme-Linked Immunosorbent Assay. 8-OHdG of peripheral blood leukocytes was evaluated using immunocytochemical staining. 8-OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs), but not in monocytes (MNs). The 8-OHdG staining of PMN cytoplasm was observed in all investigated populations, while the 8-OHdG staining of PMN nuclei was frequently found along with the elevated amounts of cell debris in individuals with skin lesion. Urinary arsenic levels were increased in the severe skin lesion group compared with the normal group. No relationship was observed between drinking water arsenic or urine 8-OHdG and the degree of skin lesions. These findings indicated that the target and persistent oxidative stress in peripheral blood PMNs may be employed as a sensitive biomarker directly to assess adverse health effects caused by chronic exposure to lower levels of arsenic. -- Highlights: ► Male inhabitants were investigated from an As-endemic region of China. ► 8-OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs).

  17. Advances in researches on polymorphonuclear neutrophil elastase in semen%精液中性粒细胞弹性蛋白酶的研究进展

    Institute of Scientific and Technical Information of China (English)

    冯瑞祥; 卢坤刚; 张红烨; 陆金春


    Reproductive tract infection is one of the important factors of male reproduction. Polymorphonuclear neutrophil elas-tase (PMNE) in semen, as a marker of male reproductive tract inflammation, especially recessive infection, potentially affects male fertility. The concentration of PMNE in semen is correlated significantly not only with semen white blood cell count and seminal plasma ROS level, but also with the levels of other inflammation related cytokines, such as IL-6, IL-8, and TNF-ot. Furthermore, PMNE has a negative impact on sperm quality by decreasing sperm motility, increasing the percentage of morphologically abnormal sperm and interfering with DNA integrity. PMNE inhibitors in semen can form a compound with PMNE, and theimbalanced proportions of the two may promote the development of chronic inflammation, and consequently lead to male infertility. At present, PMNE in semen is detected mainly by enzyme immunoassay, but this method still needs to be standardized, and the diagnostic standards to be unified. Natl JAndrol, 2011, 17 (11): 1023 -1028%影响男性生殖的因素很多,生殖道感染是其中重要因素之一.精液中性粒细胞弹性蛋白酶( polymorphonuclear neutrophil elastase,PMNE)作为男性生殖道感染尤其是隐性感染诊断的重要炎症指标,对男性生育能力有潜在的负面影响.精液PMNE浓度不仅与精液白细胞数、精浆ROS水平显著相关,而且与其他炎症相关细胞因子如IL-6、IL-8、TNF-α水平等密切相关.PMNE对精子质量亦有影响,可以削弱精子活力,影响精子形态和DNA完整性等.精液中存在PMNE抑制剂,可与PMNE形成复合物,两者比例的失衡可以促进慢性炎症的发生,进而可能导致男性不育.检测精液PMNE的方法主要为酶免疫分析法,但检测方法仍需标准化,诊断标准尚需统一.

  18. Construction of a Mammary-specific Expression Vector of Humanα-defensin-1 (HNP-1) Gene

    Institute of Scientific and Technical Information of China (English)


    1 IntroductionDefensins, also called human neutrophil peptides(HNP), are small cationic peptides with broad antimicrobial activity~([1]). Human defensins are highly abundant in the cytoplasmic granules of polymorphonuclear neutrophils. Alpha-defensin-1 is an important mediator in either innate immunity or anti-infection. It can be developed to be an ideal new type antibiotic and may provide a better solution for the present situation of extensive antibiotics-resistence. It is difficult to achieve amount of ...

  19. Fewer Bacteria Adhere to Softer Hydrogels. (United States)

    Kolewe, Kristopher W; Peyton, Shelly R; Schiffman, Jessica D


    Clinically, biofilm-associated infections commonly form on intravascular catheters and other hydrogel surfaces. The overuse of antibiotics to treat these infections has led to the spread of antibiotic resistance and underscores the importance of developing alternative strategies that delay the onset of biofilm formation. Previously, it has been reported that during surface contact, bacteria can detect surfaces through subtle changes in the function of their motors. However, how the stiffness of a polymer hydrogel influences the initial attachment of bacteria is unknown. Systematically, we investigated poly(ethylene glycol) dimethacrylate (PEGDMA) and agar hydrogels that were 20 times thicker than the cumulative size of bacterial cell appendages, as a function of Young's moduli. Soft (44.05-308.5 kPa), intermediate (1495-2877 kPa), and stiff (5152-6489 kPa) hydrogels were synthesized. Escherichia coli and Staphylococcus aureus attachment onto the hydrogels was analyzed using confocal microscopy after 2 and 24 h incubation periods. Independent of hydrogel chemistry and incubation time, E. coli and S. aureus attachment correlated positively to increasing hydrogel stiffness. For example, after a 24 h incubation period, there were 52 and 82% fewer E. coli adhered to soft PEGDMA hydrogels than to the intermediate and stiff PEGDMA hydrogels, respectively. A 62 and 79% reduction in the area coverage by the Gram-positive microbe S. aureus occurred after 24 h incubation on the soft versus intermediate and stiff PEGDMA hydrogels. We suggest that hydrogel stiffness is an easily tunable variable that could potentially be used synergistically with traditional antimicrobial strategies to reduce early bacterial adhesion and therefore the occurrence of biofilm-associated infections.

  20. Fewer Bacteria Adhere to Softer Hydrogels (United States)

    Kolewe, Kristopher W.; Peyton, Shelly R.; Schiffman, Jessica D.


    Clinically, biofilm-associated infections commonly form on intravascular catheters and other hydrogel surfaces. The overuse of antibiotics to treat these infections has led to the spread of antibiotic resistance and underscores the importance of developing alternative strategies that delay the onset of biofilm formation. Previously, it has been reported that during surface contact, bacteria can detect surfaces through subtle changes in the function of their motors. However, how the stiffness of a polymer hydrogel influences the initial attachment of bacteria is unknown. Systematically, we investigated poly(ethylene glycol) dimethacrylate (PEGDMA) and agar hydrogels that were twenty times thicker than the cumulative size of bacterial cell appendages, as a function of Young’s moduli. Soft (44.05 – 308.5 kPa), intermediate (1495 – 2877 kPa), and stiff (5152 – 6489 kPa) hydrogels were synthesized. Escherichia coli and Staphylococcus aureus attachment onto the hydrogels was analyzed using confocal microscopy after 2 and 24 hr incubation periods. Independent of hydrogel chemistry and incubation time, E. coli and S. aureus attachment correlated positively to increasing hydrogel stiffness. For example, after a 24 hr incubation period, there were 52% and 82% less E. coli adhered to soft PEGDMA hydrogels, than to the intermediate and stiff PEGDMA hydrogels, respectively. A 62% and 79% reduction in the area coverage by the Gram-positive microbe S. aureus occurred after 24 hr incubation on the soft versus intermediate and stiff PEGDMA hydrogels. We suggest that hydrogel stiffness is an easily tunable variable that, potentially, could be used synergistically with traditional antimicrobial strategies to reduce early bacterial adhesion, and therefore the occurrence of biofilm-associated infections. PMID:26291308

  1. Older Adults' Uptake and Adherence to Exercise Classes: Instructors' Perspectives. (United States)

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


    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.

  2. Method of detaching adherent cells for flow cytometry

    KAUST Repository

    Kaur, Mandeep


    In one aspect, a method for detaching adherent cells can include adding a cell lifting solution to the media including a sample of adherent cells and incubating the sample of adherent cells with the cell lifting solution. No scraping or pipetting is needed to facilitate cell detachment. The method do not require inactivation of cell lifting solution and no washing of detaching cells is required to remove cell lifting solution. Detached cells can be stained with dye in the presence of cell lifting solution and are further analyzed using flow cytometer. The method has been tested using 6 different cell lines, 4 different assays, two different plate formats (96 and 384 well plates) and two different flow cytometry instruments. The method is simple to perform, less time consuming, with no cell loss and makes high throughput flow cytometry on adherent cells a reality.

  3. In vitro adherence of Moraxella bovis to intact corneal epithelium. (United States)

    Jackman, S H; Rosenbusch, R F


    An in vitro assay is described using radiolabeled Moraxella bovis for studying adherence to intact bovine corneal epithelial surfaces. The assay was optimized for time (45 min) and for the ratio of epithelial cells to bacteria (1:1000) that demonstrated a significant difference in adherence between M. bovis strain 118F, a piliated organism and a nonpiliated variant, strain 118F/4-2. Adherence of these organisms correlated with previous pathogenicity studies involving experimental infection of calves. Scanning electron microscopy of tissues treated in the assay revealed a predilection of M. bovis for dark epithelial cells and for association with depressions in the tissue surface. This assay technique is discussed in comparison with other in vitro adherence assay methods.

  4. Predictors of duloxetine adherence and persistence in patients with fibromyalgia

    Directory of Open Access Journals (Sweden)

    Cui Z


    Full Text Available Zhanglin Cui, Yang Zhao, Diego Novick, Douglas FariesEli Lilly and Company, Indianapolis, IN, USAObjectives: Adherence to medication for the treatment of fibromyalgia (FM is predictive of lower overall health-care costs, and thus a lower burden on both patients and providers. The objectives of this study were to examine the predictors of adherence to and persistence with duloxetine therapy among commercially insured FM patients, and to identify subgroups of patients with high duloxetine persistence and adherence.Study design: This cross-sectional, retrospective study analyzed medical and pharmacy records over 1 year for patients in the US aged 18–64 years with FM who initiated (no prior 90-day use duloxetine treatment in 2008.Methods: Adherence to duloxetine was measured by medication possession ratio (MPR, with high adherence defined as MPR ≥ 0.8. Persistence was defined as the duration of therapy from the index date to the earliest of: the ending date of the last prescription, the date of the first gap of >15 days between prescriptions, or the end of the study period (12 months. Demographic and clinical predictors of adherence were examined via multiple logistic regression (MLR, and subgroups of duloxetine-persistent and -adherent patients were identified using classification and regression trees (CART.Results: Among 4660 duloxetine patients, 33% achieved high adherence. Factors associated with high adherence from MLR included older age, North Central and Northeast regions, prior venlafaxine, pregabalin, selective serotonin reuptake inhibitor (SSRI, or other antidepressant use, or comorbid dyslipidemia or osteoarthritis (all P < 0.05. CART analysis revealed that patients with prior antidepressant use, aged ≥46, or prior osteoarthritis had higher MPR (all P < 0.05, and patients aged ≥45 with a history of SSRI, venlafaxine, or anticonvulsant use had longer duration of therapy (all P < 0.05.Conclusions: Patients with high adherence to and

  5. Non-adherence to topical treatments for actinic keratosis

    Directory of Open Access Journals (Sweden)

    Shergill B


    Full Text Available Bav Shergill,1 Simon Zokaie,2 Alison J Carr3 1Department of Dermatology, Brighton and Sussex University Hospitals, Elm Grove, Brighton, UK; 2Leo Pharma, Princes Risborough, 3Hamell, London, UK Background: There is limited information on the patterns of use, adherence rates, and factors that impact adherence with topical treatments for actinic keratosis (AK. Objectives: To establish patterns of use and adherence with topical treatments for AK and to identify treatment-related factors that impact on adherence. Methods: A community-based, cross-sectional study was performed using a standardized questionnaire completed online or via telephone interview. Patients were stratified according to the presence of AK lesions on the scalp and/or other extremities; and presence of scarring resulting from treatment. Results: This study included 305 patients with AK who were currently using a patient-applied topical therapy for AK or had used one within the previous 12 months. In total, 88% (n = 268/305 of patients were either non-adherent, non-persistent or both non-adherent and non-persistent to topical therapy. Duration of treatment was associated with increasing rates of non-adherence (adjusted odds ratio [OR]; for treatment durations greater than 4 weeks, 2.2, P < 0.01: 52% of patients were non-adherent with 3–4 week treatment duration; 69% of patients with 4–8 week treatment duration; and 71% of patients with 6–12 week treatment duration. There were similar increases in non-persistence with increasing treatment duration (adjusted OR; for treatment durations greater than 4 weeks, 2.1, P < 0.05. Conclusion: This study found high rates of non-adherence and non-persistence in patients with AK. Duration of treatment was a significant factor contributing to non-adherence and non-persistence to topical treatments. Patient-applied topical therapies that require less frequent application and have shorter treatment duration may be associated with improved

  6. Older adults' uptake and adherence to exercise classes: Instructors' perspectives.


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


    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, ...

  7. Elderly adherence to hypertension treatment and nursing interventions


    Jênifa Cavalcante dos Santos; Raquel Sampaio Florêncio; Célida Juliana de Oliveira; Thereza Maria Magalhães Moreira


    Adherence to the treatment of arterial hypertension is a challenge to health professionals. Thus, this study aimed at verifying adherence to treatment of hypertension of elderly patients followed in a group and describe the possible nursing interventions on the clientele. The descriptive research was developed in two phases: between December/2008 and January/2009, we used data collection instrument to assess compliance to treatment; from February to April/2009, we used the technique Focus Gro...

  8. Engineering adherent bacteria by creating a single synthetic curli operon. (United States)

    Drogue, Benoît; Thomas, Philippe; Balvay, Laurent; Prigent-Combaret, Claire; Dorel, Corinne


    The method described here consists in redesigning E. coli adherence properties by assembling the minimum number of curli genes under the control of a strong and metal-overinducible promoter, and in visualizing and quantifying the resulting gain of bacterial adherence. This method applies appropriate engineering principles of abstraction and standardization of synthetic biology, and results in the BBa_K540000 Biobrick (Best new Biobrick device, engineered, iGEM 2011). The first step consists in the design of the synthetic operon devoted to curli overproduction in response to metal, and therefore in increasing the adherence abilities of the wild type strain. The original curli operon was modified in silico in order to optimize transcriptional and translational signals and escape the "natural" regulation of curli. This approach allowed to test with success our current understanding of curli production. Moreover, simplifying the curli regulation by switching the endogenous complex promoter (more than 10 transcriptional regulators identified) to a simple metal-regulated promoter makes adherence much easier to control. The second step includes qualitative and quantitative assessment of adherence abilities by implementation of simple methods. These methods are applicable to a large range of adherent bacteria regardless of biological structures involved in biofilm formation. Adherence test in 24-well polystyrene plates provides a quick preliminary visualization of the bacterial biofilm after crystal violet staining. This qualitative test can be sharpened by the quantification of the percentage of adherence. Such a method is very simple but more accurate than only crystal violet staining as described previously with both a good repeatability and reproducibility. Visualization of GFP-tagged bacteria on glass slides by fluorescence or laser confocal microscopy allows to strengthen the results obtained with the 24-well plate test by direct observation of the phenomenon.

  9. Medication adherence: the critical step towards better patient outcome

    Directory of Open Access Journals (Sweden)

    Anish Desai


    Full Text Available Medication adherence is defined as patient's adherence to take their medications as prescribed and continue to take the prescribed medication for stipulated time frame. Medication non-adherence is a growing concern to physicians, healthcare systems, and other stakeholders (e.g., payers and there is an increasing evidence of its prevalence and is associated with adverse clinical outcomes eventually resulting into higher costs of care. The cost of non-adherence has been estimated at $100 billion to $300 billion annually, including costs from avoidable hospitalizations, nursing home admissions, and premature deaths. Improving adherence to medication is critical to improve the quality of health care, to encourage better chronic care management, and promote better health outcomes. Reasons for non-adherence are multiple and complex. Studies have reported that poor adherence to drug dosage is due to patient perception that the disease is non-significant, adverse drug effects, lack of treatment effectiveness, and the patient's poor or incomplete knowledge of the disease and (cost. A multifactorial approach is required to tackle this complex problem as a single approach will be ineffective for all patients. The most effective intervention is to use a combination of approaches and address literacy, behavior, and organizational issues. There are challenges as well as opportunities in addressing the public health issue of medication adherence. Changing healthcare reforms, advances in digital health media, social media and modern technologies can now provide alternatives to tackle this issue. [Int J Basic Clin Pharmacol 2014; 3(5.000: 748-754

  10. Treatment non-adherence in pseudo-refractory epilepsy. (United States)

    Brodtkorb, Eylert; Samsonsen, Christian; Sund, Janne Kutschera; Bråthen, Geir; Helde, Grethe; Reimers, Arne


    Non-adherence to antiepileptic drug treatment strongly affects the outcome of epilepsy and is frequently clinically unrecognized. This review addresses current knowledge on medication-taking behavior in people with epilepsy, as well as the importance of tailoring interventions to the individual patterns of non-adherence. Non-adherence can be categorized as non-initiation, poor execution (accidental or intentional) or non-persistence and are related to clinical characteristics and health care barriers. All available methods to assess adherence are hampered by shortcomings. Self-reports are indirect and subjective. Pill-counts, electronic bottle-tops and pharmacy records are objective, but indirect measures of drug ingestion. Therapeutic drug monitoring is both direct and objective, but pharmacokinetic and diurnal variability must be taken into account. Young adults with generalized epilepsy may be particularly vulnerable to non-adherence. The drug burden in the form of polytherapy, multiple dosing and side effects are obvious obstacles. Poor understanding of the principles of prophylactic treatment as well as drug costs may be important in people with low socioeconomic status. Depression is also associated with low adherence. In people with multihandicaps, failed oral intake may be due to behavioral or physical problems, as well as insufficient education of the caregivers. Non-adherence often results in seizure breakthrough and hospital admissions, but the consequences may be more dramatic. It is the leading cause of status epilepticus in people with epilepsy, and the association with sudden death (SUDEP) is clear. The management of poor drug-taking behavior should be based on the identification of the specific causes in each individual and corresponding multiprofessional interventions. Non-adherence to antiepileptic drugs needs more clinical and scientific attention.


    Directory of Open Access Journals (Sweden)

    Ramona DUMITRIU


    Full Text Available This paper explores the monetary expectations induced to the managers of Romanian firms by adheration. It is based on an investigation among twenty Romanian executives regarding the impact on adheration over monetary aspects: inflation, exchange rates and adoption of euro. We conclude that the results of the monetary policy in the last years made the executives confident that the Romanian authorities could maintain the monetary stability after theadheration.

  12. Mannose binding lectin plays a crucial role in innate immunity against yeast by enhanced complement activation and enhanced uptake of polymorphonuclear cells

    Directory of Open Access Journals (Sweden)

    Herpers Bjorn L


    Full Text Available Abstract Background Mannose binding lectin (MBL is an important host defence protein against opportunistic fungal pathogens. This carbohydrate-binding protein, an opsonin and lectin pathway activator, binds through multiple lectin domains to the repeating sugar arrays displayed on the surface of a wide range of clinically relevant microbial species. We investigated the contribution of MBL to antifungal innate immunity towards C. parapsilosis in vitro. Results High avidity binding was observed between MBL and C. albicans and C. parapsilosis. Addition of MBL to MBL deficient serum increased the deposition of C4 and C3b and enhanced the uptake of C. albicans, C. parapsilosis and acapsular C. neoformans by polymorphonuclear cells (PMNs. Compared to other microorganisms, such as Escherichia coli, Staphylococcus aureus and Cryptococcus neoformans, C. parapsilosis and Candida albicans were potent activators of the lectin pathway. Conclusion Our results suggest that MBL plays a crucial role in the innate immunity against infections caused by yeast by increasing uptake by PMN.

  13. Changes of pulmonary intercellular adhesion molecule-1 and CD11b/CD18 in peripheral polymorphonuclear neutrophils and their significance at the early stage of burns

    Institute of Scientific and Technical Information of China (English)

    金榕兵; 朱佩芳; 王正国; 刘大维; 周继红


    Objective: To investigate the role of intercellular adhesion molecule-1 (ICAM-1) in the accumulation of polymorphonuclear neutrophils (PMN) in the lungs at the early stage of burns. Methods: Myeloperoxidase content in lung tissues and bronchoalveolar lavage fluid (BALF) were detected. ICAM-1 and its mRNA expression in lung tissues were determined by immunohistochemical method and in situ hybridization. CD11b/CD18 expression on the peripheral PMNs was measured by flowcytometry. Results: The levels of myeloperoxidase in lung tissues and BALF after burn injury were markedly higher than those of control. Expression of ICAM-1 and its mRNA in the lung tissues and CD11b/CD18 on peripheral PMNs surface was significantly increased at 2, 6, 12, 24 h after burns. Conclusions: PMNs accumulation in the lungs is related to increased ICAM-1 expression on pulmonary microvascular endothelial cells and CD11b/CD18 expression on PMN at the early stage of burn injury.

  14. Myeloid derived suppressor cells (MDSCs are increased and exert immunosuppressive activity together with polymorphonuclear leukocytes (PMNs in chronic myeloid leukemia patients.

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    Cesarina Giallongo

    Full Text Available Tumor immune tolerance can derive from the recruitment of suppressor cell population, including myeloid derived suppressor cells (MDSCs, able to inhibit T cells activity. We identified a significantly expanded MDSCs population in chronic myeloid leukemia (CML patients at diagnosis that decreased to normal levels after imatinib therapy. In addition, expression of arginase 1 (Arg1 that depletes microenvironment of arginine, an essential aminoacid for T cell function, resulted in an increase in patients at diagnosis. Purified CML CD11b+CD33+CD14-HLADR- cells markedly suppressed normal donor T cell proliferation in vitro. Comparing CML Gr-MDSCs to autologous polymorphonuclear leukocytes (PMNs we observed a higher Arg1 expression and activity in PMNs, together with an inhibitory effect on T cells in vitro. Our data indicate that CML cells create an immuno-tolerant environment associated to MDSCs expansion with immunosuppressive capacity mediated by Arg1. In addition, we demonstrated for the first time also an immunosuppressive activity of CML PMNs, suggesting a strong potential immune escape mechanism created by CML cells, which control the anti-tumor reactive T cells. MDSCs should be monitored in imatinib discontinuation trials to understand their importance in relapsing patients.

  15. The influence of different anticoagulants and sample preparation methods on measurement of mCD14 on bovine monocytes and polymorphonuclear neutrophil leukocytes

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    Ibeagha-Awemu Eveline M


    Full Text Available Abstract Background Membrane-CD14 (mCD14 is expressed on the surface of monocytes, macrophages and polymorphonuclear neutrophil leukocytes (PMN. mCD14 acts as a co-receptor along with Toll like receptor 4 (TLR 4 and MD-2 for the detection of lipopolysaccharide (LPS. However, studies using different sample preparation methods and anticoagulants have reported different levels of mCD14 on the surface of monocytes and neutrophils. In this study, the influence of various anticoagulants and processing methods on measurement of mCD14 on monocytes and neutrophils was examined. Results Whole blood samples were collected in vacutainer tubes containing either sodium heparin (HEPARIN, ethylenediaminetetraacetic acid (EDTA or sodium citrate (CITRATE. mCD14 on neutrophils and monocytes in whole blood samples or isolated cells was measured by the method of flow cytometry using fluorescein isothiocyanate (FITC-labeled monoclonal antibody. There was a significant difference (p p Conclusion From these results, it is suggested that sodium heparin should be the preferred anticoagulant for use in the reliable quantification of the surface expression of mCD14. Furthermore, measurement of mCD14 is best carried out in whole blood samples, both for neutrophils and monocytes.

  16. Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Jensen, Peter Østrup; Burmølle, Mette;


    The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis (CF) patients. P. aeruginosa colonizes the CF lungs by forming biofilm structures in the alveoli. In the biofilm mode of growth the bacteria are highly tolerant...

  17. Medication Days Supply, Adherence, Wastage, and Cost (United States)

    U.S. Department of Health & Human Services — In an attempt to contain Medicaid pharmacy costs, nearly all states impose dispensing limits on medication days supply. Although longer days supply appears to...

  18. Adherence to antiretroviral treatment and correlation with risk of hospitalization among commercially insured HIV patients in the United States.

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    Paul E Sax

    Full Text Available PURPOSE: A lower daily pill burden may improve adherence to antiretroviral treatment (ART and clinical outcomes in patients with human immunodeficiency virus (HIV. This study assessed differences in adherence using the number of pills taken per day, and evaluated how adherence correlated with hospitalization. METHODOLOGY: Commercially insured patients in the LifeLink database with an HIV diagnosis (International Classification of Diseases, 9th Revision, Clinical Modification code 042.xx between 6/1/2006 and 12/31/2008 and receipt of a complete ART regimen were selected for inclusion. Patients were grouped according to their daily pill count and remained on ART for at least 60 days. Outcomes included adherence and rates of hospitalization. Adherence was measured as the proportion of days between the start and end of the regimen in which the patient maintained supply of all initiated ART components. Logistic regressions assessed the relationship between pills per day, adherence, and hospitalization, controlling for demographics, comorbidities, and ART-naïve (vs. experienced status. RESULTS: 7,073 patients met the study inclusion criteria, and 33.4%, 5.8%, and 60.8% received an ART regimen comprising one, two, or three or more pills per day, respectively. Regression analysis showed patients receiving a single pill per day were significantly more likely to reach a 95% adherence threshold versus patients receiving three or more pills per day (odds ratio [OR] = 1.59; P<0.001. Regardless of the number of pills received per day, patients were over 40% less likely to have a hospitalization if they were adherent to therapy (OR = 0.57; P<0.001. Patients receiving a single pill per day were 24% less likely to have a hospitalization versus patients receiving three or more pills per day (OR = 0.76; P = 0.003. CONCLUSIONS: ART consisting of a single pill per day was associated with significantly better adherence and lower risk of hospitalization in patients

  19. Comparison of photonic and electromagnetic effects on the human leukocyte (United States)

    DellaVecchia, Michael A.; Beard, Richard B.; Feng, D.; Dai, Xiaoyan; Pourrezaei, Kambiz; Priezzhev, Alexander V.


    The dielectric and magnetic influence on human cells have been widely studied previously by the authors. Recently, the effects of energy in the visible electromagnetic spectrum have been investigated. In this subsequent study, the photonic effects on the in vitro migration of the polymorphonuclear and mononuclear leukocytes are compared with the corresponding electromagnetic field effects. Dielectric spectra of the polymorph in the 300 KHz to 400 KHz and 700 KHz to 800 KHz range have been measured. At frequencies of 350 KHz and 720 KHz an increase in the migration of the polymorphonuclear leukocyte have been observed. This stimulation was attributed to the charges on the nuclear surface. Recent preliminary data have shown a similar increased migration in the 20 MHz range. Photonic studies have indicated an enhanced migration for the polymorphonuclear leukocytes at a wavelength of 660 nm (red) and an inhibited migration at 565 nm (green). The photonic effects were postulated to be the results of a biochemical interaction rather than a membranous surface charge displacement secondary to an electric field. The migration of the white blood cells were measurement via the Boyden chamber technique and expressed in terms of a cytokinetic index which expresses the cellular movement independent of its environmental concentration gradient.

  20. Epic Allies: Development of a Gaming App to Improve Antiretroviral Therapy Adherence Among Young HIV-Positive Men Who Have Sex With Men (United States)

    Muessig, Kathryn Elizabeth; McNulty, Tobias; Soni, Karina; Knudtson, Kelly; Lemann, Alex; Nwoko, Nkechinyere; Hightow-Weidman, Lisa B


    Background In the United States, the human immunodeficiency virus (HIV) disproportionately affects young men who have sex with men (YMSM). For HIV-positive individuals, adherence to antiretroviral therapy (ART) is critical for achieving optimal health outcomes and reducing secondary transmission of HIV. However, YMSM often struggle with ART adherence. Novel mobile phone apps that incorporate game-based mechanics and social networking elements represent a promising intervention approach for improving ART adherence among YMSM. Objective This study used a multiphase, iterative development process to create an ART adherence app for YMSM. Methods The three-phase development process included: (1) theory-based concept development jointly by public health researchers and the technology team, (2) assessment of the target population’s ART adherence needs and app preferences and development and testing of a clickable app prototype, and (3) development and usability testing of the final app prototype. Results The initial theory-based app concept developed in Phase One included medication reminders, daily ART adherence tracking and visualization, ART educational modules, limited virtual interactions with other app users, and gamification elements. In Phase Two, adherence needs, including those related to information, motivation, and behavioral skills, were identified. Participants expressed preferences for an ART adherence app that was informational, interactive, social, and customizable. Based on the findings from Phase Two, additional gaming features were added in Phase Three, including an interactive battle, superhero app theme, and app storyline. Other features were modified to increase interactivity and customization options and integrate the game theme. During usability testing of the final prototype, participants were able to understand and navigate the app successfully and rated the app favorably. Conclusions An iterative development process was critical for the

  1. Common mental health problems and antiretroviral therapy adherence. (United States)

    Nel, Adriaan; Kagee, Ashraf


    This paper reviews the literature on various mental health problems and their impact on adherence to antiretroviral therapy (ART). Depression, anxiety disorders, and disorders related to substance abuse were identified as key role-players influencing adherence. The severity of symptoms related to these disorders was found to be inversely related to ART adherence, with the possible exception of post-traumatic stress disorder (PTSD). PTSD was found to have both positive and negative implications for adherence, with severity of symptoms ranging from health-protective concern to disabling distress. Possible solutions aimed at addressing the adverse effects of mental health problems on adherence are discussed. Routine screening in ART settings is suggested in settings where follow-up of positive screen scores are possible, along with the necessary interventions to resolve the disorder of concern. Suggested interventions include utilising psychotherapeutic treatment, both in isolation and in conjunction with medication, to address mental health problems. Furthermore, finding effective ways of marshalling social support is recommended for ensuring optimal adherence, and possibly mitigating the adverse effects of mental health problems. Further research is needed to find feasible ways of identifying, assessing and treating patients with mental health problems in resource-constrained settings where HIV prevalence is highest.

  2. Fibrinogen-Induced Streptococcus mutans Biofilm Formation and Adherence to Endothelial Cells

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    Telma Blanca Lombardo Bedran


    Full Text Available Streptococcus mutans, the predominant bacterial species associated with dental caries, can enter the bloodstream and cause infective endocarditis. The aim of this study was to investigate S. mutans biofilm formation and adherence to endothelial cells induced by human fibrinogen. The putative mechanism by which biofilm formation is induced as well as the impact of fibrinogen on S. mutans resistance to penicillin was also evaluated. Bovine plasma dose dependently induced biofilm formation by S. mutans. Of the various plasma proteins tested, only fibrinogen promoted the formation of biofilm in a dose-dependent manner. Scanning electron microscopy observations revealed the presence of complex aggregates of bacterial cells firmly attached to the polystyrene support. S. mutans in biofilms induced by the presence of fibrinogen was markedly resistant to the bactericidal effect of penicillin. Fibrinogen also significantly increased the adherence of S. mutans to endothelial cells. Neither S. mutans cells nor culture supernatants converted fibrinogen into fibrin. However, fibrinogen is specifically bound to the cell surface of S. mutans and may act as a bridging molecule to mediate biofilm formation. In conclusion, our study identified a new mechanism promoting S. mutans biofilm formation and adherence to endothelial cells which may contribute to infective endocarditis.

  3. Hydrogen peroxide release and hydroxyl radical formation in mixtures containing mineral fibres and human neutrophils.


    Leanderson, P; Tagesson, C


    The ability of different mineral fibres (rock wool, glass wool, ceramic fibres, chrysotile A, chrysotile B, amosite, crocidolite, antophyllite, erionite, and wollastonite) to stimulate hydrogen peroxide (H2O2) and hydroxyl radical (OH.) formation in mixtures containing human polymorphonuclear leucocytes (PMNLs) was investigated. In the presence of azide, all the fibres caused considerable H2O2 formation, and about twice as much H2O2 was found in mixtures with the natural fibres (asbestos, eri...

  4. Treatment adherence and quality of life in patients on antihypertensive medications in a Middle Eastern population: adherence

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    Alhaddad IA


    Full Text Available Imad A Alhaddad,1 Omar Hamoui,2 Ayman Hammoudeh,3 Samir Mallat4 1Cardiovascular Department, Jordan Hospital, Amman, Jordan; 2Cardiology Department, Clemenceau Medical Center, Beirut, Lebanon; 3Cardiology Department, Istishari Hospital, Amman, Jordan; 4Department of Internal Medicine, Nephrology Division, American University of Beirut Medical Center, Beirut, Lebanon Background: Poor adherence to antihypertensive treatment remains a clinical challenge worldwide. The objectives of this study were to assess the adherence level to antihypertensive treatment and to identify its associated factors in a sample of hypertensive patients in Lebanon and Jordan. Methods: We conducted an observational study between May 2011 and September 2012. A total of 1,470 eligible hypertensive patients were enrolled in our study and followed up for a period of 6 months. Data were collected regarding sociodemographic, health behavior, and hypertension-related characteristics. The adherence to treatment and the quality of life were self-reported using the Morisky, Green & Levine Scale and the Hypertension Quality of Life Questionnaire. Results: Our results revealed that 55.9 % of the patients were adherent to their antihypertensive medication. Older age was associated with better adherence, whereas being divorced or widowed, having a poorer quality of life, and being classified as having stage 1 or 2 hypertension at the end of the study were all associated with poorer adherence. Conclusion: Efforts should be exerted on all levels in order to increase the adherence to antihypertensive treatment through the implementation of educational campaigns. Keywords: adherence, NC 7 guidelines, Morisky, Green & Levine Scale, Hypertension Quality of Life Questionnaire, Lebanon, Jordan

  5. Newly-synthesized chalcones-inhibition of adherence and biofilm formation of methicillin-resistant Staphylococcus aureus. (United States)

    Bozic, Dragana D; Milenkovic, Marina; Ivkovic, Branka; Cirkovic, Ivana


    Biofilm formation and adherence of bacteria to host tissue are one of the most important virulence factors of methicillin-resistant strains of Staphylococcus aureus (MRSA). The number of resistant strains is seriously increasing during the past years and bacteria have become resistant, not only to methicillin, but also to other commonly used antistaphylococcal antibiotics. There is a great need for discovering a novel antimicrobial agent for the treatment of staphylococcal infections. One of the most promising groups of compounds appears to be chalcones. In present study we evaluated the in vitro effect of three newly synthesized chalcones: 1,3- Bis-(2-hydroxy-phenyl)-propenone, 3-(3-Hydroxy-phenyl)-1-(2-hydroxy-phenyl)-propenone and 3-(4-Hydroxy-phenyl)-1-(2-hydroxy-phenyl)-propenone on glycocalyx production, biofilm formation and adherence to human fibronectin of clinical isolates and laboratory control strain of MRSA (ATCC 43300). Subinhibitory concentrations of the tested compounds reduced the production of glycocalyx, biofilm formation and adherence to human fibronectin of all MRSA strains. Inhibition of biofilm formation was dose dependent and the most effective was 1,3- Bis-(2-hydroxy-phenyl)-propenone. In our study we demonstrated that three newly-synthesized chalcones exhibited significant effect on adherence and biofilm formation of MRSA strains. Chalcones may be considered as promising new antimicrobial agents that can be used for prevention of staphylococcal infections or as adjunct to antibiotics in conventional therapy.

  6. Newly-synthesized chalcones-inhibition of adherence and biofilm formation of methicillin-resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Dragana D. Bozic


    Full Text Available Biofilm formation and adherence of bacteria to host tissue are one of the most important virulence factors of methicillin-resistant strains of Staphylococcus aureus (MRSA. The number of resistant strains is seriously increasing during the past years and bacteria have become resistant, not only to methicillin, but also to other commonly used antistaphylococcal antibiotics. There is a great need for discovering a novel antimicrobial agent for the treatment of staphylococcal infections. One of the most promising groups of compounds appears to be chalcones. In present study we evaluated the in vitro effect of three newly synthesized chalcones: 1,3-Bis-(2-hydroxy-phenyl-propenone, 3-(3Hydroxy-phenyl-1-(2-hydroxy-phenyl-propenone and 3-(4-Hydroxy-phenyl-1-(2-hydroxyphenyl-propenone on glycocalyx production, biofilm formation and adherence to human fibronectin of clinical isolates and laboratory control strain of MRSA (ATCC 43300. Subinhibitory concentrations of the tested compounds reduced the production of glycocalyx, biofilm formation and adherence to human fibronectin of all MRSA strains. Inhibition of biofilm formation was dose dependent and the most effective was 1,3-Bis-(2-hydroxy-phenyl-propenone. In our study we demonstrated that three newly-synthesized chalcones exhibited significant effect on adherence and biofilm formation of MRSA strains. Chalcones may be considered as promising new antimicrobial agents that can be used for prevention of staphylococcal infections or as adjunct to antibiotics in conventional therapy.

  7. Self-reported adherence to antiretroviral therapy in HIV+ population from Bata, Equatorial Guinea. (United States)

    Salmanton-García, Jon; Herrador, Zaida; Ruiz-Seco, Pilar; Nzang-Esono, Jesús; Bendomo, Veronica; Bashmakovic, Emma; Nseng-Nchama, Gloria; Benito, Agustín; Aparicio, Pilar


    The human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome (AIDS) represent a serious public health problem in Equatorial Guinea, with a prevalence of 6.2% among adults. the high-activity antiretroviral treatment (HAART) coverage data is 10 points below the overall estimate for Sub-Saharan Africa, and only 61% patients continue with HAART 12 months after it started. This study aims to assess HAART adherence and related factors in Litoral Province of Equatorial Guinea. In this cross-sectional study, socio-demographic and clinical data were collected at Regional Hospital of Bata, during June-July 2014. Adherence to treatment was assessed by using the Spanish version of CEAT-VIH. Bivariate and linear regression analyses were employed to assess HAART adherence-related factors. We interviewed 50 men (35.5%) and 91 women (64.5%), with a mean age of 47.7 ± 8.9 and 36.2 ± 11.2, respectively (p VIH score varied by ethnic group (p = .005). There was a positive correlation between CEAT-VIH score and current CD4 T-cells count (p = .013). The Cronbach's α value was 0.52. To our knowledge, this is the first study to assess HAART adherence in Equatorial Guinea. Internal reliability for CEAT-VIH was low, nonetheless the positive correlation between the CEAT-VIH score and the immunological status of patients add value to our findings. Our results serve as baseline for future research and will also assist stakeholders in planning and undertaking contextual and evidence-based policy initiatives.

  8. Interventions to increase medication adherence in African-American and Latino populations: a literature review. (United States)

    Hu, Daniel; Juarez, Deborah Taira; Yeboah, Michelle; Castillo, Theresa P


    The objective of this systematic review was to investigate the effectiveness of interventions to improve medication adherence in ethnic minority populations. A literature search from January 2000 to August 2012 was conducted through PubMed/Medline, Web of Science, The Cochrane Library, and Google Scholar. Search terms used included: medication (MeSH), adherence, medication adherence (MeSH), compliance (MeSH), persistence, race, ethnicity, ethnic groups (MeSH), minority, African-American, Hispanic, Latino, Asian, Pacific Islander, and intervention. Studies which did not have ≥75% of the sample population comprised of individuals of any one ethnic background were excluded, unless the authors performed sub-group analyses by race/ethnicity. Of the 36 studies identified, 20 studies showed significant post-intervention differences. Sample population sizes ranged from 10 to 520, with a median of 126.5. The studies in this review were conducted with patients of mainly African-American and Latino descent. No studies were identified which focused on Asians, Pacific Islanders, or Native Americans. Interventions demonstrating mixed results included motivational interviewing, reminder devices, community health worker (CHW) delivered interventions, and pharmacist-delivered interventions. Directly observed therapy (DOT) was a successful intervention in two studies. Interventions which did not involve human contact with patients were ineffective. In this literature review, studies varied significantly in their methods and design as well as the populations studied. There was a lack of congruence among studies in the way adherence was measured and reported. No single intervention has been seen to be universally successful, particularly for patients from ethnic minority backgrounds.

  9. Evaluating adherence to ocular hypotensives using the Travatan dosing aid

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    O'Dell L


    Full Text Available Leslie O'Dell1, Amy L Hennessy2,3, Alan L Robin2–41May Eye Care Center, Hanover, PA, USA; 2Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 3Glaucoma Specialists, Baltimore, MD, USA; 4Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USAPurpose: The Travatan™ Dosing Aid (TDA is the first commercially available device designed to aid in patients' adherence to their glaucoma therapies and to record patients' eyedrop administration, so that doctors can better assess adherence. No prior studies have objectively evaluated adherence to glaucoma medications and its relationship to the severity of glaucoma or the use of multiple systemic medications.Methods: We enrolled 100 consecutive subjects from a private glaucoma practice, all currently using topical travoprost 0.004%. Each subject was issued a TDA to record the time and date of each drop instilled. Informed consents were signed and the subjects were aware that their medication use was being monitored. Patients returned for follow-up 30–60 days after their initial exam.Results: 89 subjects completed the study: 44 were male, with a mean age of 67 years, and 69.7% were Caucasian. Overall, patient adherence was 74.8% (range 22%–100% improving to 85.4% on the day prior to follow-up. The mean number of missed doses per month was 6.24 ± 5.9. Only 7.9% of the study population never missed a dose and 23.6% ± 4.3% missed more than ten drops per month. No marked association was observed between the severity of glaucoma, race, or the number of systemic medications and adherence. A marked improvement in adherence was noted in patients using travoprost 0.004% as monocular therapy rather than binocular therapy, 84.0% ± 17.1% vs 67.4% ± 23.5% (P < 0.005.Conclusion: Patient adherence to glaucoma medical therapy is a major barrier in the management and treatment of glaucoma patients given the chronic nature and asymptomatic course of the disease. Until recently

  10. An exploration of factors influencing ambulance and emergency nurses protocol adherence in the Netherlands

    NARCIS (Netherlands)

    Ebben, Remco; Vloet, Lilian; Mintjes, Joke; Achterberg, Theo van


    Adherence to ambulance and ED protocols is often suboptimal. Insight into factors influencing adherence is a requisite for improvement of adherence. This study aims to gain an in-depth understanding of factors that influence ambulance and emergency nurses’ adherence to protocols.

  11. Factors influencing long-term adherence to two previously implemented hospital guidelines

    NARCIS (Netherlands)

    A.M. Knops; M.N. Storm-Versloot; A.P.M. Mank; D.T. Ubbink; H. Vermeulen; P.M.M. Bossuyt; A. Goossens


    After successful implementation, adherence to hospital guidelines should be sustained. Long-term adherence to two hospital guidelines was audited. The overall aim was to explore factors accounting for their long-term adherence or non-adherence. A fluid balance guideline (FBG) and body temperature gu

  12. The relationship between clinical outcomes and medication adherence in difficult-to-control asthma. (United States)

    Murphy, Anna C; Proeschal, Amandine; Brightling, Christopher E; Wardlaw, Andrew J; Pavord, Ian; Bradding, Peter; Green, Ruth H


    Medication non-adherence and the clinical implications in difficult-to-control asthma were audited. Prescription issue data from 115 patients identified sub-optimal adherence (asthma (p=0.008). The majority of patients with difficult-to-control asthma are non-adherent with their asthma medication. Non-adherence is correlated with poor clinical outcomes.

  13. Perceived barriers to guideline adherence: A survey among general practitioners

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    Besters Casper F


    Full Text Available Abstract Background Despite considerable efforts to promote and support guideline use, adherence is often suboptimal. Barriers to adherence vary not only across guidelines but also across recommendations within guidelines. The aim of this study was to assess the perceived barriers to guideline adherence among GPs by focusing on key recommendations within guidelines. Methods We conducted a cross-sectional electronic survey among 703 GPs in the Netherlands. Sixteen key recommendations were derived from four national guidelines. Six statements were included to address the attitudes towards guidelines in general. In addition, GPs were asked to rate their perceived adherence (one statement and the perceived barriers (fourteen statements for each of the key recommendations, based on an existing framework. Results 264 GPs (38% completed the questionnaire. Although 35% of the GPs reported difficulties in changing routines and habits to follow guidelines, 89% believed that following guidelines leads to improved patient care. Perceived adherence varied between 52 and 95% across recommendations (mean: 77%. The most perceived barriers were related to external factors, in particular patient ability and behaviour (mean: 30% and patient preferences (mean: 23%. Lack of applicability of recommendations in general (mean: 22% and more specifically to individual patients (mean: 25% were also frequently perceived as barriers. The scores on perceived barriers differed largely between recommendations [minimum range 14%; maximum range 67%]. Conclusions Dutch GPs have a positive attitude towards the NHG guidelines, report high adherence rates and low levels of perceived barriers. However, the perceived adherence and perceived barriers varied largely across recommendations. The most perceived barriers across recommendations are patient related, suggesting that current guidelines do not always adequately incorporate patient preferences, needs and abilities. It may be

  14. Adherence to the Mediterranean dietary pattern among Balearic Islands adolescents. (United States)

    Martínez, Elisa; Llull, Rosa; Del Mar Bibiloni, Maria; Pons, Antoni; Tur, Josep A


    The aim of the present work was to assess the prevalence of the Mediterranean dietary pattern (MDP) in Balearic Islands adolescents, and socio-demographic and lifestyle factors that might determine adherence to the MDP. A cross-sectional nutritional survey was carried out in the Balearic Islands between 2007 and 2008. A random sample (n 1231) of the adolescent population (12-17 years old) was interviewed. Dietary questionnaires and a general questionnaire incorporating questions related to socio-economic status, parental education level and lifestyle factors were used. Dietary habits were assessed by means of two 24 h recalls and a quantitative FFQ. Adherence to the MDP was defined according to a score constructed considering the consumption of nine MDP characteristic components: high MUFA:SFA ratio, moderate ethanol consumption, high legumes, cereals and roots, fruits, vegetables and fish consumption, and low consumption of meat and milk. Then, socio-demographic, lifestyle and health status variables that could determine a higher or ower adherence were assessed. The mean adherence was 57.9 (sd 8.9) % and the median adherence was 57.3 %. Half of the Balearic Islands adolescents (50.5 %) showed an adherence to the MDP comprised between 52.7 and 62.8 %. By multivariate analyses, a high maternal level of education, increased physical activity, reduced alcohol intake and abstinence from smoking were independent associations of better adherence to the MDP. The promotion of not only the MDP but also the Mediterranean lifestyle, including greater physical activity, should be reinforced among the Balearic younger generations.

  15. Surface modification of closed plastic bags for adherent cell cultivation (United States)

    Lachmann, K.; Dohse, A.; Thomas, M.; Pohl, S.; Meyring, W.; Dittmar, K. E. J.; Lindenmeier, W.; Klages, C.-P.


    In modern medicine human mesenchymal stem cells are becoming increasingly important. However, a successful cultivation of this type of cells is only possible under very specific conditions. Of great importance, for instance, are the absence of contaminants such as foreign microbiological organisms, i.e., sterility, and the chemical functionalization of the ground on which the cells are grown. As cultivation of these cells makes high demands, a new procedure for cell cultivation has been developed in which closed plastic bags are used. For adherent cell growth chemical functional groups have to be introduced on the inner surface of the plastic bag. This can be achieved by a new, atmospheric-pressure plasma-based method presented in this paper. The method which was developed jointly by the Fraunhofer IST and the Helmholtz HZI can be implemented in automated equipment as is also shown in this contribution. Plasma process gases used include helium or helium-based gas mixtures (He + N2 + H2) and vapors of suitable film-forming agents or precursors such as APTMS, DACH, and TMOS in helium. The effect of plasma treatment is investigated by FTIR-ATR spectroscopy as well as surface tension determination based on contact angle measurements and XPS. Plasma treatment in nominally pure helium increases the surface tension of the polymer foil due to the presence of oxygen traces in the gas and oxygen diffusing through the gas-permeable foil, respectively, reacting with surface radical centers formed during contact with the discharge. Primary amino groups are obtained on the inner surface by treatment in mixtures with nitrogen and hydrogen albeit their amount is comparably small due to diffusion of oxygen through the gas-permeable bag, interfering with the plasma-amination process. Surface modifications introducing amino groups on the inner surface turned out to be most efficient in the promotion of cell growth.

  16. Factors associated with suboptimal adherence to antiretroviral therapy in Asia

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    Awachana Jiamsakul


    Full Text Available Introduction: Adherence to antiretroviral therapy (ART plays an important role in treatment outcomes. It is crucial to identify factors influencing adherence in order to optimize treatment responses. The aim of this study was to assess the rates of, and factors associated with, suboptimal adherence (SubAdh in the first 24 months of ART in an Asian HIV cohort. Methods: As part of a prospective resistance monitoring study, the TREAT Asia Studies to Evaluate Resistance Monitoring Study (TASER-M collected patients’ adherence based on the World Health Organization-validated Adherence Visual Analogue Scale. SubAdh was defined in two ways: (i 14 days. Time was divided into four intervals: 0–6, 6–12, 12–18 and 18–24 months. Factors associated with SubAdh were analysed using generalized estimating equations. Results: Out of 1316 patients, 32% ever reported 2 assessments per patient per year had an odds ratio (OR=0.7 (95% confidence interval (CI (0.55 to 0.90, p=0.006, compared to sites with ≤2 assessments per patient per year. Compared to heterosexual exposure, SubAdh was higher in injecting drug users (IDUs (OR=1.92, 95% CI (1.23 to 3.00, p=0.004 and lower in homosexual exposure (OR=0.52, 95% CI (0.38 to 0.71, p<0.001. Patients taking a nucleoside transcriptase inhibitor and protease inhibitor (NRTI+PI combination were less likely to report adherence <100% (OR=0.36, 95% CI (0.20 to 0.67, p=0.001 compared to patients taking an NRTI and non-nucleoside transcriptase inhibitor (NRTI+NNRTI combination. SubAdh decreased with increasing time on ART (all p<0.001. Similar associations were found with adherence <95% as the outcome. Conclusions: We found that SubAdh, defined as either <100% and <95%, was associated with mode of HIV exposure, ART regimen, time on ART and frequency of adherence measurement. The more frequently sites assessed patients, the lower the SubAdh, possibly reflecting site resourcing for patient counselling. Although social

  17. Approaches to improve adherence to pharmacotherapy in patients with schizophrenia

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    Shuler KM


    Full Text Available Kimberly M Shuler Shuler Counseling and Consulting, Fayetteville, AR, USA Purpose: In patients with schizophrenia, nonadherence to prescribed medications increases the risk of patient relapse and hospitalization, key contributors to the costs associated with treatment. The objectives of this review were to evaluate the impact of nonadherence to pharmacotherapy in patients with schizophrenia as it relates to health care professionals, particularly social workers, and to identify effective team approaches to supporting patients based on studies assessing implementation of assertive community treatment teams. Materials and methods: A systematic review of the medical literature was conducted by searching the Scopus database to identify articles associated with treatment adherence in patients with schizophrenia. Articles included were published from January 1, 2003, through July 15, 2013, were written in English, and reported findings concerning any and all aspects of nonadherence to prescribed treatment in patients with schizophrenia. Results: Of 92 unique articles identified and formally screened, 47 met the inclusion criteria for the systematic review. The burden of nonadherence in schizophrenia is significant. Factors with the potential to affect adherence include antipsychotic drug class and formulation, patient-specific factors, and family/social support system. There is inconclusive evidence suggesting superior adherence with an atypical versus typical antipsychotic or with a long-acting injectable versus an oral formulation. Patient-specific factors that contribute to adherence include awareness/denial of illness, cognitive issues, stigma associated with taking medication, substance abuse, access to health care, employment/poverty, and insurance status. Lack of social or family support may adversely affect adherence, necessitating the assistance of health care professionals, such as social workers. Evidence supports the concept that an

  18. Value-based insurance design yields near- and long-term improvements in medication adherence. (United States)

    Collado, Megan


    Key findings. (1) Value-based insurance design (VBID) improves medication adherence by 1 to 3 percent in the first year after implementation; (2) Improvements in adherence were sustained and amplified in the second year post-implementation, ranging from 2 to 5 percent; (3) Adherence improvements varied ac­cording to VBID participants' baseline adherence, with greatest improve­ments evident in those with poorer baseline adherence

  19. Adherence with tobramycin inhaled solution and health care utilization

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    Sacco Patricia


    Full Text Available Abstract Background Adherence with tobramycin inhalation solution (TIS during routine cystic fibrosis (CF care may differ from recommended guidelines and affect health care utilization. Methods We analyzed 2001-2006 healthcare claims data from 45 large employers. Study subjects had diagnoses of CF and at least 1 prescription for TIS. We measured adherence as the number of TIS therapy cycles completed during the year and categorized overall adherence as: low ≤ 2 cycles, medium >2 to Results Among 804 individuals identified with CF and a prescription for TIS, only 7% (n = 54 received ≥ 4 cycles of TIS per year. High adherence with TIS was associated with a decreased risk of hospitalization when compared to individuals receiving ≤ 2 cycles (adjusted odds ratio 0.40; 95% confidence interval 0.19-0.84. High adherence with TIS was also associated with lower outpatient service costs (IQR: $2,159-$8444 vs. $2,410-$14,423 and higher outpatient prescription drug costs (IQR: $35,125-$60,969 vs. $10,353-$46,768. Conclusions Use of TIS did not reflect recommended guidelines and may impact other health care utilization.

  20. Determinants of CPAP Adherence in Hispanics with Obstructive Sleep Apnea

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    Montserrat Diaz-Abad


    Full Text Available Purpose. We hypothesized that socioeconomic factors and a language barrier would impact adherence with continuous positive airway pressure (CPAP among Hispanics with obstructive sleep apnea (OSA. Methods. Patients with OSA who were prescribed CPAP for at least 1 year and completed a questionnaire evaluating demographic data, socioeconomic status, and CPAP knowledge and adherence participated in the study. Results. Seventy-nine patients (26 males; 53±11 yrs; body mass index (BMI=45±9 kg/m2 with apnea-hypopnea index (AHI 33±30 events/hr completed the study. Included were 25 Hispanics, 39 African Americans, and 15 Caucasians, with no difference in age, AHI, CPAP use, or BMI between the groups. While there was a difference in educational level (P=0.006, income level (P<0.001, and employment status (P=0.03 between the groups, these did not influence CPAP adherence. Instead, overall improvement in quality of life and health status and perceived benefit from CPAP influenced adherence, both for the group as a whole (P=0.03, P=0.004, and P=0.001, resp., as well as in Hispanics (P=0.02, P=0.02, P=0.03, resp.. Conclusion. In Hispanic patients with OSA, perceived benefit with therapy, rather than socioeconomic status or a language barrier, appears to be the most important factor in determining CPAP adherence.

  1. Bacterial adherence to SiO2-based multifunctional bioceramics. (United States)

    Kinnari, Teemu J; Esteban, Jaime; Gomez-Barrena, Enrique; Zamora, Nieves; Fernandez-Roblas, Ricardo; Nieto, Alejandra; Doadrio, Juan C; López-Noriega, Adolfo; Ruiz-Hernández, Eduardo; Arcos, Daniel; Vallet-Regí, María


    The bacterial adherence onto different multifunctional silica-based bioceramics has been evaluated. Staphylococcus aureus and Staphylococcus epidermidis were chosen, as they cause the majority of the implant-related infections in this field. Two SiO2 mesoporous materials (MCM-41, SBA-15), an ordered SiO2-CaO-P2O5 mesoporous glass (OMG), and a biphasic magnetic bioceramic (BMB), were incubated with S. aureus and S. epidermidis for 90 min, and subsequently sonicated to quantify the number of adhered bacteria on each material. It was found that S. aureus and S. epidermidis (10(8) CFU/mL) adhered significantly less to BMB samples when compared to MCM-41, SBA-15, or OMG. However, when the material pores accessible for bacteria in each material were taken into account, the lowest bacterial adherence was found in MCM-41, and the highest in SBA-15. The results show that bacterial adherence is higher on mesoporous bioceramics, although this higher microbial attachment is mainly due to the intergranular porosity and grain size morphology rather than to the mesoporous structure.

  2. Improving patient outcomes in psoriasis: strategies to ensure treatment adherence

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    Yélamos O


    Full Text Available Oriol Yélamos, Sandra Ros, Lluís Puig Department of Dermatology, Hospital de la Santa Creu i Sant Pau – Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain Abstract: Psoriasis is a frequent inflammatory disease with a chronic and relapsing course. Therefore, patients with psoriasis are likely to undergo different treatments for long periods of time. Traditionally, therapies used in psoriasis have been associated with poor levels of adherence due to the complexity of the regimens and the poor results obtained with the topical therapies. These poor outcomes are associated with high levels of frustration and anxiety, which decrease adherence and worsen the disease. With the recent introduction of highly efficacious biologic therapies, patients can achieve very good and prolonged responses. However, most patients with psoriasis have mild disease and may be treated with skin-directed therapies. Therefore, it is important to develop strategies to improve adherence in order to achieve better outcomes, and to improve the overall quality of life. Hence, acknowledging the causes of nonadherence is crucial for implementing these strategies. In this summary, we review the causes of nonadherence, and we provide behavioral strategies in order to improve adherence and, ultimately, the outcome of patients with psoriasis. Keywords: psoriasis, adherence, outcome, drug therapy, psychotherapy

  3. The therapeutic relationship and adherence to antipsychotic medication in schizophrenia.

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    Rosemarie McCabe

    Full Text Available OBJECTIVE: Previous research has shown that a better therapeutic relationship (TR predicts more positive attitudes towards antipsychotic medication, but did not address whether it is also linked with actual adherence. This study investigated whether the TR is associated with adherence to antipsychotics in patients with schizophrenia. METHODS: 134 clinicians and 507 of their patients with schizophrenia or a related psychotic disorder participated in a European multi-centre study. A logistic regression model examined how the TR as rated by patients and by clinicians is associated with medication adherence, adjusting for clinician clustering and symptom severity. RESULTS: Patient and clinician ratings of the TR were weakly inter-correlated (r(s = 0.13, p = 0.004, but each was independently linked with better adherence. After adjusting for patient rated TR and symptom severity, each unit increase in clinician rated TR was associated with an increase of the odds ratio of good compliance by 65.9% (95% CI: 34.6% to 104.5%. After adjusting for clinician rated TR and symptom severity, for each unit increase in patient rated TR the odds ratio of good compliance was increased by 20.8% (95% CI: 4.4% to 39.8%. CONCLUSIONS: A better TR is associated with better adherence to medication among patients with schizophrenia. Patients' and clinicians' perspectives of the TR are both important, but may reflect distinct aspects.

  4. Differential expression of interleukin-8 by polymorphonuclear leukocytes of two closely related species, Ovis canadensis and Ovis aries, in response to Mannheimia haemolytica infection. (United States)

    Herndon, Caroline N; Foreyt, William J; Srikumaran, Subramaniam


    The pneumonic lesions and mortality caused by Mannheimia haemolytica in bighorn sheep (BHS; Ovis canadensis) are more severe than those in the related species, domestic sheep (DS; Ovis aries), under both natural and experimental conditions. Leukotoxin (Lkt) and lipopolysaccharide (LPS) are the most important virulence factors of this organism. One hallmark of pathogenesis of pneumonia is the influx of polymorphonuclear leukocytes (PMNs) into the lungs. Lkt-induced cytolysis of PMNs results in the release of cytotoxic compounds capable of damaging lung tissue. Interleukin-8 (IL-8) is a potent PMN chemoattractant. The objective of the present study was to determine if there is differential expression of IL-8 by the macrophages and PMNs of BHS and DS in response to M. haemolytica. Macrophages and PMNs of BHS and DS were stimulated with heat-killed M. haemolytica or LPS. IL-8 expression by the cells was measured by enzyme-linked immunosorbent assays and real-time reverse transcription-PCR (RT-PCR). The PMNs of BHS expressed severalfold higher levels of IL-8 than those of DS upon stimulation. Lesional lung tissue of M. haemolytica-infected BHS contained significantly higher levels of IL-8 than nonlesional tissue. The bronchoalveolar lavage (BAL) fluid of infected BHS also contained higher levels of IL-8 than that of infected DS. Depletion of IL-8 reduced migration of PMNs toward BAL fluid by approximately 50%, indicating that IL-8 is integral to PMN recruitment to the lung during M. haemolytica infection. Excessive production of IL-8, enhanced recruitment of PMNs, and PMN lysis by Lkt are likely responsible for the severity of the lung lesions in M. haemolytica-infected BHS.

  5. IFN-γ regulates xanthine oxidase-mediated iNOS-independent oxidative stress in maneb- and paraquat-treated rat polymorphonuclear leukocytes. (United States)

    Singh, Deepali; Kumar, Vinod; Singh, Chetna


    Maneb (MB) and paraquat (PQ) provoke oxidative stress-mediated cell damage. Role of xanthine oxidase (XO) in oxidative stress and its association with nitric oxide (NO)/NO synthase (NOS) have been widely reported. While inducible NOS (iNOS) is implicated in MB+PQ-induced toxicity in rat polymorphonuclear leukocytes (PMNs), role of XO and its alliance with iNOS have not yet been established. The study investigated the role of XO in MB+PQ-induced oxidative stress in rat PMNs and its regulation by iNOS and inflammatory cytokines. MB+PQ-augmented reactive oxygen species (ROS), superoxide, nitro-tyrosine, lipid peroxidation (LPO), and nitrite levels along with the catalytic activity of iNOS, superoxide dismutase (SOD), and XO. XO inhibitor, allopurinol (AP), alleviated MB+PQ-induced changes except nitrite content and iNOS activity. Conversely, an iNOS inhibitor, aminoguanidine, mitigated MB+PQ-induced LPO, nitrite, iNOS, and nitro-tyrosine levels; however, no change was observed in ROS, SOD, and XO. Nuclear factor-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), tumor necrosis factor-alpha (TNF-α) inhibitor, pentoxyfylline, and an anti-inflammatory agent, dexamethasone, attenuated MB+PQ-induced increase in XO, superoxide, and ROS with parallel reduction in the expression of interferon-gamma (IFN-γ), TNF-α, and interleukin-1β (IL-1β) in rat PMNs. Exogenous IFN-γ, TNF-α, and IL-1β enhanced superoxide, ROS, and XO in the PMNs of control and MB+PQ-treated rats; however, IFN- γ was found to be the most potent inducer. Moreover, AP ameliorated cytokine-induced free radical generation and restored XO activity towards normalcy. The results thus demonstrate that XO mediates oxidative stress in MB+PQ-treated rat PMNs via iNOS-independent but cytokine (predominantly IFN-γ)-dependent mechanism.

  6. Differential effect of exogenous interleukin-10 versus glucocorticoids on gene expression and pro-inflammatory cytokine release by polymorphonuclear leukocytes and monocytes of the newly born (United States)

    Davidson, Dennis; Patel, Hardik; Degoy, Ana C; Gershkovich, Irina; Vancurova, Ivana; Miskolci, Veronika


    Bronchopulmonary dysplasia (BPD) is one of the most common causes of mortality and morbidity in neonatal intensive care units. Persistent inflammation, with an abnormal influx of polymorphonuclear leukocytes (PMNs) followed by monocytes (MONOs), occurs early in the pathogenesis of BPD. Anti-inflammatory therapy with better efficacy and safety than dexamethasone (DEX) is needed. In the present study we determined cell-specific gene expression and cytokine release in response to glucocorticoids versus interleukin-10 (IL-10). Subsequently, we hypothesized that the insensitivity of MONOs to DEX was associated with a failure of the glucocorticoid receptor to translocate to the nucleus. PMNs and MONOs were isolated from umbilical cord blood at birth, and pretreated with PBS vehicle, IL-10 or glucocorticoids prior to endotoxin (LPS)-stimulation for 4 and 18h. Genome-wide gene expressions were determined by microarray and validated by RT-qPCR. Interleukin 8 release in cell culture supernatant was measured by ELISA. To examine the mechanism of monocyte insensitivity to glucocorticoids, nuclear translocation of the glucocorticoid receptor was determined by Western blots. MONOs had 6 times the number of genes changing expression with IL-10 compared to PMNs at 4h. DEX at the therapeutic level for neonates with BPD had no effect on gene expression in MONOs. The order of potency for inhibition of interleukin-8 release from MONOs was IL-10 >betamethasone >dexamethasone and hydrocortisone. Glucocorticoid potency in MONOs was directly related to glucocorticoid receptor translocation to nucleus. Gene expression profiling for IL-10 versus glucocorticoids indicates there may be major differences in therapeutic efficacy for BPD. PMID:23390570

  7. Correlation between lamivudine plasma concentrations and patient self-reported adherence to antiretroviral treatment in experienced HIV patients

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    Minzi OM


    Full Text Available OM Minzi1, V Mugoyela2, LL Gustafsson31Unit of Pharmacology and Therapeutics, 2Department of Medicinal Chemistry, School of Pharmacy, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania; 3Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, SwedenBackground: Adherence to antiretroviral treatment (ART is important to achieve treatment success in human immunodeficiency virus (HIV-infected patients. Most HIV clinics apply the patient self-report (PSR method. However, the reliability of this method in experienced HIV patients remains questionable.Purpose: To validate the PSR method for measuring adherence to ART using lamivudine (3TC plasma concentrations in experienced HIV patients.Methods: The study was conducted in Dar Es Salaam and involved 220 patients who were receiving ART services at HIV clinics for more than 12 months. Self-reported adherence information to ART was obtained on the day of HIV clinic visit. The patients were asked to mention the number of doses missed within the past 7 days. In addition, blood samples (2 mL were collected from each patient on the same day. The blood samples were determined for 3TC plasma concentrations. The target 3TC plasma concentration as indicator concentration for adherent patients was determined in 20 patients who took their evening dose of antiretrovirals under supervision. The blood from these patients was drawn 3 hours after drug administration.Results: Complete drug levels of 3TC and self-reported adherence data was obtained in 200 treatment-experienced HIV patients. Lamivudine plasma concentrations obtained in these patients ranged between 0.02–17.36 µg/mL. The mean time from dose administration to blood drawing was 3.1 ± 1.2 hours with coefficient of variation >39%. The mean 3TC plasma concentration obtained in 20 patients who took their antiretroviral dose under supervision was

  8. Sonoporation of adherent cells under regulated ultrasound cavitation conditions. (United States)

    Muleki Seya, Pauline; Fouqueray, Manuela; Ngo, Jacqueline; Poizat, Adrien; Inserra, Claude; Béra, Jean-Christophe


    A sonoporation device dedicated to the adherent cell monolayer has been implemented with a regulation process allowing the real-time monitoring and control of inertial cavitation activity. Use of the cavitation-regulated device revealed first that adherent cell sonoporation efficiency is related to inertial cavitation activity, without inducing additional cell mortality. Reproducibility is enhanced for the highest sonoporation rates (up to 17%); sonoporation efficiency can reach 26% when advantage is taken of the standing wave acoustic configuration by applying a frequency sweep with ultrasound frequency tuned to the modal acoustic modes of the cavity. This device allows sonoporation of adherent and suspended cells, and the use of regulation allows some environmental parameters such as the temperature of the medium to be overcome, resulting in the possibility of cell sonoporation even at ambient temperature.

  9. Decisional capacity and medication adherence among youth with HIV. (United States)

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


    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.

  10. Bridging the gap between antiretroviral access and adherence in Mexico. (United States)

    Campero, Lourdes; Herrera, Cristina; Kendall, Tamil; Caballero, Marta


    The goal in this article is to examine social problems associated with highly active antiretroviral therapy (HAART) adherence in Mexico and the related challenges for Mexican persons living with HIV/AIDS (PLWHAs). The study was conducted from the perspective of infected and affected individuals. The authors completed 64 in-depth interviews with heterosexual male and female PLWHAs, as well as with some key individuals from their social network. Following the principles of grounded theory, they carried out inductive analysis to create codes and organize central themes. The authors identified problems related to accessing HAART and found that conditions for implementing recommendations made in the international literature to improve adherence are poor. The findings highlight the importance of social factors, such as health care system irregularities, ineffective physician-patient communication, and availability of family and other sources of social support such as self-help groups for PLWHAs' access and adherence to antiretroviral therapy in Mexico.

  11. Stick to your gums: mechanisms of oral microbial adherence. (United States)

    Nobbs, A H; Jenkinson, H F; Jakubovics, N S


    Studies on the adherence properties of oral bacteria have been a major focus in microbiology research for several decades. The ability of bacteria to adhere to the variety of surfaces present in the oral cavity, and to become integrated within the resident microbial communities, confers growth and survival properties. Molecular analyses have revealed several families of Gram-positive bacterial surface proteins, including serine-rich repeat, antigen I/II, and pilus families, that mediate adherence to a variety of salivary and oral bacterial receptors. In Gram-negative bacteria, pili, auto-transporters, and extracellular matrix-binding proteins provide components for host tissue recognition and building of complex microbial communities. Future studies will reveal in greater detail the binding pockets for these adhesin families and their receptors. This information will be crucial for the development of new inhibitors or vaccines that target the functional regions of bacterial proteins that are involved in colonization and pathogenesis.

  12. Suppression of polymorphonuclear (PMN) and monocyte-mediated inhibition of Candida albicans growth by delta-9-tetrahydrocannabinol

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    Djeu, J.Y.; Parapanios, A.; Halkias, D.; Friedman, H.


    This study was an in vitro attempt to identify the effector cells responsible for growth inhibition of the opportunistic fungus, candida albicans, and to determine if THC or another marijuana derivatives, 11-hydroxyTHC, would adversely affect their function. Using a 24h radiolabel assay, the authors found that growth inhibition of C. albicans was primarily mediated by PMN and monocytes that could be isolated normal human peripheral blood. Both effector cell types caused almost complete inhibition of Candida growth at effector/target ratio of 300/1 and inhibition was often still seen at 30/1-. Incubation of PMN, PBL, or monocytes for 1 hr at 37C with THC or 11-hydroxyTHC caused a marked suppression of function in all 3 cell populations. Maximal suppression was obtained with of the drugs in medium containing 10% fetal bovine serum (FBS) or with in 1% FBS. These drug concentrations did not affect lymphoid cell viability or candida growth in the absence of lymphoid effector cells. Marijuana derivatives, therefore, are doubly dangerous in that opportunistic fungi such as C. albicans can grow in their presence while the effector cells that control fungal growth are readily inactivated.

  13. Association of Continuity of Primary Care and Statin Adherence.

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    James R Warren

    Full Text Available Deficiencies in medication adherence are a major barrier to effectiveness of chronic condition management. Continuity of primary care may promote adherence. We assessed the association of continuity of primary care with adherence to long-term medication as exemplified by statins.We linked data from a prospective study of 267,091 Australians aged 45 years and over to national data sets on prescription reimbursements, general practice claims, hospitalisations and deaths. For participants having a statin dispense within 90 days of study entry, we computed medication possession ratio (MPR and usual provider continuity index (UPI for the subsequent two years. We used multivariate Poisson regression to calculate the relative risk (RR and 95% confidence interval (CI for the association between tertiles of UPI and MPR adjusted for socio-demographic and health-related patient factors, including age, gender, remoteness of residence, smoking, alcohol intake, fruit and vegetable intake, physical activity, prior heart disease and speaking a language other than English at home. We performed a comparison approach using propensity score matching on a subset of the sample.36,144 participants were eligible and included in the analysis among whom 58% had UPI greater than 75%. UPI was significantly associated with 5% increased MPR for statin adherence (95% CI 1.04-1.06 for highest versus lowest tertile. Dichotomised analysis using a cut-off of UPI at 75% showed a similar effect size. The association between UPI and statin adherence was independent of socio-demographic and health-related factors. Stratification analyses further showed a stronger association among those who were new to statins (RR 1.33, 95% CI 1.15-1.54.Greater continuity of care has a positive association with medication adherence for statins which is independent of socio-demographic and health-related factors.

  14. Characteristics of HIV antiretroviral regimen and treatment adherence

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    Vera Lúcia da Silveira


    Full Text Available The relationship between characteristics of HIV antiretroviral regimens and treatment adherence was studied in adolescent and adult patients who underwent antiretroviral therapy from January 1998 to September 2000, at the Service for Specialized Assistance in Pelotas. The patients were interviewed on two occasions, and the use of antiretrovirals during the previous 48 hours was investigated by a self-report. Adherence was defined as use of 95% or more of the prescribed medication. Social-demographic variables were collected through direct questionnaires. The antiretroviral regimen and clinical data were copied from the patients' records. Associations between the independent variables and adherence were analyzed by means of logistic regression. The multivariate analysis included characteristics of the antiretroviral regimens, social-demographic variables, as well as perception of negative effects, negative physiological states, and adverse effects of the treatment. Among the 224 selected patients, 194 participated in our study. Their ages varied from 17 to 67 years; most patients were men, with few years of schooling and a low family income. Only 49% adhered to the treatment. Adherence to treatment regimens was reduced when more daily doses were indicated: three to four doses (odds ratio of adherence to treatment (OR=0.47, 95% confidence interval (CI 0.22-1.01 and five to six (OR=0.24, 95% CI 0.09-0.62; two or more doses taken in a fasting state (OR=0.59, 95% CI 0.11-0.68, and for patients who reported adverse effects to the treatment (OR=0.39, 95% CI 0.19-0.77. Most of the regimens with more than two daily doses of medication included at least one dose apart from mealtimes. The results suggest that, if possible, regimens with a reduced number of doses should be chosen, with no compulsory fasting, and with few adverse effects. Strategies to minimize these effects should be discussed with the patients.

  15. Adherence and neurocognitive screening in Romanian HIV patients

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    M Arbune


    Full Text Available Background: Adherence is critical for the effectiveness of antiretroviral HIV therapy (ART, accordingly decreasing the opportunistic diseases and increasing the quality of life. Neurocognitive disorders (NCD are still frequent in ART era and could impair the adherence, but how ethical is to refer ART in patients with NCD? Objective: To assess the relation between NCD and adherence in HIV Romanian patients. Material and methods: Cross-sectional screening study on 151 patients under ART, no drug users, from HIV Clinic - Galati, assessed by HIV-Associated Dementia Scale (HDS, Hospital Anxiety and Depression Scale (HADS [1], ART CNS-effectiveness Letendre scores [2] and adherence assessment questionnaire CNLAS- Romania. Normal values: HDS >10; anxiety/ depression <8. Statistical analysis performed: Chi-square test and Mann-Whitney test, with 5% significance level. Results: Characteristics of the patients: median age 22 [20; 56] years old; sex ratio F/M 1.17; median educational level 8 [0; >12] years; HBV co-infection 27.8%; AIDS stage 85.3%; current median CD4 526/mm3 [8; 1605] and 65% undetectable HIV-RNA levels. 49.6% (75/151 patients attain HDS scores <10 and imply probable NCD. Scores below 8 for anxiety are more frequent than for depression: 24% vs 13%. The median ART CNS penetration score is 8 [5; 12]. Adherence is considered for 66% patients and is correlating with CD4 number (p=0.001, educational level >4 years (p=0.001; OR=4.2, HDS >10 (p=0.01; OR=2.4 and ART-CNS penetration score >7 (p=0.023; OR=2.4. Low HDS are influenced by old age (p=0.003, depression (p=0.02 and ART-CNS penetration scores <7 (p=0.01. Anxiety is related neither with adherence nor with NCD by HDS, but females are obvious anxious than males (p<0.001. Conclusions: Basic educational level is sufficient for developing ART adherence. High scores of HDS screening should be predictors for ART adherence. Referring ART as well to patients with low HDS scores is rational and

  16. Treating depression in HIV-positive patients affects adherence

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    M Y H Moosa


    Full Text Available Aim. To determine changes in adherence to antiretroviral therapy (ART in HIV-positive patients with depression, following treatment with an antidepressant or psychotherapy. Methods. The study was prospective, randomised and controlled. Consenting volunteers aged ≥18 years and stable on ART for ≥6 months were included in the study. Sociodemographic data were obtained, and a clinical diagnostic evaluation and the Hamilton Depression rating scale (HAMD were performed on all subjects at entry to and at the end of the study. Participants found to be depressed were randomly assigned antidepressant treatment (20 mg citalopram or interpersonal psychotherapy (IPT (5 sessions. Medication was dispensed at each visit and patients were asked to return all unused medication to determine ART adherence. The study was approved by the University of the Witwatersrand. Results. Sixty-two HIV-positive persons receiving ART participated; 30 were not depressed (control group and 32 were depressed (patient group. No significant differences in demographic characteristics existed between the control and patient groups. Mean ART adherence at the start of the study was 99.5% (standard error (SE ±0.46 and 92.1% (SE ±1.69 in the control and patients groups, respectively. Mean ART adherence at the end of the study changed marginally in the control group (99.7%; SE ±0.46 and increased significantly in the patient group (99.5%; SE± 0.13 (p>0.05. The mean ART adherence rate of patients who received pharmacotherapy increased from 92.8% to 99.5%, and of those who received psychotherapy increased from 91.1% to 99.6% (p>0.05. There was no significant association between the increased adherence in the patient group and baseline demographic and clinical characteristics, irrespective of antidepressant therapy or IPT (p>0.05. Conclusion. Successful treatment of depression with an antidepressant or psychotherapy was associated with improved ART adherence, independent of the type

  17. Clinic Attendance for Medication Refills and Medication Adherence amongst an Antiretroviral Treatment Cohort in Uganda: A Prospective Study

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    Setor Kunutsor


    Full Text Available Background. Regular clinic attendance for antiretroviral (ARV drug refills is important for successful clinical outcomes in HIV management. Methods. Clinic attendance for ARV drug refills and medication adherence using a clinic-based pill count in 392 adult patients receiving antiretroviral therapy (ART in a district hospital in Uganda were prospectively monitored over a 28-week period. Results. Of the 2267 total scheduled clinic visits, 40 (1.8% were missed visits. Among the 392 clients, 361 (92% attended all appointments for their refills (regular attendance. Clinic attendance for refills was statistically significantly associated with medication adherence with regular attendant clients having about fourfold greater odds of achieving optimal (≥95% medication adherence [odds ratio (OR=3.89, 95% CI: 1.48 to 10.25, exact P=.013]. In multivariate analysis, clients in age category 35 years and below were less likely to achieve regular clinic attendance. Conclusion. Monitoring of clinic attendance may be an objective and effective measure and could be a useful adjunct to an adherence measure such as pill counting in resource-constrained settings. Where human resource constraints do not allow pill counts or other time-consuming measures, then monitoring clinic attendance and acting on missed appointments may be an effective proxy measure.

  18. Lethal effect of polymorphonuclear neutrophils on squamous cell carcinoma of the lung%中性粒细胞对肺鳞状细胞癌杀伤效应的研究

    Institute of Scientific and Technical Information of China (English)

    钟梅; 王琼; 邰艳红; 董周寰; 赵坡; 吕亚莉


    Objective To investigate the antitumor effect of polymorphonuclear neutrophils (PMNs) towards human lung squamous cell carcinoma ( SCC ) . Methods 300 human lung squamous cancer samples were randomly selected, and G-CSF expression in the tumors were detected immunohistochemically, and the relationship between the intensity of G-CSF expression and PMNs distribution status were analyzed. 5 cases of PMNs in peripheral blood of lung SCC patients and healthy volunteers were purified respectively. The antitumor effect of PMNs on lung SCC cell line and primary cultured lung SCC cells were detected by MTT method, and the morphologic change of PMNs and lung SCC cells were observed microscopically. Results The variable levels of PMNs infiltration in 221 cases were found in the whole 300 samples, and the infiltrating degree positively related to G-CSF expression level significantly (p < 0. 01). Morphologically, PMNs required direct contact to cancer cells in rosette formation so as to perform antitumor effect on lung SCC cells. The maximal killing efficiency was obtained under the ratio of PMNs: cancer cells = 500 ~ 600: 1. Conclusion PMNs could perform the antitumor effect in vivo and in vitro on squamous cell carcinoma of the lung, the killing effect requires the direct contact of PMNs and cancer cells, and G-CSF secreted by cancer cells could promote PMNs' antitumor effect.%目的 探索中性粒细胞(PMNS)对人肺鳞状细胞癌的杀伤效应.方法 随机选取人肺鳞状细胞癌石蜡 包埋标本300例,行G-CSF的免疫组化染色,分析其阳性强度与中性粒细胞分布的关系;分离人肺鳞状细胞癌患者及健康志愿者的外周血中性粒细胞各5例,体外杀伤建系及原代培养的肺鳞状细胞癌细胞;MTT法检测杀伤效应,观察中性粒细胞和肺癌细胞的形态变化.结果 300例人肺鳞状细胞癌中221例可见中性粒细胞浸润,且其浸润程度和G-CSF的阳性强度成显著正相关(P<0.01),HE切片可见

  19. 牙龈卟啉单胞菌脂多糖对多形核白细胞凋亡的影响%Effects of porphyromonas gingivalis lipopolysaccharide on polymorphonuclear leukocyte

    Institute of Scientific and Technical Information of China (English)

    王惠宁; 余杰


    Objective The aim of our study was to determine whether the polymorphonuclear leukocyte ( PMN ) undergo apoptosis in response to porphyromonas gingivalis lipopolysaccharide(LPS). Methods Freshly isolated peripheral blood polymorphonuclear leukocyte obtained from 10 healthy volunteers was incubated with( experimental group )or without( control group) LPS to investigate the capacity of LPS to induce polymorphonuelear leukocyte's apoptosis. Results Our results revealed that there was a marked decrease in alyoptosis of polymorphonuclear leuk ooyte in experimental group compared with control group( P < O. 05 ). Conclusions The findings of the presem study demonstrate that LPS delays PMN apoptosis in a dose-dependent fashion. It suggests that haeterial-delayed apoptesis may be an important role in the pathogenesis of periodontal disease.%目的 研究牙龈卟啉单胞菌脂多糖对人的外周血中多形核白细胞的凋亡作用.方法 通过流式细胞仪对10名健康人外周血中多形核白细胞培养组(对照组)与不同浓度的牙龈卟啉单胞菌脂多糖和多形核白细胞共同培养组(实验组)进行比较研究,观察多形核白细胞的凋亡情况.结果 实验组和对照组相比,多形核白细胞凋亡数明显减少(P<0.05).结论 牙龈卟啉单胞菌脂多糖以浓度依赖的形式延缓多形核白细胞的凋亡,细菌延缓细胞凋亡在牙周可疑致病菌的致病机制中可能具有重要的作用.

  20. Promoting adherence to nebulized therapy in cystic fibrosis: poster development and a qualitative exploration of adherence

    Directory of Open Access Journals (Sweden)

    Jones S


    Full Text Available Stephen Jones,1 Nathan Babiker,2 Emma Gardner,2,3 Jane Royle,2 Rachael Curley,3,4 Zhe Hui Hoo,3,4 Martin J Wildman3,4 1Psychology Department, University of Sheffield, 2Psychological Services, Sheffield Teaching Hospitals NHS Foundation Trust, 3Adult Cystic Fibrosis Unit, Northern General Hospital, 4School of Health and Related Research (ScHARR, University of Sheffield, Sheffield, UK Background: Cystic fibrosis (CF health care professionals recognize the need to motivate people with CF to adhere to nebulizer treatments, yet little is known about how best to achieve this. We aimed to produce motivational posters to support nebulizer adherence by using social marketing involving people with CF in the development of those posters. Methods: The Sheffield CF multidisciplinary team produced preliminary ideas that were elaborated upon with semi-structured interviews among people with CF to explore barriers and facilitators to the use of nebulized therapy. Initial themes and poster designs were refined using an online focus group to finalize the poster designs. Results: People with CF preferred aspirational posters describing what could be achieved through adherence in contrast to posters that highlighted the adverse consequences of nonadherence. A total of 14 posters were produced through this process. Conclusion: People with CF can be engaged to develop promotional material to support adherence, providing a unique perspective differing from that of the CF multidisciplinary team. Further research is needed to evaluate the effectiveness of these posters to support nebulizer adherence. Keywords: behavior change, social marketing, patient participation, nebulizers, medication adherence

  1. A systematic review of medication non-adherence in persons with dementia or cognitive impairment (United States)

    Weller, Carolina; Kennedy, Briohny; Winbolt, Margaret; Young, Carmel


    Background Adherence to medication is vital for disease management while simultaneously reducing healthcare expenditure. Older persons with cognitive impairment (CI) are at risk for non-adherence as cognitive processes are needed to manage medications. This systematic review focuses on the relationship between medication non-adherence and specific cognitive domains in persons with CI, and explores determinants of medication non-adherence. When available, relationships and factors are compared with cognitively intact populations. Methods A seven database systematic search of studies published between 1 January 1949–31 December 2015 examining medication non-adherence in community dwelling persons with CI or dementia was conducted. Articles reporting medication non-adherence in people with CI or dementia in the community, with or without caregiver supports were eligible for inclusion. Papers reporting adherence to treatments in cognitively intact populations, populations from hospital or institutional settings, for non-prescribed medication or those describing dementia as a factor predicting medication non-adherence were excluded. Data on study and population characteristics, research design, data sources and analysis, specific cognitive domains, non-adherence prevalence, measurement of adherence, salient findings, factors associated with adherence and strategies to improve medication adherence were extracted. Study limitations included inconsistencies between data sources and definitions, resulting in a loss of fidelity in the value and comprehensiveness of data, as well as exclusion of non-pharmacological treatments and regimens. Findings Fifteen studies met inclusion criteria. Adherence among CI subjects ranged from 10.7%-38% with better rates of adherence in non-CI individuals. Medication non-adherence definitions varied considerably. New-learning, memory and executive functioning were associated with improved adherence and formed the focus of most studies

  2. Medication adherence in schizophrenia: Exploring patients', carers' and professionals' views

    NARCIS (Netherlands)

    M.J. Kikkert; A.H. Schene; M.W.J. Koeter; D. Robson; A. Born; H. Helm; M. Nose; C. Goss; G. Thornicroft; R.J. Gray


    One of the major clinical problems in the treatment of people with schizophrenia is suboptimal medication adherence. Most research focusing on determinants of nonadherence use quantitative research methods. These studies have some important limitations in exploring the decision-making process of pat

  3. Novel Aggregative Adherence Fimbria Variant of Enteroaggregative Escherichia coli

    DEFF Research Database (Denmark)

    Jønsson, Rie; Struve, Carsten; Boisen, Nadia


    Enteroaggregative Escherichia coli (EAEC) organisms belong to a diarrheagenic pathotype known to cause diarrhea and can be characterized by distinct aggregative adherence (AA) in a stacked-brick pattern to cultured epithelial cells. In this study, we investigated 118 EAEC strains isolated from...

  4. Adherence of paclitaxel drug in magnetite chitosan nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Escobar Zapata, Edna V.; Martinez Perez, Carlos A.; Rodriguez Gonzalez, Claudia A.; Castro Carmona, Javier S. [Instituto de Ingenieria y Tecnologia, Universidad Autonoma de Ciudad Juarez, Ave. Del Charro 610 norte, Col. Partido Romero, C.P. 32320, Cd. Juarez Chihuahua (Mexico); Quevedo Lopez, Manuel A. [Departamento de Polimeros y Materiales, Universidad de Sonora, Blvd. Luis Encinas y Rosales, Hermosillo, Sonora (Mexico); Garcia-Casillas, Perla E., E-mail: [Instituto de Ingenieria y Tecnologia, Universidad Autonoma de Ciudad Juarez, Ave. Del Charro 610 norte, Col. Partido Romero, C.P. 32320, Cd. Juarez Chihuahua (Mexico)


    Highlights: Black-Right-Pointing-Pointer Chitosan silica magnetite adsorbs antineoplastic drug. Black-Right-Pointing-Pointer Silica coating improve the drug adherence. - Abstract: Cancer treatment is a big challenge in medicine where chemotherapies and radiotherapies are aggressive and poorly effective having side effects as delirium, fatigue, insomnia, nausea and vomiting which are common problems for cancer patients. For this reason, during the last two decades, many researchers have developed several techniques to improve the current therapies; one of them is the functionalization of magnetic nanoparticles for drug delivery. In this work, magnetic nanoparticles with an average crystallite size 21.8 nm were covered in a core/shell type; magnetite/silica, magnetite/chitosan, and a double shell magnetite/silica/chitosan were developed for attaching an antineoplastic drug. The mechanism for the functionalization of the nanoparticles with a single and double shell was studied with Fourier transformed infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The adherence of an antineoplastic drug, paclitaxel, onto functionalized nanoparticles was analyzed with a UV-Visible spectroscopy at a wavelength of 253 nm. It was found that the adherence of the drug is improved up to 18% when magnetite nanoparticles are coated with a single chitosan shell, and when the nanoparticles are coated with a silica/chitosan shell the adherence increases up to 29%.

  5. Factors influencing adherence to an emergency department national protocol.

    NARCIS (Netherlands)

    Ebben, R.H.A.; Vloet, L.C.M.; Groot, J.M. de; Achterberg, T. van


    The objective of this study was to identify factors that influence emergency nurses' adherence to an emergency department national protocol (EDNP). A survey of emergency nurses (n=200) and physicians with medical end responsibility on an emergency department (n=103) was carried out. Emergency nurses

  6. Adherence to preventive statin therapy according to socioeconomic position

    DEFF Research Database (Denmark)

    Wallach-Kildemoes, Helle; Andersen, Morten; Diderichsen, Finn;


    AIM: To explore whether long-term adherence to preventive statin therapy depends on socioeconomic position (SEP). METHODS: A cohort of individuals without established cardiovascular disease (CVD) or diabetes initiating preventive statin therapy during 2002-2005 was followed in the individual...

  7. Telephone interventions for adherence to colpocytological examination 1 (United States)

    Lima, Thais Marques; Nicolau, Ana Izabel Oliveira; Carvalho, Francisco Herlânio Costa; Vasconcelos, Camila Teixeira Moreira; Aquino, Priscila de Souza; Pinheiro, Ana Karina Bezerra


    ABSTRACT Objective: to test the effects of behavioral and educational intervention by telephone on adherence of women with inappropriate periodicity to colpocytological examination. Method: quasi-experimental study with a sample of 524 women, selected with the following inclusion criteria: be aged between 25 and 64 years, have initiated sexual activity, have inappropriate periodicity of examination and have mobile or landline phone. The women were divided into two groups for application of behavioral and educational intervention by telephone. It was used an intervention script according to the principles of Motivational Interviewing. Results: on comparing the results before and after the behavioral and educational interventions, it was found that there was a statistically significant change (p = 0.0283) with increase of knowledge of women who participated in the educational intervention. There was no change in the attitude of women of any of the groups and there was an increase of adherence to colpocytological examination in both groups (p < 0.0001), with greater adherence of women participating in the behavioral group (66.8%). Conclusion: the behavioral and educational interventions by phone were effective in the adherence of women to colpocytological examination, representing important strategies for permanent health education and promotion of care for the prevention of cervical cancer. PMID:28177055

  8. Interaction of adhered metallic dust with transient plasma heat loads

    NARCIS (Netherlands)

    Ratynskaia, S.; Tolias, P.; I. Bykov,; Rudakov, D.; de Angeli, M.; Vignitchouk, L.; Ripamonti, D.; Riva, G.; Bardin, S.; van der Meiden, H.; Vernimmen, J.; Bystrov, K.; De Temmerman, G.


    The first study of the interaction of metallic dust (tungsten, aluminum) adhered on tungsten substrates with transient plasma heat loads is presented. Experiments were carried out in the Pilot-PSI linear device with transient heat fluxes up to 550 MW m −2 and in the DIII-D divertor tokamak. The cent

  9. Generic substitution of antihypertensive drugs : does it affect adherence?

    NARCIS (Netherlands)

    Van Wijk, Boris L G; Klungel, Olaf H; Heerdink, Eibert R; de Boer, Anthonius


    BACKGROUND: Generic substitution is an important opportunity to reduce the costs of pharmaceutical care. However, pharmacists and physicians often find that patients and brand-name manufacturers have doubt about the equivalence of the substituted drug. This may be reflected by decreased adherence to

  10. Adherence Process Research on Developmental Interventions: Filling in the Middle. (United States)

    Hogue, Aaron


    Presents a framework and some practical examples for using rigorous implementation research to inform program outcomes and foster program development for developmental interventions. Focuses on: (1) role of process research, specifically developing developmental interventions; (2) characteristics of adherence process research; and (3)…

  11. Intervention Adherence for Research and Practice: Necessity or Triage Outcome? (United States)

    Barnett, David; Hawkins, Renee; Lentz, F. Edward, Jr.


    Intervention integrity or adherence describes qualities of carrying out an intervention plan and in research is fundamentally linked to experimental validity questions addressed by measurement of independent and dependent variables. Integrity has been well described in conceptual writing but has been a continuing thorny subject in research and…

  12. Adherence with Universal Precautions after Immediate, Personalized Performance Feedback (United States)

    Luke, Molli M.; Alavosius, Mark


    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.)

  13. Noninfectious uveitis: strategies to optimize treatment compliance and adherence

    Directory of Open Access Journals (Sweden)

    Dolz-Marco R


    Full Text Available Rosa Dolz-Marco,1 Roberto Gallego-Pinazo,1 Manuel Díaz-Llopis,2 Emmett T Cunningham Jr,3–6 J Fernando Arévalo7,8 1Unit of Macula, Department of Ophthalmology, University and Polytechnic Hospital La Fe, 2Faculty of Medicine, University of Valencia, Spain; 3Department of Ophthalmology, California Pacific Medical Center, San Francisco, 4Department of Ophthalmology, Stanford University School of Medicine, Stanford, 5The Francis I Proctor Foundation, University of California San Francisco Medical Center, 6West Coast Retina Medical Group, San Francisco, CA, USA; 7Vitreoretina Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 8Retina Division, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: Noninfectious uveitis includes a heterogenous group of sight-threatening ocular and systemic disorders. Significant progress has been made in the treatment of noninfectious uveitis in recent years, particularly with regard to the effective use of corticosteroids and non-corticosteroid immunosuppressive drugs, including biologic agents. All of these therapeutic approaches are limited, however, by any given patient’s ability to comply with and adhere to their prescribed treatment. In fact, compliance and adherence are among the most important patient-related determinants of treatment success. We discuss strategies to optimize compliance and adherence. Keywords: noninfectious uveitis, intraocular inflammation, immunosuppressive treatment, adherence, compliance, therapeutic failure

  14. Saul Bellow’s Adherence and Breakthrough to Jewish Tradition

    Institute of Scientific and Technical Information of China (English)



    As one of the most significant American Jewish writers in the 20th century, Saul Bellow was influenced by the Jewish tradition and American mainstream thoughts in his writing creations. The conflicts and amalgamation between these two different cultures in his novels indicate that Bellow not only adheres to the Jewish traditional culture, but also breaks through the narrow-mindedness of it.

  15. Microfluidic bioreactors for culture of non-adherent cells

    DEFF Research Database (Denmark)

    Shah, Pranjul Jaykumar; Vedarethinam, Indumathi; Kwasny, Dorota


    Microfluidic bioreactors (μBR) are becoming increasingly popular for cell culture, sample preparation and analysis in case of routine genetic and clinical diagnostics. We present a novel μBR for non-adherent cells designed to mimic in vivo perfusion of cells based on diffusion of media through...

  16. Elder and Caregiver Solutions to Improve Medication Adherence (United States)

    O'Quin, K. E.; Semalulu, T.; Orom, H.


    Medication mismanagement is a growing public health concern, especially among elders. Annually, it is a major contributor to emergency hospitalization and nursing home placement. Elders and their caregivers, as healthcare consumers and stakeholders in this issue, are uniquely qualified to inform strategies to improve medication adherence. We…

  17. Adherence measured by microtiter assay as a virulence marker for Staphylococcus epidermidis infections. (United States)

    Deighton, M A; Balkau, B


    Staphylococcus epidermidis strains isolated from clinical sources showed a wide range of abilities to adhere to glass and plastic materials. The degree of adherence depended on a number of factors, most notably, the composition of the growth medium. Adherence was enhanced by the addition of glucose or oleic acid to the growth medium and inhibited by serum. We have demonstrated a statistically significant association between the quantitative assessment of adherence to polystyrene tissue culture plates and clinical relevance. No such association was found when adherence was assessed by the qualitative adherence assay. Possible new approaches for assessing the clinical relevance of coagulase-negative staphylococcal isolates are discussed.

  18. Adherence to Infliximab Treatment in a Pediatric Inflammatory Bowel Disease Cohort. (United States)

    Vitale, David S; Greenley, Rachel N; Lerner, Diana G; Mavis, Alisha M; Werlin, Steven L


    The aims of the study were to describe infliximab adherence in a pediatric inflammatory bowel disease cohort, to identify demographic and disease factors associated with adherence, and to examine differences in acute care use among adherent and nonadherent patients. Charts of patients who received infliximab at the Children's Hospital of Wisconsin (CHW) between October 2010 and October 2012 were retrospectively reviewed. A total of 151 patients met the inclusion criteria; 91.4% of the patients were adherent. Nonadherent patients had more emergency room visits and hospitalizations than adherent patients. The study is the first to show high adherence rates to infliximab in a pediatric cohort.

  19. The effect of Taurolidine on adherent and floating subpopulations of melanoma cells. (United States)

    Shrayer, D P; Lukoff, H; King, T; Calabresi, P


    The annual incidence of malignant melanoma is estimated at 10-12 per 100000 inhabitants in countries of Central Europe and the US, with more recent estimates showing a dramatic upward trend. Taurolidine (Carter/Wallace, Cranberry, NJ) is a novel, potentially effective, antitumor chemotherapeutic agent. We hypothesized that Taurolidine could inhibit the growth, induce apoptosis, affect the cell cycle and change morphology of melanoma cells. We expected this process to be different in adherent and floating subpopulations that may be reflective of solid tumors and their metastases. Analysis of MNT-1 human and B16F10 murine melanoma cells showed that at 72 h the IC(50) of Taurolidine was 25.4+/-3.3 microM for MNT-1 human melanoma cells and 30.9+/-3.6 microM for B16F10 murine melanoma cells. Taurolidine induced DNA fragmentation of melanoma cells in a dose-dependent manner. Taurolidine (75 and 100 microM) induced 52-97% Annexin-V binding (apoptosis), respectively. Evaluation of cell cycle after 72 h exposure to Taurolidine (0-100 microM) revealed that the percentage of melanoma cells in S phase increased from 27 to 40% in the adherent subpopulation and from 33 to 49% in the floating subpopulation. Phase contrast microscopy revealed a marked swelling of melanoma cells and decreasing cell numbers in adherent subpopulation starting at 24 h with 25 microM Taurolidine. Shrinkage of cells dominated at 75-100 microM Taurolidine. Using Cytospin assay in the floating population, we observed swelling of melanoma cells induced by 25-100 micro Taurolidine and appearance of giant (multinuclear) forms resulting from exposure to 75-100 micro Taurolidine. Some floating cells with normal morphology were observed with low concentrations of Taurolidine (0-25 microM). These data show that effects of Taurolidine may be different in adherent and floating subpopulations of melanoma cells. More importantly, floating subpopulations that may contain some viable melanoma cells, may be reflective

  20. Developing a generic, individualised adherence programme for chronic medication users

    Directory of Open Access Journals (Sweden)

    Herborg H


    Full Text Available Objective: The scope of this article is to describe the background for and content of an adherence counselling programme with a specific focus on an individualised, multi-dimensional adherence model for patients with a potential adherence problem (a so-called ‘individualised systems model’.Methods: An intervention programme based on WHO’s systems model for adherence was developed for implementation in primary health care and tested in a development project in Danish pharmacies in 2004-2005 in three pharmacies and 4 GP practices by 27 patients. Data were collected from the participants by registration forms, questionnaires, and focus groups. Since the programme was to support patients in the self-management process regarding choice and implementation of medication treatment, various strategies were used and different theoretical assumptions and choices made prior to setting up the study. These strategies include distinguishing between different types of non-adherence, a model for stages of change, self-efficacy, narratives, motivating interviewing strategies and coaching techniques. These strategic and theoretical choices are described in the article. Results: The strategies and theoretical reflections formed the platform for the creation of a counselling programme, which was tested in two forms, a basic and an extended version - provided by either a pharmaconomist or a pharmacist. The result section also describes a toolbox of instruments to enable pharmacy staff and GPs to tailor a counselling programme for patients individually called ‘Safe and effective use of medicines’. Besides, the results include a description of how the WHO-model is transformed into an individualised counselling model.

  1. Immediate diagnostic criteria for bacterial infection of ascitic fluid. Evaluation of ascitic fluid polymorphonuclear leukocyte count, pH, and lactate concentration, alone and in combination. (United States)

    Stassen, W N; McCullough, A J; Bacon, B R; Gutnik, S H; Wadiwala, I M; McLaren, C; Kalhan, S C; Tavill, A S


    We prospectively evaluated the ascitic fluid (AF) polymorphonuclear cell (PMN) count, pH, and lactate concentration in single ascitic fluids from 60 patients to determine their relative predictive values for the immediate diagnosis of ascitic fluid infection. Nine of the 60 ascitic fluids were malignant. Of the remaining 51 samples, nine from cirrhotic patients were infected. The mean AF pH, lactate concentration, and PMN count in the infected group were 7.20 +/- 0.19, 80 +/- 51 mg/dl, and 18,199 +/- 19,650 cells/mm3, respectively, and all were significantly different from the corresponding values in noninfected ascites. Mean arterial blood-ascitic fluid (B-AF) pH and lactate gradients in the infected group were 0.23 +/- 0.17 and -46 +/- 31 mg/dl, respectively, and were significantly different from the corresponding values in noninfected ascites (p less than 0.05). Significant differences were not found between infected and malignant ascites, except for the AF PMN count (p less than 0.001). In cirrhosis with ascites, an AF pH less than or equal to 7.34 was the most specific single test (100%) and had the highest diagnostic accuracy (98%). In the larger group of patients with ascites of diverse etiology, a B-AF pH gradient greater than or equal to 0.10 or an AF PMN count greater than or equal to 500 cells/mm3 were the single tests with the highest diagnostic accuracy (92%). Combining an AF PMN count greater than 500 cells/mm3 with any of the other diagnostic criteria increased the specificity and diagnostic accuracy (up to 98%) compared to the best single criterion. Although our data support the use of a number of different combinations of AF measurements for the immediate diagnosis of infection, the simplest and most readily obtainable measurements are the pH and PMN count. Therefore, in the clinical setting we recommend the use of either an AF pH less than or equal to 7.34 or a B-AF pH gradient greater than or equal to 0.10 in combination with an AF PMN count

  2. The atherogenic bacterium Porphyromonas gingivalis evades circulating phagocytes by adhering to erythrocytes

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Holmstrup, Palle; Damgaard, Christian


    A relationship between periodontitis and coronary heart disease has been investigated intensively. A pathogenic role for the oral bacterium Porphyromonas gingivalis has been suggested for both diseases. We examined whether complement activation by P. gingivalis strain ATCC 33277 allows the bacter......A relationship between periodontitis and coronary heart disease has been investigated intensively. A pathogenic role for the oral bacterium Porphyromonas gingivalis has been suggested for both diseases. We examined whether complement activation by P. gingivalis strain ATCC 33277 allows...... the bacterium to adhere to human red blood cells (RBCs) and thereby evade attack by circulating phagocytes. On incubation with normal human serum, the P. gingivalis strain efficiently fixed complement component 3 (C3). Incubation of bacteria with washed whole blood cells suspended in autologous serum resulted....... gingivalis exploits RBCs as a transport vehicle, rendering it inaccessible to attack by phagocytes, and by doing so plays a role in the development of systemic diseases....

  3. Surface structures and adherence properties of diverse strains of Haemophilus influenzae biogroup aegyptius. (United States)

    St Geme, J W; Gilsdorf, J R; Falkow, S


    Haemophilus influenzae biogroup aegyptius is an important cause of conjunctivitis and has recently been associated with Brazilian purpuric fever (BPF), a fulminant systemic disease of children. To gain insight into the bacterial factors involved in the pathogenesis of this disease, we investigated the surface structures and adherence properties of eight different strains of H. influenzae biogroup aegyptius, including both BPF and non-BPF isolates. All eight strains were able to express long peritrichous pili similar to those observed in H. influenzae. As in H. influenzae, piliation correlated with colony binding of human erythrocytes. However, two strains were capable of hemagglutination in the absence of pili; in these strains, hemagglutination was insensitive to protease treatment, suggesting a nonproteinaceous hemagglutinin. All strains possessed short, thin, surface fibers distinct from long pili and demonstrated efficient attachment to cultured human conjunctival cells. Attachment to conjunctival cells occurred independently of long pili or a capacity for hemagglutination.

  4. Aggregative adherence fimbriae I (AAF/I) mediate colonization of fresh produce and abiotic surface by Shiga toxigenic enteroaggregative Escherichia coli O104:H4 (United States)

    The Shiga toxigenic Escherichia coli O104:H4 bares the characteristics of both enterohemorrhagic (EHEC) and enteroaggregative (EAEC) E. coli. It produces plasmid encoded aggregative adherence fimbriae I (AAF/I) which mediate cell aggregation and biofilm formation in human intestine and promote Shiga...

  5. Computer controlled chamber measurements for clay adherence relevant for potential dioxin exposure through skin. (United States)

    Ferguson, Alesia; Bursac, Zoran; Johnson, Wayne; Davis, Jasmine


    A computer-controlled mechanical chamber was used to control the contact between aluminum sheet samples laden with clay, and cotton sheet samples for the measurement of mass transfer. The contact parameters of pressure (20 to 60 kPa) and time (10 to 70 sec) were varied for 160 multiple experiments of mass soil transfer. Before log transformation the average transfer for 'First Transfer' of clay particles was 34.4 ± 6.3 mg/8.97 cm(2) while that for 'Total Transfer' was 36.1 ± 6.8 mg/8.97 cm(2). Second contact, therefore, resulted in an average transfer of 1.70 ± 0.76 mg/8.97 cm(2). These values are well above adherence values measured for potting soil and sand as reported for previous experiments using the same methodologies. Based on the univariate analysis and the multiple regression analysis we were able to see some effect of parameters on the clay adherence values. The effect of pressure increases was significant for the higher levels of 50 and 60 kPa. In addition, we observed that increases in temperature were significant for 'First Transfer,' and less so for 'Total Transfer'. Past experiments using potting soil and play sand show high adherence values to human cadaver skin over cotton sample; the same scenario would be expected for clay. This data set can be used to improve estimates of dermal exposure to dioxins found in ball clays often used by artisans in the making of pottery.

  6. Interleukin-3 greatly expands non-adherent endothelial forming cells with pro-angiogenic properties

    Directory of Open Access Journals (Sweden)

    Lachlan M. Moldenhauer


    Full Text Available Circulating endothelial progenitor cells (EPCs provide revascularisation for cardiovascular disease and the expansion of these cells opens up the possibility of their use as a cell therapy. Herein we show that interleukin-3 (IL3 strongly expands a population of human non-adherent endothelial forming cells (EXnaEFCs with low immunogenicity as well as pro-angiogenic capabilities in vivo, making their therapeutic utilisation a realistic option. Non-adherent CD133+ EFCs isolated from human umbilical cord blood and cultured under different conditions were maximally expanded by day 12 in the presence of IL3 at which time a 350-fold increase in cell number was obtained. Cell surface marker phenotyping confirmed expression of the hematopoietic progenitor cell markers CD133, CD117 and CD34, vascular cell markers VEGFR2 and CD31, dim expression of CD45 and absence of myeloid markers CD14 and CD11b. Functional experiments revealed that EXnaEFCs exhibited classical properties of endothelial cells (ECs, namely binding of Ulex europaeus lectin, up-take of acetylated-low density lipoprotein and contribution to EC tube formation in vitro. These EXnaEFCs demonstrated a pro-angiogenic phenotype within two independent in vivo rodent models. Firstly, a Matrigel plug assay showed increased vascularisation in mice. Secondly, a rat model of acute myocardial infarction demonstrated reduced heart damage as determined by lower levels of serum creatinine and a modest increase in heart functionality. Taken together, these studies show IL3 as a potent growth factor for human CD133+ cell expansion with clear pro-angiogenic properties (in vitro and in vivo and thus may provide clinical utility for humans in the future.

  7. ART adherence changes among patients in community substance use treatment: a preliminary analysis from MACH14

    Directory of Open Access Journals (Sweden)

    Rosen Marc I


    Full Text Available Abstract Background Opiate substitution treatment has been associated with better adherence to lifesaving antiretroviral medications, but the impact of other substance abuse treatment on adherence is unknown. Findings In this study, 215 patients who had been in adherence-focused research studies provided electronically-measured adherence data and a measure of whether the patient had recently been in substance abuse treatment. Recent engagement in substance abuse treatment was independently associated with significantly higher adherence, after covarying for recent substance use and other factors potentially affecting adherence. Conclusions The findings suggest that substance abuse treatment is associated with better adherence. Potential mechanisms by which substance abuse treatment improves adherence, such as more stability or more future-orientation, require further study.

  8. Development of new concepts of non-adherence measurements among users of antihypertensives medicines

    DEFF Research Database (Denmark)

    Kjeldsen, Lene Juel; Bjerrum, Lars; Herborg, Hanne;


    nonadherence (associated with aspects of self-regulation and effect concerns, respectively) and one measure of non-intentional non-adherence. Prevalence of the developed measures of behaviour related non-adherence ranged from 10.3 to 34.9% depending on which type of non-adherence measure was used. Established...... measures of non-adherence resulted in prevalence between 2.2 and 39.6%. CONCLUSIONS: The study showed that concepts of non-adherence measurements could be determined including self-efficacy aspects, unintentional non-adherence and intentional non-adherence related to self-regulation and effect concerns......: Users of antihypertensive medication were included in the study. 2,914 medication users received questionnaires by mail. Participating patients were asked to fill in two questionnaire regarding demographics, self-reported blood pressure, and various adherence measures. Two factor analyses were conducted...

  9. Can the common-sense model predict adherence in chronically ill patients? A meta-analysis. (United States)

    Brandes, Kim; Mullan, Barbara


    The aim of this meta-analysis was to explore whether mental representations, derived from the common-sense model of illness representations (CSM), were able to predict adherence in chronically ill patients. Electronic databases were searched for studies that used the CSM and measured adherence behaviour in chronically ill patients. Correlations from the included articles were meta-analysed using a random-size effect model. A moderation analysis was conducted for the type of adherence behaviour. The effect sizes for the different mental representations and adherence constructs ranged from -0.02 to 0.12. Further analyses showed that the relationship between the mental representations and adherence did not differ by the type of adherence behaviour. The low-effect sizes indicate that the relationships between the different mental representations of the CSM and adherence are very weak. Therefore, the CSM may not be the most appropriate model to use in predictive studies of adherence.

  10. Adherence to inhaled therapies, health outcomes and costs in patients with asthma and COPD

    DEFF Research Database (Denmark)

    Mäkelä, Mika J; Backer, Vibeke; Hedegaard, Morten;


    Suboptimal adherence to pharmacological treatment of asthma and chronic obstructive pulmonary disease (COPD) has adverse effects on disease control and treatment costs. The reasons behind non-adherence revolve around patient knowledge/education, inhaler device convenience and satisfaction, age...

  11. Adherence to a Yoga Program in Older Women with Knee Osteoarthritis. (United States)

    Cheung, Corjena; Wyman, Jean F; Savik, Kay


    Yoga is beneficial for osteoarthritis (OA) management in older adults; however, adherence to yoga practice is unknown. The purposes of this secondary analysis were to examine: (1) yoga adherence during the intervention and follow-up periods; (2) the relationship between social cognitive theory (SCT) constructs and adherence; and (3) the impact of adherence on OA-related symptoms in 36 community-dwelling older women with knee OA. SCT was used as a framework to promote adherence to a yoga intervention program that included both group/homebased practices. Adherence to yoga was high during the intervention period but decreased over time. Although SCT was a useful framework for reducing attrition during the intervention, self-efficacy was the only construct that correlated with class attendance. Higher yoga adherence was correlated with improved symptoms, physical function, sleep quality, and quality of life. Yoga adherers were likely to be older, less educated, and had a lower body mass index than nonadherers.

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

    Directory of Open Access Journals (Sweden)

    Costa E


    Full Text Available Elísio Costa,1 Anna Giardini,2 Magda Savin,3 Enrica Menditto,4 Elaine Lehane,5 Olga Laosa,6 Sergio Pecorelli,7,8 Alessandro Monaco,7 Alessandra Marengoni9On behalf of the A1 Action group “Prescription and Adherence to Medical Plans”, European Innovation Partnership on Active and Healthy Ageing1UCIBIO, REQUIMTE, Faculty of Pharmacy, University of Porto, Porto, Portugal; 2Psychology Unit, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Montescano (PV, Pavia, Italy; 3European Association of Pharmaceutical Full-line Wholesalers, Brussels, Belgium; 4CIRFF/Center of Pharmacoeconomics, School of Pharmacy, University of Naples FedericoII, Nápoles, Italy; 5Catherine McAuley School of Nursing and Midwifery, Brookfield Health Sciences Complex, University College Cork, Cork, Ireland; 6Centro de Investigación Clínica del Anciano Fundación para la Investigación Biomédica, Hospital Universitario de Getafe, Madrid, Spain; 7Italian Medicines Agency – AIFA, Rome, Italy; 8University of Brescia, Brescia, Italy; 9Department of Clinical and Experimental Science, University of Brescia, Brescia, Italy Abstract: 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

  13. Modeling the impact of increased adherence to asthma therapy.

    Directory of Open Access Journals (Sweden)

    Amory Schlender

    Full Text Available BACKGROUND: Nonadherence to medications occurs in up to 70% of patients with asthma. The effect of improving adherence is not well quantified. We developed a mathematical model with which to assess the population-level effects of improving medication prescribing and adherence for asthma. METHODS: A mathematical model, calibrated to clinical trial data from the U.S. NHLBI-funded SOCS trial and validated using data from the NHLBI SLIC trial, was used to model the effects of increased prescribing and adherence to asthma controllers. The simulated population consisted of 4,930 individuals with asthma, derived from a sample the National Asthma Survey. Main outcomes were controller use, reliever use, unscheduled doctor visits, emergency department (ED visits, and hospitalizations. RESULTS: For the calibration, simulated outcomes agreed closely with SOCS trial outcomes, with treatment failure hazard ratios [95% confidence interval] of 0.92 [0.58-1.26], 0.97 [0.49-1.45], and 1.01 [0-1.87] for simulation vs. trial in the in placebo, salmeterol, and triamcinolone arms, respectively. For validation, simulated outcomes predicted mid- and end-point treatment failure rates, hazard ratios 1.21 [0.08-2.34] and 0.83 [0.60-1.07], respectively, for patients treated with salmeterol/triamcinolone during the first half of the SLIC study and salmeterol monotherapy during the second half. The model performed less well for patients treated with salmeterol/triamcinolone during the entire study duration, with mid- and end-point hazard ratios 0.83 [0.00-2.12] and 0.37 [0.10-0.65], respectively. Simulation of optimal adherence and prescribing indicated that closing adherence and prescription gaps could prevent as many as nine million unscheduled doctor visits, four million emergency department visits, and one million asthma-related hospitalizations each year in the U.S. CONCLUSIONS: Improvements in medication adherence and prescribing could have a substantial impact on

  14. Significant improvement in statin adherence and cholesterol levels after acute myocardial infarction

    DEFF Research Database (Denmark)

    Brogaard, Hilde Vaiva Tonstad; Køhn, Morten Ganderup; Berget, Oline Sofie


    Not all patients recovering from acute myocardial infarction (AMI) are optimally treated with statin, and their adherence to statin treatment may be inadequate. We set out to describe changes in statin treatment adherence and cholesterol values over time.......Not all patients recovering from acute myocardial infarction (AMI) are optimally treated with statin, and their adherence to statin treatment may be inadequate. We set out to describe changes in statin treatment adherence and cholesterol values over time....

  15. Factors influencing adherence to paediatric antiretroviral therapy in Portharcourt, South- South Nigeria


    Ugwu, Rosemary; Eneh, Augusta


    Introduction The efficiency of antiretroviral therapy (ART) depends on a near-perfect level of patient's adherence. Adherence in children poses peculiar challenges. The aim of the study was to determine the adherence level and factors influencing adherence among HIV-infected children and adolescents in University of Port Harcourt Teaching Hospital, Nigeria. Methods A cross-sectional survey of HIV-infected children and adolescents on ART using self-report by the caregiver/child in the past one...

  16. Cognitive functioning, depression, and HIV medication adherence in India: a randomized pilot trial


    Cook, Ryan; Waldrop-Valverde, Drenna; Sharma, Aman; Vamos, Szonja; Mahajan, Biraaj; Weiss, Stephen M.; Kumar, Mahendra; Nehra, Ritu; Jones, Deborah L


    Objective: India is home to the third-largest number of people living with HIV in the world, and no-cost antiretroviral therapy (ART) has been available across the country since 2004. However, rates of adherence to ART are often subpar in India, and interventions to increase adherence are warranted. Cognitive impairment and depression have been associated with ART non-adherence, and may also limit the impact of behavioral interventions designed to improve adherence. Studies have not evaluated...

  17. Three types of self-efficacy associated with medication adherence in patients with co-occurring HIV and substance use disorders, but only when mood disorders are present

    Directory of Open Access Journals (Sweden)

    Reif S


    Full Text Available Susan Reif,1 Rae Jean Proeschold-Bell,1,2 Jia Yao,1 Sara LeGrand,1,2 Anna Uehara,2 Edgar Asiimwe,2 Evelyn Byrd Quinlivan31Duke Center for Health Policy and Inequalities Research, 2Duke Global Health Institute, Duke University, Durham, NC, 3Center for Infectious Diseases, University of North Carolina Chapel Hill, Chapel Hill, NC, USABackground: Adherence with medication regimens for human immunodeficiency virus (HIV is a life-saving behavior for people with HIV infection, yet adherence is challenging for many individuals with co-occurring substance use and/or mood disorders. Medication-taking self-efficacy, which is the confidence that one can take one's medication as prescribed, is associated with better adherence with HIV medication. However, little is known about the influence that other kinds of self-efficacy have on adherence with HIV medication, especially among HIV-infected individuals with co-occurring substance use and/or mood disorders. We sought to examine the relationship between adherence with HIV medication among substance users and three specific kinds of self-efficacy, ie, one's confidence that one can communicate with medical providers, get support, and manage one's mood. We further sought to examine whether symptoms of depression and anxiety moderate these relationships.Methods: Patients were recruited from three HIV clinics in the southeastern United States as part of an integrated study of treatment for HIV and substance use.Results: We interviewed 154 patients with HIV and substance use who reported taking HIV medications. Based on symptoms of depression and anxiety using the Patient Health Questionnaire-9 and the Hospital Anxiety and Depression Scale-Anxiety, 63% had probable depression and/or anxiety. Higher levels of self-efficacy in provider communication (β = 3.86, P < 0.01, getting needed support (β = 2.82, P < 0.01, and mood management (β = 2.29, P < 0.05 were related to better self-reported adherence with HIV

  18. Regulation of adherence and virulence by the Entamoeba histolytica lectin cytoplasmic domain, which contains a beta2 integrin motif. (United States)

    Vines, R R; Ramakrishnan, G; Rogers, J B; Lockhart, L A; Mann, B J; Petri, W A


    Killing of human cells by the parasite Entamoeba histolytica requires adherence via an amebic cell surface lectin. Lectin activity in the parasite is regulated by inside-out signaling. The lectin cytoplasmic domain has sequence identity with a region of the beta2 integrin cytoplasmic tail implicated in regulation of integrin-mediated adhesion. Intracellular expression of a fusion protein containing the cytoplasmic domain of the lectin has a dominant negative effect on extracellular lectin-mediated cell adherence. Mutation of the integrin-like sequence abrogates the dominant negative effect. Amebae expressing the dominant negative mutant are less virulent in an animal model of amebiasis. These results suggest that inside-out signaling via the lectin cytoplasmic domain may control the extracellular adhesive activity of the amebic lectin and provide in vivo demonstration of the lectin's role in virulence.

  19. An exploration of patient perceptions of adherence to tuberculosis treatment in Tanzania.

    NARCIS (Netherlands)

    Boogaard, J. van den; Msoka, E.; Homfray, M.; Kibiki, G.S.; Heldens, J.J.; Felling, A.J.; Aarnoutse, R.E.


    In this study, we aimed to explore patient perceptions of adherence to tuberculosis (TB) treatment and construct a theoretical model of treatment adherence behavior. We conducted semistructured interviews with 11 adherent patients from Tanzania whom we recruited by purposive sampling. The interview

  20. Non-Adherence to Study Time Management Strategies among NOUN Students and Implications for Academic Stress (United States)

    Okopi, Fidel O.


    The study was designed to investigate the NOUN students' non-adherence to their time management strategies (TMS) during the course of their studies. The researcher also wanted to find out whether their gender, age, marital and employment statuses have influence on their adherence/non-adherence to the plan or not. The researcher also examined the…

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

    NARCIS (Netherlands)

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


    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-

  2. Refill adherence and polypharmacy among patients with type 2 diabetes in general practice

    NARCIS (Netherlands)

    van Bruggen, Rykel; Gorter, Kees; Stolk, Ronald P.; Zuithoff, Peter; Klungel, Olaf H.; Rutten, Guy E. H. M.


    Background and Aims Non-adherence is considered a major barrier to better outcomes of diabetes care. A relationship has been established between polypharmacy and patients' adherence. This study aims to investigate the occurrence of polypharmacy and non-adherence in general practice, their mutual rel

  3. Adherence to Inhaled Corticosteroids and Patient Perception : Towards a better understanding and individualised care

    NARCIS (Netherlands)

    Menckeberg, T.T.


    In this thesis we aimed to further deepen knowledge on factors associated with nonadherence to provide means to improve adherence. We evaluated several methods of assessing adherence. At first, we evaluated the accuracy of the Medication Adherence Rating Scale (MARS), a structured method for eliciti

  4. Factors Associated with the Accuracy of Physicians’ Predictions of Patient Adherence (United States)

    Phillips, L. Alison; Leventhal, Elaine A.; Leventhal, Howard


    Objective Physicians are inaccurate in predicting non-adherence in patients, a problem that interferes with physicians’: 1) appropriate prescribing decisions and 2) effective prevention/intervention of non-adherence. The purpose of the current study is to investigate potential reasons for the poor accuracy of physicians’ adherence-predictions and conditions under which their predictions may be more accurate. Methods After the medical encounter, predictions of patient-adherence and other ratings from primary-care physicians (n=24) regarding patient-factors that may have influenced their predictions were collected. Patients (n=288) rated their agreement regarding the prescribed treatment after the encounter and reported adherence one month later. Results Several factors were related to physicians’ adherence-predictions, including physicians’ perceptions of patient-agreement regarding treatment. However, some factors were not related to adherence and agreement-perceptions were inaccurate overall, potentially contributing to the poor accuracy of adherence-predictions. The degree to which physicians discussed treatment-specifics with the patient moderated agreement-perception accuracy but not adherence-prediction accuracy. Conclusions Training providers to discuss certain treatment-specifics with patients may improve their ability to perceive patient-agreement regarding treatment and may directly improve patient-adherence. Practice Implications Discussing treatment-specifics with patients may directly improve adherence, but providers should not rely on these discussions to give them accurate estimates of the patients’ likely adherence. PMID:21501943

  5. Lactobacilli interfere with Streptococcus pyogenes hemolytic activity and adherence to host epithelial cells

    Directory of Open Access Journals (Sweden)

    Sunil D Saroj


    Full Text Available Streptococcus pyogenes (Group A streptococcus (GAS, a frequent colonizer of the respiratory tract mucosal surface, causes a variety of human diseases, ranging from pharyngitis to the life-threatening streptococcal toxic shock-like syndrome. Lactobacilli have been demonstrated to colonize the respiratory tract. In this study, we investigated the interference of lactobacilli with the virulence phenotypes of GAS. The Lactobacillus strains L. rhamnosus Kx151A1 and L. reuteri PTA-5289, but not L. salivarius LMG9477, inhibited the hemolytic activity of GAS. The inhibition of hemolytic activity was attributed to a decrease in the production of streptolysin S (SLS. Conditioned medium (CM from the growth of L. rhamnosus Kx151A1 and L. reuteri PTA-5289 was sufficient to down-regulate the expression of the sag operon, encoding SLS. The Lactobacillus strains L. rhamnosus Kx151A1, L. reuteri PTA-5289 and L. salivarius LMG9477 inhibited the initial adherence of GAS to host epithelial cells. Intriguingly, competition with a combination of Lactobacillus species reduced GAS adherence to host cells most efficiently. The data suggest that an effector molecule released from certain Lactobacillus strains attenuates the production of SLS at the transcriptional level and that combinations of Lactobacillus strains may protect the pharyngeal mucosa more efficiently from the initial colonization of GAS. The effector molecules released from Lactobacillus strains affecting the virulence phenotypes of pathogens hold potential in the development of a new generation of therapeutics.

  6. Lactobacilli Interfere with Streptococcus pyogenes Hemolytic Activity and Adherence to Host Epithelial Cells (United States)

    Saroj, Sunil D.; Maudsdotter, Lisa; Tavares, Raquel; Jonsson, Ann-Beth


    Streptococcus pyogenes [Group A streptococcus (GAS)], a frequent colonizer of the respiratory tract mucosal surface, causes a variety of human diseases, ranging from pharyngitis to the life-threatening streptococcal toxic shock-like syndrome. Lactobacilli have been demonstrated to colonize the respiratory tract. In this study, we investigated the interference of lactobacilli with the virulence phenotypes of GAS. The Lactobacillus strains L. rhamnosus Kx151A1 and L. reuteri PTA-5289, but not L. salivarius LMG9477, inhibited the hemolytic activity of S. pyogenes S165. The inhibition of hemolytic activity was attributed to a decrease in the production of streptolysin S (SLS). Conditioned medium (CM) from the growth of L. rhamnosus Kx151A1 and L. reuteri PTA-5289 was sufficient to down-regulate the expression of the sag operon, encoding SLS. The Lactobacillus strains L. rhamnosus Kx151A1, L. reuteri PTA-5289, and L. salivarius LMG9477 inhibited the initial adherence of GAS to host epithelial cells. Intriguingly, competition with a combination of Lactobacillus species reduced GAS adherence to host cells most efficiently. The data suggest that an effector molecule released from certain Lactobacillus strains attenuates the production of SLS at the transcriptional level and that combinations of Lactobacillus strains may protect the pharyngeal mucosa more efficiently from the initial colonization of GAS. The effector molecules released from Lactobacillus strains affecting the virulence phenotypes of pathogens hold potential in the development of a new generation of therapeutics. PMID:27524981

  7. Lactobacilli Interfere with Streptococcus pyogenes Hemolytic Activity and Adherence to Host Epithelial Cells. (United States)

    Saroj, Sunil D; Maudsdotter, Lisa; Tavares, Raquel; Jonsson, Ann-Beth


    Streptococcus pyogenes [Group A streptococcus (GAS)], a frequent colonizer of the respiratory tract mucosal surface, causes a variety of human diseases, ranging from pharyngitis to the life-threatening streptococcal toxic shock-like syndrome. Lactobacilli have been demonstrated to colonize the respiratory tract. In this study, we investigated the interference of lactobacilli with the virulence phenotypes of GAS. The Lactobacillus strains L. rhamnosus Kx151A1 and L. reuteri PTA-5289, but not L. salivarius LMG9477, inhibited the hemolytic activity of S. pyogenes S165. The inhibition of hemolytic activity was attributed to a decrease in the production of streptolysin S (SLS). Conditioned medium (CM) from the growth of L. rhamnosus Kx151A1 and L. reuteri PTA-5289 was sufficient to down-regulate the expression of the sag operon, encoding SLS. The Lactobacillus strains L. rhamnosus Kx151A1, L. reuteri PTA-5289, and L. salivarius LMG9477 inhibited the initial adherence of GAS to host epithelial cells. Intriguingly, competition with a combination of Lactobacillus species reduced GAS adherence to host cells most efficiently. The data suggest that an effector molecule released from certain Lactobacillus strains attenuates the production of SLS at the transcriptional level and that combinations of Lactobacillus strains may protect the pharyngeal mucosa more efficiently from the initial colonization of GAS. The effector molecules released from Lactobacillus strains affecting the virulence phenotypes of pathogens hold potential in the development of a new generation of therapeutics.

  8. Fucoidans Disrupt Adherence of Helicobacter pylori to AGS Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Eng-Guan Chua


    Full Text Available Fucoidans are complex sulphated polysaccharides derived from abundant and edible marine algae. Helicobacter pylori is a stomach pathogen that persists in the hostile milieu of the human stomach unless treated with antibiotics. This study aims to provide preliminary data to determine, in vitro, if fucoidans can inhibit the growth of H. pylori and its ability to adhere to gastric epithelial cells (AGS. We analysed the activity of three different fucoidan preparations (Fucus A, Fucus B, and Undaria extracts. Bacterial growth was not arrested or inhibited by the fucoidan preparations supplemented into culture media. All fucoidans, when supplemented into tissue culture media at 1000 µg mL−1, were toxic to AGS cells and reduced the viable cell count significantly. Fucoidan preparations at 100 µg mL−1 were shown to significantly reduce the number of adherent H. pylori. These in vitro findings provide the basis for further studies on the clinical use of sulphated polysaccharides as complementary therapeutic agents.

  9. Identifying solutions to medication adherence in the visually impaired elderly. (United States)

    Smith, Miranda; Bailey, Trista


    Adults older than 65 years of age with vision impairment are more likely to have difficulty managing medications compared with people having normal vision. This patient population has difficulty reading medication information and may take the wrong medication or incorrect doses of medication, resulting in serious consequences, including overdose or inadequate treatment of health problems. Visually impaired patients report increased anxiety related to medication management and must rely on others to obtain necessary drug information. Pharmacists have a unique opportunity to pursue accurate medication adherence in this special population. This article reviews literature illustrating how severe medication mismanagement can occur in the visually impaired elderly and presents resources and solutions for pharmacists to take a larger role in adherence management in this population.

  10. A social work study on measuring adherence to religious values

    Directory of Open Access Journals (Sweden)

    Mahsa Allahyari


    Full Text Available This study aims to investigate the effects of demographic characteristics, including gender, marital status, level of education and age on adherence to religious values among young people in city of Shahin Dezh and Takab, located in province of West Azerbaijan, Iran in 2014. The study has accomplished between two groups of Turk and Kurd with the population of 85,000 and 89,000, respectively. The study uses a sample of 20 and 30 people from Turkish and Kurdish tribes, respectively, and uses t-student test as well as regression analysis to examine different hypotheses of the survey. The results show that there was a meaningful difference among various variables of gender, marital status, education level and age in adherence to religious values among the youth who live in this city.

  11. Clinical pharmacist interventions to support adherence to thrombopreventive therapy

    DEFF Research Database (Denmark)

    Hedegaard, Ulla

    individualised interventions and team-based care, e.g. integrating a clinical pharmacist with particular focus on patients’ drug-related problems. One approach with growing evidence of improving medication adherence is motivational interviewing (MI). So far, no clinical pharmacist intervention using MI has...... to the different results in the two trials is that the stroke patients - compared to the hypertension patients - may have been more motivated for taking their medication as they just experienced a serious event. Another factor is that a secondary prevention clinic was established during the stroke study, which may...... by the clinical pharmacists and the patients.  Sensitivity and specificity for the two scales of the adherence questionnaire demonstrating the best agreement with prescription-based measures were about 90% and 30%, and the agreement with refill data was fairly low with kappa values below 0.3, suggesting...

  12. Optimal shapes and stresses of adherent cells on patterned substrates

    CERN Document Server

    Banerjee, Shiladitya; Marchetti, M Cristina


    We investigate a continuum mechanical model for an adherent cell on two dimensional adhesive micropatterned substrates. The cell is modeled as an isotropic and homogeneous elastic material subject to uniform internal contractile stresses. The build-up of tension from cortical actin bundles at the cell periphery is incorporated by introducing an energy cost for bending of the cell boundary, resulting to a resistance to changes in local curvature. Integrin-based adhesions are modeled as harmonic springs, that pin the cell to adhesive patches of a predefined geometry. Using Monte Carlo simulations and analytical techniques we investigate the competing effects of bulk contractility and cortical bending rigidity in regulating cell shapes on non-adherent regions. We show that the crossover from convex to concave cell edges is controlled by the interplay between contractile stresses and boundary bending rigidity. In particular, the cell boundary becomes concave beyond a critical value of the contractile stress that ...

  13. Metacognition and medication adherence: how do older adults remember? (United States)

    Gould, O N; McDonald-Miszczak, L; King, B


    Fifty-one older adults (M age = 75.9 years, SD = 6.9) reported their use of memory strategies for taking of medication using the Prospective Memory for Medication Questionnaire. Older adults used internal strategies more often when the domain was restricted to medication taking but used external strategies more often when queried across a variety of everyday situations. Surprisingly, the hypothesis that medical factors would be the primary determinants of older adults' reports of memory strategy use and perceived adherence was not supported. Metamemorial variables of non-domain-specific memory self-efficacy and memory anxiety in everyday life were significant predictors of strategy use and perceived adherence over and above variables related to the domain of health.

  14. Asthma Education, Action Plans, Psychosocial Issues and Adherence

    Directory of Open Access Journals (Sweden)

    John Kolbe


    Full Text Available This article deals with four separate but not disparate topics. The first section discusses asthma education, reviews the current literature and attempts to challenge some of the dogma that is associated with this area. Knowledge alone does not guarantee appropriate behaviour, due to a variety of adverse socioeconomic and psychological factors that need to be considered for each patient. Action plans and peak flow monitoring have both been disappointing in terms of reducing asthma morbidity; the former needs to be individualized, and the latter may be useful in specific situations. Space precludes an in-depth discussion of psychological issues and adherence, but an attempt has been made to address salient issues, particularly related to the first two topics. Psychological factors, especially anxiety, play an important role in asthma outcome. Adherence to medication prescriptions and other management strategies need to be taken into account when an individual’s treatment program is planned.

  15. [Patients on chemotherapy: depression and adherence to treatment]. (United States)

    de Souza, Bianca Fresche; Pires, Flavia Helena; Dewulf, Nathalie de Lourdes Souza; Inocenti, Aline; Silva, Ana Elisa Bauer de Camargo; Miasso, Adriana Inocenti


    This analytical, cross-sectional study applied a quantitative approach to verify the presence of depression and the adherence to a chemotherapy treatment in patients with cancer at the central chemotherapy pharmacy of a university hospital. The sample consisted of 102 patients, and data were collected from October 2010 to May 2011. A structured interview was used to obtain sociodemographic, clinical and therapeutic data; the Morisky Test and Beck Depression Inventory were also applied. The results revealed that 10.8% and 1.9% of participants had moderate and severe depression, respectively. The presence of depression was significantly associated with variables such as income per capita, the number of surgeries, and disease duration. A lack of treatment adherence was identified in 48% of participants. These results indicate the need for health staff training to detect depressive disorders and chemotherapy treatment attrition among patients with cancer.

  16. Control and adherence: living with diabetes in Bangkok, Thailand. (United States)

    Naemiratch, Bhensri; Manderson, Lenore


    Diabetes is managed via a regimen of control. Physicians advise adults living with type 2 diabetes to control blood sugar levels by controlling diet, maintaining regular exercise, and complying with medication. The extent to which individuals are able to adhere to such recommendations varies. In this article, we explore lay perceptions of diabetes and its control, drawing on data from an ethnographic study conducted in Bangkok, Thailand. Between August 2001 and February 2003 the first author spent time with twelve man and women living with type 2 diabetes, their spouses, children and health providers. An additional 21 people were interviewed to extend the data and test for generalisibility. It was found that individual explanations of control, and adherence or resistance to medical advice, are interpreted and adapted in ways consistent with Buddhist philosophy and Thai norms that govern everyday life. Notions of moderation and cultural values of being and behaving, and ideals of interaction, provide a philosophical basis and practical guidelines for control.

  17. Adherence of Model Molecules to Silica Surfaces: First Principle Calculations (United States)

    Nuñez, Matías; Prado, Miguel Oscar

    The adherence of "model molecules" methylene blue and eosine Y ("positive" and "negatively" charged respectively) to crystal SiO2 surfaces is studied from first principle calculations at the DFT level. Adsorption energies are calculated which follow the experimental threads obtained elsewhere (Rivera et al., 2013). We study the quantum nature of the electronic charge transfer between the surface and the molecules, showing the localized and delocalized patterns associated to the repulsive and attractive case respectively.

  18. The Effect of Customer Empowerment on Adherence to Expert Advice


    Camacho, Nuno; Jong, Martijn; Stremersch, Stefan


    textabstractCustomers often receive expert advice related to their health, finances, taxes or legal procedures, to name just a few. A noble stance taken by some is that experts should empower customers to make their own decisions. In this article, we distinguish informational from decisional empowerment and study whether empowerment leads customers to adhere more or less to expert advice. We empirically test our model using a unique dataset involving 11,735 respondents in 17 countries on four...



    Lelogeais, M.; Ducarroir, M.; Berjoan, R.


    Coatings of silicon carbide with various compositions have been obtained in a r.f plasma assisted process using tetramethylsilane and argon as input gases. Some properties against mechanical applications of such deposits on steel have been investigated. Residual stresses and hardness are reported and discussed in relation with plasma parameters and deposit composition. By scratch testing, it was shown that the silicon carbide films on steel denote a good adherence when compared with previous ...

  20. Treating depression in HIV-positive patients affects adherence


    M Y H Moosa; F Y Jeenah


    Aim. To determine changes in adherence to antiretroviral therapy (ART) in HIV-positive patients with depression, following treatment with an antidepressant or psychotherapy. Methods. The study was prospective, randomised and controlled. Consenting volunteers aged ≥18 years and stable on ART for ≥6 months were included in the study. Sociodemographic data were obtained, and a clinical diagnostic evaluation and the Hamilton Depression rating scale (HAMD) were performed on all subjects at en...