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Sample records for azithromycin suppresses interleukin-12p40

  1. A protease-activated receptor 2 agonist (AC-264613) suppresses interferon regulatory factor 5 and decreases interleukin-12p40 production by lipopolysaccharide-stimulated macrophages: Role of p53.

    PubMed

    Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Ishimaru, Yasuji; Narahara, Shinji; Sugiuchi, Hiroyuki; Yamaguchi, Yasuo

    2016-06-01

    The transcription factor interferon regulatory factor 5 (IRF5) has a key role in the production of interleukin (IL)-12 by macrophages. IRF5 is also a central mediator of toll-like receptor signaling and is a direct target of p53. Activation of protease-activated receptor 2 (PAR-2) upregulates p53 and suppresses apoptosis. This study investigated the influence of human neutrophil elastase (HNE) and PAR-2 agonists on expression of IRF5 and IL-12p40 by macrophages stimulated with lipopolysaccharide. Granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent macrophages showed upregulation of IRF5 expression, while HNE reduced expression of p53 and IRF5 in a concentration-dependent manner. HNE also caused a concentration-dependent decrease of IRF5 in macrophages transfected with small interfering RNA to silence p53, while silencing of β-arrestin 2 blunted the reduction of p53 or IRF5 by HNE. Incubation of macrophages with a PAR-2 agonist, AC-264613, caused a decrease of IRF5 expression and also significantly reduced p53 protein expression. HNE upregulated the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) and caused transactivation of TLR4, while AC-264613 did not promote TLR4 transactivation. In conclusion, the PAR-2 agonist AC-264613 attenuated IRF5-associated IL-12p40 production by macrophages.

  2. Diagnostic value of interleukin-12 p40 in tuberculous pleural effusions.

    PubMed

    Valdés, L; San José, E; Alvarez Dobaño, J M; Golpe, A; Valle, J M; Penela, P; González Barcala, F J

    2009-04-01

    The diagnosis of tuberculous pleural effusion (TBPE) is frequently problematic. Several markers of TBPE in pleural fluid have been evaluated, with different results. Pleural effusions from 96 patients were classified on the basis of definitive diagnosis as tuberculous (n = 39), neoplastic (n = 42) or parapneumonic (n = 15). Adenosine deaminase (ADA), ADA isoform ADA-2, interferon (IFN)-gamma, CD3(+)/DR(+) T-lymphocytes and interleukin (IL)-12 p40 were determined in all 96 effusions. The efficiency of IL-12 p40 for diagnosis of TBPEs was evaluated, in comparison with those of the other parameters, by comparing the areas under their receiver operating characteristics. With the threshold value of 550 pg.mL(-1), IL-12 p40 had a sensitivity of 92.3% (36 out of 39) and specificity of 70.2% (17 false positives). The misclassification rate of IL-12 p40 was significantly greater than those of ADA-2 and ADA. Among TBPEs, ADA correlated significantly with ADA-2, and IFN-gamma with ADA and IL-12 p40. Although tuberculous pleural effusions show values of interleukin-12 p40 that are significantly higher than neoplastic and parapneumonic fluids, this parameter is less efficient than adenosine deaminase, adenosine deaminase isoform 2 and interferon-gamma. Its routine determination is, accordingly, not justified.

  3. Azithromycin

    MedlinePlus

    ... cup (60 mL) of water to the same glass, mix, and consume the entire contents to ensure that you receive the entire dose.If you receive azithromycin extended-release suspension as a dry powder you must first add water to the bottle ...

  4. Azithromycin Dose To Maximize Efficacy and Suppress Acquired Drug Resistance in Pulmonary Mycobacterium avium Disease

    PubMed Central

    Deshpande, Devyani; Pasipanodya, Jotam G.

    2016-01-01

    Mycobacterium avium complex is now the leading mycobacterial cause of chronic pneumonia in the United States. Macrolides and ethambutol form the backbone of the regimen used in the treatment of pulmonary disease. However, therapy outcomes remain poor, with microbial cure rates of 4% in cavitary disease. The treatment dose of azithromycin has mostly been borrowed from that used to treat other bacterial pneumonias; there are no formal dose-response studies in pulmonary M. avium disease and the optimal dose is unclear. We utilized population pharmacokinetics and pharmacokinetics/pharmacodynamics-derived azithromycin exposures associated with optimal microbial kill or resistance suppression to perform 10,000 patient Monte Carlo simulations of dose effect studies for daily azithromycin doses of 0.5 to 10 g. The currently recommended dose of 500 mg per day achieved the target exposures in 0% of patients. Exposures associated with optimal kill and resistance suppression were achieved in 87 and 54% of patients, respectively, only by the very high dose of 8 g per day. The azithromycin susceptibility breakpoint above which patients failed therapy on the very high doses of 8 g per day was an MIC of 16 mg/liter, suggesting a critical concentration of 32 mg/liter, which is 8-fold lower than the currently used susceptibility breakpoint of 256 mg/liter. If the standard dose of 500 mg a day were used, then the critical concentration would fall to 2 mg/liter, 128-fold lower than 256 mg/liter. The misclassification of resistant isolates as susceptible could explain the high failure rates of current doses. PMID:26810646

  5. Azithromycin anaphylaxis in children.

    PubMed

    Mori, F; Pecorari, L; Pantano, S; Rossi, M E; Pucci, N; De Martino, M; Novembre, E

    2014-01-01

    Allergic reactions associated to the use of macrolides are uncommon; in particular only two cases of anaphylaxis with erithromycin and clarithromycin have been reported to date. The aim of this study was to investigate macrolide-induced anaphylaxis. Between December 2007 and December 2011, 136 consecutive children were referred to the Allergy Unit of A. Meyer Children's Hospital because of a past history of reactions to macrolides. Allergy work-ups were carried out according to the European Network for Drug Allergy protocol. Anaphylaxis was diagnosed according to the clinical criteria proposed by Sampson et al. and graded according to Brown SGA et al. Sixty-six out of 136 patients completed the allergologic work-up and among them we investigated three cases of anaphylaxis due to azithromycin which included one child with anaphylaxis to both clarithromycin and azithromycin. In two of the children with anaphylaxis, the diagnosis was only confirmed with the skin prick test, the third was positive to the Intradermal Test. The azithromycin allergy shows a surprisingly high sensitivity to the in-vivo tests. Moreover, this study shows that cross-reactivity may occur between different macrolidic molecules; it has even been suggested that macrolide allergies are unlikely to be class allergies.

  6. Effect of azithromycin on Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages.

    PubMed

    Choi, Eun-Young; Jin, Ji-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2014-04-15

    Interleukin-6 (IL-6) is a key proinflammatory cytokine which plays a central role in the pathogenesis of periodontal disease. Host modulatory agents targeting at inhibiting IL-6, therefore, appear to be beneficial in slowing the progression of periodontal disease and potentially reducing destructive aspects of the host response. The present study was designed to investigate the effect of the macrolide antibiotic azithromycin on IL-6 generation in murine macrophages treated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. Azithromycin significantly suppressed IL-6 production as well as its mRNA expression in P. intermedia LPS-activated RAW264.7 cells. LPS-induced activation of JNK and p38 was not affected by azithromycin treatment. Azithromycin failed to prevent P. intermedia LPS from degrading IκB-α. Instead, azithromycin significantly diminished nuclear translocation and DNA binding activity of NF-κB p50 subunit induced with LPS. Azithromycin inhibited P. intermedia LPS-induced STAT1 and STAT3 phosphorylation. In addition, azithromycin up-regulated the mRNA level of SOCS1 in cells treated with LPS. In conclusion, azithromycin significantly attenuated P. intermedia LPS-induced production of IL-6 in murine macrophages via inhibition of NF-κB, STAT1 and STAT3 activation, which is possibly related to the activation of SOCS1 signaling. Further in vivo studies are required to better evaluate the potential of azithromycin in the treatment of periodontal disease.

  7. Periodontal tissue disposition of azithromycin.

    PubMed

    Malizia, T; Tejada, M R; Ghelardi, E; Senesi, S; Gabriele, M; Giuca, M R; Blandizzi, C; Danesi, R; Campa, M; Del Tacca, M

    1997-12-01

    The tissue penetration of azithromycin, the prototype of a new class of macrolide antibiotics named azalides, was studied in patients undergoing surgery for third-molar removal. Drug concentrations in plasma, saliva, and periodontal tissues were evaluated in 28 patients treated with azithromycin 500 mg/day per os for 3 consecutive days. Samples of blood, saliva, gingiva, and alveolar bone were collected during oral surgery, 12 hours, and 2.5, 4.5, and 6.5 days after the last dosing, and the azithromycin concentration was measured microbiologically by using Micrococcus luteus NCTC 8440 as the reference organism. The highest concentrations of azithromycin were observed 12 hours after the last dose in plasma, saliva, gingiva, and bone (0.33 +/- 0.04 mg/l, 2.14 +/- 0.30 mg/l, 6.47 +/- 0.57 mg/kg, and 1.86 +/- 0.15 mg/kg, respectively) and then declined gradually. However, consistent levels of the drug in saliva and periodontal tissues could be detected up to 6.5 days, indicating that azithromycin was retained in target tissues and fluids for a long time after the end of treatment. Among the samples examined, the highest concentration of azithromycin was found in the gingiva at each time studied. Moreover, the ratios of salivary or periodontal tissue levels versus plasma concentrations remained nearly unmodified from 12 hours up to 6.5 days. Overall, these results indicate a favorable disposition of azithromycin into saliva and periodontal tissues and suggest that this macrolide antibiotic represents a valuable option in the pharmacologic treatment of odontogenic infections.

  8. Azithromycin use in paediatrics: A practical overview.

    PubMed

    Ovetchkine, Philippe; Rieder, Michael J

    2013-06-01

    Azithromycin is an antibiotic that is commonly prescribed for upper and lower respiratory tract infections in children. While it has proven benefits, some concerns regarding azithromycin use have arisen in recent years. This practice point considers azithromycin therapy for acute respiratory infections in otherwise healthy children. Pharmacokinetics, spectrum of activity, the problem of resistant bacteria and clinical aspects are considered, along with recommendations for use and contraindications. Azithromycin should be avoided in patients with a significant risk of bacteremia. It is associated with pneumococcal resistance and, with stated exceptions, is generally not recommended for the treatment of acute pharyngitis, acute otitis media or pneumococcal community-acquired pneumonia in the paediatric population.

  9. Effects of azithromycin on shiga toxin production by Escherichia coli and subsequent host inflammatory response.

    PubMed

    Ohara, Tatsuki; Kojio, Seiichi; Taneike, Ikue; Nakagawa, Saori; Gondaira, Fumio; Tamura, Yukiko; Gejyo, Fumitake; Zhang, Hui-Min; Yamamoto, Tatsuo

    2002-11-01

    Shiga toxin (Stx)-producing Escherichia coli (STEC) colonizes the human intestinal mucosa, produces Stx from phage, and causes the development of hemolytic-uremic syndrome via Stx-induced inflammatory cytokine production. Azithromycin exhibited strong in vitro activity against STEC without inducing Stx-converting phage, in marked contrast to norfloxacin. Azithromycin decreased the tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 production from Stx-treated human peripheral mononuclear cells or monocytes to a greater extent than did clarithromycin. In Stx-injected mice, azithromycin significantly suppressed Stx-induced TNF-alpha, IL-1beta, and IL-6 levels in serum and improved the outcome as assessed by survival rate. In the STEC oral infection experiment using immature mice immediately after weaning (weaned immature-mouse model), all mice died within 7 days postinfection. Azithromycin administration gave the mice 100% protection from killing, while ciprofloxacin administration gave them 67% protection. The data suggest that azithromycin (at least at higher concentrations) has a strong effect on Stx production by STEC and on the Stx-induced inflammatory host response and prevents death in mice. Azithromycin may have a beneficial effect on STEC-associated disease.

  10. Scavenger receptor for lipoteichoic acid is involved in the potent ability of Lactobacillus plantarum strain L-137 to stimulate production of interleukin-12p40.

    PubMed

    Hatano, Shinya; Hirose, Yoshitaka; Yamamoto, Yoshihiro; Murosaki, Shinji; Yoshikai, Yasunobu

    2015-04-01

    Heat-killed Lactobacillus plantarum strain L-137 (HK L-137) is a more potent inducer of interleukin (IL)-12 than other heat-killed Lactobacillus strains. To elucidate the mechanism involved in this IL-12p40 induction, we compared HK L-137 with heat-killed L. plantarum strain JCM1149 (HK JCM1149) by nuclear magnetic resonance and mass spectrometry. Results showed that HK L-137 contained lipoteichoic acid (LTA) with a chemical structure similar to that of JCM1149, except for a lower degree of glucosyl substitution in the poly(glycerol phosphate) backbone. Lysozyme sensitivity and electrophoretic moiety analysis revealed that HK L-137 exposed more LTA on its cell surface than HK JCM1149. Phagocytosis of HK L-137 by splenic adherent cells was significantly greater than that of HK JCM1149. Anti-LTA antibody and anti-scavenger receptor-A (SR-A) antibody selectively inhibited phagocytosis of HK L-137, as well as IL-12p40 production, by splenic adherent cells. Thus, a higher efficiency of phagocytosis of HK L-137 via SR-A for LTA is responsible for the potent IL-12p40 induction.

  11. Cloning, promoter analysis and expression in response to bacterial exposure of sea bass (Dicentrarchus labrax L.) interleukin-12 p40 and p35 subunits.

    PubMed

    Nascimento, Diana S; do Vale, Ana; Tomás, Ana M; Zou, Jun; Secombes, Christopher J; dos Santos, Nuno M S

    2007-03-01

    Interleukin-12 (IL-12) is a heterodimeric cytokine pivotal in resistance to microbial and viral infections. In the search for immunoregulatory genes in sea bass the genes for the two IL-12 subunits p40 and p35 were cloned and sequenced. Molecular characterization of these two genes was performed at both the cDNA and genomic levels. Sea bass IL-12 p40 and p35 conserve most cysteines involved in the intra-chain disulfide bonds of human IL-12 subunits as well as the important structural residues for human IL-12 heterodimerization. The gene organization of sea bass IL-12 p40 is similar to the human orthologue, whilst the sea bass IL-12 p35 gene structure, as reported for pufferfish, differs from the human one in containing an additional exon and lacking a second copy of a duplicated exon present in the mammalian genes. The promoter analysis of both sea bass and pufferfish IL-12 genes showed the presence of the main cis-acting elements involved in the transcriptional regulation of human and mouse orthologues. The involvement of IL-12 in sea bass anti-bacterial immune responses was demonstrated by investigating the expression profiles of IL-1beta, IL-12 p40 and p35 in the head-kidney and spleen following intraperitoneal injection of UV-killed and live Photobacterium damselae ssp. piscicida (Phdp). Finally, the importance of nuclear factor (NF)-kappaB on UV-killed Phdp-induced IL-12 p40 and p35 gene transcription was shown by the use of pyrrolidine dithiocarbamate (PDTC).

  12. Oral Azithromycin for Treatment of Intractable Rosacea

    PubMed Central

    Kim, Jae-Hong; Oh, Yoon Seok

    2011-01-01

    Rosacea is a common chronic cutaneous disorder that primarily occurs on the convex surfaces of the central face and is often characterized by exacerbations and remissions. A case of a 52-yr-old woman visited our clinic in February 2008 complaining typical features of rosacea including multiple pinhead to rice-sized erythematous papules. We applied various conventional treatments including topical benzoyl peroxide and metronidazole as well as oral metronidazole, isotretinoin, and doxycycline. The lesions were not controlled but were rather aggravated by complications from these treatments. Therefore, we prescribed oral azithromycin, which has anti-inflammatory effects and reduces reactive oxygen species. Ten weeks after the administration of oral azithromycin, 500 mg per day for 2 weeks, the lesions had mostly disappeared and no specific side effects related to the azithromycin were noted. Oral azithromycin dosing 500 mg/day for 2 weeks is effective for treatment of intractable rosacea. PMID:21532865

  13. [Azithromycin therapy in cystic fibrosis].

    PubMed

    Máiz Carro, Luis; Cantón Moreno, Rafael

    2004-03-06

    Progressive lung disease, caused by chronic endobronchial colonization, is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). Several pathogens, including Staphylococcus aureus and Pseudomonas aeruginosa are responsible for this effect. The steadily improving prognosis of CF has been attributed to the use of antibiotics with activity against these organisms. Despite a significant increase in the amount of published material demonstrating the potential role of macrolide antibiotics as antiinflammatory agents and their effects on bacterial virulence, their mechanism of action in CF patients is still unknown. Although there is a limited number of clinical trials assessing the efficacy and safety of azithromycin (AZM) in CF, increasing evidence suggests that 3 to 6-month AZM treatment in CF patients is safe and well tolerated. This treatment results in clinical improvement, decreasing the number of pulmonary exacerbations and increasing pulmonary function. Therefore, chronic treatment with AZM should be considered in CF patients added to conventional therapy. Clinical experience with macrolides other than AZM in CF patients is very limited.

  14. A case of clinical and microbiological failure of azithromycin therapy in Salmonella enterica serotype Typhi despite low azithromycin MIC.

    PubMed

    Manesh, Abi; Balaji, Veeraraghavan; Kumar, Devanga Ragupathi Naveen; Rupali, Priscilla

    2017-01-01

    Typhoid fever remains a serious problem in many developing countries. Due to resistance to multiple first line drugs, azithromycin has evolved as an important drug in the treatment of typhoid. While therapy with azithromycin is highly effective, no clinically validated mean inhibitory concentration (MIC) break points or disc diffusion cutoff guidelines are available so far. We describe an Indian adult with clinical and microbiological failure to azithromycin despite low azithromycin MIC.

  15. Adjunctive Azithromycin Prophylaxis for Cesarean Delivery

    PubMed Central

    Tita, Alan T.N.; Szychowski, Jeff M.; Boggess, Kim; Saade, George; Longo, Sherri; Clark, Erin; Esplin, Sean; Cleary, Kirsten; Wapner, Ron; Letson, Kellett; Owens, Michelle; Abramovici, Adi; Ambalavanan, Namasivayam; Cutter, Gary; Andrews, William

    2016-01-01

    BACKGROUND The addition of azithromycin to standard regimens for antibiotic prophylaxis before cesarean delivery may further reduce the rate of postoperative infection. We evaluated the benefits and safety of azithromycin-based extended-spectrum prophylaxis in women undergoing nonelective cesarean section. METHODS In this trial conducted at 14 centers in the United States, we studied 2013 women who had a singleton pregnancy with a gestation of 24 weeks or more and who were undergoing cesarean delivery during labor or after membrane rupture. We randomly assigned 1019 to receive 500 mg of intravenous azithromycin and 994 to receive placebo. All the women were also scheduled to receive standard antibiotic prophylaxis. The primary outcome was a composite of endometritis, wound infection, or other infection occurring within 6 weeks. RESULTS The primary outcome occurred in 62 women (6.1%) who received azithromycin and in 119 (12.0%) who received placebo (relative risk, 0.51; 95% confidence interval [CI], 0.38 to 0.68; P<0.001). There were significant differences between the azithromycin group and the placebo group in rates of endometritis (3.8% vs. 6.1%, P = 0.02), wound infection (2.4% vs. 6.6%, P<0.001), and serious maternal adverse events (1.5% vs. 2.9%, P = 0.03). There was no significant between-group difference in a secondary neonatal composite outcome that included neonatal death and serious neonatal complications (14.3% vs. 13.6%, P = 0.63). CONCLUSIONS Among women undergoing nonelective cesarean delivery who were all receiving standard antibiotic prophylaxis, extended-spectrum prophylaxis with adjunctive azithromycin was more effective than placebo in reducing the risk of postoperative infection. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; C/SOAP ClinicalTrials.gov number, NCT01235546.) PMID:27682034

  16. Adjunctive Azithromycin Prophylaxis for Cesarean Delivery.

    PubMed

    Tita, Alan T N; Szychowski, Jeff M; Boggess, Kim; Saade, George; Longo, Sherri; Clark, Erin; Esplin, Sean; Cleary, Kirsten; Wapner, Ron; Letson, Kellett; Owens, Michelle; Abramovici, Adi; Ambalavanan, Namasivayam; Cutter, Gary; Andrews, William

    2016-09-29

    Background The addition of azithromycin to standard regimens for antibiotic prophylaxis before cesarean delivery may further reduce the rate of postoperative infection. We evaluated the benefits and safety of azithromycin-based extended-spectrum prophylaxis in women undergoing nonelective cesarean section. Methods In this trial conducted at 14 centers in the United States, we studied 2013 women who had a singleton pregnancy with a gestation of 24 weeks or more and who were undergoing cesarean delivery during labor or after membrane rupture. We randomly assigned 1019 to receive 500 mg of intravenous azithromycin and 994 to receive placebo. All the women were also scheduled to receive standard antibiotic prophylaxis. The primary outcome was a composite of endometritis, wound infection, or other infection occurring within 6 weeks. Results The primary outcome occurred in 62 women (6.1%) who received azithromycin and in 119 (12.0%) who received placebo (relative risk, 0.51; 95% confidence interval [CI], 0.38 to 0.68; P<0.001). There were significant differences between the azithromycin group and the placebo group in rates of endometritis (3.8% vs. 6.1%, P=0.02), wound infection (2.4% vs. 6.6%, P<0.001), and serious maternal adverse events (1.5% vs. 2.9%, P=0.03). There was no significant between-group difference in a secondary neonatal composite outcome that included neonatal death and serious neonatal complications (14.3% vs. 13.6%, P=0.63). Conclusions Among women undergoing nonelective cesarean delivery who were all receiving standard antibiotic prophylaxis, extended-spectrum prophylaxis with adjunctive azithromycin was more effective than placebo in reducing the risk of postoperative infection. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; C/SOAP ClinicalTrials.gov number, NCT01235546 .).

  17. Intracellular activity of azithromycin against bacterial enteric pathogens.

    PubMed Central

    Rakita, R M; Jacques-Palaz, K; Murray, B E

    1994-01-01

    Azithromycin, a new azalide antibiotic, is active in vitro against a variety of enteric bacterial pathogens. Since it is concentrated inside human neutrophils and other cells, it might be particularly useful in the treatment of infections caused by enteropathogens that invade host tissues. The intracellular activity of azithromycin against several enteric pathogens that had been phagocytosed by neutrophils was determined. Azithromycin was effective in reducing the intracellular viabilities of almost all strains tested, including representative strains of Salmonella, Shigella, and enteroinvasive, enteropathogenic, enterotoxigenic, and enterohemorrhagic Escherichia coli. Erythromycin was also effective in this model system, although azithromycin was generally more effective than erythromycin against strains of invasive enteric pathogens. Cefotaxime reduced intracellular bacterial viability to a lesser extent than either azithromycin or erythromycin. The presence of neutrophils did not significantly affect the activity of azithromycin in this system. Azithromycin may be a useful agent for the treatment of bacterial diarrhea, and clinical trials should be considered. PMID:7810998

  18. A new HPLC method for azithromycin quantitation.

    PubMed

    Zubata, Patricia; Ceresole, Rita; Rosasco, Maria Ana; Pizzorno, Maria Teresa

    2002-02-01

    A simple liquid chromatographic method was developed for the estimation of azithromycin raw material and in pharmaceutical forms. The sample was chromatographed on a reverse phase C18 column and eluants monitored at a wavelength of 215 nm. The method was accurate, precise and sufficiently selective. It is applicable for its quantitation, stability and dissolution tests.

  19. Cardiac risks associated with antibiotics: azithromycin and levofloxacin

    PubMed Central

    Lu, Zhiqiang Kevin; Yuan, Jing; Li, Minghui; Sutton, S Scott; Rao, Gowtham A; Jacob, Sony; Bennett, Charles L

    2015-01-01

    Introduction Azithromycin and levofloxacin have been shown to be efficacious in treating infections. The adverse drug events associated with azithromycin and levofloxacin were considered rare. However, the US FDA released warnings regarding the possible risk of QT prolongation with azithromycin and levofloxacin. Areas covered Case reports/case series, observational studies and clinical trials assessing cardiovascular risks associated with azithromycin and levofloxacin were critically reviewed, including 15 case reports/series, 5 observational studies and 5 clinical trials that investigated the cardiac risks associated azithromycin and levofloxacin. Expert opinion Results are discordant. Two retrospective studies utilizing large databases demonstrated an increased risk of cardiovascular death with azithromycin, when azithromycin was compared with amoxicillin. Two other retrospective studies found no difference in cardiovascular death associated with azithromycin and other antibiotics. For levofloxacin, the increased risk of cardiovascular death was only found in one retrospective study. Therefore, the risks and benefits of antibacterial therapies should be considered when making prescription decisions. This study should not preclude clinicians from avoiding azithromycin and levofloxacin. If a patient has an indication to receive an antibiotic and if azithromycin or levofloxacin is needed, it may be used, but the potential risks must be understood. PMID:25494485

  20. Corticosteroid and Azithromycin in Idiopathic Granulomatous Mastitis

    PubMed Central

    Salehi, Marzieh; Salehi, Maryam; Kalbasi, Nader; Hakamifard, Atousa; Salehi, Hassan; Salehi, Mohammad Mahdi; Sharifian, Jalil

    2017-01-01

    Background: Mastitis is an inflammatory disorder in breast tissues due to bacterial factors, mycobacterial infections or autoimmune diseases. Idiopathic granulomatous mastitis (IGM) is a form of mastitis which may be affected by systematic diseases such as sarcoidosis, and infectious causes such as mycobacterium and fungus. This study evaluates the efficacy of medical therapy with a combination of corticosteroid and Azithromycin in patients with IGM. Materials and Methods: This study is a clinical trial research carried out in Alzahra Hospital (Isfahan, Iran) in 2013 on granulomatous mastitis patients. It was administered 250 mg of Azithromycin per 12 hour and 60 mg of Prednisolone per day within 2 weeks. Next, they took 40 mg/day within 8 weeks, and this dosage was tapered during 6 months and the patients clinically and radiologically followed up. The studied patients were examined within 1 week, 2 weeks, 1 month, 3 months, and 6 months, from the beginning of treatment. Results: This study investigated granulomatous mastitis patients in Alzahra hospital in 2013. The mean age of these patients was 33.6 ± 8.9, and their age range was 18–56 years old. Among 26 studied patients, 24 persons (92.3%) according to follow-up the patients by physical examination and sonography responded to treatment of corticosteroid and Azithromycin. The remaining (7.7%) underwent surgery. Treatment periods in case of drug use were respectively, 8.5 ± 0.71 months. Conclusion: Treatment with corticosteroid and Azithromycin is an effective and appropriate treatment for IGM. PMID:28217653

  1. Azithromycin induced bullous fixed drug eruption.

    PubMed

    Das, Anupam; Sancheti, Karan; Podder, Indrashis; Das, Nilay Kanti

    2016-01-01

    Fixed drug eruption (FDE) is a common type of drug eruption seen in skin clinics. It is characterized by solitary or multiple, round to oval erythematous patches with dusky red centers, some of which may progress to bulla formation. Bullous FDE may be caused by a number of drugs. We hereby describe a case of azithromycin-induced bullous FDE; to the best of our knowledge, this is the first such case being reported.

  2. Quality of life after tonsillectomy versus azithromycin

    PubMed Central

    El Hennawi, Diaa El Din Mohamed; Rifaat Ahmed, Mohamed

    2016-01-01

    Background Recurrent tonsillitis is a common disease with marked evidence of affecting children quality of life (QOL) such as their progression in school and increased burden to extended families. The aim of this study was to compare the QOL outcomes after conventional dissection tonsillectomy versus azithromycin treatment in controlling recurrent tonsillitis. Methods A double-blind, randomized clinical trial was carried out in 184 children with recurrent tonsillitis randomly divided into two groups: Group A was subjected to conventional dissection tonsillectomy, whereas Group B received single 250 mg (children ≤25 kg) and 500 mg (children ≥25 kg) of oral azithromycin once weekly. Results There were no significant differences between the groups with regard to ear, nose, and throat infections during the 5-year follow-up. Better QOL was observed in both groups when compared with the pretreatment, but similar QOL in both groups QOL after treatment. Conclusion Azithromycin is an effective method as a prophylaxis against recurrent tonsillitis with a great benefit for better QOL outcomes. PMID:28180002

  3. Use and safety of azithromycin in neonates: a systematic review

    PubMed Central

    Smith, Coral; Egunsola, Oluwaseun; Choonara, Imti; Kotecha, Sailesh; Jacqz-Aigrain, Evelyne; Sammons, Helen

    2015-01-01

    Objectives To identify the use and adverse drug reactions associated with azithromycin in neonates. Setting Databases MEDLINE (1948–August 2015), EMBASE (1980–August 2015) and Pubmed (August 2015) were searched for studies on azithromycin in neonates. Participants All studies involving neonates (<28 days old) who have received at least a single dose of azithromycin for which safety was evaluated. Primary and secondary outcome measures The primary outcome was adverse event (AE) associated with use of azithromycin. Use of azithromycin in neonates was the secondary outcome. Results A total of 11 articles involving 473 neonates were identified. 371 AEs were reported. Adverse events were mainly respiratory (358/1000 neonate), neurological (273/1000 neonates) and gastrointestinal (196/1000 neonates) in origin. Azithromycin significantly reduced the risk of bronchopulmonary dysplasia (BPD) in extremely premature neonates (RR=0.83, 95% CI 0.71 to 0.98, p=0.02). There was no significant difference in the incidence of elevated liver enzymes between the azithromycin and placebo group (p=0.76). There were four cases of infantile hypertrophic pyloric stenosis (IHPS). Conclusions Azithromycin significantly reduces the risk of BPD in preterm neonates. The relationship between azithromycin and IHPS requires further investigation. PMID:26656010

  4. Azithromycin kills invasive Aggregatibacter actinomycetemcomitans in gingival epithelial cells.

    PubMed

    Lai, Pin-Chuang; Walters, John D

    2013-03-01

    Aggregatibacter actinomycetemcomitans invades periodontal pocket epithelium and is therefore difficult to eliminate by periodontal scaling and root planing. It is susceptible to azithromycin, which is taken up by many types of mammalian cells. This led us to hypothesize that azithromycin accumulation by gingival epithelium could enhance the killing of intraepithelial A. actinomycetemcomitans. [(3)H]azithromycin transport by Smulow-Glickman gingival epithelial cells and SCC-25 oral epithelial cells was characterized. To test our hypothesis, we infected cultured Smulow-Glickman cell monolayers with A. actinomycetemcomitans (Y4 or SUNY 465 strain) for 2 h, treated them with gentamicin to eliminate extracellular bacteria, and then incubated them with azithromycin for 1 to 4 h. Viable intracellular bacteria were released, plated, and enumerated. Azithromycin transport by both cell lines exhibited Michaelis-Menten kinetics and was competitively inhibited by l-carnitine and several other organic cations. Cell incubation in medium containing 5 μg/ml azithromycin yielded steady-state intracellular concentrations of 144 μg/ml in SCC-25 cells and 118 μg/ml in Smulow-Glickman cells. Azithromycin induced dose- and time-dependent intraepithelial killing of both A. actinomycetemcomitans strains. Treatment of infected Smulow-Glickman cells with 0.125 μg/ml azithromycin killed approximately 29% of the intraepithelial CFU of both strains within 4 h, while treatment with 8 μg/ml azithromycin killed ≥82% of the CFU of both strains (P < 0.05). Addition of carnitine inhibited the killing of intracellular bacteria by azithromycin (P < 0.05). Thus, human gingival epithelial cells actively accumulate azithromycin through a transport system that facilitates the killing of intraepithelial A. actinomycetemcomitans and is shared with organic cations.

  5. Pharmacokinetics and preliminary safety evaluation of azithromycin in adult horses.

    PubMed

    Leclere, M; Magdesian, K G; Cole, C A; Szabo, N J; Ruby, R E; Rhodes, D M; Edman, J; Vale, A; Wilson, W D; Tell, L A

    2012-12-01

    Azithromycin is widely used in foals but has not been studied in adult horses. The goals of this study were to determine the pharmacokinetic profile and to make a preliminary assessment of the safety of azithromycin in adult horses. Azithromycin was administered intravenously (5 mg/kg) and intragastrically (10 mg/kg) to six healthy mares in a crossover design. Serial plasma samples, blood neutrophils, and pulmonary macrophages were collected for the measurement of azithromycin concentrations. Azithromycin was also administered orally (10 mg/kg) once a day for 5 days to five healthy mares for preliminary evaluation of safety in adult horses. The bioavailability of azithromycin following intragastric administration was 45 ± 12%. Concentrations within peripheral neutrophils and bronchoalveolar macrophages were several fold higher than that of plasma. Mild decreases in appetite (n = 3) and alterations in fecal consistency (n = 3) were noted following repeated oral administration. The pharmacokinetic profiles of azithromycin in adult horses, especially the slow elimination rate and intraneutrophil and intrapulmonary macrophage accumulation, demonstrate that it is conducive to use in this age group. Because of the gastrointestinal alterations noted, further studies are warranted before azithromycin can be recommended for use in adult horses.

  6. Azithromycin metabolite identification in plasma, bile, and tissues of the ball python (Python regius).

    PubMed

    Hunter, R P; Koch, D E; Coke, R L; Goatley, M A; Isaza, R

    2003-04-01

    Azithromycin is the first of a class of antibiotics classified as azalides. Six ball pythons (Python regius) were given a single dose of azithromycin at 10 mg/kg p.o. and i.v. in a crossover design. Serial blood samples were collected for unchanged azithromycin and to determine, if possible, the structure and number of circulating azithromycin metabolites. After a 4-month wash-out period, the snakes were given azithromycin p.o. as a single dose of 10 mg/kg for the study of azithromycin metabolism and metabolite tissue distribution. Bile, liver, lung, kidney, and skin samples were analyzed for the metabolites identified from the first experiment. Unchanged azithromycin accounted for 80, 68, and 60% of the total material at 12, 24, and 48 h postadministration in plasma, independent of route of administration. At both 24 and 72 h postadministration, azithromycin accounted for 70% of total azithromycin- associated material in bile. In liver and kidney, unchanged azithromycin accounted for 40% of the total azithromycin-associated material; this doubled in lung and skin. Fifteen metabolites were positively or tentatively identified in plasma, bile, or tissues of all snakes. Four of these possible metabolites: 3'-desamine-3-ene-azithromycin, descladinose dehydroxy-2-ene-azithromycin, 3'-desamine-3-ene descladinose-azithromycin, and 3'-N-nitroso,9a-N-desmethyl-azithromycin are unique to this species. Descladinose-azithromycin, 3'-N-desmethyl,9a-N-desmethyl-azithromycin, and 3'-N-desmethyl, 3'-O-desmethyl-azithromycin were the only metabolites identified in skin. Kidney tissue contained a greater number of metabolites than liver tissue, with 3'-N-didesmethyl-azithromycin being identified only in the kidney. Compared with the dog and cat, a greater number of metabolites were identified in ball python plasma. The percentage of unchanged azithromycin in bile is not different between the three species.

  7. Topical azithromycin or ofloxacin for endophthalmitis prophylaxis after intravitreal injection

    PubMed Central

    Romero-Aroca, Pedro; Sararols, Laura; Arias, Lluis; Casaroli-Marano, Ricardo P; Bassaganyas, Francisca

    2012-01-01

    Background The number of patients who have undergone intravitreal injections has increased enormously in recent years, but a consensus is still lacking on prophylaxis for endophthalmitis. The aim of this prospective, observational study was to evaluate the prophylactic effect of azithromycin eye drops versus ofloxacin eye drops. Methods The study was conducted in five hospitals in Spain and included all patients undergoing intravitreal injections of triamcinolone, bevacizumab, ranibizumab, or pegaptanib over one year. Patients received azithromycin 15 mg/g eye drops (twice daily on the day prior to injection and for another 2 days) or ofloxacin 3 mg/g eye drops (every 6 hours on the day prior to injection and for another 7 days). Results In the azithromycin group, there were 4045 injections in 972 eyes of 701 patients. In the ofloxacin group, there were 4151 injections in 944 eyes of 682 patients. There were two cases of endophthalmitis (0.049%) in the azithromycin group and five (0.12%) in the ofloxacin group. The odds ratio of presenting with endophthalmitis in the ofloxacin group compared with the azithromycin group was 2.37 (95% confidence interval [CI] 1.32–3.72, P < 0.001). There were two cases of noninfectious uveitis after triamcinolone injection in the azithromycin group (0.049%) and two (0.048%) in the ofloxacin group; no significant differences were observed (odds ratio 0.902, 95% CI 0.622–1.407, P = 0.407). Conjunctival hyperemia was observed in 12 cases in the azithromycin group and none in the ofloxacin group. Conclusion The risk of endophthalmitis was significantly greater with ofloxacin than with azithromycin. These findings provide a valuable addition to the ever-increasing pool of information on endophthalmitis prophylaxis after intravitreal injection, although further large-scale studies are required to provide definitive conclusions. PMID:23109798

  8. The Efficacy and Safety of Gentamicin Plus Azithromycin and Gemifloxacin Plus Azithromycin as Treatment of Uncomplicated Gonorrhea

    PubMed Central

    Kirkcaldy, Robert D.; Weinstock, Hillard S.; Moore, Page C.; Philip, Susan S.; Wiesenfeld, Harold C.; Papp, John R.; Kerndt, Peter R.; Johnson, Shacondra; Ghanem, Khalil G.; Hook, Edward W.; Newman, Lori M.; Dowell, Deborah; Deal, Carolyn; Glock, Jonathan; Venkatasubramanian, Lalitha; McNeil, Linda; Perlowski, Charlotte; Lee, Jeannette Y.; Lensing, Shelly; Trainor, Nikole; Fuller, Shannon; Herrera, Amelia; Carlson, Jonathan S.; Harbison, Hanne; Lenderman, Connie; Dixon, Paula; Whittington, Allison; Macio, Ingrid; Priest, Carol; Jett, Abi; Campbell, Tracy; Uniyal, Apurva; Royal, LaShawnda; Mejia, Marisol; Vonghack, Jennifer; Tobias, Susan; Zenilman, Jonathan; Long, Jill; Harvey, Alesia; Pettus, Kevin; Sharpe, Samera

    2014-01-01

    Background. Ceftriaxone is the foundation of currently recommended gonorrhea treatment. There is an urgent need for backup treatment options for patients with cephalosporin allergy or infections due to suspected cephalosporin-resistant Neisseria gonorrhoeae. We evaluated the efficacy and tolerability of 2 combinations of existing noncephalosporin antimicrobials for treatment of patients with urogenital gonorrhea. Methods. We conducted a randomized, multisite, open-label, noncomparative trial in 5 outpatient sexually transmitted disease clinic sites in Alabama, California, Maryland, and Pennsylvania. Patients aged 15–60 years diagnosed with uncomplicated urogenital gonorrhea were randomly assigned to either gentamicin 240 mg intramuscularly plus azithromycin 2 g orally, or gemifloxacin 320 mg orally plus azithromycin 2 g orally. The primary outcome was microbiological cure of urogenital infections (negative follow-up culture) at 10–17 days after treatment among 401 participants in the per protocol population. Results. Microbiological cure was achieved by 100% (lower 1-sided exact 95% confidence interval [CI] bound, 98.5%) of 202 evaluable participants receiving gentamicin/azithromycin, and 99.5% (lower 1-sided exact 95% CI bound, 97.6%) of 199 evaluable participants receiving gemifloxacin/azithromycin. Gentamicin/azithromycin cured 10 of 10 pharyngeal infections and 1 of 1 rectal infection; gemifloxacin/azithromycin cured 15 of 15 pharyngeal and 5 of 5 rectal infections. Gastrointestinal adverse events were common in both arms. Conclusions. Gentamicin/azithromycin and gemifloxacin/azithromycin were highly effective for treatment of urogenital gonorrhea. Gastrointestinal adverse events may limit routine use. These non-cephalosporin-based regimens may be useful alternative options for patients who cannot be treated with cephalosporin antimicrobials. Additional treatment options for gonorrhea are needed. Clinical Trials Registration. NCT00926796. PMID

  9. Whole blood stimulation with Toll-like receptor (TLR)-7/8 and TLR-9 agonists induces interleukin-12p40 expression in plasmacytoid dendritic cells in rhesus macaques but not in humans.

    PubMed

    Koopman, G; Beenhakker, N; Burm, S; Bouwhuis, O; Bajramovic, J; Sommandas, V; Mudde, G; Mooij, P; 't Hart, B A; Bogers, W M J M

    2013-10-01

    Macaques provide important animal models in biomedical research into infectious and chronic inflammatory disease. Therefore, a proper understanding of the similarities and differences in immune function between macaques and humans is needed for adequate interpretation of the data and translation to the human situation. Dendritic cells are important as key regulators of innate and adaptive immune responses. Using a new whole blood assay we investigated functional characteristics of blood plasmacytoid dendritic cells (pDC), myeloid dendritic cells (mDC) and monocytes in rhesus macaques by studying induction of activation markers and cytokine expression upon Toll-like receptor (TLR) stimulation. In a head-to-head comparison we observed that rhesus macaque venous blood contained relatively lower numbers of pDC than human venous blood, while mDC and monocytes were present at similar percentages. In contrast to humans, pDC in rhesus macaques expressed the interleukin (IL)-12p40 subunit in response to TLR-7/8 as well as TLR-9 stimulation. Expression of IL-12p40 was confirmed by using different monoclonal antibodies and by reverse transcription-polymerase chain reaction (RT-PCR). Both in humans and rhesus macaques, TLR-4 stimulation induced IL-12p40 expression in mDC and monocytes, but not in pDC. The data show that, in contrast to humans, pDC in macaques are able to express IL-12p40, which could have consequences for evaluation of human vaccine candidates and viral infection.

  10. Association of interferon γ T+874A and interleukin 12 p40 promoter CTCTAA/GC polymorphism with the need for respiratory support and perinatal complications in low birthweight neonates

    PubMed Central

    Bokodi, G; Derzbach, L; Bányász, I; Tulassay, T; Vásárhelyi, B

    2007-01-01

    Background Data support the role of interferon (IFN)γ and interleukin (IL)12 in perinatal complications. IFNγ T+874A and IL12 p40 promoter CTCTAA/GC polymorphisms may have an effect on cytokine production. Methods DNA was extracted from dried blood samples of 153 low birthweight (LBW) infants and 172 healthy term infants. IFNγ and IL12 genetic polymorphisms were determined to investigate the association between polymorphisms and ventilation characteristics, bronchopulmonary dysplasia (BPD) and other perinatal disorders. Results The IFNγ+874A allele was over‐represented in LBW infants. Carriers of the IFNγ+874T allele required mechanical ventilation and oxygen supplementation for time periods 41% and 35%, respectively, shorter than those required by those not carrying the IFNγ+874T allele. Stepwise logistic regression analysis showed that carriers of the IFNγ+874T allele were protected against BPD (odds ratio (OR) 0.35 (95% confidence interval (CI) (0.12 to 0.99))) and patent ductus arteriosus (OR 0.43 (95% CI 0.19 to 0.97)), whereas carriers of the IFNγ+874A allele were at higher risk of severe hypotension (OR 3.40 (95% CI 1.01 to 11.52)) and respiratory distress syndrome (OR 4.03 (95% CI 1.30 to 12.50)). Carriers of the IL12 GC allele were protected against pneumonia (OR 0.32 (95% CI 0.14 to 0.75)). Carriers of the IL12 CTCTAA allele were at higher risk of developing necrotising enterocolitis (NEC; OR 2.37 (95% CI 1.01 to 5.53)). Conclusions Carrier state of the IFNγ+874A allele presents an increased risk for premature birth and lung damage, as well as other perinatal complications. The risks of pneumonia and NEC are higher in heterozygotic carriers of the IL12 CTCTAA/GC polymorphism. Further studies are needed to determine whether these associations are the result of altered cytokine‐producing capacity in infants carrying the tested alleles. PMID:16754651

  11. Use of azithromycin ophthalmic solution in the treatment of chronic mixed anterior blepharitis.

    PubMed

    John, Thomas; Shah, Ami A

    2008-01-01

    We tested the efficacy of azithromycin ophthalmic solution for the treatment of chronic mixed anterior blepharitis. The findings suggest that patients with chronic mixed anterior blepharitis can be more effectively treated with azithromycin ophthalmic solution than erythromycin ophthalmic ointment. Patients treated with azithromycin ophthalmic solution show an extraordinary clinical response with shorter treatment duration.

  12. Azithromycin Activities against Orientia tsutsugamushi Strains Isolated in Cases of Scrub Typhus in Northern Thailand

    PubMed Central

    Watt, George; Kantipong, Pacharee; Jongsakul, Krisada; Watcharapichat, Pochaman; Phulsuksombati, Duangporn

    1999-01-01

    Azithromycin was given to mice and humans infected with strains of Orientia tsutsugamushi from northern Thailand, where drug-resistant scrub typhus occurs. Azithromycin and doxycycline yielded comparable mouse survival rates (73 and 79%, respectively; P > 0.5). Symptoms, signs, and fever in two pregnant women abated rapidly with azithromycin. Prospective human trials are needed. PMID:10543774

  13. Effect of single oral dose of azithromycin, clarithromycin, and roxithromycin on polymorphonuclear leukocyte function assessed ex vivo by flow cytometry.

    PubMed Central

    Wenisch, C; Parschalk, B; Zedtwitz-Liebenstein, K; Weihs, A; el Menyawi, I; Graninger, W

    1996-01-01

    Azithromycin was given as a single oral dose (20 mg/kg of body weight) to 12 volunteers in a crossover study with roxithromycin (8 to 12 mg/kg) and clarithromycin (8 to 12 mg/kg). Flow cytometry was used to study the phagocytic functions and the release of reactive oxygen products following phagocytosis by neutrophil granulocytes prior to administration of the three drugs, 16 h after azithromycin administration, and 3 h after clarithromycin and roxithromycin administration. Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labeled bacteria. Reactive oxygen generation after phagocytosis of unlabeled bacteria was estimated by the amount of dihydrorhodamine 123 converted to rhodamine 123 intracellularly. Azithromycin resulted in decreased capacities of the cells to phagocytize Escherichia coli (median [range], 62% [27 to 91%] of the control values; P < 0.01) and generate reactive oxygen products (75% [34 to 26%] of the control values; P < 0.01). Clarithromycin resulted in reduced phagocytosis (82% [75 to 98%] of control values; P < 0.01) but did not alter reactive oxygen production (84% [63 to 113%] of the control values; P > 0.05). Roxithromycin treatment did not affect granulocyte phagocytosis (92% [62 to 118%] of the control values; P > 0.05) or reactive oxygen production (94% [66 to 128%] of the control value; P > 0.05). No relation between intra- and/or extracellular concentrations of azithromycin and/or roxithromycin and the polymorphonuclear phagocyte function and/or reactive oxygen production existed (P > 0.05 for all comparisons). These results demonstrate that the accumulation of macrolides in neutrophils can suppress the response of phagocytic cells to bacterial pathogens after a therapeutic dose. PMID:8878577

  14. Mechanism of azithromycin inhibition of HSL synthesis in Pseudomonas aeruginosa

    PubMed Central

    Zeng, Jianming; Zhang, Ni; Huang, Bin; Cai, Renxin; Wu, Binning; E, Shunmei; Fang, Chengcai; Chen, Cha

    2016-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen and a leading cause of nosocomial infections. Unfortunately, P. aeruginosa has low antibiotic susceptibility due to several chromosomally encoded antibiotic resistance genes. Hence, we carried out mechanistic studies to determine how azithromycin affects quorum sensing and virulence in P. aeruginosa. lasI and rhlI single and double mutants were constructed. We then undertook a quantitative approach to determine the optimal concentration of azithromycin and culture time that can affect the expression of HSLs. Furthermore, based on the above results, the effect on quorum sensing was analyzed at a transcriptional level. It was found that 2 μg/mL azithromycin caused a 79% decrease in 3-oxo-C12-HSL secretion during cultivation, while C4-HSL secretion was strongly repressed in the early stages. Azithromycin acts on ribosomes; to determine whether this can elicit alternative modes of gene expression, transcriptional regulation of representative virulence genes was analyzed. We propose a new relationship for lasI and rhlI: lasI acts as a cell density sensor, and rhlI functions as a fine-tuning mechanism for coordination between different quorum sensing systems. PMID:27075730

  15. Effects of azithromycin in Pseudomonas aeruginosa burn wound infection

    PubMed Central

    Nichols, DP; Caceres, S; Caverly, L; Fratelli, C; Kim, SH; Malcolm, KC; Poch, KR; Saavedra, M; Solomon, G; Taylor-Cousar, J; Moskowitz, SM; Nick, JA

    2013-01-01

    Background Cutaneous thermal injuries (i.e. burns) remain a common form of debilitating trauma and outcomes are often worsened by wound infection with environmental bacteria, chiefly Pseudomonas aeruginosa. Materials and Methods We tested the effects of early administration of a single dose of azithromycin, with or without subsequent anti-pseudomonal antibiotics, in a mouse model of standardized thermal injury infected with P. aeruginosa on both wound site and systemic infection. We also tested the antimicrobial effects of these antibiotics alone or combined in comparative biofilm and planktonic cultures in vitro. Results In our model, early azithromycin administration significantly reduced wound and systemic infection without altering wound site or circulating neutrophil activity. The antimicrobial effect of azithromycin was additive with ciprofloxacin but significantly reduced the antimicrobial effect of tobramycin. This pattern was reproduced in biofilm cultures and not observed in planktonic cultures of P. aeruginosa. Conclusion these data suggest that early administration of azithromycin following burn-related trauma and infection may reduce P. aeruginosa infection and potential interactions with other antibiotics should be considered when designing future studies. PMID:23478086

  16. Pharmacokinetics of azithromycin after intravenous and intramuscular administration to goats.

    PubMed

    Cárceles, C M; Font, A; Espuny, A; Fernández-Varón, E; Serrano, J M; Escudero, E

    2005-02-01

    Azithromycin is the first of a class of antimicrobial agents designated azalides. The aim of the present study was to investigate the disposition pharmacokinetics of azithromycin in goats and determine its bioavailability. A cross-over study was carried out in two phases separated by 30 days. Azithromycin was administered at a single dose of 20 mg/kg body weight by i.v. and i.m. routes. Plasma concentrations of azithromycin were determined by a modified agar diffusion bioassay. After a single i.v. dose plasma concentrations were best fitted to a three-compartment open model. A two-compartment open model with first-order absorption fitted best after i.m. administration. The values of the pharmacokinetic parameters after i.v. administration were: half-life 32.5 h, apparent volume of distribution at the steady-state 34.5 L/kg, clearance 0.85 L/kg. and mean residence time (MRT) 40.1 h. After i.m. administration half-life of 45.2 h, a MRT of 60.3 h, maximum plasma concentration 0.64 mg/L and a bioavalability 92.2% were obtained. The pharmacokinetic parameters of azithromycin after i.m. administration, principally its long half-life and high bioavailability, could provide an alternative to the oral route of administration in goats, although more studies are needed to establish a suitable pharmaceutical formulation, propose optimun dosage regimens, investigate clinical efficacy and study the tolerability of repeated doses.

  17. Evaluation of azithromycin, trovafloxacin and grepafloxacin as prophylaxis for experimental murine melioidosis.

    PubMed

    Kenny, Dermot J; Sefton, Armine M; Brooks, Timothy J G; Laws, Thomas R; Simpson, Andrew J H; Atkins, Helen S

    2010-07-01

    The efficacies of the azalide azithromycin and the fluoroquinolones trovafloxacin and grepafloxacin for pre- and post-exposure prophylaxis of infection with high or low challenge doses of Burkholderia pseudomallei strain 576 were assessed in an experimental mouse model. Trovafloxacin and grepafloxacin afforded significant levels of protection, whereas azithromycin was ineffective and potentially detrimental. Overall, the data suggest that some fluoroquinolones may have potential utility in prophylaxis of melioidosis and suggest that azithromycin would not be effective in prophylaxis of B. pseudomallei infection.

  18. Inhaled therapies, azithromycin and Mycobacterium abscessus in cystic fibrosis patients.

    PubMed

    Catherinot, Emilie; Roux, Anne-Laure; Vibet, Marie-Anne; Bellis, Gil; Lemonnier, Lydie; Le Roux, Evelyne; Bernède-Bauduin, Claire; Le Bourgeois, Muriel; Herrmann, Jean-Louis; Guillemot, Didier; Gaillard, Jean-Louis

    2013-05-01

    Cystic fibrosis (CF) patients are at particularly high risk of developing lung disease caused by Mycobacterium abscessus complex (MABSC). Over the last 10 years, changes in CF treatment, with increasing use of inhaled therapies and low-dose azithromycin, have been accompanied by an increase in the prevalence of MABSC infections in CF patients. There is therefore some concern about the role of new CF treatments in the emergence of MABSC infections. We addressed this issue by means of a case-control study including 30 MABSC-positive cases and 60 nontuberculous mycobacteria-negative CF controls matched for age, sex and centre. We also compared practices at the CF centres with the highest prevalence of MABSC with those at the other centres. No positive association was found between MABSC lung disease and the use of inhaled therapies or low-dose azithromycin in the 4 years preceding MABSC isolation. These treatments were not significantly more frequently used at the CF centres with the highest MABSC prevalence rates. In conclusion, there is no evidence for a link between M. abscessus complex lung disease and inhaled therapies or low-dose azithromycin in patients with CF.

  19. Amorphous azithromycin with improved aqueous solubility and intestinal membrane permeability.

    PubMed

    Aucamp, Marique; Odendaal, Roelf; Liebenberg, Wilna; Hamman, Josias

    2015-01-01

    Azithromycin (AZM) is a poorly soluble macrolide antibacterial agent. Its low solubility is considered as the major contributing factor to its relatively low oral bioavailability. The aim of this study was to improve the solubility of this active pharmaceutical ingredient (API) by preparing an amorphous form by quench cooling of the melt and to study the influence of the improved solubility on membrane permeability. The amorphous azithromycin (AZM-A) exhibited a significant increase in water solubility when compared to the crystalline azithromycin dihydrate (AZM-DH). The influence that the improved solubility could have on membrane permeability was also studied. The apparent permeability coefficient (Papp) values of AZM-A were statistically significantly higher (p < 0.05) than crystalline AZM-DH at pH values of 6.8 and 7.2. The results therefore indicated that the improved solubility of AZM in the amorphous form also produced improved permeability across excised intestinal tissue at physiological pH values found in the small intestine.

  20. Pharmaceutical development and optimization of azithromycin suppository for paediatric use.

    PubMed

    Kauss, Tina; Gaubert, Alexandra; Boyer, Chantal; Ba, Boubakar B; Manse, Muriel; Massip, Stephane; Léger, Jean-Michel; Fawaz, Fawaz; Lembege, Martine; Boiron, Jean-Michel; Lafarge, Xavier; Lindegardh, Niklas; White, Nicholas J; Olliaro, Piero; Millet, Pascal; Gaudin, Karen

    2013-01-30

    Pharmaceutical development and manufacturing process optimization work was undertaken in order to propose a potential paediatric rectal formulation of azithromycin as an alternative to existing oral or injectable formulations. The target product profile was to be easy-to-use, cheap and stable in tropical conditions, with bioavailability comparable to oral forms, rapidly achieving and maintaining bactericidal concentrations. PEG solid solution suppositories were characterized in vitro using visual, HPLC, DSC, FTIR and XRD analyses. In vitro drug release and in vivo bioavailability were assessed; a study in rabbits compared the bioavailability of the optimized solid solution suppository to rectal solution and intra-venous product (as reference) and to the previous, non-optimized formulation (suspended azithromycin suppository). The bioavailability of azithromycin administered as solid solution suppositories relative to intra-venous was 43%, which compared well to the target of 38% (oral product in humans). The results of 3-month preliminary stability and feasibility studies were consistent with industrial production scale-up. This product has potential both as a classical antibiotic and as a product for use in severely ill children in rural areas. Industrial partners for further development are being sought.

  1. Pharmaceutical development and optimization of azithromycin suppository for paediatric use

    PubMed Central

    Kauss, Tina; Gaubert, Alexandra; Boyer, Chantal; Ba, Boubakar B.; Manse, Muriel; Massip, Stephane; Léger, Jean-Michel; Fawaz, Fawaz; Lembege, Martine; Boiron, Jean-Michel; Lafarge, Xavier; Lindegardh, Niklas; White, Nicholas J.; Olliaro, Piero; Millet, Pascal; Gaudin, Karen

    2013-01-01

    Pharmaceutical development and manufacturing process optimization work was undertaken in order to propose a potential paediatric rectal formulation of azithromycin as an alternative to existing oral or injectable formulations. The target product profile was to be easy-to-use, cheap and stable in tropical conditions, with bioavailability comparable to oral forms, rapidly achieving and maintaining bactericidal concentrations. PEG solid solution suppositories were characterized in vitro using visual, HPLC, DSC, FTIR and XRD analyses. In vitro drug release and in vivo bioavailability were assessed; a study in rabbits compared the bioavailability of the optimized solid solution suppository to rectal solution and intra-venous product (as reference) and to the previous, non-optimized formulation (suspended azithromycin suppository). The bioavailability of azithromycin administered as solid solution suppositories relative to intra-venous was 43%, which compared well to the target of 38% (oral product in humans). The results of 3-month preliminary stability and feasibility studies were consistent with industrial production scale-up. This product has potential both as a classical antibiotic and as a product for use in severely ill children in rural areas. Industrial partners for further development are being sought. PMID:23220079

  2. Efficacy and safety of azithromycin versus benzylpenicillin or erythromycin in community-acquired pneumonia.

    PubMed

    Bohte, R; van't Wout, J W; Lobatto, S; Blussé van Oud Alblas, A; Boekhout, M; Nauta, E H; Hermans, J; van den Broek, P J

    1995-03-01

    Azithromycin, a recently introduced antibiotic, offers the potential advantages of short-course administration and lower toxicity compared to other macrolides. Approved for the treatment of mild pneumonia, this drug was investigated in a study of patients hospitalized for community-acquired pneumonia. In an open-labelled randomized study, oral azithromycin was compared with intravenous benzylpenicillin in patients suspected to have pneumococcal pneumonia. Azithromycin was also compared with erythromycin, both administered orally, in all other patients. Three hundred thirty-four patients with community-acquired pneumonia were hospitalized, 108 of whom were randomized; 104 could be evaluated. A need for intravenous therapy was the most common reason for exclusion. In the pneumococcal group, 35 patients received azithromycin and 29 benzylpenicillin. The clinical and radiological success rate achieved with azithromycin (83%) was considerably higher than that achieved with benzylpenicillin (66%), though the difference was not significant. In the non-pneumococcal group, 19 patients received azithromycin and 21 erythromycin; no differences in the success rate were found (79% and 76%, respectively). Eight patients on azithromycin had a blood culture positive for Streptococcus pneumoniae; in three of these patients therapy was changed. None of the five patients with pneumococcal bacteraemia who received benzylpenicillin required a change in therapy. It is concluded that oral azithromycin, administered as short-course therapy, is an appropriate antibiotic for treating patients with community-acquired pneumonia. However, it is not yet certain that azithromycin is a good choice for patients with pneumococcal bacteraemia.

  3. Intravenous azithromycin as salvage therapy in a patient with Legionnaire's disease

    PubMed Central

    Dorrell, L; Fulton, B; Ong, E L C

    1994-01-01

    A patient with proven Legionnaire's disease is described whose clinical condition improved with intravenous azithromycin after failure to respond to treatment with erythromycin and rifampicin. Images PMID:8016806

  4. [Azithromycin: an anti-inflammatory effect in chronic recurrent multifocal osteomyelitis? A preliminary report].

    PubMed

    Schilling, F; Wagner, A D

    2000-10-01

    In this preliminary communication we report our experience with Azithromycin in patients with Chronic Recurring Multifocal Osteomyelitis (CRMO). Seven out of 13 patients, mainly teenager, showed a fast clinical improvement after they were started on Azithromycin. The immediate therapeutic effect of Azithromycin in patients with CRMO was surprising and lead us to the hypothesis that Azithromycin could have an antiphlogistic in addition to it's antibiotic effect in this disease setting. In patients with reactive chronic pelvic osteomyelitis Azithromycin obviously had a direct influence on the sympathic coxitis. Half of the patients reported an immediate reduction of pain and a significant improvement in range of movement after they were started on Azithromycin. In all cases the clinical and radiographic signs on MRI showed a reduction of the inflammatory process. Experimental animal models have recently shown that macrolids have independent additional antiinflammatory and immunomodulatory effects. The assumed local immunomodulatory effect of Azithromycin potentially is an additional activity to the already known synergistic antimicrobial and antiinflammatory effect. Right now we are in the process of collecting data from patients with SAPHO Syndrome who underwent bone-biopsies for microbiologic and histomorphologic investigations. All patients with the growth of propionibacterium acnes were started on a long-term antibiotic therapy with Azithromycin. This study will possibly help to answer the question of the additional antiphogistic/immunomodulatory effect of Azithromycin in this disease entity and the related CRMO.

  5. Azithromycin. A review of its antimicrobial activity, pharmacokinetic properties and clinical efficacy.

    PubMed

    Peters, D H; Friedel, H A; McTavish, D

    1992-11-01

    Azithromycin is an acid stable orally administered macrolide antimicrobial drug, structurally related to erythromycin, with a similar spectrum of antimicrobial activity. Azithromycin is marginally less active than erythromycin in vitro against Gram-positive organisms, although this is of doubtful clinical significance as susceptibility concentrations fall within the range of achievable tissue azithromycin concentrations. In contrast, azithromycin appears to be more active than erythromycin against many Gram-negative pathogens and several other pathogens, notably Haemophilus influenzae, H. parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Urea-plasma urealyticum and Borrelia burgdorferi. Like erythromycin and other macrolides, the activity of azithromycin is unaffected by the production of beta-lactamase. However, erythromycin-resistant organisms are also resistant to azithromycin. Following oral administration, serum concentrations of azithromycin are lower than those of erythromycin, but this reflects the rapid and extensive movement of the drug from the circulation into intracellular compartments resulting in tissue concentrations exceeding those commonly seen with erythromycin. Azithromycin is subsequently slowly released, reflecting its long terminal phase elimination half-life relative to that of erythromycin. These factors allow for a single dose or single daily dose regimen in most infections, with the potential for increased compliance among outpatients where a more frequent antimicrobial regimen might traditionally be indicated. The potential disadvantage of low azithromycin serum concentrations, however, is that breakthrough bacteraemia may occur in patients who are severely ill; nevertheless, animal studies suggest that tissue concentrations of azithromycin are more important than those in serum when treating respiratory and other infections. The clinical efficacy of azithromycin has been confirmed in the treatment of infections of the lower

  6. The safety of azithromycin in the treatment of adults with community-acquired respiratory tract infections.

    PubMed

    Treadway, Glenda; Pontani, Dennis; Reisman, Arlene

    2002-03-01

    The comparative safety of azithromycin was assessed in adult patients (> or =12 years) with community-acquired respiratory tract infections. Of 3229 patients evaluated, 1616 received azithromycin 500 mg once daily for 3 days and 1613 received standard regimens of amoxycillin, amoxycillin/clavulanic acid, cefaclor, clarithromycin, or roxithromycin. A similar incidence of treatment-related adverse events occurred with azithromycin (10.3%) and comparators (11.5%). Significantly fewer patients were withdrawn from azithromycin than comparator treatment (0.4 versus 2.1%; P=0.0001). Most adverse events were mild/moderate in intensity and affected the gastrointestinal system. Azithromycin was as well tolerated as other antibiotics commonly used for bacterial infections in adults.

  7. Macrolide resistance mechanisms in Enterobacteriaceae: Focus on azithromycin.

    PubMed

    Gomes, Cláudia; Martínez-Puchol, Sandra; Palma, Noemí; Horna, Gertrudis; Ruiz-Roldán, Lidia; Pons, Maria J; Ruiz, Joaquim

    2017-02-01

    From its introduction in 1952 onwards, the clinical use of macrolides has been steadily increasing, both in human and veterinary medicine. Although initially designed to the treatment of Gram-positive microorganisms, this antimicrobial family has also been used to treat specific Gram-negative bacteria. Some of them, as azithromycin, are considered in the armamentarium against Enterobacteriaceae infections. However, the facility that this bacterial genus has to gain or develop mechanisms of antibiotic resistance may compromise the future usefulness of these antibiotics to fight against Enterobacteriaceae infections. The present review is focused on the mechanisms of macrolide resistance, currently described in Enterobacteriaceae.

  8. Azithromycin analogue CSY0073 attenuates lung inflammation induced by LPS challenge

    PubMed Central

    Balloy, V; Deveaux, A; Lebeaux, D; Tabary, O; le Rouzic, P; Ghigo, J M; Busson, P F; Boëlle, P Y; Guez, J Guez; Hahn, U; Clement, A; Chignard, M; Corvol, H; Burnet, M; Guillot, L

    2014-01-01

    Background and Purpose Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulating effects. Long-term azithromycin therapy in patients with chronic lung diseases such as cystic fibrosis has been associated with increased antimicrobial resistance, emergence of hypermutable strains, ototoxicity and cardiac toxicity. The aim of this study was to assess the anti-inflammatory effects of the non-antibiotic azithromycin derivative CSY0073. Experimental Approach We compared the effects of CSY0073 with those of azithromycin in experiments on bacterial cultures, Pseudomonas aeruginosa biofilm, lung cells and mice challenged intranasally with P. aeruginosa LPS. Key Results In contrast to azithromycin, CSY0073 did not inhibit the growth of P. aeruginosa, Staphylococcus aureus or Haemophilus influenzae and had no effect on an established P. aeruginosa biofilm. Bronchoalveolar lavage (BAL) fluids and lung homogenates collected after the LPS challenge in mice showed that CSY0073 and azithromycin (200 mg·kg−1, i.p.) decreased neutrophil counts at 24 h and TNF-α, CXCL1 and CXCL2 levels in the BAL fluid after 3 h and IL-6, CXCL2 and IL-1β levels in the lung after 3 h compared with the vehicle. However, only azithromycin reduced IL-1β levels in the lung 24 h post LPS challenge. CSY0073 and azithromycin similarly diminished the production of pro-inflammatory cytokines by macrophages, but not lung epithelial cells, exposed to P. aeruginosa LPS. Conclusions and Implications Unlike azithromycin, CSY0073 had no antibacterial effects but it did have a similar anti-inflammatory profile to that of azithromycin. Hence, CSY0073 may have potential as a long-term treatment for patients with chronic lung diseases. PMID:24417187

  9. Randomized, multicentre study of the efficacy and tolerance of azithromycin versus clarithromycin in the treatment of adults with mild to moderate community-acquired pneumonia. Azithromycin Study Group.

    PubMed

    O'Doherty, B; Muller, O

    1998-12-01

    Adults with mild to moderate community-acquired pneumonia were treated with azithromycin (500 mg once daily for 3 days) or clarithromycin (250 mg twice daily for 10 days) and clinically assessed between days 3 and 7 and days 12 and 16. Patients classified as improved at the day 12-16 visit were also evaluated between days 19 and 23. Two hundred three patients were treated (101 with azithromycin, 102 with clarithromycin). A satisfactory clinical response was recorded at the end of therapy in 83 of 88 (94%) evaluable azithromycin-treated and 84 of 88 (95%) evaluable clarithromycin-treated patients (P=0.518). At day 19-23, only one patient in each treatment group had relapsed. Thirty-one of 32 (97%) pathogens isolated from patients in the azithromycin group were eradicated, compared with 32 of 35 (91%) isolated from clarithromycin patients. In all patients with atypical pneumonia, the clinical response was satisfactory at follow-up. Incidences of treatment-related adverse events were similar for the two groups (P=0.815). Two (2%) clarithromycin patients discontinued therapy due to severe treatment-related adverse events; none in the azithromycin group did. This study shows that a 3-day, once-daily course of azithromycin is as clinically effective and well tolerated as a 10-day, twice-daily course of clarithromycin in the treatment of mild to moderate community-acquired pneumonia.

  10. Pharmacokinetics of azithromycin in the blue and gold macaw (Ara ararauna) after intravenous and oral administration.

    PubMed

    Carpenter, James W; Olsen, John H; Randle-Port, Mary; Koch, David E; Isaza, Ramiro; Hunter, Robert P

    2005-12-01

    Azithromycin is classified as an azalide, a subclass of macrolide antimicrobials with a broad spectrum of activity in vitro against many potential bacterial pathogens including spirochetes, anaerobes, and Chlamydia trachomatis. Because of limited data on the use of azithromycin in avian medicine, this study was designed to determine the pharmacokinetics of azithromycin in blue and gold macaws (Ara ararauna), a species commonly seen in clinical practice. Azithromycin (10 mg/kg) was administered via crop lavage to five birds and intravenously to five birds, and blood samples were obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hr post-azithromycin administration. Following a 4-wk washout period, the study was repeated with a complete crossover study performed. Concentration of azithromycin in plasma samples was quantified using a validated liquid chromatography/mass spectrometry assay. Pharmacokinetic parameters were determined using noncompartmental analysis. Based on the pharmacokinetic data generated from this study, a starting dose of azithromycin at 10 mg/kg p.o. every 48 hr for susceptible bacterial infections in blue and gold macaws is recommended.

  11. Azithromycin induces anti-viral effects in cultured bronchial epithelial cells from COPD patients

    PubMed Central

    Menzel, Mandy; Akbarshahi, Hamid; Bjermer, Leif; Uller, Lena

    2016-01-01

    Rhinovirus infection is a major cause of chronic obstructive pulmonary disease (COPD) exacerbations and may contribute to the development into severe stages of COPD. The macrolide antibiotic azithromycin may exert anti-viral actions and has been reported to reduce exacerbations in COPD. However, little is known about its anti-viral actions on bronchial epithelial cells at clinically relevant concentrations. Primary bronchial epithelial cells from COPD donors and healthy individuals were treated continuously with azithromycin starting 24 h before infection with rhinovirus RV16. Expression of interferons, RIG-I like helicases, pro-inflammatory cytokines and viral load were analysed. Azithromycin transiently increased expression of IFNβ and IFNλ1 and RIG-I like helicases in un-infected COPD cells. Further, azithromycin augmented RV16-induced expression of interferons and RIG-I like helicases in COPD cells but not in healthy epithelial cells. Azithromycin also decreased viral load. However, it only modestly altered RV16-induced pro-inflammatory cytokine expression. Adding budesonide did not reduce interferon-inducing effects of azithromycin. Possibly by inducing expression of RIG-I like helicases, azithromycin increased rhinovirus-induced expression of interferons in COPD but not in healthy bronchial epithelium. These effects would reduce bronchial viral load, supporting azithromycin’s emerging role in prevention of exacerbations of COPD. PMID:27350308

  12. Azithromycin: assessment of intrinsic cytotoxic effects on corneal epithelial cell cultures

    PubMed Central

    Mencucci, Rita; Pellegrini-Giampietro, Domenico E; Paladini, Iacopo; Favuzza, Eleonora; Menchini, Ugo; Scartabelli, Tania

    2013-01-01

    Purpose To compare the cytotoxic effects of preservative-free azithromycin on corneal epithelial cells in vivo with those of preservative-free netilmicin and levofloxacin, and the preservative benzalkonium chloride (BAK). Methods Rabbit corneal epithelial cells in vitro were incubated for 15 minutes or 6 hours with commercially available ophthalmic preservative-free netilmicin 0.3%, levofloxacin 0.3%, or azithromycin 1.5% preparations or different concentrations of unpreserved azithromycin and different concentrations of BAK. Qualitative analysis was undertaken using phase-contrast optics to examine the morphological aspects of cell cultures and quantitative analysis was undertaken by measuring the release of the cytoplasmic enzyme lactate dehydrogenase into the medium immediately and 24 hours after exposure to drugs. Finally, we observed the wound-healing rate of mechanically injured corneal epithelial cells exposed to each antibiotic ophthalmic preparation for 48 hours. Results Our results show that both the commercially available unpreserved mono-dose preparation of azithromycin and ophthalmic preparations of azithromycin up to a concentration of 1.5% were virtually devoid of harmful effects under our experimental conditions. This was not significantly different from the results obtained for the other antibiotic preparations (P > 0.05) tested, but was unlike the results obtained for BAK. Azithromycin 1.5% also showed good recovery properties after a mechanical wound test. Conclusion Under our experimental conditions, unpreserved azithromycin 1.5% showed a much lower toxicity than BAK and did not interfere with the wound-healing process. PMID:23737659

  13. Does Mass Azithromycin Distribution Impact Child Growth and Nutrition in Niger? A Cluster-Randomized Trial

    PubMed Central

    Amza, Abdou; Yu, Sun N.; Kadri, Boubacar; Nassirou, Baido; Stoller, Nicole E.; Zhou, Zhaoxia; West, Sheila K.; Bailey, Robin L.; Gaynor, Bruce D.; Keenan, Jeremy D.; Porco, Travis C.; Lietman, Thomas M.

    2014-01-01

    Background Antibiotic use on animals demonstrates improved growth regardless of whether or not there is clinical evidence of infectious disease. Antibiotics used for trachoma control may play an unintended benefit of improving child growth. Methodology In this sub-study of a larger randomized controlled trial, we assess anthropometry of pre-school children in a community-randomized trial of mass oral azithromycin distributions for trachoma in Niger. We measured height, weight, and mid-upper arm circumference (MUAC) in 12 communities randomized to receive annual mass azithromycin treatment of everyone versus 12 communities randomized to receive biannual mass azithromycin treatments for children, 3 years after the initial mass treatment. We collected measurements in 1,034 children aged 6–60 months of age. Principal Findings We found no difference in the prevalence of wasting among children in the 12 annually treated communities that received three mass azithromycin distributions compared to the 12 biannually treated communities that received six mass azithromycin distributions (odds ratio = 0.88, 95% confidence interval = 0.53 to 1.49). Conclusions/Significance We were unable to demonstrate a statistically significant difference in stunting, underweight, and low MUAC of pre-school children in communities randomized to annual mass azithromycin treatment or biannual mass azithromycin treatment. The role of antibiotics on child growth and nutrition remains unclear, but larger studies and longitudinal trials may help determine any association. PMID:25210836

  14. Comparison of azithromycin versus clarithromycin in the treatment of patients with upper respiratory tract infections.

    PubMed

    Müller, O

    1993-06-01

    The efficacy and safety of azithromycin and clarithromycin were compared in an open multicentre study involving 380 adult patients with acute otitis media, acute sinusitis, or acute streptococcal pharyngitis or tonsillitis. Patients were assigned randomly to receive azithromycin as a single dose of 500 mg daily for three days, or clarithromycin 250 mg bid for ten days. Overall clinical efficacy was found to be similar in each treatment group at day 10-14, with a satisfactory outcome (cured or improved) in 95% of azithromycin and 96% of clarithromycin patients. Bacteriological efficacy was also similar, with eradication of the pathogen in 94% and 95% of isolates, respectively, in the azithromycin and clarithromycin groups. In otitis media, a satisfactory clinical response was seen in 97% of patients in each treatment group. Azithromycin therapy resulted in a clinical response rate of 93% in sinusitis patients, with bacteriological eradication in 93% of patients. Two patients (who were cured clinically) had persistent pathogens. Similarly, clarithromycin achieved clinical response and bacteriological eradication in 95% and 92% of sinusitis patients, respectively. Pathogens persisted in two patients with clinical cure, and in one case of clinical failure. In pharyngitis or tonsillitis, Streptococcus pyogenes was eradicated successfully in 95% of patients in both groups, and the clinical success rates were 96% and 97% for azithromycin and clarithromycin, respectively. No case of clinical failure was associated with persistence of S. pyogenes infection. At the follow-up assessment of this diagnosis group, reinfection had occurred in three (8%) azithromycin patients and one (3%) clarithromycin patient, and all but one patient remained asymptomatic. Both drugs were well-tolerated, with 8.4% of patients on azithromycin and 7.4% on clarithromycin reporting adverse events, mainly gastrointestinal. It was concluded that a three-day course of azithromycin was as effective and

  15. Azithromycin for the Prevention of COPD Exacerbations: The Good, Bad, and Ugly.

    PubMed

    Taylor, Stephanie Parks; Sellers, Eric; Taylor, Brice T

    2015-12-01

    Long-term azithromycin therapy has been shown to reduce exacerbations of chronic obstructive pulmonary disease (COPD), and is recommended by recent society guidelines for use in COPD patients who are at risk for recurrent exacerbations. However, concerns about adverse effects have limited its widespread adoption. Physicians deciding whether to use long-term azithromycin therapy must weigh each patient's individual risk of cardiovascular complications and both the individual and population impact of macrolide resistance against the expected benefit. This review will summarize evidence on the effectiveness and safety of chronic azithromycin for the prevention of COPD exacerbations.

  16. Evaluation of azithromycin, trovafloxacin and grepafloxacin as prophylaxis against experimental murine Brucella melitensis infection.

    PubMed

    Atkins, Helen S; Spencer, Stephen; Brew, Simon D; Jenner, Dominic C; Sefton, Armine M; MacMillan, Alastair P; Brooks, Timothy J G; Simpson, Andrew J H

    2010-07-01

    The prophylactic potential of the azalide azithromycin as well as the fluoroquinolones trovafloxacin and grepafloxacin was assessed for the control of infection with Brucella melitensis in an experimental mouse model, determined by reduction in splenic bacterial burden. Trovafloxacin showed limited protective efficacy when administered 2h following a low-dose B. melitensis challenge, whereas grepafloxacin was ineffective. In comparison, azithromycin provided significant control of infection both following low- and high-dose challenges. Overall, the data confirm the potential utility of azithromycin in the prophylaxis of brucellosis and suggest that neither trovafloxacin nor grepafloxacin would likely be valuable for post-exposure prophylaxis of Brucella infection.

  17. Mass Spectrometry Analysis of Pseudomonas aeruginosa Treated With Azithromycin

    PubMed Central

    Phelan, Vanessa V.; Fang, Jinshu; Dorrestein, Pieter C.

    2015-01-01

    In microbiology, changes in specialized metabolite production (cell-to-cell signaling metabolites, virulence factors and natural products) are measured using phenotypic assays. However, advances in mass spectrometry based techniques including imaging mass spectrometry (IMS) now allow researchers to directly visualize the production of specialized metabolites from microbial colony biofilms. In this study, a combination of IMS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to visualize the effect of the macrolide antibiotic azithromycin (AZM) on colony biofilms of Pseudomonas aeruginosa. While previous research suggested that AZM may inhibit cell-to-cell signaling of P. aeruginosa and thereby reducing pathogenicity, we observed no clear decrease in specialized metabolite production. PMID:25801585

  18. Mass Spectrometry Analysis of Pseudomonas aeruginosa Treated with Azithromycin

    NASA Astrophysics Data System (ADS)

    Phelan, Vanessa V.; Fang, Jinshu; Dorrestein, Pieter C.

    2015-06-01

    In microbiology, changes in specialized metabolite production (cell-to-cell signaling metabolites, virulence factors, and natural products) are measured using phenotypic assays. However, advances in mass spectrometry-based techniques including imaging mass spectrometry (IMS) now allow researchers to directly visualize the production of specialized metabolites from microbial colony biofilms. In this study, a combination of IMS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to visualize the effect of the macrolide antibiotic azithromycin (AZM) on colony biofilms of Pseudomonas aeruginosa. Although previous research suggested that AZM may inhibit cell-to-cell signaling of P. aeruginosa and thereby reduce pathogenicity, we observed no clear decrease in specialized metabolite production.

  19. Benefits of additional courses of systemic azithromycin in periodontal disease case report.

    PubMed

    Schmidt, Edgard F; Bretz, Walter A

    2007-01-01

    The strong association of subgingival anaerobic bacteria, such as Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, with destructive periodontal disease has been well documented in the literature. Several double-blind studies have also shown the beneficial use of systemic antimicrobials that are active against these microorganisms in conjunction with conventional periodontal treatment, especially when periodontal abscesses and/or suppuration upon probing are present. Four cases with periodontal abscesses were treated with scaling/root planing in conjunction with systemic azithromycin. Partial improvement led to retreatment with two additional courses of azithromycin. Bone formation was noted on periapical radiographs after the patients took additional courses of azithromycin. In view of the benefits of using additional courses of azithromycin in the treatment of destructive periodontal disease, we conclude that the single course of systemic antimicrobials currently used in periodontal therapy may be insufficient to reach necessary therapeutic levels in infected sites.

  20. Ureaplasma, bronchopulmonary dysplasia, and azithromycin in European neonatal intensive care units: a survey

    PubMed Central

    Pansieri, Claudia; Pandolfini, Chiara; Elie, Valery; Turner, Mark A.; Kotecha, Sailesh; Jacqz-Aigrain, Evelyne; Bonati, Maurizio

    2014-01-01

    A survey was set up to gauge the opinions of neonatologists on the role of Ureaplasma in bronchopulmonary dysplasia (BPD) development, the use of azithromycin for BPD prevention, and the factors influencing azithromycin use in European neonatal intensive care units (NICUs). 167 NICUs participated in the survey, representing 28 European countries. For respondents, the two major perceived risk factors for BPD were prematurity of <28 weeks and high oxygen requirements. Only 38% of NICUs had a protocol for BPD prevention and 47% routinely tested for Ureaplasma. In cases of infection, macrolides were the first choice. Most (78%) NICUs were interested in participating in a trial evaluating azithromycin safety and efficacy in reducing BPD rates. Opinions and clinical practice varied between European neonatal units, and differences in Ureaplasma treatment and prevention of BPD highlight the need for further azithromycin evaluation and for improved therapeutic knowledge in preterms. PMID:24518104

  1. Comparison of azithromycin versus clarithromycin in the treatment of patients with lower respiratory tract infection.

    PubMed

    Bradbury, F

    1993-06-01

    The efficacy and safety of azithromycin and clarithromycin in lower respiratory tract infection (LRTI) were compared in an open, multicentre study. Five hundred and ten adult patients with a diagnosis of LRTI, including acute bronchitis, acute infective exacerbations of chronic bronchitis (AIECB) or pneumonia were enrolled. The patients were randomly assigned to receive either azithromycin (n = 252) as a single daily dose of 500 mg for three days, or clarithromycin (n = 258) 250 mg twice daily for ten days. In AIECB patients, baseline comparisons of the two treatment groups showed that there were no differences in the number of previous episodes of infection or in the incidence of current or past smokers. The overall clinical efficacy was found to be similar in each treatment group on day 10 to 14, with a satisfactory response (cured or improved) in 94% of azithromycin- and 97% of clarithromycin-treated patients. At follow-up evaluation (day 18 to 22), 97% of azithromycin- and 100% of clarithromycin-treated patients who had improved at day 10 to 14, showed satisfactory outcomes. Bacteriological efficacy was similar in both treatment groups, with eradication of 100% vs 95% of isolates in the azithromycin and clarithromycin groups, respectively. In AIECB, 100% of pathogens were eradicated by azithromycin, although one patient was clinically assessed as failed. Clarithromycin eradicated 93% of pathogens in this group; all patients being assessed as cured or improved. Both drugs were well tolerated, with 9% and 6% of patients reporting adverse events with azithromycin and clarithromycin, respectively. These adverse events were largely gastrointestinal in origin. It was concluded that a three-day course of azithromycin is as effective and well tolerated as a ten-day course of clarithromycin in adults with acute LRTIs.

  2. Efficacy of oral azithromycin versus topical tetracycline in mass treatment of endemic trachoma.

    PubMed Central

    Fraser-Hurt, N.; Bailey, R. L.; Cousens, S.; Mabey, D.; Faal, H.; Mabey, D. C.

    2001-01-01

    OBJECTIVE: To compare the impact of mass treatment with oral azithromycin and topical tetracycline on the prevalence of active trachoma. METHODS: A total of 1803 inhabitants from 106 households of eight Gambian villages were randomized, in pairs, to receive either three doses of azithromycin at weekly intervals, or daily topical tetracycline over 6 weeks. Ocular examinations were conducted before treatment, and 2, 6 and 12 months after treatment. FINDINGS: Prior to treatment, 16% of the study participants had active trachoma. Two months after treatment, the prevalence of trachoma was 4.6% and 5.1% in the azithromycin and the tetracycline groups, respectively (adjusted odds ratio (OR) = 1.09; 95% confidence interval (CI) = 0.53, 2.02). Subsequently, the prevalence rose to 16% in the tetracycline group, while remaining at 7.7% in the azithromycin group (adjusted OR at 12 months = 0.52; 95% CI = 0.34, 0.80). At 12 months post-treatment, there were fewer new prevalent cases in the azithromycin group, and trachoma resolution was significantly better for this group (adjusted OR = 2.02; 95% CI = 1.42, 3.50). CONCLUSION: Oral azithromycin therefore appears to offer a means for controlling blinding trachoma. It is easy to administer and higher coverages may be possible than have been achieved hitherto. PMID:11477966

  3. Household willingness to pay for azithromycin treatment for trachoma control in the United Republic of Tanzania.

    PubMed Central

    Frick, Kevin D.; Lynch, Matthew; West, Sheila; Munoz, Beatriz; Mkocha, Harran A.

    2003-01-01

    OBJECTIVE: Household willingness to pay for treatment provides important information for programme planning. We tested for relationships between socioeconomic status, risk of trachoma, perceptions of the effects of azithromycin, and the household willingness to pay for future mass treatment with azithromycin. METHODS: We surveyed 394 households in 6 villages located in central United Republic of Tanzania regarding their willingness to pay for future azithromycin treatment. A random sample of households with children under 8 years of age was selected and interviewed following an initial treatment programme in each village. Data were gathered on risk factors for trachoma, socioeconomic status, and the perceived effect of the initial azithromycin treatment. Ordered probit regression analysis was used to test for statistically significant relationships. FINDINGS: 38% of responding households stated that they would not be willing to pay anything for future azithromycin treatment, although they would be willing to participate in the treatment. A proxy for cash availability was positively associated with household willingness to pay for future antibiotic treatment. Cattle ownership (a risk factor) and being a household headed by a female not in a polygamous marriage (lower socioeconomic status) were associated with a lower willingness to pay for future treatment. A perceived benefit from the initial treatment was marginally associated with a willingness to pay a higher amount. CONCLUSIONS: As those at greatest risk of active trachoma indicated the lowest willingness to pay, imposing a cost recovery fee for azithromycin treatment would likely reduce coverage and could prevent control of the disease at the community level. PMID:12751418

  4. Novel Effects of Azithromycin on Tight Junction Proteins in Human Airway Epithelia

    PubMed Central

    Asgrimsson, Valthor; Gudjonsson, Thorarinn; Gudmundsson, Gudmundur Hrafn; Baldursson, Olafur

    2006-01-01

    The macrolide antibiotic azithromycin improves lung function and prognosis among patients with cystic fibrosis or diffuse panbronchiolitis, independently of bacterial eradication. Anti-inflammatory effects have been implicated, but data from in vivo studies are scarce, and the link between abnormal electrolyte content in airway surface liquid and bronchial infections remains uncertain. In the present study, we treated human airway epithelia on filter supports with azithromycin and monitored transepithelial electrical resistance. We found that azithromycin increased transepithelial electrical resistance of airway epithelia in a dose-dependent manner. Immunocytochemistry and Western blotting showed that addition of azithromycin changed the locations of proteins in cell cultures and induced processing of the tight junction proteins claudin-1 and claudin-4, occludin, and junctional adhesion molecule-A. These effects were reversible, and no effect was seen when cells were treated with penicillin or erythromycin. The data indicate that azithromycin increases the transepithelial electrical resistance of human airway epithelia by changing the processing of tight junction proteins. The results are novel and may help explain the beneficial effects of azithromycin in patients with cystic fibrosis, diffuse panbronchiolitis, and community-acquired pneumonia. PMID:16641453

  5. Effectiveness, tolerability and safety of azithromycin 1% in DuraSite® for acute bacterial conjunctivitis

    PubMed Central

    McLean, Susannah; Sheikh, Aziz

    2010-01-01

    Purpose: Bacterial eye infections are commonly treated with topical antibiotics, despite limited evidence of effectiveness. Azithromycin 1% in DuraSite® is a new formulation of azithromycin in a gel polymer designed for use in acute bacterial conjunctivitis. Methods: We conducted systematic searches of the Cochrane Database of Clinical Trials, PubMed and Google Scholar to find randomized controlled trials of “azithromycin DuraSite®”. These searches of published literature were supplemented with searches for unpublished trials and trials in progress. Results: We found six reports of randomized controlled trials investigating the role of azithromycin 1% in DuraSite® for the management of acute bacterial conjunctivitis. The quality of these trials was judged to be moderate to high. These trials assessed effectiveness, tolerability and safety outcomes, but we found no trials looking at cost-effectiveness. DuraSite® is a relatively stable formulation and so azithromycin 1% in DuraSite® has a simpler dosing schedule than other available topical antibiotics. It appears to be similar to other topical antibiotics in its effectiveness, but minor side effects are quite common. Conclusion: Acute bacterial conjunctivitis is a relatively mild, typically self-limiting, infection. Antibiotics should seldom be required. If, however, a decision to prescribe antibiotics is made, azithromycin 1% in DuraSite® is likely to be broadly comparable in its effectiveness to most other antibiotics used to treat acute bacterial conjunctivitis. Further research is needed to determine its cost-effectiveness. PMID:20517467

  6. Comparison of therapeutic effects of topical azithromycin solution and systemic doxycycline on posterior blepharitis

    PubMed Central

    Zandian, Mehdi; Rahimian, Neda; Soheilifar, Sanaz

    2016-01-01

    AIM To compare the effect of azithromycin drop and doxycycline capsule on treatment of posterior blepharitis. METHODS Fifty patients (100 eyes) with moderate posterior blepharitis, randomly divided into two therapeutic groups; all the patients got warm eyelid compress and massage three times a day for 3wk. In addition the first group got azithromycin 1% drop, twice daily for 1wk and then one drop daily for 2wk. The second group got oral doxycycline 100 mg daily for 3wk. At the end of the research, patients' signs and symptoms were compared together. ANOVA, Chi-square and Mann-Whitney tests were used for statistical analysis. RESULTS Topical therapy with azithromycin and oral therapy with doxycycline relieved signs and symptoms after 3wk. There were no significant differences between symptoms healing rate and foreign body sensation healing in these two groups (P>0.05). However, azithromycin drop was more effective in reduction of eye redness and doxycycline was more effective in meibomian glands plugging healing and reducing the corneal staining. CONCLUSION Topical azithromycin could have similar effects as oral doxycycline on posterior blepharitis in improving subjective symptoms. However, doxycycline can reduce objective signs such as ocular surface staining and meibomian gland plugging more than azithromycin. PMID:27500111

  7. Pharmacokinetics of a single 1g dose of azithromycin in rectal tissue in men

    PubMed Central

    Rupasinghe, Thusitha W.; Simpson, Julie A.; Vodstrcil, Lenka A.; Fairley, Christopher K.; McConville, Malcolm J.; Hocking, Jane S.

    2017-01-01

    Chlamydia is the most common bacterial sexually transmitted infection among men who have sex with men. Repeat infection following treatment with 1g azithromycin is common and treatment failure of up to 22% has been reported. This study measured the pharmacokinetics of azithromycin in rectal tissue in men following a single 1g dose to assess whether azithromycin reaches the rectal site in adequate concentrations to kill chlamydia. Ten healthy men took a single oral dose of 1g azithromycin and provided nine self-collected swabs and one blood sample over 14 days. Participant demographics, medications, sexual behaviour, treatment side effects, lubricant use and douching practices were recorded with each swab. Drug concentration over time was determined using liquid chromatography–mass spectrometry and total exposure (AUC0-∞) was estimated from the concentration-time profiles. Following 1g of azithromycin, rectal concentrations peaked after a median of 24 hours (median 133mcg/g) and remained above the minimum inhibitory concentration for chlamydia (0.125mcg/mL) for at least 14 days in all men. AUC0-∞ was the highest ever reported in human tissue (13103((mcg/g).hr)). Tissue concentrations were not associated with weight (mg/kg), but data suggest that increased gastric pH could increase azithromycin levels and diarrhoea or use of water-based lubricants could decrease concentrations. High and sustained concentrations of azithromycin were found in rectal tissue following a single 1g dose suggesting that inadequate concentrations are unlikely to cause treatment failure. Factors effecting absorption (pH and diarrhoea) or drug depletion (douching and water-based lubricants) may be more important determinants of concentrations in situ. PMID:28350806

  8. Once weekly azithromycin in secondary prevention of rheumatic fever.

    PubMed

    Gopal, Rakesh; Harikrishnan, S; Sivasankaran, S; Ajithkumar, V K; Titus, T; Tharakan, J M

    2012-01-01

    Rheumatic fever and rheumatic heart disease (RHD) are still important problems in developing countries. Secondary prophylaxis which is the most cost-effective method in preventing recurrences of rheumatic fever is fraught with problems of drug compliance. The utility of 500 mg once weekly azithromycin (AZT), an orally effective long-acting antibiotic was evaluated against oral penicillin (phenoxy methyl penicillin 250 mg twice daily) in this study. Forty-eight consecutive patients (44% males, mean age 29.4 years) with established RHD were randomised into two groups-26 patients received AZT and 22 received oral penicillin. Patients were evaluated at randomisation, at 1 month, 3 months, and 6 months, clinically, serologically and by throat swab culture. End points were absence of streptococcal colonisation, infection or fever at the end of 6 months. During the study, 4 patients (15.4%) in the AZT group developed sore throat and fever, had positive throat culture and positive serology indicating streptococcal infection. None satisfied the criteria for rheumatic fever reactivation. None in the oral penicillin group developed streptococcal infection. In conclusion, weekly 500 mg of AZT is not effective in the prevention of streptococcal throat infection compared to oral penicillin therapy in adult patients with established RHD.

  9. Antimicrobial susceptibility to azithromycin among Salmonella enterica Typhi and Paratyphi A isolates from India.

    PubMed

    Misra, Richa; Prasad, Kashi Nath

    2016-12-01

    Decreased ciprofloxacin susceptibility (DCS) and multidrug resistance in typhoidal Salmonella isolates in areas of endemicity are significant therapeutic problems. Guidelines for azithromycin disc diffusion and MIC interpretive criteria for Salmonella enterica serovar Typhi were published recently by the Clinical and Laboratory Standards Institute in 2015. We investigated the antimicrobial susceptibility pattern of azithromycin in 100 isolates of Salmonella Typhi (n=80), Paratyphi A (n=18) and B (n=2) recovered from bloodstream infections from January 2013 to December 2015. Zone sizes were extrapolated against MIC values, and a scatter plot was constructed. The azithromycin MICs by Etest ranged from 2 to 16 µg ml-1, while the disc diffusion diameters were from 13 to 22 mm. We observed that the margin of the zone of inhibition around the azithromycin disc may not be very clear and therefore difficult to interpret and that there was wide variation in the zone sizes for the same MIC value in both serovars. DCS was observed in 85 % of Salmonella Typhi recovered (68/80) and in 15/18 (83.3 %) Paratyphi A isolates. Judicious use of azithromycin is advocated as an alternative oral agent in endemic areas where DCS is common.

  10. Malaria prophylaxis using azithromycin: a double-blind, placebo-controlled trial in Irian Jaya, Indonesia.

    PubMed

    Taylor, W R; Richie, T L; Fryauff, D J; Picarima, H; Ohrt, C; Tang, D; Braitman, D; Murphy, G S; Widjaja, H; Tjitra, E; Ganjar, A; Jones, T R; Basri, H; Berman, J

    1999-01-01

    New drugs are needed for preventing drug-resistant Plasmodium falciparum malaria. The prophylactic efficacy of azithromycin against P. falciparum in malaria-immune Kenyans was 83%. We conducted a double-blind, placebo-controlled trial to determine the prophylactic efficacy of azithromycin against multidrug-resistant P. falciparum malaria and chloroquine-resistant Plasmodium vivax malaria in Indonesian adults with limited immunity. After radical cure therapy, 300 randomized subjects received azithromycin (148 subjects, 750-mg loading dose followed by 250 mg/d), placebo (77), or doxycycline (75, 100 mg/d). The end point was slide-proven parasitemia. There were 58 P. falciparum and 29 P. vivax prophylaxis failures over 20 weeks. Using incidence rates, the protective efficacy of azithromycin relative to placebo was 71.6% (95% confidence interval [CI], 50.3-83.8) against P. falciparum malaria and 98.9% (95% CI, 93.1-99.9) against P. vivax malaria. Corresponding figures for doxycycline were 96.3% (95% CI, 85.4-99.6) and 98% (95% CI, 88.0-99.9), respectively. Daily azithromycin offered excellent protection against P. vivax malaria but modest protection against P. falciparum malaria.

  11. In vitro and in vivo activities of azithromycin, a new azalide antibiotic, against chlamydia.

    PubMed Central

    Niki, Y; Kimura, M; Miyashita, N; Soejima, R

    1994-01-01

    The in vitro and in vivo activities of azithromycin against chlamydia were investigated. The MIC of azithromycin for five standard strains of different species of chlamydia and six wild-type strains of Chlamydia pneumoniae was 0.125 microgram/ml, which was superior to that of erythromycin but inferior to those of clarithromycin and minocycline. However, the therapeutic effect of a 7-day course of azithromycin at a dose of 10 mg/kg of body weight administered orally once daily to mice with experimental Chlamydia psittaci pneumonia was excellent, with a 100% survival rate at 14 days after infection, which was the same as that for treatment with minocycline administered at 10 mg/kg twice daily; all erythromycin treated animals died within 10 days. When treatment was discontinued 3 days after the infection, the survival rate for mice treated with azithromycin was 90% and that for mice administered minocycline was 30%. These results suggest that azithromycin may be useful in the treatment of respiratory infections caused by intracellular pathogens, including chlamydia because of its excellent accumulation within host cells. PMID:7840560

  12. Azithromycin-Nonsusceptible Shigella flexneri 3a in Men Who Have Sex with Men, Taiwan, 2015–2016

    PubMed Central

    Liao, Ying-Shu; Liu, Yen-Yi; Lo, Yi-Chun

    2017-01-01

    We report an outbreak of azithromycin-nonsusceptible Shigella flexneri 3a infection in Taiwan associated with men who have sex with men. The bacterial strains belonged to the sublineage A of a recently reported outbreak lineage associated with men who have sex with men, characterized by reduced azithromycin susceptibility and circulation in shigellosis low-risk regions. PMID:28098533

  13. Degradation studies of azithromycin and its spectrophotometric determination in pharmaceutical dosage forms.

    PubMed

    Sultana, Najma; Arayne, M Saeed; Hussain, Fida; Fatima, Aizaz

    2006-04-01

    A simple, accurate and rapid spectrophotometric method for the estimation of azithromycin has been developed by the acidic hydrolysis of the drug with sulfuric acid and monitoring the absorbance at 482 nm. All variables affecting the reaction conditions such as sulfuric acid concentration, heating time, temperature and dilution solvents were carefully studied. Analytical parameters such as stability, selectivity, accuracy and precision have been established for the method and evaluated statistically to assess the application of the method. The method was applied successfully for the assay of azithromycin dihydrate in pure and pharmaceutical dosage forms as tablets, capsules and suspensions. The method was found to have the advantages for simplicity, stability, sensitivity, reproducibility and accuracy for using as an alternate to the existing non-spectrophotometric methods for the routine analysis of the drug in pharmaceutical formulations and also in pharmaceutical investigations involving azithromycin dihydrate.

  14. Screening paediatric rectal forms of azithromycin as an alternative to oral or injectable treatment.

    PubMed

    Kauss, Tina; Gaudin, Karen; Gaubert, Alexandra; Ba, Boubakar; Tagliaferri, Serena; Fawaz, Fawaz; Fabre, Jean-Louis; Boiron, Jean-Michel; Lafarge, Xavier; White, Nicholas J; Olliaro, Piero L; Millet, Pascal

    2012-10-15

    The aim of this study was to identify a candidate formulation for further development of a home or near-home administrable paediatric rectal form of a broad-spectrum antibiotic - specially intended for (emergency) use in tropical rural settings, in particular for children who cannot take medications orally and far from health facilities where injectable treatments can be given. Azithromycin, a broad-spectrum macrolide used orally or intravenously for the treatment of respiratory tract, skin and soft tissue infections, was selected because of its pharmacokinetic and therapeutic properties. Azithromycin in vitro solubility and stability in physiologically relevant conditions were studied. Various pharmaceutical forms, i.e. rectal suspension, two different rectal gels, polyethylene glycol (PEG) suppository and hard gelatin capsule (HGC) were assessed for in vitro dissolution and in vivo bioavailability in the rabbit. Azithromycin PEG suppository appears to be a promising candidate.

  15. Pharmacokinetics and tissue tolerance of azithromycin after intramuscular administration to rabbits.

    PubMed

    Escudero, E; Fernández-Varón, E; Marín, P; Espuny, A; Nájera, M D; Cárceles, C M

    2006-12-01

    The pharmacokinetics of azithromycin after intravenous and intramuscular injection at a single dose rate of 10mg/kg bodyweight were investigated in rabbits by using a modified agar diffusion bioassay for determining plasma concentrations. The plasma creatine kinase activity was determined after i.m. administration for the evaluation of the tissue tolerance. The elimination half-lives of azithromycin after intravenous and intramuscular administration were 24.1 and 25.1h, respectively. After intramuscular administration mean peak plasma concentration was 0.26+/-0.01 mg/L and bioavailability was 97.7%. Plasma CK activity rose sharply within 8h after i.m. injection of azithromycin; activity returned to pre-treatment level by 48-72 h post-treatment. The transient rise in serum CK activity indicates some degree of muscle tissue damage at the injection site.

  16. Azithromycin buccal patch in treatment of chronic periodontitis

    PubMed Central

    Latif, Sajith Abdul; Vandana, K. L.; Thimmashetty, J.; Dalvi, Priyanka Jairaj

    2016-01-01

    Aim: This study aims to explore the clinical, microbiological, and biochemical impact of azithromycin (AZM) buccal patch in chronic generalized patients as a monotherapy as well as an adjunct to nonsurgical therapy. Materials and Methods: A parallel design was used forty periodontitis patients were randomly allocated into five groups, namely Group 1 scaling root planing (SRP) alone, Group 2 (SRP + AZM patch group), Group 3 (SRP + AZM tablet group), Group 4 (AZM patch monotherapy), and Group 5 (AZM tablet as monotherapy). Plaque index, gingival bleeding index, modified gingival index, probing pocket depth (PPD), and clinical attachment level (CAL) were assessed at baseline and 21 and 90 days. Subgingival pooled plaque sample was collected to assess periodontopathogens like Porphyromonas gingivalis and Prevotella intermedia (Pi) by anaerobic culture method. Tumor necrosis factor alpha (TNF-α) was also evaluated at baseline and 21 days. Periodontal maintenance was performed in Group 1 until 90th day, and clinical parameter was assessed at the end of 90th day. Results: SRP + AZM tablets showed greater reduction in clinical parameters (P < 0.05) AZM as monotherapy did not offer clinical benefits over SRP. Baseline data were compared at the end, i.e., 90th day a significant reduction in plaque scores, gingival bleeding, and PPD was observed however no significant gain in the clinical attachment was observed. Conclusion: The monotherapy resulted in no improvement of periodontal parameters, microbial parameters, and TNF-α level. It is safe to use AZM + SRP as a mode of nonsurgical treatment in periodontitis patients. PMID:27127325

  17. The activity of azithromycin against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis in the golden hamster model.

    PubMed

    Sinagra, Angel; Luna, Concepción; Abraham, David; Iannella, Maria del Carmen; Riarte, Adelina; Krolewiecki, Alejandro J

    2007-01-01

    New therapeutic alternatives against leishmaniasis remain a priority. The activity of azithromycin against Leishmania (Leishmania) major has been previously demonstrated. Different responses among species of Leishmania make species-specific drug screening necessary. The activity of azithromycin against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis was evaluated in golden hamsters infected through footpad injections of metacyclic promastigotes, and compared with untreated controls and animals treated with meglumine antimoniate. Footpad thickness, lesion cultures and dissemination sites were analyzed. Treatment of golden hamsters with oral azithromycin at 450mg/kg had no activity against infections with Leishmania (Leishmania) amazonensis. For infections due to Leishmania (Viannia) braziliensis, azithromycin demonstrated significant activity relative to untreated controls, but inferior to meglumine antimoniate, for controlling lesion size. Neither drug was able to totally eliminate parasites from the lesions. It was concluded that azithromycin has activity against Leishmania (Viannia) braziliensis but not against Leishmania (Leishmania) amazonensis in this model.

  18. Tolerability of 3-day, once-daily azithromycin suspension versus standard treatments for community-acquired paediatric infectious diseases.

    PubMed

    Treadway, G; Reisman, A

    2001-11-01

    Tolerability of azithromycin oral suspension, 10 mg/kg once daily for 3 days, was assessed in paediatric patients (< or = 18 years) with respiratory or skin and soft-tissue infections. Of 2425 patients evaluated, 1213 received azithromycin and 1212 received standard regimens of amoxycillin/clavulanic acid, cefaclor, cefixime, ceftriaxone, clarithromycin, erythromycin, or penicillin V. The incidence of treatment-related adverse events was significantly lower in patients receiving azithromycin than comparators (7.9 vs. 11.5%, P=0.003), while discontinuation rates were similar (1.0 and 1.1%, respectively). Significantly fewer gastrointestinal events were recorded for azithromycin than comparators (6.5 vs. 9.9%, P=0.002), and their duration was significantly shorter (mean 2.3 vs. 5.0 days, P=0.0001). Azithromycin paediatric oral suspension is well tolerated and associated with significantly fewer adverse events than comparators.

  19. Long-term azithromycin therapy in patients with severe COPD and repeated exacerbations

    PubMed Central

    Pomares, Xavier; Montón, Concepción; Espasa, Mateu; Casabon, Jordi; Monsó, Eduard; Gallego, Miguel

    2011-01-01

    Background The aim of this study was to determine whether long-term intermittent azithromycin therapy reduces the frequency of exacerbation in severe chronic obstructive pulmonary disease (COPD). Methods We retrospectively investigated the clinical benefits of long-term azithromycin (500 mg orally three times per week) over 12 months in patients with severe COPD and a minimum of four acute exacerbations (AECOPD) per year or chronic bronchial colonization by Pseudomonas aeruginosa, comparing the number of AECOPD, hospitalizations due to respiratory disease, days of hospital stay, and bacterial infections during azithromycin treatment and in the year prior to this therapy. Results Twenty patients who completed the 12-month treatment period were analyzed. No clinically significant adverse events were observed during azithromycin treatment. Compared with baseline data, azithromycin therapy significantly reduced the number of AECOPD (2.8 ± 2.5 versus 6.8 ± 2.8, P < 0.001), hospitalizations (1.4 ± 1.5 versus 3.6 ± 1.4, P < 0.001), and cumulative annual days of hospital stay (25 ± 32.2 versus 43.7 ± 21.4, P = 0.01). The improvement was particularly significant in patients with exacerbations caused by common potentially pathogenic microorganisms, who had 70% fewer AECOPD and hospitalizations. Patients colonized by P. aeruginosa had reductions of 43% in AECOPD and 47% in hospitalizations. Conclusion Long-term azithromycin is well tolerated and associated with significant reductions in AECOPD, hospitalizations, and length of hospital stay in patients with severe COPD. PMID:22003290

  20. Comparison between azithromycin and cefixime in the treatment of typhoid fever in children.

    PubMed

    Begum, B; Haque, M A; Ahmed, M S; Islam, M N; Ahsan, M M; Khan, A H; Hasan, M M; Akhtaruzzaman, M; Hossain, M A; Khaleque, M A; Choudhury, A M; Khatun, A A

    2014-07-01

    An intervention study was carried out in the department of paediatrics of Mymensingh Medical College Hospital, Mymensingh to compare the clinical efficacy of Azithromycin in the treatment of childhood typhoid fever with that of cefixime for a period of one year from January 2011 to December 2011. A total of 60 cases of typhoid fever were enrolled in to a randomized clinical trial and was divided into two groups. The inclusion criteria of the cases were: Documented fever for more than 4 days plus two or more of the following clinical features: toxic physical appearance, intestinal complaints, coated tongue, ceacal gurgling, hepatomegaly and splenomegaly, diarrhoea and constipation plus positive Widal test and/or blood culture positivity. Patients who had complication like GIT heamorrhage; intestinal perforaion and/or shock were excluded from the study. Data were collected in a structured questionnaire. Azithromycin was given at a dose of 10mg/kg/day for a period of 07 days Cefixime was given at a dose of 20mg/kg/day in two divided dose for 14 days. The mean time of defervesence was 4.05+1.14 days with azithromycin and 3.41+0.95 with cefixime respectively. The minimum defervesence time was 02 days and maximum defervesence time was 07 days. Clinical cure rate was 87% in azithromycin group and 93% in cefixime group. No serious adverse effect was noted related to azithromycin and cefixime therapy except nausea, vomiting, diarrhoea and jaundice. It was found that azithromycin is almost as effective as cefixime in the treatment of typhoid fever.

  1. Efficacy of short-term treatment of pertussis with clarithromycin and azithromycin.

    PubMed

    Aoyama, T; Sunakawa, K; Iwata, S; Takeuchi, Y; Fujii, R

    1996-11-01

    The recommended treatment for pertussis is erythromycin, 40 to 50 mg/kg per day for 2 weeks. The newly developed macrolides, clarithromycin and azithromycin, have been demonstrated to be superior to erythromycin because of improved absorption and a longer half-life. As a result, we conducted two separate comparison studies to evaluate the efficacies of clarithromycin, 10 mg/kg per day, twice a day for 7 days, and azithromycin, 10 mg/kg per day, once a day for 5 days, compared with the standard erythromycin regimen. A total of 17 patients, including 10 infants 1 year of age or less, for whom pertussis had been confirmed by culture, were allocated to receive either clarithromycin or azithromycin treatment, and each patient was matched (age, sex, and immunization status) with historical control subjects who had been treated with erythromycin. Eradication rates examined at 1 week after treatment were as follows: 9 of 9 with clarithromycin versus 16 of 18 with erythromycin (psi M-H = 1.13), and 8 of 8 with azithromycin versus 13 of 16 with erythromycin (psi M-H = 1.23). No bacterial relapse after treatment was detected in either group. All isolated strains of Bordetella pertussis were susceptible to clarithromycin, azithromycin, and erythromycin, and no change in drug susceptibility has been confirmed for the past 20 years in Japan. Because of the very low incidence of pertussis resulting from widespread use of acellular pertussis vaccination, this study did not enroll a large number of patients; however we conclude that short-term treatment with clarithromycin or azithromycin is expected to be equal or superior to the standard long-term erythromycin regimen for pertussis.

  2. Pilot study of the use of community volunteers to distribute azithromycin for trachoma control in Ghana.

    PubMed Central

    Solomon, A. W.; Akudibillah, J.; Abugri, P.; Hagan, M.; Foster, A.; Bailey, R. L.; Mabey, D. C.

    2001-01-01

    OBJECTIVE: To assess the skills of community health volunteers in diagnosing active trachoma and distributing azithromycin in the Northern Region of Ghana. METHODS: Six community health volunteers from Daboya were trained to diagnose trachoma and to treat the disease using azithromycin. They were also informed of the drug's possible side-effects. Under supervision, each volunteer then examined, and if necessary treated, 15 households. The dose of azithromycin was determined by weight; height was also measured. Tablets were given in preference to suspension when possible. RESULTS: The volunteers' diagnostic sensitivity for active trachoma was 63%; their specificity was 96%. At the household level, their "decision to treat" was correct in 83% of households. In 344 treatment episodes, volunteers planned a dose of azithromycin outside the range 15-30 mg/kg on only seven occasions (2.0% of all planned treatments). The volunteers' drug management skills were good, the response of the community was excellent, and adverse reactions were infrequent. Diagnosis of active trachoma, record-keeping skills, and knowledge of side-effects were found to need greater emphasis in any future education programme. Most people aged four years or older were able to swallow tablets. For those taking tablets, the correlation between the data gathered for height and weight shows that calculating azithromycin doses by height is a valid alternative to calculating it by weight. CONCLUSION: Trained community health volunteers have a potential role in identifying active trachoma and distributing azithromycin. To simplify training and logistics, it may be better to base dosage schedules on height rather than weight for those taking tablets, which included most people aged four years or more in the population studied. PMID:11217675

  3. Association of azithromycin with mortality and cardiovascular events among older patients hospitalized with pneumonia

    PubMed Central

    Mortensen, Eric M.; Halm, Ethan A.; Pugh, Mary Jo; Copeland, Laurel A.; Metersky, Mark; Fine, Michael J.; Johnson, Christopher S.; Alvarez, Carlos A.; Frei, Christopher R.; Good, Chester; Restrepo, Marcos I.; Downs, John R.; Anzueto, Antonio

    2014-01-01

    Importance Although clinical practice guidelines recommend combination therapy with macrolides, including azithromycin, as first line therapy for patients hospitalized with pneumonia, recent research suggests that azithromycin may be associated with increased cardiovascular events. Objective The purpose of this study was to examine the association of azithromycin use with all-cause mortality and cardiovascular events for patients hospitalized with pneumonia. Design Retrospective, cohort study comparing older patients hospitalized with pneumonia between fiscal years 2002–2012 prescribed azithromycin therapy and patients receiving other guideline-concordant antibiotic therapy Setting This study was conducted using national Department of Veterans Affairs administrative data of patients hospitalized at any Veterans Administration acute care hospital. Participants Patients were included if they were ≥65 years of age hospitalized with pneumonia and received antibiotic therapy concordant with national clinical practice guidelines. Main Outcome Measures Outcomes included 30 and 90-day all-cause mortality, and 90-day cardiac arrhythmias, heart failure, myocardial infarction, and any cardiac event. Propensity score matching was used to control for the possible effects of known confounders with conditional logistic regression. Results Out of the 73,690 patients from 118 hospitals identified, propensity-matched groups were composed of 31,863 azithromycin-exposed and 31,863 matched unexposed. There were no significant differences in potential confounders between groups after matching. 90-day mortality was significantly lower in those who received azithromycin (exposed- 17.4% vs. unexposed- 22.3%, odds ratio [OR] 0.73, 95% confidence interval [CI] 0.70–0.76). However, we found significant increased odds of myocardial infarctions (5.1% vs. 4.4%, OR 1.17, 95% CI 1.08–1.25) but not any cardiac event (43.0% vs. 42.7%, OR 1.01, 95% CI 0.98–1.05), cardiac arrhythmias (25

  4. Effects of azithromycin on ozone-induced airway neutrophilia and cytokine release.

    PubMed

    Criqui, G I; Solomon, C; Welch, B S; Ferrando, R E; Boushey, H A; Balmes, J R

    2000-05-01

    Exposure of humans to ozone causes increased neutrophils and inflammatory cytokines in airway lining fluid. Recent research shows that macrolide antibiotics may reduce interleukin (IL)-8 production by bronchial epithelial cells and inhibit neutrophil chemotaxis. A double-blind, cross-over study was performed in which 12 healthy subjects underwent two separate 4-h exposures to 0.2 parts per million ozone while exercising intermittently. In the 73.5 h before exposure, subjects were pretreated with either 1,250 mg azithromycin or placebo. Sputum induction conducted 74 h pre- and 18 h post-exposure was used to measure total cells, per cent neutrophils, IL-6, and IL-8. There were significant (p<0.05) pre- to post-exposure increases in total cells, neutrophils, IL-6 and IL-8 in both the azithromycin and placebo arms. However, no significant differences were found between azithromycin and placebo conditions in the post- minus pre-exposure value for these variables. The results suggest that in healthy subjects, in the design used, azithromycin, in usual clinical doses, does not have anti-inflammatory effects on human airways as indicated in the measured variables.

  5. Antimicrobial susceptibility to azithromycin among Salmonella enterica isolated from the United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Due to emerging resistance to traditional antimicrobial agents such as ampicillin, trimethoprim-sulfamethoxazole and chloramphenicol, azithromycin is increasingly used for the treatment of invasive Salmonella infections. In the present study, 696 isolates of non-Typhi Salmonella collected from human...

  6. Clarithromycin versus azithromycin in the treatment of Mediterranean spotted fever in children: a randomized controlled trial.

    PubMed

    Cascio, Antonio; Colomba, Claudia; Antinori, Spinello; Paterson, David L; Titone, Lucina

    2002-01-15

    We conducted an open-label randomized controlled trial to compare the efficacy and safety of clarithromycin (15/mg/kg/day in 2 divided doses for 7 days) with those of azithromycin (10 mg/kg/day in 1 dose for 3 days) in the treatment of children with Mediterranean spotted fever. Until now, there has not been a gold-standard therapy for this rickettsial disease in children. Eighty-seven children were randomized to receive 1 of the 2 drugs. The mean time to defervescence (+/- standard deviation) was 46.2+/-36.4 h in the clarithromycin group and 39.3+/-31.3 h in the azithromycin group. These differences were not statistically significant and both drugs were equally well-tolerated. Clarithromycin and azithromycin could be acceptable therapeutic alternatives to chloramphenicol and tetracyclines for children aged < or =8 years with Mediterranean spotted fever. Azithromycin, because it has a long half-life, offers the advantages of administration in a single daily dose and a shorter duration of therapy, which could increase compliance in children.

  7. Azithromycin and erythromycin ameliorate the extent of colonic damage induced by acetic acid in rats

    SciTech Connect

    Mahgoub, Afaf . E-mail: afaf_mahgoub@yahoo.com; El-Medany, Azza; Mustafa, Ali; Arafah, Maha; Moursi, Mahmoud

    2005-05-15

    Ulcerative colitis is a common inflammatory bowel disease (IBD) of unknown etiology. Recent studies have revealed the role of some microorganisms in the initiation and perpetuation of IBD. The role of antibiotics in the possible modulation of colon inflammation is still uncertain. In this study, we evaluated the effects of two macrolides, namely azithromycin and erythromycin, at different doses on the extent and severity of ulcerative colitis caused by intracolonic administration of 3% acetic acid in rats. The lesions and the inflammatory response were assessed by histology and measurement of myeloperoxidase (MPO) activity, nitric oxide synthetase (NOS) and tumor necrosis factor alpha (TNF{alpha}) in colonic tissues. Inflammation following acetic acid instillation was characterized by oedema, diffuse inflammatory cell infiltration and necrosis. Increase in MPO, NOS and TNF{alpha} was detected in the colonic tissues. Administration of either azithromycin or erythromycin at different dosage (10, 20 and 40 mg/kg orally, daily for 5 consecutive days) significantly (P < 0.05) reduced the colonic damage, MPO and NOS activities as well as TNF{alpha} level. This reduction was highly significant with azithromycin when given at a dose of 40 mg/kg. It is concluded that azithromycin and erythromycin may have a beneficial therapeutic role in ulcerative colitis.

  8. Single-dose intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime in volunteer subjects.

    PubMed Central

    Conte, J E; Golden, J; Duncan, S; McKenna, E; Lin, E; Zurlinden, E

    1996-01-01

    The intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime were studied in 68 volunteers who received single, oral doses of azithromycin (0.5 g), clarithormycin (0.5 g), ciprofloxacin (0.5 g), or cefuroxime (0.5 g). In subgroups of four subjects each, the subjects underwent bronchoscopy and bronchoalveolar lavage at timed intervals following drug administration. Drug concentrations, including those of 14-hydroxyclarithromycin (14H), were determined in serum, bronchoalveolar lavage fluid, and alveolar cells (ACs) by high-pressure liquid chromatography. Concentrations in epithelial lining fluid (ELF) were calculated by the urea diffusion method. The maximum observed concentrations (mean +/- standard deviation) of azithromycin, clarithromycin, 14H, ciprofloxacin, and cefuroxime in serum were 0.13 +/- 0.07, 1.0 +/- 0.6, 0.60 +/- 0.41, 0.95 +/- 0.32, and 1.1 +/- 0.3 microgram/ml, respectively (all at 6 h). None of the antibiotics except clarithromycin (39.6 +/- 41.1 micrograms/ml) was detectable in ELF at the 6-h bronchoscopy. The movement into and persistence in cells was different for azithromycin and clarithromycin. In ACs azithromycin was not detectable at 6 h, reached its highest concentration at 120 h, and exhibited the greatest area under the curve (7,403 micrograms.hr ml-1). The peak concentration of clarithromycin (181 +/- 94.1 micrograms/ml) was greater and occurred earlier (6 h), but the area under the curve (2,006 micrograms.hr ml-1) was less than that observed for azithromycin. 14H was detectable in ACs at 6 h (40.3 +/- 5.2 micrograms/ml) and 12 h (32.8 +/- 57.2 micrograms/ml). The peak concentration of ciprofloxacin occurred at 6 h (4.3 +/- 5.2 micrograms/ml), and the area under the curve was 35.0 micrograms.hr ml-1. The data indicate that after the administration of a single dose, azithromycin, clarithromycin, and ciprofloxacin penetrated into ACs in therapeutic concentrations and that only clarithromycin was

  9. Pharmacokinetics of azithromycin after i.v. and i.m. administration to sheep.

    PubMed

    Cárceles, C M; Font, A; Escudero, E; Espuny, A; Marín, P; Fernández-Varón, E

    2005-10-01

    The pharmacokinetics (PK) of azithromycin after i.v. and i.m. injection at a single dosage of 20 mg/kg bodyweight was studied in sheep. Blood samples were collected from the jugular vein until 120 h after dosing for both routes. Plasma concentrations of azithromycin were determined by bioassay. The plasma concentration-time data of azithromycin best fitted a three-compartment model after i.v. administration and a two-compartment model with first-order absorption after i.m. administration. The elimination half-life (t(1/2lambdaz)) was 47.70 +/- 7.49 h after i.v. administration and 61.29 +/- 13.86 h after i.m. administration. Clearance value after i.v. dosing was 0.52 +/- 0.08 L/kg.h. After i.m. administration a peak azithromycin concentration (C(max)) of 1.26 +/- 0.19 mg/L was achieved at 1.24 +/- 0.31 h (t(max)). Area under the curve (AUC) were 38.85 +/- 5.83 mg.h/L and 36.03 +/- 1.52 mg.h/L after i.v. and i.m. administration respectively. Bioavailability obtained after i.m. administration was 94.08 +/- 11.56%. The high tolerability of this i.m. preparation and the favourable PK behaviour such as the long half-life and high bioavailability make azithromycin likely to be effective in sheep.

  10. Revisit of fluoroquinolone and azithromycin susceptibility breakpoints for Salmonella enterica serovar Typhi.

    PubMed

    Das, Surojit; Ray, Ujjwayini; Dutta, Shanta

    2016-07-01

    In recent years, increase in occurrence of fluoroquinolone (FQ)-resistant S almonella Typhi isolates has caused considerable inconvenience in selecting appropriate antimicrobials for treatment of typhoid. The World Health Organization (WHO) recommends azithromycin for the empirical treatment option of uncomplicated typhoid. The CLSI updated the breakpoints of disc diffusion (DD) and MIC results of FQs and azithromycin for Salmonella Typhi in 2015, but DD breakpoints of ofloxacin and levofloxacin were not included. In this study, the inhibition zone diameters and MICs of nalidixic acid, ciprofloxacin, ofloxacin, levofloxacin and azithromycin were determined in Salmonella Typhi Kolkata isolates (n =146) over a 16-year period (1998 to 2013) and the data were compared with the available CLSI breakpoints. Very major error and major error (ME) of FQs were not observed in the study isolates, but the minor error of ciprofloxacin (15.8 %) and ME of azithromycin (3.5 %) exceeded the acceptable limit. A positive correlation between MICs of FQ and mutations in the quinolone-resistance-determining region (QRDR) showed the reliability of MIC results to determine FQ susceptibility of Salmonella Typhi (n =74). Isolates showing decreased ciprofloxacin susceptibility (MIC 0.125-0.5 µg  ml-1) were likely to have at least one mutation in the QRDR region. The results on DD breakpoints of ofloxacin (resistant, ≤15 mm; intermediate, 16-24 mm, and susceptible, ≥25 mm) and levofloxacin (resistant, ≤18 mm; intermediate, 19-27 mm, and susceptible, ≥28 mm) corroborated those of earlier studies. In view of the emerging FQ- and azithromycin-resistant Salmonella Typhi isolates, DD and MIC breakpoints of those antimicrobials should be revisited routinely.

  11. Three month treatment of reactive arthritis with azithromycin: a EULAR double blind, placebo controlled study

    PubMed Central

    Kvien, T; Gaston, J; Bardin, T; Butrimiene, I; Dijkmans, B; Leirisalo-Repo, M; Solakov, P; Altwegg, M; Mowinckel, P; Plan, P; Vischer, T

    2004-01-01

    Objective: To determine the efficacy of weekly treatment with oral azithromycin for 13 weeks on the severity and resolution of reactive arthritis (ReA). Methods: 186 patients from 12 countries were enrolled in a randomised, double blind, placebo controlled trial. Inclusion criteria were inflammatory arthritis of ⩽6 swollen joints, and disease duration of ⩽2 months. All patients received a single azithromycin dose (1 g) as conventional treatment for possible Chlamydia infection, and were then randomly allocated to receive weekly azithromycin or placebo. Clinical assessments were made at 4 week intervals for 24 weeks. Results: 152 patients were analysable (34 failed entry criteria), with a mean (SD) age of 33.8 (9.4) and duration of symptoms 30.7 (17.5) days. Mean C reactive protein (CRP) was 48 mg/l, and ∼50% of those typed were HLA-B27+, suggesting that the inclusion criteria successfully recruited patients with acute ReA. Treatment and placebo groups were well matched for baseline characteristics. There were no statistical differences for changes in any end point (swollen and tender joint count, joint pain, back pain, heel pain, physician and patient global assessments, and CRP) between the active treatment and placebo groups, analysed on an intention to treat basis or according to protocol completion. The time to resolution of arthritis and other symptoms or signs by life table analyses was also not significantly different. Adverse events were generally mild, but were more commonly reported in the azithromycin group. Conclusions: This large trial has demonstrated that prolonged treatment with azithromycin is ineffective in ReA. PMID:15308521

  12. In Vitro and In Vivo Antimicrobial Activities of Minocycline in Combination with Azithromycin, Clarithromycin, or Tigecycline against Pythium insidiosum

    PubMed Central

    Jesus, Francielli P. K.; Loreto, Érico S.; Ferreiro, Laerte; Driemeier, David; Souza, Suyene O.; França, Raqueli T.; Lopes, Sonia T. A.; Pilotto, Maiara B.; Ludwig, Aline; Azevedo, Maria I.; Ribeiro, Tatiana C.; Tondolo, Juliana S. M.

    2015-01-01

    The present study investigated the in vitro and the in vivo interactions among azithromycin, clarithromycin, minocycline, and tigecycline against Pythium insidiosum. In vitro antimicrobial activities were determined by the broth microdilution method in accordance with CLSI document M38-A2, and the antibiotic interactions were assayed using the checkerboard MIC format. In vivo efficacy was determined using a rabbit infection model. The geometric mean MICs of azithromycin, clarithromycin, minocycline, and tigecycline against P. insidiosum were, respectively, 1.91, 1.38, 0.91, and 0.79 μg/ml. By checkerboard testing, all combinations resulted in in vitro synergistic interactions (>60%). Antagonism was not observed. The in vivo studies showed that azithromycin (20 mg/kg/day twice daily) alone or in combination with minocycline (10 mg/kg/day twice daily) significantly decreased the fungal burden. This study demonstrates that azithromycin possesses potent curative efficacy against subcutaneous pythiosis in the rabbit model. PMID:26459895

  13. In Vitro and In Vivo Antimicrobial Activities of Minocycline in Combination with Azithromycin, Clarithromycin, or Tigecycline against Pythium insidiosum.

    PubMed

    Jesus, Francielli P K; Loreto, Érico S; Ferreiro, Laerte; Alves, Sydney H; Driemeier, David; Souza, Suyene O; França, Raqueli T; Lopes, Sonia T A; Pilotto, Maiara B; Ludwig, Aline; Azevedo, Maria I; Ribeiro, Tatiana C; Tondolo, Juliana S M; Santurio, Janio M

    2015-10-12

    The present study investigated the in vitro and the in vivo interactions among azithromycin, clarithromycin, minocycline, and tigecycline against Pythium insidiosum. In vitro antimicrobial activities were determined by the broth microdilution method in accordance with CLSI document M38-A2, and the antibiotic interactions were assayed using the checkerboard MIC format. In vivo efficacy was determined using a rabbit infection model. The geometric mean MICs of azithromycin, clarithromycin, minocycline, and tigecycline against P. insidiosum were, respectively, 1.91, 1.38, 0.91, and 0.79 μg/ml. By checkerboard testing, all combinations resulted in in vitro synergistic interactions (>60%). Antagonism was not observed. The in vivo studies showed that azithromycin (20 mg/kg/day twice daily) alone or in combination with minocycline (10 mg/kg/day twice daily) significantly decreased the fungal burden. This study demonstrates that azithromycin possesses potent curative efficacy against subcutaneous pythiosis in the rabbit model.

  14. Sub-MICs of Azithromycin Decrease Biofilm Formation of Streptococcus suis and Increase Capsular Polysaccharide Content of S. suis

    PubMed Central

    Yang, Yan-Bei; Chen, Jian-Qing; Zhao, Yu-Lin; Bai, Jing-Wen; Ding, Wen-Ya; Zhou, Yong-Hui; Chen, Xue-Ying; Liu, Di; Li, Yan-Hua

    2016-01-01

    Streptococcus suis (S. suis) caused serious disease symptoms in humans and pigs. S. suis is able to form thick biofilms and this increases the difficulty of treatment. After growth with 1/2 minimal inhibitory concentration (MIC) of azithromycin, 1/4 MIC of azithromycin, or 1/8 MIC of azithromycin, biofilm formation of S. suis dose-dependently decreased in the present study. Furthermore, scanning electron microscopy analysis revealed the obvious effect of azithromycin against biofilm formation of S. suis. Especially, at two different conditions (1/2 MIC of azithromycin non-treated cells and treated cells), we carried out comparative proteomic analyses of cells by using iTRAQ technology. Finally, the results revealed the existence of 19 proteins of varying amounts. Interestingly, several cell surface proteins (such as ATP-binding cassette superfamily ATP-binding cassette transporter (G7SD52), CpsR (K0FG35), Cps1/2H (G8DTL7), CPS16F (E9NQ13), putative uncharacterized protein (G7SER0), NADP-dependent glyceraldehyde-3-phosphate dehydrogenase (G5L259), putative uncharacterized protein (G7S2D6), amino acid permease (B0M0G6), and NsuB (G5L351)) were found to be implicated in biofilm formation. More importantly, we also found that azithromycin affected expression of the genes cps1/2H, cpsR and cps16F. Especially, after growth with 1/2 MIC of azithromycin and 1/4 MIC of azithromycin, the capsular polysaccharide content of S. suis was significantly higher. PMID:27812354

  15. Comparison of Azithromycin and Amoxicillin Prior to Dental Implant Placement: An Exploratory Study of Bioavailability and Resolution of Postoperative Inflammation

    PubMed Central

    Escalante, Mariana Gil; Eubank, Tim D.; Leblebicioglu, Binnaz; Walters, John D.

    2015-01-01

    Background Studies suggest that a single prophylactic dose of amoxicillin reduces early implant complications, but it is unclear whether other antibiotics are also effective. This study compared the local antimicrobial and anti-inflammatory effects resulting from a single dose of azithromycin or amoxicillin prior to surgical placement of one-stage dental implants. Methods Healthy adult patients requiring one-stage dental implant placement were randomly allocated to receive either 2g amoxicillin (n=7) or 500mg azithromycin (n=6) prior to surgery. Peri-implant crevicular fluid (PICF) samples from the new implant and gingival crevicular fluid (GCF) from adjacent teeth were sampled on postoperative days 6, 13 and 20. Inflammatory mediators in the samples were analyzed by immunoassay and antibiotic levels were measured by bioassay. Results On day 6, azithromycin concentrations in GCF and PICF were 3.39±0.73μg/ml and 2.77±0.90μg/ml, respectively, while amoxicillin was below the limit of detection. During early healing, patents in the azithromycin group exhibited a significantly greater decrease in GCF volume (p=0.03, ANOVA). At specific times during healing, the azithromycin group exhibited significantly lower levels of IL-6 and IL-8 in GCF than the amoxicillin group and exhibited significantly lower levels of G-CSF, IL-8, MIP-1β and IP-10 in PICF. Conclusions Azithromycin was available at the surgical site for a longer period of time than amoxicillin, and patients taking azithromycin exhibited lower levels of specific pro-inflammatory cytokines and chemokines in GCF and PICF. Thus, preoperative azithromycin may enhance resolution of postoperative inflammation to a greater extent than amoxicillin. PMID:26252749

  16. Comparison of two azithromycin distribution strategies for controlling trachoma in Nepal.

    PubMed Central

    Holm, S. O.; Jha, H. C.; Bhatta, R. C.; Chaudhary, J. S.; Thapa, B. B.; Davis, D.; Pokhrel, R. P.; Yinghui, M.; Zegans, M.; Schachter, J.; Frick, K. D.; Tapert, L.; Lietman, T. M.

    2001-01-01

    OBJECTIVE: The study compares the effectiveness of two strategies for distributing azithromycin in an area with mild-to-moderate active trachoma in Nepal. METHODS: The two strategies investigated were the use of azithromycin for 1) mass treatment of all children, or 2) targeted treatment of only those children who were found to be clinically active, as well as all members of their household. FINDINGS: Mass treatment of children was slightly more effective in terms of decreasing the prevalence of clinically active trachoma (estimated by clinical examination) and of chlamydial infection (estimated by DNA amplification tests), although neither result was statistically significant. CONCLUSION: Both strategies appeared to be effective in reducing the prevalence of clinically active trachoma and infection six months after the treatment. Antibiotic treatment reduced the prevalence of chlamydial infection more than it did the level of clinically active trachoma. PMID:11285662

  17. Restoration of Chloride Efflux by Azithromycin in Airway Epithelial Cells of Cystic Fibrosis Patients▿

    PubMed Central

    Saint-Criq, Vinciane; Rebeyrol, Carine; Ruffin, Manon; Roque, Telma; Guillot, Loïc; Jacquot, Jacky; Clement, Annick; Tabary, Olivier

    2011-01-01

    Azithromycin (AZM) has shown promising anti-inflammatory properties in chronic obstructive pulmonary diseases, and clinical studies have presented an improvement in the respiratory condition of cystic fibrosis (CF) patients. The aim of this study was to investigate, in human airway cells, the mechanism by which AZM has beneficial effects in CF. We demonstrated that AZM did not have any anti-inflammatory effect on CF airway cells but restored Cl− efflux. PMID:21220528

  18. The HPLC assay of concentration of azithromycin from two different manufacturers in gingival crevicular fluid (GCF)

    PubMed Central

    Khosravi-Samani, Mahmoud; Dehshiri, Khashayar; Kazemi, Sohrab; Shiran, Mohamadreza; Mohgadamnia, Ali-Akbar

    2016-01-01

    Background: Azithromycin (AZM) is used in periodontal infections. The present study compared gingival crevicular fluid concentration of azithromycin of two pharmaceutical companies through the HPLC method. Methods: Two groups (n=15) of healthy volunteers participated in this study. The first group received an imported azithromycin (ImAZM) tablet (250 mg, PO) and the second group received an azithromycin tablet (250 mg PO) manufactured by an Iranian pharmaceutical company (IrAZM). Intrasulcular paper points (#30) were used in inter-proximal areas of molars and canines to collect gingival crevicular fluid samples at 6, 12, 36, 84 and 156 hours after drug administration. Results: The maximum concentration of AZM in gingival crevicular fluid was detected in each group 36 hour after administration. The concentration levels for the participants receiving ImAZM and IrAZM were 14.38±5.75 and 12.64±3.53 ng/mL, respectively. The pharmacokinetic (PK) modeling data showed half-life of AZM was 107.47 hr & 91.42 hr while the clearance was 113.02 hr &119.0 hr for the group receiving ImAZM and IrAZM, respectively. No significant differences were observed in other PK parameters, areas under the concentration time curves for the groups were almost identical. Conclusion: According to the results, there were no significant differences between the PK parameters of ImAZM and IrAZM products. It may be concluded that different doses of AZM have relatively similar PK parameters among the healthy participants. PMID:27999643

  19. Higher organism load associated with failure of azithromycin to treat rectal chlamydia.

    PubMed

    Kong, F Y S; Tabrizi, S N; Fairley, C K; Phillips, S; Fehler, G; Law, M; Vodstrcil, L A; Chen, M; Bradshaw, C S; Hocking, J S

    2016-09-01

    Repeat rectal chlamydia infection is common in men who have sex with men (MSM) following treatment with 1 g azithromycin. This study describes the association between organism load and repeat rectal chlamydia infection, genovar distribution, and efficacy of azithromycin in asymptomatic MSM. Stored rectal chlamydia-positive samples from MSM were analysed for organism load and genotyped to assist differentiation between reinfection and treatment failure. Included men had follow-up tests within 100 days of index infection. Lymphogranuloma venereum and proctitis diagnosed symptomatically were excluded. Factors associated with repeat infection, treatment failure and reinfection were investigated. In total, 227 MSM were included - 64 with repeat infections [28·2%, 95% confidence interval (CI) 22·4-34·5]. Repeat positivity was associated with increased pre-treatment organism load [odds ratio (OR) 1·7, 95% CI 1·4-2·2]. Of 64 repeat infections, 29 (12·8%, 95% CI 8·7-17·8) were treatment failures and 35 (15·4%, 95% CI 11·0-20·8) were reinfections, 11 (17·2%, 95% CI 8·9-28·7) of which were definite reinfections. Treatment failure and reinfection were both associated with increased load (OR 2·0, 95% CI 1·4-2·7 and 1·6, 95% CI 1·2-2·2, respectively). The most prevalent genovars were G, D and J. Treatment efficacy for 1 g azithromycin was 83·6% (95% CI 77·2-88·8). Repeat positivity was associated with high pre-treatment organism load. Randomized controlled trials are urgently needed to evaluate azithromycin's efficacy and whether extended doses can overcome rectal infections with high organism load.

  20. Review of Azithromycin Ophthalmic 1% Solution (AzaSite®) for the Treatment of Ocular Infections

    PubMed Central

    Opitz, Dominick L.; Harthan, Jennifer S.

    2012-01-01

    AzaSite® (azithromomycin 1.0%) ophthalmic solution was approved in 2007 by the US Food and Drug Administration (FDA) as the first commercially available formulation of ophthalmic azithromycin for the treatment of bacterial conjunctivitis. AzaSite® utilizes a vehicle delivery system called DuraSite®, which stabilizes and sustains the release of azithromycin to the ocular surface, leading to a longer drug residence time, less frequent dosing, and an increase in patient compliance. AzaSite® is a broad spectrum antibiotic, effective against Gram-positive, Gram-negative, and atypical bacteria. AzaSite® has been studied for the treatment of ocular conditions beyond its clinical indication. A number of clinical studies have evaluated its efficacy and safety in the management of ocular conditions such as bacterial conjunctivitis and blepharitis on both the pediatric and adult populations. This article aims to evaluate the peer-reviewed published literature on the use of azithromycin 1.0% ophthalmic for current and possible future ophthalmic uses. PMID:23650453

  1. Azithromycin for the treatment of eosinophilic nasal polyposis: Clinical and histologic analysis

    PubMed Central

    Borges Crosara, Paulo Fernando Tormin; Cassali, Geovanni Dantas; dos Reis, Diego Carlos; Rodrigues, Danilo Santana; Nunes, Flavio Barbosa; Guimarães, Roberto Eustáquio Santos

    2016-01-01

    Introduction: Macrolides used as immunomodulators are a promising tool for chronic inflammatory airway diseases. Eosinophilic nasal polyposis (ENP) is still considered a disease that is difficult to control with the currently standardized treatments. Objectives: To evaluate prolonged treatment with low-dose azithromycin for ENP based on clinical and histopathologic variables. Methods: The present investigation was a self-paired case study of 33 patients with ENP. A comparison was performed between patients before and after treatment with azithromycin for 8 weeks. The patients were subjected to clinical examinations, staging (three-dimensional imaging by endoscopy), application of the questionnaire, and biopsy of nasal polyps at the beginning and at the end of the treatment. Results: The treatment yielded a clinical improvement regarding the two variables studied: polyposis staging (69.7%) and questionnaire (57.6%). We did not find significant differences in the inflammatory pattern and in the percentage or absolute number of eosinophils per field between samples obtained before and after the treatment (p > 0.05). There was no difference between the answers obtained from groups with and without asthma and/or aspirin intolerance (p > 0.3). The patients with advanced initial staging exhibited lower subjective improvement index and staging reduction (p = 0.031 and p = 0.012, respectively). Conclusion: Based on this study, azithromycin may be considered as another therapeutic option for ENP. However, further studies are necessary to define the real mechanism of action involved. PMID:27465667

  2. Efficacy of a three day course of azithromycin in moderately severe community-acquired pneumonia.

    PubMed

    Rizzato, G; Montemurro, L; Fraioli, P; Montanari, G; Fanti, D; Pozzoli, R; Magliano, E

    1995-03-01

    This study was designed to evaluate the efficacy of a 3 day course of azithromycin in low to moderately severe community-acquired pneumonia. Forty patients with low to moderately severe community-acquired pneumonia (29 males, 11 females, mean age 46 +/- 17 yrs; 20 pretreated with betalactams for 2-10 days with no results before admission to hospital; 18 with evidence of co-morbidity) were enrolled in an open, randomized study with azithromycin, 500 mg q.d. oral therapy for 3 days, versus clarithromycin, 250 mg b.i.d. oral therapy for 10 +/- 2 days. The aetiology of pneumonia was identified in 18 patients by serology (nine Mycoplasma pneumoniae, four Chlamydia pneumoniae, five Legionella pneumophila; one patient with chlamydial infection also had Klebsiella pneumoniae bacteraemia). A presumptive aetiological diagnosis was obtained with sputum culture in three other patients (one Haemophilus influenzae, two Haemophilus parainfluenzae), all strains were sole isolates with 10(8) Colony forming units (CFU), and with Gram stain in one patient with Streptococcus pneumoniae. All patients in the azithromycin group (one after a second 3 day course), and all but two (of those available for evaluation) of the clarithromycin group were cured. Defervescence occurred after 2.6 +/- 1.6 days, and chest roentgenogram cleared after 8.9 +/- 3.3 days, with no difference between the two groups. Tolerance was good, and there were no withdrawals from therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Azithromycin-chloroquine and the intermittent preventive treatment of malaria in pregnancy

    PubMed Central

    Chico, R Matthew; Pittrof, Rudiger; Greenwood, Brian; Chandramohan, Daniel

    2008-01-01

    In the high malaria-transmission settings of sub-Saharan Africa, malaria in pregnancy is an important cause of maternal, perinatal and neonatal morbidity. Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) reduces the incidence of low birth-weight, pre-term delivery, intrauterine growth-retardation and maternal anaemia. However, the public health benefits of IPTp are declining due to SP resistance. The combination of azithromycin and chloroquine is a potential alternative to SP for IPTp. This review summarizes key in vitro and in vivo evidence of azithromycin and chloroquine activity against Plasmodium falciparum and Plasmodium vivax, as well as the anticipated secondary benefits that may result from their combined use in IPTp, including the cure and prevention of many sexually transmitted diseases. Drug costs and the necessity for external financing are discussed along with a range of issues related to drug resistance and surveillance. Several scientific and programmatic questions of interest to policymakers and programme managers are also presented that would need to be addressed before azithromycin-chloroquine could be adopted for use in IPTp. PMID:19087267

  4. Case report: failure under azithromycin treatment in a case of bacteremia due to Salmonella enterica Paratyphi A

    PubMed Central

    2014-01-01

    Background Limited information is available regarding the clinical efficacy of azithromycin for the treatment of enteric fever due to fluoroquinolone-resistant Salmonella Typhi and Salmonella Paratyphi among travelers returning to their home countries. Case presentation We report a case of a 52-year-old Japanese man who returned from India, who developed a fever of 39°C with no accompanying symptoms 10 days after returning to Japan from a 1-month business trip to Delhi, India. His blood culture results were positive for Salmonella Paratyphi A. He was treated with 14 days of ceftriaxone, after which he remained afebrile for 18 days before his body temperature again rose to 39°C with no apparent symptoms. He was then empirically given 500 mg of azithromycin, but experienced clinical and microbiological failure of azithromycin treatment for enteric fever due to Salmonella Paratyphi A. However, the minimum inhibitory concentration (MIC) of azithromycin was not elevated (8 mg/L). He was again given ceftriaxone for 14 days with no signs of recurrence during the follow-up. Conclusion There are limited data available for the treatment of enteric fever using azithromycin in travelers from developed countries who are not immune to the disease, and thus, careful follow-up is necessary. In our case, the low azithromycin dose might have contributed the treatment failure. Additional clinical data are needed to determine the rate of success, MIC, and contributing factors for success and/or failure of azithromycin treatment for both Salmonella Typhi and Salmonella Paratyphi infections. PMID:25041573

  5. Frequency of development and associated physiological cost of azithromycin resistance in Chlamydia psittaci 6BC and C. trachomatis L2.

    PubMed

    Binet, Rachel; Maurelli, Anthony T

    2007-12-01

    Azithromycin is a major drug used in the treatment and prophylaxis of chlamydial infections. Spontaneous azithromycin-resistant mutants of Chlamydia psittaci 6BC were isolated in vitro in the plaque assay at a frequency of about 10(-8). Isogenic clonal variants with A(2058)C, A(2059)G, or A(2059)C mutations in the unique 23S rRNA gene (Escherichia coli numbering system) displayed MICs for multiple macrolides (i.e., azithromycin, erythromycin, josamycin, and spiramycin) at least 100 times higher than those of the parent strain and were also more resistant to the lincosamide clindamycin. Chlamydia trachomatis L2 variants with a Gln-to-Lys substitution in ribosomal protein L4 at position 66 (E. coli numbering system), conferring an eightfold decrease in azithromycin and erythromycin sensitivities and a fourfold decrease in josamycin and spiramycin sensitivities, were isolated following serial passage in subinhibitory concentrations of azithromycin. Each mutation was stably maintained in the absence of selection but severely affected chlamydial infectivity, as determined by monitoring the development of each isolate over 46 h in the absence of selection, in pure culture or in 1:1 competition with the isogenic parent. Data in this study support the hypothesis that the mechanisms which confer high-level macrolide resistance in chlamydiae carry a prohibitive physiological cost and may thus limit the emergence of highly resistant clones of these important pathogens in vivo.

  6. Effects of Fluoroquinolones and Azithromycin on Biofilm Formation of Stenotrophomonas maltophilia

    PubMed Central

    Wang, Aihua; Wang, Qinqin; Kudinha, Timothy; Xiao, Shunian; Zhuo, Chao

    2016-01-01

    Stenotrophomonas maltophilia is an opportunistic pathogen that causes respiratory and urinary tract infections, as well as wound infections in immunocompromised patients. This pathogen is difficult to treat due to increased resistance to many antimicrobial agents. We investigated the in vitro biofilm formation of S. maltophilia, including effects of fluoroquinolones (FQs) and azithromycin on biofilm formation. The organism initiated attachment to polystyrene surfaces after a 4 h incubation period, and reached maximal growth at 18–24 h. In the presence of FQs (moxifloxacin, levofloxacin or ciprofloxacin), the biofilm biomass was significantly reduced (P < 0.05). A lower concentration of moxifloxacin (10 μg/mL) exhibited a better inhibiting effect on biofilm formation than 100 μg/mL (P < 0.01), but with no difference in effect compared to the 50 μg/mL concentration (P > 0.05). However, the inhibitory effects of 10 μg/mL of levofloxacin or ciprofloxacin were slightly less pronounced than those of the higher concentrations. A combination of azithromycin and FQs significantly reduced the biofilm inhibiting effect on S. maltophilia preformed biofilms compared to azithromycin or FQs alone. We conclude that early use of clinically acceptable concentrations of FQs, especially moxifloxacin (10 μg/mL), may possibly inhibit biofilm formation by S. maltophilia. Our study provides an experimental basis for a possible optimal treatment strategy for S. maltophilia biofilm-related infections. PMID:27405358

  7. Trends in antimicrobial susceptibility for azithromycin and ceftriaxone in Neisseria gonorrhoeae isolates in Amsterdam, the Netherlands, between 2012 and 2015.

    PubMed

    Wind, Carolien M; Schim van der Loeff, Maarten F; van Dam, Alje P; de Vries, Henry Jc; van der Helm, Jannie J

    2017-01-05

    Resistance of Neisseria gonorrhoeae to azithromycin and ceftriaxone has been increasing in the past years. This is of concern since the combination of these antimicrobials is recommended as the first-line treatment option in most guidelines. To analyse trends in antimicrobial resistance, we retrospectively selected all consultations with a positive N. gonorrhoeae culture at the sexually transmitted infection clinic, Amsterdam, the Netherlands, from January 2012 through September 2015. Minimum inhibitory concentrations (MICs) for azithromycin and ceftriaxone were analysed per year, and determinants associated with decreased susceptibility to azithromycin (MIC > 0.25 mg/L) or ceftriaxone (MIC > 0.032 mg/L) were assessed. Between 2012 and 2015 azithromycin resistance (MIC > 0.5 mg/L) was around 1.2%, the percentage of isolates with intermediate MICs (> 0.25 and ≤ 0.5 mg/L) increased from 3.7% in 2012, to 8.6% in 2015. Determinants associated with decreased azithromycin susceptibility were, for men who have sex with men (MSM), infections diagnosed in the year 2014, two infected sites, and HIV status (HIV; associated with less decreased susceptibility); for heterosexuals this was having ≥ 10 sex partners (in previous six months). Although no ceftriaxone resistance (MIC > 0.125 mg/L) was observed during the study period, the proportion of isolates with decreased ceftriaxone susceptibility increased from 3.6% in 2012, to 8.4% in 2015. Determinants associated with decreased ceftriaxone susceptibility were, for MSM, infections diagnosed in 2014, and pharyngeal infections; and for heterosexuals, infections diagnosed in 2014 or 2015, being of female sex, and having ≥ 10 sex partners. Continued decrease of azithromycin and ceftriaxone susceptibility will threaten future treatment of gonorrhoea. Therefore, new treatment strategies are warranted.

  8. In Vitro Synergism between Azithromycin or Terbinafine and Topical Antimicrobial Agents against Pythium insidiosum

    PubMed Central

    Itaqui, Sabrina R.; Verdi, Camila M.; Tondolo, Juliana S. M.; da Luz, Thaisa S.; Alves, Sydney H.; Santurio, Janio M.

    2016-01-01

    We describe here in vitro activity for the combination of azithromycin or terbinafine and benzalkonium, cetrimide, cetylpyridinium, mupirocin, triclosan, or potassium permanganate. With the exception of potassium permanganate, the remaining antimicrobial drugs were active and had an MIC90 between 2 and 32 μg∕ml. The greatest synergism was observed for the combination of terbinafine and cetrimide (71.4%). In vivo experimental evaluations will clarify the potential of these drugs for the topical treatment of lesions caused by Pythium insidiosum. PMID:27216049

  9. Use of whole-genome sequencing data to analyze 23S rRNA-mediated azithromycin resistance.

    PubMed

    Johnson, Steven R; Grad, Yonatan; Abrams, A Jeanine; Pettus, Kevin; Trees, David L

    2017-02-01

    The whole-genome sequences of 24 isolates of Neisseria gonorrhoeae with elevated minimum inhibitory concentrations (MICs) to azithromycin (≥2.0 µg/mL) were analyzed against a modified sequence derived from the whole-genome sequence of N. gonorrhoeae FA1090 to determine, by signal ratio, the number of mutant copies of the 23S rRNA gene and the copy number effect on 50S ribosome-mediated azithromycin resistance. Isolates that were predicted to contain four mutated copies were accurately identified compared with the results of direct sequencing. Fewer than four mutated copies gave less accurate results but were consistent with elevated MICs.

  10. Anti Pneumococcal Activity of Azithromycin-Eudragit RS100 Nano-Formulations

    PubMed Central

    Adibkia, Khosro; Khorasani, Golrokh; Payab, Shahriar; Lotfipour, Farzaneh

    2016-01-01

    Purpose: Bacterial pneumonia is a common lung infection caused by different types of bacteria. Azithromycin (AZI), an azalide antibiotic, is widely used to manage pneumococcal infections. Studies have shown that antibiotics in nanocarriers may lead to increased antibacterial activity and reduced toxicity. The aim of this work was to valuate in vitro antibacterial performance azithromycin-Eudragit RS100 nano-formulations against Streptococcus pneumoniae and Staphylococcus aureus. Methods: AZI-Eudragit RS100 nanoparticles were prepared via electrospinning technique and the in vitro antibacterial performance against S. pneumoniae and S. aureus were assessed using agar dilution method. Results: Nanofibers in the sizes about 100-300 nm in diameter and micro scale in length and nanobeads in the range of 100-500 nm were achieved. The Minimum Inhibitory Concentrations (MIC) showed an enhancement in the antimicrobial effect of AZI-Eudragit RS100 nanofibers (40 µg/ml) compare to untreated AZI solution (>160 µg/ml) against S. pneumonia. The MIC value for AZI-Eudragit RS100 nanofibers against S. aureus was >128 µg/ml, same as that of the untreated AZI solution. Conclusion: The enhanced efficiency of AZI in nanofibers could be related to the more adsorption opportunity of nanofibers to S. pneumonia capsulated cell wall which provides an antibiotic depot on the bacterial surface compared to S. aureus. AZI-Eudragit RS100 nanofibers with enhanced antimicrobial effect against S. pneumonia can be considered as a candidate for in vivo evaluations in antibiotic therapy of Pneumococcal infections. PMID:27766231

  11. Tissue disposition of azithromycin after intravenous and intramuscular administration to rabbits.

    PubMed

    Cárceles, Carlos M; Fernández-Varón, Emilio; Marín, Pedro; Escudero, Elisa

    2007-07-01

    Tissue disposition of azithromycin after intravenous (IV) or intramuscular (IM) injection at a single dose rate of 10mg/kg bodyweight were investigated in rabbits using a modified agar diffusion bioassay for determining tissue concentrations. The pharmacokinetic behaviour of azithromycin was characterized by low and sustained plasma concentrations but high and persistent tissue concentrations. Kinetic parameters indicated a high retention of the drug in peripheral compartments. The plasma half-lives after IV and IM administrations were similar being 21.8h and 23.1h, respectively, while the half-lives obtained in tissues after IV and IM administration were at least 1.4 and 1.9 times longer than in plasma, respectively. The highest tissue concentrations were found in bile, liver and spleen whereas the lowest ones were found in skeletal muscle (although they were higher than those in plasma). From the results of the single administration in this study an IM dosage regimen can be proposed that achieves minimum concentrations over 2mg/L in rabbits: three doses of 4-5mg/kg/day would provide suitable therapeutic concentrations in pulmonary tissues over seven days.

  12. Comparison effect of azithromycin gel 2% with clindamycin gel 1% in patients with acne

    PubMed Central

    Mokhtari, Fatemeh; Faghihi, Gita; Basiri, Akram; Farhadi, Sadaf; Nilforoushzadeh, Mohammadali; Behfar, Shadi

    2016-01-01

    Background: Acne vulgaris is the most common skin disease. Local and systemic antimicrobial drugs are used for its treatment. But increasing resistance of Propionibacterium acnes to antibiotics has been reported. Materials and Methods: In a double-blind clinical trial, 40 patients with mild to moderate acne vulgaris were recruited. one side of the face was treated with Clindamycin Gel 1% and the other side with Azithromycin Topical Gel 2% BID for 8 weeks and then they were assessed. Results: Average age was 21. 8 ± 7 years. 82.5% of them were female. Average number of papules, pustules and comedones was similarly reduced in both groups and, no significant difference was observed between the two groups (P > 0.05, repeated measurs ANOVA). The mean indexes of ASI and TLC also significantly decreased during treatment in both groups, no significant difference was observed between the two groups. (P > 0.05, repeated measurs ANOVA). Also, impact of both drugs on papules and pustules was 2-3 times greater than the effect on comedones. Average satisfaction score was not significant between the two groups (P = 0.6, repeated measurs ANOVA). finally, frequency distribution of complications was not significant between the two groups (P > 0.05, Fisher Exact test). Conclusion: Azithromycin gel has medical impact at least similar to Clindamycin Gel in treatment of mild to moderate acne vulgaris, and it may be consider as suitable drug for resistant acne to conventional topical therapy. PMID:27169103

  13. Evidence of improved small airways function after azithromycin treatment in diffuse panbronchiolitis.

    PubMed

    Hanon, Shane; Verbanck, Sylvia; Schuermans, Daniel; Vanden Berghe, Bram; Vanderhelst, Eef; Vincken, Walter

    2012-01-01

    A 67-year-old never-smoker was diagnosed with diffuse panbronchiolitis (DPB) and was started on 250 mg azithromycin twice weekly. Over a 16-month observation period, lung function was assessed monthly, including a dedicated small airways test, the multiple breath nitrogen washout (MBW) with indices S(cond) and S(acin) of ventilation heterogeneity at the level of the conductive and acinar air spaces, respectively. Baseline measurements indicated moderate airway obstruction, air trapping and considerable dysfunction of the small airways around the acinar entrance. Treatment resulted in excellent symptomatic improvement paralleled by marked improvements in FEV(1), FVC, RV/TLC, S(cond) and S(acin); by contrast, there were no consistent changes in FEF(75) or TL(CO). While improvements were such that S(cond) fell within normal limits after 5 months, S(acin) remained abnormal even after 16 months of treatment. This suggests a distinct acinar structural abnormality in DPB that cannot be reversed by azithromycin.

  14. Azithromycin in DuraSite® for the treatment of blepharitis

    PubMed Central

    Luchs, Jodi

    2010-01-01

    Blepharitis is a common inflammatory disease of the eyelid. Posterior blepharitis affects the posterior lamella of the eyelid and involves inflammation of the meibomian glands, whereas anterior blepharitis affects the anterior lamella of the eyelid and the eyelashes; either version can be inflammatory or infectious in nature. Each of these conditions can incite or propagate the other; anterior blepharitis, if not treated, can lead to meibomian gland disease, and vice versa. Blepharitis is typically chronic, and can be associated with a variety of systemic diseases such as dermatitis, as well as ocular diseases such as dry eye, conjunctivitis, or keratitis. The standard treatment regimen historically consists of lid hygiene with warm compresses and eyelid scrubs, although these treatment modalities may have limited efficacy for many patients, especially those with more severe disease. Adjunctive treatment includes systemic and topical antibiotics, topical corticosteroids, and tear replacement therapy. Topical antibiotics are recommended to decrease the bacterial load, and topical corticosteroids may help in cases of severe inflammation. Azithromycin ophthalmic solution 1% in DuraSite® (AzaSite®; Inspire Pharmaceuticals, Durham, North Carolina, USA) has been proposed as a novel treatment for posterior blepharitis, based on its well-known anti-infective profile, its anti-inflammatory properties, its excellent tissue penetration, and its regulatory approval for the treatment of bacterial conjunctivitis. This review focuses on an off-label indication for topical azithromycin 1% in DuraSite for the treatment of blepharitis. PMID:20689782

  15. Determination of benzalkonium chloride in viscous ophthalmic drops of azithromycin by high-performance liquid chromatography *

    PubMed Central

    Shen, Yan; Xu, Sheng-jie; Wang, Shi-chun; Tu, Jia-sheng

    2009-01-01

    A high-performance liquid chromatography (HPLC) system was used in the reversed phase mode for the determination of benzalkonium chloride (BKC) in azithromycin viscous ophthalmic drops. A Venusil-XBP(L)-C18 (150 mm×4.6 mm, 5 μm) column was used at 50 °C. The mobile phase consisted of a mixture of methanol-potassium phosphate (16:5, v/v). Two sample preparation methods were compared. The results suggested that, compared with an extraction procedure, a deproteinization procedure was much quicker and more convenient. Using the deproteinization procedure for sample preparation, calibration curves were linear in the range 5.0~50 μg/ml. The within-day and inter-day coefficients of variation were less than 10%. The average recoveries were determined as 96.70%, 98.52%, and 97.96% at concentrations of 10.0, 30.0, and 50.0 μg/ml, respectively. Variability in precision did not exceed 5%. In conclusion, this HPLC method using a simple sample treatment procedure appears suitable for monitoring BKC content in azithromycin viscous ophthalmic drops. PMID:19946951

  16. Attenuation of Pseudomonas aeruginosa biofilm formation by Vitexin: A combinatorial study with azithromycin and gentamicin

    NASA Astrophysics Data System (ADS)

    Das, Manash C.; Sandhu, Padmani; Gupta, Priya; Rudrapaul, Prasenjit; de, Utpal C.; Tribedi, Prosun; Akhter, Yusuf; Bhattacharjee, Surajit

    2016-03-01

    Microbial biofilm are communities of surface-adhered cells enclosed in a matrix of extracellular polymeric substances. Extensive use of antibiotics to treat biofilm associated infections has led to the emergence of multiple drug resistant strains. Pseudomonas aeruginosa is recognised as a model biofilm forming pathogenic bacterium. Vitexin, a polyphenolic group of phytochemical with antimicrobial property, has been studied for its antibiofilm potential against Pseudomonas aeruginosa in combination with azithromycin and gentamicin. Vitexin shows minimum inhibitory concentration (MIC) at 260 μg/ml. It’s antibiofilm activity was evaluated by safranin staining, protein extraction, microscopy methods, quantification of EPS and in vivo models using several sub-MIC doses. Various quorum sensing (QS) mediated phenomenon such as swarming motility, azocasein degrading protease activity, pyoverdin and pyocyanin production, LasA and LasB activity of the bacteria were also evaluated. Results showed marked attenuation in biofilm formation and QS mediated phenotype of Pseudomonas aeruginosa in presence of 110 μg/ml vitexin in combination with azithromycin and gentamicin separately. Molecular docking of vitexin with QS associated LuxR, LasA, LasI and motility related proteins showed high and reasonable binding affinity respectively. The study explores the antibiofilm potential of vitexin against P. aeruginosa which can be used as a new antibiofilm agent against microbial biofilm associated pathogenesis.

  17. From Erythromycin to Azithromycin and New Potential Ribosome-Binding Antimicrobials

    PubMed Central

    Jelić, Dubravko; Antolović, Roberto

    2016-01-01

    Macrolides, as a class of natural or semisynthetic products, express their antibacterial activity primarily by reversible binding to the bacterial 50S ribosomal subunits and by blocking nascent proteins’ progression through their exit tunnel in bacterial protein biosynthesis. Generally considered to be bacteriostatic, they may also be bactericidal at higher doses. The discovery of azithromycin from the class of macrolides, as one of the most important new drugs of the 20th century, is presented as an example of a rational medicinal chemistry approach to drug design, applying classical structure-activity relationship that will illustrate an impressive drug discovery success story. However, the microorganisms have developed several mechanisms to acquire resistance to antibiotics, including macrolide antibiotics. The primary mechanism for acquiring bacterial resistance to macrolides is a mutation of one or more nucleotides from the binding site. Although azithromycin is reported to show different, two-step process of the inhibition of ribosome function of some species, more detailed elaboration of that specific mode of action is needed. New macrocyclic derivatives, which could be more potent and less prone to escape bacterial resistance mechanisms, are also continuously evaluated. A novel class of antibiotic compounds—macrolones, which are derived from macrolides and comprise macrocyclic moiety, linker, and either free or esterified quinolone 3-carboxylic group, show excellent antibacterial potency towards key erythromycin-resistant Gram-positive and Gram-negative bacterial strains, with possibly decreased potential of bacterial resistance to macrolides. PMID:27598215

  18. Ion-activated In Situ Gelling Ophthalmic Delivery Systems of Azithromycin

    PubMed Central

    Vijaya, C.; Goud, K. Swetha

    2011-01-01

    Gelation of pectin caused by divalent cations especially calcium ions has been applied to develop an ophthalmic formulation of azithromycin in the present study. Rapid elimination of drug on instillation into cul de sac would be minimal with in situ gelling ophthalmic solution leading to increased precorneal contact time and prolonged drug delivery. In the formulation development studies pectin was used in different concentrations (1-5% w/v) and different proportions of the hydrocolloids hydroxypropyl methylcellulose and sodium carboxymethyl cellulose of different grades of viscosity were used. The primary criteria for formulation optimization were gelling capacity and rheological behaviour. In addition, formulations were evaluated for pH, and antimicrobial efficacy and drug release. The clarity, pH, gelation in simulated tear fluid and rheological properties of the optimized formulations were satisfactory. The formulations inhibited the growth of Staphylococcus aureus effectively in cup–plate method and were proved to be safe and non irritant on rabbit eyes. The results indicate that pectin based in situ gels can be successfully used to prolong the duration of action of azithromycin. PMID:23112394

  19. Determination of benzalkonium chloride in viscous ophthalmic drops of azithromycin by high-performance liquid chromatography.

    PubMed

    Shen, Yan; Xu, Sheng-jie; Wang, Shi-chun; Tu, Jia-sheng

    2009-12-01

    A high-performance liquid chromatography (HPLC) system was used in the reversed phase mode for the determination of benzalkonium chloride (BKC) in azithromycin viscous ophthalmic drops. A Venusil-XBP(L)-C(18) (150 mmx4.6 mm, 5 microm) column was used at 50 degrees C. The mobile phase consisted of a mixture of methanol-potassium phosphate (16:5, v/v). Two sample preparation methods were compared. The results suggested that, compared with an extraction procedure, a deproteinization procedure was much quicker and more convenient. Using the deproteinization procedure for sample preparation, calibration curves were linear in the range 5.0 to approximately 50 microg/ml. The within-day and inter-day coefficients of variation were less than 10%. The average recoveries were determined as 96.70%, 98.52%, and 97.96% at concentrations of 10.0, 30.0, and 50.0 microg/ml, respectively. Variability in precision did not exceed 5%. In conclusion, this HPLC method using a simple sample treatment procedure appears suitable for monitoring BKC content in azithromycin viscous ophthalmic drops.

  20. Azithromycin, fluoroquinolone and chloramphenicol resistance of non-chlamydia conjunctival bacteria in rural community of Ethiopia

    PubMed Central

    Abera, Bayeh; Kibret, Mulugeta

    2014-01-01

    Aim: To determine profiles of non-chlamydia conjunctival bacteria and their antimicrobial susceptibility from adults who underwent trachomatous trichiasis surgery in rural areas of Ethiopia. Materials and Methods: A cross-sectional study was conducted in rural districts in West Gojjam administrative zone. Conjunctival swabs were collected during surgery and transported using Stuart transport broth (Oxoid, UK). Antibiotic susceptibility of conjunctival isolates was determined using the Kirby-Bauer disc-diffusion method. Results: Non-chlamydia pathogenic bacteria were recovered from conjunctiva of 438 (31%) participants before treatment. The isolated conjunctival bacteria were Staphylococcus aureus, coagulase-negative Staphylococci, Streptococcus group (A, C, F and G), Enterococci, Streptococcus pneumoniae, Moraxella spp., Escherichia coli, Citrobacter spp., Proteus spp., Klebsiella spp., Pseudomonas spp. and Enterobacter spp. Overall, resistance rates of 57.8% to azithromycin and 68.5% to chloramphenicol were found. However, 86-94.4% sensitivity was demonstrated to ciprofloxacin and norfloxacin. Moderate sensitivity rates (61.8-78.4%) were observed to ceftriaxone, tetracycline and cotrimoxazole. Conclusion: Fluoroquinolones that have activity against the majority of bacterial isolates were potent at in vitro. However, unacceptably high levels of resistance to azithromycin and chloramphenicol in rural community indicated a need for further study and antimicrobial resistance surveillance. PMID:23571246

  1. Attenuation of Pseudomonas aeruginosa biofilm formation by Vitexin: A combinatorial study with azithromycin and gentamicin

    PubMed Central

    Das, Manash C.; Sandhu, Padmani; Gupta, Priya; Rudrapaul, Prasenjit; De, Utpal C.; Tribedi, Prosun; Akhter, Yusuf; Bhattacharjee, Surajit

    2016-01-01

    Microbial biofilm are communities of surface-adhered cells enclosed in a matrix of extracellular polymeric substances. Extensive use of antibiotics to treat biofilm associated infections has led to the emergence of multiple drug resistant strains. Pseudomonas aeruginosa is recognised as a model biofilm forming pathogenic bacterium. Vitexin, a polyphenolic group of phytochemical with antimicrobial property, has been studied for its antibiofilm potential against Pseudomonas aeruginosa in combination with azithromycin and gentamicin. Vitexin shows minimum inhibitory concentration (MIC) at 260 μg/ml. It’s antibiofilm activity was evaluated by safranin staining, protein extraction, microscopy methods, quantification of EPS and in vivo models using several sub-MIC doses. Various quorum sensing (QS) mediated phenomenon such as swarming motility, azocasein degrading protease activity, pyoverdin and pyocyanin production, LasA and LasB activity of the bacteria were also evaluated. Results showed marked attenuation in biofilm formation and QS mediated phenotype of Pseudomonas aeruginosa in presence of 110 μg/ml vitexin in combination with azithromycin and gentamicin separately. Molecular docking of vitexin with QS associated LuxR, LasA, LasI and motility related proteins showed high and reasonable binding affinity respectively. The study explores the antibiofilm potential of vitexin against P. aeruginosa which can be used as a new antibiofilm agent against microbial biofilm associated pathogenesis. PMID:27000525

  2. A randomized, double-blind trial comparing azithromycin and clarithromycin in the treatment of disseminated Mycobacterium avium infection in patients with human immunodeficiency virus.

    PubMed

    Dunne, M; Fessel, J; Kumar, P; Dickenson, G; Keiser, P; Boulos, M; Mogyros, M; White Jr, A C; Cahn, P; O'Connor, M; Lewi, D; Green, S; Tilles, J; Hicks, C; Bissett, J; Schneider, M M; Benner, R

    2000-11-01

    Two hundred and forty-six patients infected with human immunodeficiency virus (HIV) who also had disseminated Mycobacterium avium complex received either azithromycin 250 mg every day, azithromycin 600 mg every day, or clarithromycin 500 mg twice a day, each combined with ethambutol, for 24 weeks. Samples drawn from patients were cultured and clinically assessed every 3 weeks up to week 12, then monthly thereafter through week 24 of double-blind therapy and every 3 months while on open-label therapy through the conclusion of the trial. The azithromycin 250 mg arm of the study was dropped after an interim analysis showed a lower rate of clearance of bacteremia. At 24 weeks of therapy, the likelihood of patients' developing 2 consecutive negative cultures (46% vs. 56%, P=.24) or 1 negative culture (59% vs. 61%, P=.80) was similar for azithromycin 600 mg (n=68) and clarithromycin (n=57), respectively. The likelihood of relapse was 39% versus 27% (P=.21) on azithromycin compared with clarithromycin, respectively. Of the 6 patients who experienced relapse, none of those randomized to receive azithromycin developed isolates resistant to macrolides, compared with 2 of 3 patients randomized to receive clarithromycin [corrected]. Mortality was similar in patients comprising each arm of the study (69% vs. 63%; hazard, 95.1% confidence interval, 1.1 [0.7, 1.7]). Azithromycin 600 mg, when given in combination with ethambutol, is an effective agent for the treatment of disseminated M. avium disease in patients infected with HIV.

  3. Microbiological effects of periodontal therapy plus azithromycin in patients with diabetes: results from a randomized clinical trial.

    PubMed

    Hincapié, Juan P; Castrillón, Cesar A; Yepes, Fanny L; Roldan, Natalia; Becerra, María A; Moreno, Sandra M; Consuegra, Jessika; Contreras, Adolfo; Botero, Javier E

    2014-01-01

    Current evidence suggests that periodontal infection may aggravate diabetes control. The aim of this study was to determine the changes in the frequency with which Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola and Aggregatibacter actinomycetemcomitans were detected in patients with diabetes with the use of non-surgical therapy plus azithromycin in a randomized clinical trial. One hundred and five (105) patients with diabetes and chronic periodontitis were randomly assigned to three treatment groups: subgingival mechanical therapy with azithromycin, subgingival mechanical therapy with placebo and supragingival prophylaxis with azithromycin. Complete periodontal clinical examinations and detection of periodontal pathogens using polymerase chain reaction were carried out at baseline, 3, 6 and 9 months after periodontal therapy. The frequency with which Porphyromonas gingivalis, Treponemadenticola and Aggregatibacter actinomycetemcomitans were detected decreased at 3 months in all groups. Tannerella forsythia increased after3 months in all groups. All organisms had similar frequencies at 9 months in all groups. Subgingival mechanical therapy with adjunctive azithromycin had no additional effect on the frequency with which the periodontal pathogens investigated were detected in patients with diabetes.

  4. A CASE STUDY: CROP (LETTUCE, SPINACH, AND CARROTS) UPTAKE OF THREE MACROLIDE ANTIBIOTICS (AZITHROMYCIN, CLINDAMYCIN AND ROXITHROMYCIN) AND OTHER DRUGS

    EPA Science Inventory

    It has been shown that human-use macrolide antibiotics (azithromycin, clindamycin, and roxithromycin) are environmentally available in wastewaters, source waters, and biosolids. In order to better understand the fate of these compounds into food crops via root migration, we condu...

  5. The role of Chlamydia pneumoniae in the etiology of acne rosacea: response to the use of oral azithromycin.

    PubMed

    Fernandez-Obregon, Adolfo; Patton, Dorothy L

    2007-02-01

    Acne rosacea is a chronic skin disorder that requires long-term therapy. Oral azithromycin has been used successfully to treat acne vulgaris. an observation that suggested an infectious agent may play an active role in the etiology of this disorder. Ten adults (not previously reported) with acne rosacea were selected to be treated with oral azithromycin. Nine of the 10 subjects received 250 mg 3 times weekly for periods ranging from 5 to 19 weeks, at which time follow-up examinations were performed on 8 of the 9 treated subjects: 1 subject was lost to follow-up. Prior to therapy. C pneumoniae antigen was detected in malar biopsy specimens in 4 of 10 subjects by immunoperoxidase technique (using monoclonal antibody to C pneumoniae). Serum antibodies against C pneumoniae were detected in 8 of 10 intent-to-treat subjects. Using polymerase chain reaction, C pneumoniae was not detected in peripheral blood mononuclear cells. The inflammatory response in tissues was characterized by a widespread infiltration of polymorphonuclear neutrophil cells, lymphocytes, and plasma cells, which support the clinical diagnosis of acne rosacea. Nine of 10 subjects treated with azithromycin showed moderate to marked improvement of their acne rosacea. No adverse reactions to azithromycin occurred. and the drug appeared to be safe and effective. These preliminary data suggest the need for further investigation with clinical trials to study long-term tolerability and efficacy and also strongly implicate C pneumoniae in the pathogenesis of acne rosacea.

  6. Predictive screening of M1 and M2 macrophages reveals the immunomodulatory effectiveness of post spinal cord injury azithromycin treatment

    PubMed Central

    Gensel, John C.; Kopper, Timothy J.; Zhang, Bei; Orr, Michael B.; Bailey, William M.

    2017-01-01

    Spinal cord injury (SCI) triggers a heterogeneous macrophage response that when experimentally polarized toward alternative forms of activation (M2 macrophages) promotes tissue and functional recovery. There are limited pharmacological therapies that can drive this reparative inflammatory state. In the current study, we used in vitro systems to comprehensively defined markers of macrophages with known pathological (M1) and reparative (M2) properties in SCI. We then used these markers to objectively define the macrophage activation states after SCI in response to delayed azithromycin treatment. Mice were subjected to moderate-severe thoracic contusion SCI. Azithromycin or vehicle was administered beginning 30 minutes post-SCI and then daily for 3 or 7 days post injury (dpi). We detected a dose-dependent polarization toward purportedly protective M2 macrophages with daily AZM treatment. Specifically, AZM doses of 10, 40, or 160 mg/kg decreased M1 macrophage gene expression at 3 dpi while the lowest (10 mg/kg) and highest (160 mg/kg) doses increased M2 macrophage gene expression at 7 dpi. Azithromycin has documented immunomodulatory properties and is commonly prescribed to treat infections in SCI individuals. This work demonstrates the utility of objective, comprehensive macrophage gene profiling for evaluating immunomodulatory SCI therapies and highlights azithromycin as a promising agent for SCI treatment. PMID:28057928

  7. Clinical evaluation of piroxicam-FDDF and azithromycin in the prevention of complications associated with impacted lower third molar extraction.

    PubMed

    Graziani, F; Corsi, L; Fornai, M; Antonioli, L; Tonelli, M; Cei, S; Colucci, R; Blandizzi, C; Gabriele, M; Del Tacca, M

    2005-12-01

    Combined treatments with non-steroidal anti-inflammatory drugs and antibiotics may offer significant benefits in the prevention of pain and infections associated with oral surgery. In this study, piroxicam and azithromycin were administered to patients undergoing dental extraction to examine the efficacy of piroxicam in the prevention of post-operative pain and inflammatory complications, either in the absence or in the presence of a concomitant antibiotic treatment. Thirty patients were randomly assigned to three groups and treated for 3 days, before impacted lower third molar removal, as follows: (1) sublingual piroxicam-FDDF (fast dissolving dosage formulation) 20 mg/day; (2) oral azithromycin 500 mg/day; (3) piroxicam-FDDF 20 mg/day plus azithromycin 500 mg/day. Oral acetaminophen (500 mg tablets) was allowed as rescue analgesic medication. Pain intensity was evaluated on a 100-mm visual-analogue scale after dental extraction (day 1), and at days 2, 3, 7 after surgery. Edema and trismus were estimated at days 2 and 7. At days 1 and 2, pain intensity was significantly lower in patients treated with piroxicam-FDDF, either alone (p < 0.05) or in combination with azithromycin (p < 0.05), than in patients administered with azithromycin alone. A higher acetaminophen consumption was also recorded in the latter group (p < 0.01). Pain intensity values did not differ among treatment groups at days 3 and 7. At day 2, the facial edema was significantly less intense in patients exposed to piroxicam-FDDF alone, as compared to patients treated with azithromycin, either alone (p < 0.05) or in combination with piroxicam-FDDF (p < 0.05). No significant differences were detected when comparing groups for trismus at days 2 and 7. The present results indicate that, when given alone in the pre-operative period, piroxicam-FDDF effectively counteracts post-surgical pain and inflammatory reactions in oral tissues. Upon combined treatment with piroxicam-FDDF and azithromycin, the

  8. Azithromycin for Indigenous children with bronchiectasis: study protocol for a multi-centre randomized controlled trial

    PubMed Central

    2012-01-01

    Background The prevalence of chronic suppurative lung disease (CSLD) and bronchiectasis unrelated to cystic fibrosis (CF) among Indigenous children in Australia, New Zealand and Alaska is very high. Antibiotics are a major component of treatment and are used both on a short or long-term basis. One aim of long-term or maintenance antibiotics is to reduce the frequency of acute pulmonary exacerbations and symptoms. However, there are few studies investigating the efficacy of long-term antibiotic use for CSLD and non-CF bronchiectasis among children. This study tests the hypothesis that azithromycin administered once a week as maintenance antibiotic treatment will reduce the rate of pulmonary exacerbations in Indigenous children with bronchiectasis. Methods/design We are conducting a multicentre, randomised, double-blind, placebo controlled clinical trial in Australia and New Zealand. Inclusion criteria are: Aboriginal, Torres Strait Islander, Maori or Pacific Island children aged 1 to 8 years, diagnosed with bronchiectasis (or probable bronchiectasis) with no underlying disease identified (such as CF or primary immunodeficiency), and having had at least one episode of pulmonary exacerbation in the last 12 months. After informed consent, children are randomised to receive either azithromycin (30 mg/kg once a week) or placebo (once a week) for 12–24 months from study entry. Primary outcomes are the rate of pulmonary exacerbations and time to pulmonary exacerbation determined by review of patient medical records. Secondary outcomes include length and severity of pulmonary exacerbation episodes, changes in growth, school loss, respiratory symptoms, forced expiratory volume in 1-second (FEV1; for children ≥6 years), and sputum characteristics. Safety endpoints include serious adverse events. Antibiotic resistance in respiratory bacterial pathogens colonising the nasopharynx is monitored. Data derived from medical records and clinical assessments every 3 to 4

  9. Update and critical appraisal of the use of topical azithromycin ophthalmic 1% (AzaSite) solution in the treatment of ocular infections.

    PubMed

    Utine, Canan Asli

    2011-01-01

    Azithromycin is an azalide that acts by binding to the 50S ribosomal subunit of susceptible microorganisms and interfering with microbial protein synthesis. Azithromycin is also noted by anti-inflammatory and immunomodulatory activity. AzaSite(®) (Inspire Pharmaceuticals, Inc, Durham, NC) is azithromycin ophthalmic solution, 1% formulated in polycarbophil (the aqueous mucoadhesive polymer contained in DuraSite(®)) that delivers high and prolonged azithromycin concentrations in a variety of ocular tissues, including the conjunctiva, cornea and particularly the eyelid. AzaSite was approved by the Food and Drug Administration (FDA) in the US in 2007, for the treatment of bacterial conjunctivitis caused by susceptible isolates. This article aims to evaluate the peer-reviewed published scientific literature and to define well-established uses of AzaSite eye drops in the field of ocular infections.

  10. Update and critical appraisal of the use of topical azithromycin ophthalmic 1% (AzaSite®) solution in the treatment of ocular infections

    PubMed Central

    Utine, Canan Asli

    2011-01-01

    Azithromycin is an azalide that acts by binding to the 50S ribosomal subunit of susceptible microorganisms and interfering with microbial protein synthesis. Azithromycin is also noted by anti-inflammatory and immunomodulatory activity. AzaSite® (Inspire Pharmaceuticals, Inc, Durham, NC) is azithromycin ophthalmic solution, 1% formulated in polycarbophil (the aqueous mucoadhesive polymer contained in DuraSite®) that delivers high and prolonged azithromycin concentrations in a variety of ocular tissues, including the conjunctiva, cornea and particularly the eyelid. AzaSite was approved by the Food and Drug Administration (FDA) in the US in 2007, for the treatment of bacterial conjunctivitis caused by susceptible isolates. This article aims to evaluate the peer-reviewed published scientific literature and to define well-established uses of AzaSite eye drops in the field of ocular infections. PMID:21750614

  11. The comparison of treatments with and without azithromycin in irritable bowel syndrome with diarrhea-predominant in gastrointestinal Clinic of Al-Zahra Hospital, Isfahan, Iran

    PubMed Central

    Yazdani, Mohamadreza; Aramesh, Amirhossein; Rafiei, Rahmatollah; Daghaghzadeh, Hamed; Adibi, Peyman

    2016-01-01

    Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. Recent studies suggest the importance of gut flora in the pathophysiology of it. Therefore, antibiotics have demonstrated a substantial benefit to reduce gut flora. Having few side effects, and applying one-dose per day, we studied the effect of azithromycin to treat IBS. Materials and Methods: One hundred and twenty-six patients enrolled a randomized, double-blind, placebo-controlled study. The treatment group received azithromycin in addition to common treatment. Patients were followed for 12 weeks. Patients completed daily diaries documenting their symptoms. Results: One hundred and thirteen patients completed the study. The onset of relief occurred significantly sooner, and duration of relief was significantly longer in azithromycin group. Movement, abdominal pain, bloating, and gas were significantly better in azithromycin group. Monthly results showed superior relief in bloating, gas, overall symptom, and overall bloating during 3 months. Significantly more patients in azithromycin group felt relief in bloating and gas and had greater consistency relief in almost all weeks. Conclusion: In our study, azithromycin significantly relieved most symptoms, such as abdominal pain, bloating, and gas. Overall symptom and overall bloating were relieved significantly in more patients in the intervention group in all weeks. PMID:28028528

  12. Surface plasmon resonance based selective and sensitive colorimetric determination of azithromycin using unmodified silver nanoparticles in pharmaceuticals and human plasma

    NASA Astrophysics Data System (ADS)

    Chavada, Vijay D.; Bhatt, Nejal M.; Sanyal, Mallika; Shrivastav, Pranav S.

    2017-01-01

    In this article we report a novel method for colorimetric sensing and selective determination of a non-chromophoric drug-azithromycin, which lacks native absorbance in the UV-Visible region using unmodified silver nanoparticles (AgNPs). The citrate-capped AgNps dispersed in water afforded a bright yellow colour owing to the electrostatic repulsion between the particles due to the presence of negatively charged surface and showed surface plasmon resonance (SPR) band at 394 nm. Addition of positively charged azithromycin at a concentration as low as 0.2 μM induced rapid aggregation of AgNPs by neutralizing the negative charge on the particle surface. This phenomenon resulted in the colour change from bright yellow to purple which could be easily observed by the naked eye. This provided a simple platform for rapid determination of azithromycin based on colorimetric measurements. The factors affecting the colorimetric response like pH, volume of AgNPs suspension and incubation time were suitably optimized. The validated method was found to work efficiently in the established concentration range of 0.2-100.0 μM using two different calibration models. The selectivity of the method was also evaluated by analysis of nanoparticles-aggregation response upon addition of several anions, cations and some commonly prescribed antibiotics. The method was successfully applied for the analysis of azithromycin in pharmaceuticals and spiked human plasma samples with good accuracy and precision. The simplicity, efficiency and cost-effectiveness of the method hold tremendous potential for the analysis of such non-chromophoric pharmaceuticals.

  13. Azithromycin, rifabutin, and rifapentine for treatment and prophylaxis of Mycobacterium avium complex in rats treated with cyclosporine.

    PubMed Central

    Brown, S T; Edwards, F F; Bernard, E M; Tong, W; Armstrong, D

    1993-01-01

    Azithromycin, rifabutin, and rifapentine were used to treat or prevent disseminated Mycobacterium avium complex (MAC) infections produced in rats immunosuppressed with cyclosporine. Animals with bacteremic infections were treated 1 week after intravenous inoculation with 10(7) CFU of MAC with azithromycin, 100 mg/kg of body weight administered subcutaneously for 5 days and then 75 mg/kg on Monday, Wednesday, and Friday, or with rifabutin or rifapentine, 20 mg/kg administered intraperitoneally on Monday through Friday. All three drugs showed efficacy after 1 and 2 months. Rifabutin cleared the organisms from tissues more rapidly than azithromycin or rifapentine. To approximate prophylaxis, treatment was started 2 weeks before intravenous inoculation with 10(4) organisms. MAC infections were undetectable in treated animals after 4 months, while control animals had disseminated infections. These findings support the rationale for clinical trials of treatment and prophylaxis with these agents. The cyclosporine-treated rat appears to be a useful model in which to evaluate compounds for the treatment and prophylaxis of disseminated MAC infections. PMID:8384809

  14. A Robust Liquid Chromatographic Method for Confirmation of Drug Stability of Azithromycin in Bulk Samples, Tablets and Suspensions

    PubMed Central

    Okaru, Alex O.; Abuga, Kennedy O.; Kamau, Franco N.; Ndwigah, Stanley N.; Lachenmeier, Dirk W.

    2017-01-01

    A simple, isocratic and robust RP-HPLC method for the analysis of azithromycin was developed, validated and applied for the analysis of bulk samples, tablets and suspensions. The optimum chromatographic conditions for separation were established as a mobile phase comprised of acetonitrile-0.1 M KH2PO4 pH 6.5–0.1 M tetrabutyl ammonium hydroxide pH 6.5-water (25:15:1:59 v/v/v/v) delivered at a flow rate of 1.0 mL/min. The stationary phase consisted of reverse-phase XTerra® (250 mm × 4.6 mm i.d., 5 µm particle size) maintained at a temperature of 43 °C with a UV detection at 215 nm. The method was found to be linear in the range 50%–150% (r2 = 0.997). The limits of detection and quantification were found to be 0.02% (20 µg) and 0.078% (78 µg), respectively, with a 100.7% recovery of azithromycin. Degradation products of azithromycin in acidic and oxidative environments at 37 °C were resolved from the active pharmaceutical ingredient and thus the method is fit for the purpose of drug stability confirmation. PMID:28245574

  15. Determination of azithromycin residue in pork using a molecularly imprinted monolithic microcolumn coupled to liquid chromatography with tandem mass spectrometry.

    PubMed

    Zhou, Tong; Yang, Haicui; Jin, Zhen; Liu, Qingying; Song, Xuqin; He, Limin; Fang, Binghu; Meng, Chenying

    2016-04-01

    Using spiramycin as a dummy template, a molecularly imprinted polymer monolithic micro-column with high selection to azithromycin was prepared in a micropipette tip. The imprinting factor of the monolithic micro-column prepared was approximately 2.67 and the morphological structure of the polymers was characterized by scanning electron microscopy. A simple, sensitive, and reproducible method based on the imprinted monolithic micro-column coupled to liquid chromatography with tandem mass spectrometry was developed for determining the residues of azithromycin in pork. Pork samples were extracted with acetonitrile, cleaned up under the optimal monolithic micro-column conditions, and analyzed using liquid chromatography with tandem mass spectrometry in the multiple reaction monitoring mode. The assay exhibited a linear dynamic range of 0.50-50 μg/L with the correlation coefficient (r(2) ) above 0.99. In the three spiking levels of 0.50, 1.0, and 10 μg/kg, the average recoveries of azithromycin from pork samples were between 85.8 and 96.5% with a relative standard deviation below 10%. The limit of detection and limit of quantitation were 0.03 and 0.1 μg/kg, respectively.

  16. Development, in vitro and in vivo evaluation of novel injectable smart gels of azithromycin for chronic periodontitis.

    PubMed

    Venkatesh, M P; Kumar, T M Pramod; Avinash, B S; Kumar, G Sheela

    2013-04-01

    Periodontitis is an inflammatory condition affecting teeth resulting in progressive destruction of periodontal ligaments, resorption of alveolar bone and loss of teeth. Treatment of periodontitis includes surgical and non surgical management. Systemic antibiotics are also used for the treatment of periodontitis. The aim of this research was to formulate smart gel system of azithromycin (AZT) and to evaluate in vitro and in vivo for non-surgical treatment of chronic periodontitis. Azithromycin dihydrate, used systemically in the treatment of periodontitis, was formulated into smart gels using biodegradable, thermosensitive polymer Pluronic® F-127 (PF-127) and Hydroxy Ethyl Cellulose (HEC) as copolymer. The prepared smart gels were evaluated for sterility, content uniformity, gelation temperature and time, syringeability, rheological behavior, in vitro diffusion and in vivo efficacy in human patients. The prepared smart gels were clear and transparent, sterile, thermoresponsive and injectable. Viscosity of gels increased with increase in concentration of polymer/co-polymer and also with temperature. They gelled in short response time below the body temperature. In vitro release studies showed controlled drug release which was influenced significantly by the properties and concentration of PF-127 and HEC. In vivo efficacy studies showed a significant improvement (p <0.001) in clinical parameters such as gingival index, probing pocket depth, clinical attachment level, bleeding index and plaque index. The developed azithromycin smart gel system is a novel approach for the treatment of chronic periodontitis since it reduces the dose and side effects, bypasses the usual surgical procedures and improves patient compliance.

  17. A Cluster-Randomized Controlled Trial Evaluating the Effects of Mass Azithromycin Treatment on Growth and Nutrition in Niger

    PubMed Central

    Amza, Abdou; Kadri, Boubacar; Nassirou, Baido; Stoller, Nicole E.; Yu, Sun N.; Zhou, Zhaoxia; West, Sheila K.; Mabey, David C. W.; Bailey, Robin L.; Keenan, Jeremy D.; Porco, Travis C.; Lietman, Thomas M.; Gaynor, Bruce D.

    2013-01-01

    Antimicrobials are used primarily to treat infectious disease, but they have other effects. Here, we assess anthropometry measurements in children 6–60 months in 24 communities randomized to one or two mass azithromycin distributions over a 1-year period in Niger. We compared the prevalence of wasting, low mid-upper arm circumference, stunting, and underweight in communities in the two treatment arms. We were unable to prove that there was a difference in the prevalence of wasting in the 12 communities that received one mass azithromycin distribution versus the 12 communities that received two mass azithromycin distributions (odds ratio = 0.75, 95% confidence interval = 0.46–1.23). Likewise, we were unable to detect a difference in the two treatment arms for low mid-upper arm circumference, stunting, and underweight. There may not be an association between antibiotic use and improved growth in humans, or this trial was not powerful enough to detect an association if it exists. PMID:23208876

  18. Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses

    PubMed Central

    Mauger, David T.; Boehmer, Susan; Beigelman, Avraham; Fitzpatrick, Anne M.; Jackson, Daniel J.; Baxi, Sachin N.; Benson, Mindy; Burnham, Carey-Ann D.; Cabana, Michael; Castro, Mario; Chmiel, James F.; Covar, Ronina; Daines, Michael; Gaffin, Jonathan M.; Gentile, Deborah Ann; Holguin, Fernando; Israel, Elliot; Kelly, H. William; Lazarus, Stephen C.; Lemanske, Robert F.; Ly, Ngoc; Meade, Kelley; Morgan, Wayne; Moy, James; Olin, Tod; Peters, Stephen P.; Phipatanakul, Wanda; Pongracic, Jacqueline A.; Raissy, Hengameh H.; Ross, Kristie; Sheehan, William J.; Sorkness, Christine; Szefler, Stanley J.; Teague, W. Gerald; Thyne, Shannon; Martinez, Fernando D.

    2016-01-01

    IMPORTANCE Many preschool children develop recurrent, severe episodes of lower respiratory tract illness (LRTI). Although viral infections are often present, bacteria may also contribute to illness pathogenesis. Strategies that effectively attenuate such episodes are needed. OBJECTIVE To evaluate if early administration of azithromycin, started prior to the onset of severe LRTI symptoms, in preschool children with recurrent severe LRTIs can prevent the progression of these episodes. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, placebo-controlled, parallel-group trial conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute’s AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by December 2014. Participants were 607 children aged 12 through 71 months with histories of recurrent, severe LRTIs and minimal day-to-day impairment. INTERVENTION Participants were randomly assigned to receive azithromycin (12 mg/kg/d for 5 days; n = 307) or matching placebo (n = 300), started early during each predefined RTI (child’s signs or symptoms prior to development of LRTI), based on individualized action plans, over a 12-through 18-month period. MAIN OUTCOMES AND MEASURES The primary outcome measure was the number of RTIs not progressing to a severe LRTI, measured at the level of the RTI, that would in clinical practice trigger the prescription of oral corticosteroids. Presence of azithromycin-resistant organisms in oropharyngeal samples, along with adverse events, were among the secondary outcome measures. RESULTS A total of 937 treated RTIs (azithromycin group, 473; placebo group, 464) were experienced by 443 children (azithromycin group, 223; placebo group, 220), including 92 severe LRTIs (azithromycin group, 35; placebo group, 57). Azithromycin significantly reduced the risk of progressing to severe LRTI relative to placebo (hazard ratio, 0.64 [95% CI, 0.41-0.98], P = .04; absolute risk for

  19. Protective Effects of Carvedilol and Vitamin C against Azithromycin-Induced Cardiotoxicity in Rats via Decreasing ROS, IL1-β, and TNF-α Production and Inhibiting NF-κB and Caspase-3 Expression

    PubMed Central

    El-Shitany, Nagla A.; El-Desoky, Karema

    2016-01-01

    The Food and Drug Administration recently warned of the fatal cardiovascular risks of azithromycin in humans. In addition, a recently published study documented azithromycin-induced cardiotoxicity in rats. This study aimed to justify the exact cardiovascular events accompanying azithromycin administration in rats, focusing on electrocardiographic, biochemical, and histopathological changes. In addition, the underlying mechanisms were studied regarding reactive oxygen species production, cytokine release, and apoptotic cell-death. Finally, the supposed protective effects of both carvedilol and vitamin C were assessed. Four groups of rats were used: (1) control, (2) azithromycin, (3) azithromycin + carvedilol, and (4) azithromycin + vitamin C. Azithromycin resulted in marked atrophy of cardiac muscle fibers and electrocardiographic segment alteration. It increased the heart rate, lactate dehydrogenase, creatine phosphokinase, malondialdehyde, nitric oxide, interleukin-1 beta (IL1-β), tumor necrosis factor alpha (TNF-α), nuclear factor kappa beta (NF-κB), and caspase-3. It decreased reduced glutathione, glutathione peroxidase, and superoxide dismutase. Carvedilol and vitamin C prevented most of the azithromycin-induced electrocardiographic and histopathological changes. Carvedilol and vitamin C decreased lactate dehydrogenase, malondialdehyde, IL1-β, TNF-α, NF-κB, and caspase-3. Both agents increased glutathione peroxidase. This study shows that both carvedilol and vitamin C protect against azithromycin-induced cardiotoxicity through antioxidant, immunomodulatory, and antiapoptotic mechanisms. PMID:27274777

  20. Pharmacokinetics, Microbial Response, and Pulmonary Outcomes of Multidose Intravenous Azithromycin in Preterm Infants at Risk for Ureaplasma Respiratory Colonization

    PubMed Central

    Merchan, L. Marcela; Hassan, Hazem E.; Terrin, Michael L.; Waites, Ken B.; Kaufman, David A.; Ambalavanan, Namasivayam; Donohue, Pamela; Dulkerian, Susan J.; Schelonka, Robert; Magder, Laurence S.; Shukla, Sagar; Eddington, Natalie D.

    2014-01-01

    The study objectives were to refine the population pharmacokinetics (PK) model, determine microbial clearance, and assess short-term pulmonary outcomes of multiple-dose azithromycin treatment in preterm infants at risk for Ureaplasma respiratory colonization. Fifteen subjects (7 of whom were Ureaplasma positive) received intravenous azithromycin at 20 mg/kg of body weight every 24 h for 3 doses. Azithromycin concentrations were determined in plasma samples obtained up to 168 h post-first dose by using a validated liquid chromatography-tandem mass spectrometry method. Respiratory samples were obtained predose and at three time points post-last dose for Ureaplasma culture, PCR, antibiotic susceptibility testing, and cytokine concentration determinations. Pharmacokinetic data from these 15 subjects as well as 25 additional subjects (who received either a single 10-mg/kg dose [n = 12] or a single 20-mg/kg dose [n = 13]) were analyzed by using a nonlinear mixed-effect population modeling (NONMEM) approach. Pulmonary outcomes were assessed at 36 weeks post-menstrual age and 6 months adjusted age. A 2-compartment model with all PK parameters allometrically scaled on body weight best described the azithromycin pharmacokinetics in preterm neonates. The population pharmacokinetics parameter estimates for clearance, central volume of distribution, intercompartmental clearance, and peripheral volume of distribution were 0.15 liters/h · kg0.75, 1.88 liters · kg, 1.79 liters/h · kg0.75, and 13 liters · kg, respectively. The estimated area under the concentration-time curve over 24 h (AUC24)/MIC90 value was ∼4 h. All posttreatment cultures were negative, and there were no drug-related adverse events. One Ureaplasma-positive infant died at 4 months of age, but no survivors were hospitalized for respiratory etiologies during the first 6 months (adjusted age). Thus, a 3-day course of 20 mg/kg/day intravenous azithromycin shows preliminary efficacy in eradicating Ureaplasma spp

  1. The Effect of Azithromycin in Adults with Stable Neutrophilic COPD: A Double Blind Randomised, Placebo Controlled Trial

    PubMed Central

    Simpson, Jodie L.; Powell, Heather; Baines, Katherine J.; Milne, David; Coxson, Harvey O.; Hansbro, Philip M.; Gibson, Peter G.

    2014-01-01

    Background Chronic Obstructive Pulmonary Disease (COPD) is a progressive airway disease characterised by neutrophilic airway inflammation or bronchitis. Neutrophilic bronchitis is associated with both bacterial colonisation and lung function decline and is common in exacerbations of COPD. Despite current available therapies to control inflammation, neutrophilic bronchitis remains common. This study tested the hypothesis that azithromycin treatment, as an add-on to standard medication, would significantly reduce airway neutrophil and neutrophils chemokine (CXCL8) levels, as well as bacterial load. We conducted a randomised, double-blind, placebo-controlled study in COPD participants with stable neutrophilic bronchitis. Methods Eligible participants (n = 30) were randomised to azithromycin 250 mg daily or placebo for 12 weeks in addition to their standard respiratory medications. Sputum was induced at screening, randomisation and monthly for a 12 week treatment period and processed for differential cell counts, CXCL8 and neutrophil elastase assessment. Quantitative bacteriology was assessed in sputum samples at randomisation and the end of treatment visit. Severe exacerbations where symptoms increased requiring unscheduled treatment were recorded during the 12 week treatment period and for 14 weeks following treatment. A sub-group of participants underwent chest computed tomography scans (n = 15). Results Nine participants with neutrophilic bronchitis had a potentially pathogenic bacteria isolated and the median total bacterial load of all participants was 5.22×107 cfu/mL. Azithromycin treatment resulted in a non-significant reduction in sputum neutrophil proportion, CXCL8 levels and bacterial load. The mean severe exacerbation rate was 0.33 per person per 26 weeks in the azithromycin group compared to 0.93 exacerbations per person in the placebo group (incidence rate ratio (95%CI): 0.37 (0.11,1.21), p = 0.062). For participants who underwent chest CT

  2. Molecular epidemiology in relation to azithromycin resistance in Neisseria gonorrhoeae isolates from Amsterdam, the Netherlands, between 2008 and 2015-a case-control study.

    PubMed

    Wind, Carolien M; Bruisten, Sylvia M; Schim van der Loeff, Maarten F; Dierdorp, Mirjam; de Vries, Henry J C; van Dam, Alje P

    2017-04-03

    Neisseria gonorrhoeae resistance to ceftriaxone and azithromycin increases, which threatens recommended dual therapy. We used molecular epidemiology to identify N. gonorrhoeae clusters, and associations with azithromycin resistance in Amsterdam, the Netherlands. N. gonorrhoeae isolates (n=143) were selected from patients visiting the Sexually Transmitted Infections Clinic, from January 2008 through September 2015. We included all 69 azithromycin resistant isolates (minimum inhibitory concentration [MIC] ≥2.0 mg/L), and 74 frequency matched susceptible controls (MIC ≤0.25 mg/L). Methods used were 23S rRNA and mtrR sequencing, N. gonorrhoeae multiantigen sequence typing (NG-MAST), multilocus variable-number of tandem repeat analysis (NG-MLVA) and a specific PCR to detect mosaic penA genes. A hierarchical cluster analysis of NG-MLVA related to resistance and epidemiological characteristics was performed. Azithromycin resistant isolates had significantly more often C2611T mutations of 23S rRNA (n=62, 89.9%, P<0.001), an NG-MAST genogroup G2992 (P<0.001), G5108 (P<0.001), or G359 (P=0.02), and were more often part of NG-MLVA clusters (P<0.001). Two resistant isolates (2.9%) had A2059G mutations, and five (7.3%) were wild-type 23S rRNA. No association was found between mtrR mutations and azithromycin resistance. Twenty-four isolates showed reduced susceptibility to extended-spectrum cephalosporins, including 10 azithromycin-resistant isolates. Of these, five contained a penA mosaic gene. Four of the five NG-MLVA clusters contained resistant and susceptible isolates. Two clusters consisting mainly of resistant isolates, included strains from MSM, heterosexual males and females. Co-occurrence of resistant and susceptible strains in NG-MLVA clusters and frequent occurrence of resistant strains outside of clusters suggests that azithromycin resistance develops independently from the 'background genome'.

  3. Pharmacokinetics of Transfer of Azithromycin into the Breast Milk of African Mothers.

    PubMed

    Salman, Sam; Davis, Timothy M E; Page-Sharp, Madhu; Camara, Bully; Oluwalana, Claire; Bojang, Abdoulie; D'Alessandro, Umberto; Roca, Anna

    2015-12-28

    Azithromycin (AZI) is used for its antibiotic and antimalarial properties in pregnancy. Reported estimates of AZI breast milk transfer, based on concentrations in mostly single samples from small numbers of women, have suggested that infant intake is safe. To better characterize infant intake and the associated potential benefits and risks, AZI was measured by liquid chromatography-mass spectrometry in four breast milk samples taken over 28 days postpartum from each of 20 Gambian women given 2 g AZI during labor. A population pharmacokinetic model utilizing published parameters for AZI disposition in pregnancy, the present breast milk concentrations, and increasing/decreasing sigmoid maximum-effect (Emax) functions adequately described temporal changes in the milk/plasma ratio. The median estimated absolute and relative cumulative infant doses were 4.5 mg/kg of body weight (95% prediction interval, 0.6 to 7.0 mg/kg) and 15.7% (95% prediction interval, 2.0 to 27.8%) of the maternal dose, respectively; the latter exceeded the recommended 10% safety limit. Although some infants with bacterial infections may benefit from AZI in breast milk, there is a risk of hypertrophic pyloric stenosis with a worst-case number needed to harm of 60 based on the present and available epidemiologic data. (This study has been registered at ClinicalTrials.gov under registration no. NCT01800942.).

  4. Emergence of Clinical Salmonella enterica Serovar Typhimurium Isolates with Concurrent Resistance to Ciprofloxacin, Ceftriaxone, and Azithromycin

    PubMed Central

    Wong, Marcus Ho Yin; Yan, Meiying; Chan, Edward Wai Chi; Biao, Kan

    2014-01-01

    Salmonella infection is an important public health issue for which the needs of antimicrobial treatment are increasing. A total of 546 human clinical S. enterica serovar Typhimurium isolates were recovered from patients in hospitals in China during the period of 2005 to ∼2011. Twenty percent of the isolates exhibited resistance to ciprofloxacin, and 4% were resistant to ceftriaxone. Importantly, for the first time, 12 (2%) S. Typhimurium isolates resistant to both ciprofloxacin and ceftriaxone were recovered; among these 12 isolates, two were also resistant to azithromycin, and one was resistant to all other drugs tested. The combined effects of various transferrable extended-spectrum β-lactamase determinants and a novel efflux-based ciprofloxacin resistance mechanism encoded by the mobile efflux gene oqxAB were responsible for the emergence of these extremely (highly) drug-resistant (XDR) S. Typhimurium isolates. The dissemination of resistance genes, such as those encoding ESBLs and the OqxAB pump, among Salmonella organisms will speed up the selection of XDR Salmonella, posing a huge threat to public health and Salmonella infection control. PMID:24752251

  5. New method for ophthalmic delivery of azithromycin by poloxamer/carbopol-based in situ gelling system.

    PubMed

    Cao, Feng; Zhang, Xiaolin; Ping, Qineng

    2010-01-01

    This study focused on preparation and evaluation of a thermosensitive and mucoadhesive in situ gelling ophthalmic system of azithromycin (ATM). Poloxamer 407 (P407) and poloxamer 188 (P188) were used as gelling agents. Addition of Carbopol 974P (CP 974P) to the gelling systems could increase the solubility of ATM by salt effect and enhance the mucoadhesive property of the systems. Gelation temperature of these systems ranged from 31.21-36.31 degrees C depending on the ratio of P407 and P188. Mucoadhesion force of the system composed of P407/P188/CP 974P (21/5/0.3%, w/v) was 2.3-fold that without carbopol 974P. Viscosity of the formulation was in a suitable range at 25 degrees C and pseudoplastic behavior was observed at 35 degrees C. The formulation exhibited a 24-h sustained release of ATM. In vivo resident experiments showed AUC(0-12) of ATM in rabbit tears increased by 1.78-fold for in situ gel compared with eye drop. At 12 h, tear concentrations exceeded minimum inhibitory concentration (MIC) breakpoint for the most common causative pathogens of bacterial conjunctivitis by 2.8-fold. Results in vitro and in vivo indicated that this droppable gel performed better than ATM eye drop did.

  6. Preparation and characterization of azithromycin--Aerosil 200 solid dispersions with enhanced physical stability.

    PubMed

    Li, Xuechao; Peng, Huanhuan; Tian, Bin; Gou, Jingxin; Yao, Qing; Tao, Xiaoguang; He, Haibing; Zhang, Yu; Tang, Xing; Cai, Cuifang

    2015-01-01

    The main purpose of this study was to investigate the feasibility of azithromycin (AZI)--Aerosil 200 solid dispersions specifically with high stability under accelerated condition (40 °C/75% RH). Ball milling (BM) and hot-melt extrusion (HME) were used to prepare AZI solid dispersions. The physical properties of solid dispersions were evaluated by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). For solid dispersions prepared with both methods, no crystalline of AZI was detected (except for AZI: Aerosil 200=75:25) by DSC or PXRD, indicating the amorphous state of AZI in solid dispersions. The FT-IR results demonstrated the loss of crystallization water and the formation of hydrogen bonds between Aerosil 200 and AZI during the preparation of solid dispersions. After 4 weeks storage under accelerated condition, the degree of crystallinity of AZI increased in solid dispersions prepared by BM, whereas for solid dispersions containing AZI, Aerosil 200 and glyceryl behenate (GB) prepared by HME, no crystalline of AZI was identified. This high stability can be attributed to the hydrophobic properties of GB and the presence of hydrogen bonds. Based on the above results, it is inferred the protection of hydrogen bonds between AZI and Aerosil 200 formed during preparation process effectively inhibited the recrystallization of AZI and improved the physical stability of amorphous AZI in the presence of Aerosil 200.

  7. Pharmacokinetics of Transfer of Azithromycin into the Breast Milk of African Mothers

    PubMed Central

    Page-Sharp, Madhu; Camara, Bully; Oluwalana, Claire; Bojang, Abdoulie; D'Alessandro, Umberto; Roca, Anna

    2015-01-01

    Azithromycin (AZI) is used for its antibiotic and antimalarial properties in pregnancy. Reported estimates of AZI breast milk transfer, based on concentrations in mostly single samples from small numbers of women, have suggested that infant intake is safe. To better characterize infant intake and the associated potential benefits and risks, AZI was measured by liquid chromatography-mass spectrometry in four breast milk samples taken over 28 days postpartum from each of 20 Gambian women given 2 g AZI during labor. A population pharmacokinetic model utilizing published parameters for AZI disposition in pregnancy, the present breast milk concentrations, and increasing/decreasing sigmoid maximum-effect (Emax) functions adequately described temporal changes in the milk/plasma ratio. The median estimated absolute and relative cumulative infant doses were 4.5 mg/kg of body weight (95% prediction interval, 0.6 to 7.0 mg/kg) and 15.7% (95% prediction interval, 2.0 to 27.8%) of the maternal dose, respectively; the latter exceeded the recommended 10% safety limit. Although some infants with bacterial infections may benefit from AZI in breast milk, there is a risk of hypertrophic pyloric stenosis with a worst-case number needed to harm of 60 based on the present and available epidemiologic data. (This study has been registered at ClinicalTrials.gov under registration no. NCT01800942.) PMID:26711756

  8. Differing effects of clarithromycin and azithromycin on cytokine production by murine dendritic cells

    PubMed Central

    Sugiyama, K; Shirai, R; Mukae, H; Ishimoto, H; Nagata, T; Sakamoto, N; Ishii, H; Nakayama, S; Yanagihara, K; Mizuta, Y; Kohno, S

    2007-01-01

    The macrolide antibiotics are now well known to have anti-inflammatory effects. Because dendritic cells (DCs) orchestrate immune responses, we examined the in vitro effects of clarithromycin (CAM), azithromycin (AZM) and midecamycin (MDM) on the expression of co-stimulatory molecules and production of cytokines [interleukin (IL)-10, IL-6, interferon (IFN)-γ, IL-12p40, tumour necrosis factor (TNF)-α] of murine bone marrow-derived DCs by lipopolysaccharide (LPS) stimulation. A 15-membered macrolide, AZM, and a 14-membered macrolide, CAM, significantly enhanced the intensity of a co-stimulatory molecule, CD80, on DCs but not CD86 and CD40. AZM significantly increased the production of IL-10 and CAM significantly inhibited the production of IL-6 by DCs. However, a 16-membered macrolide, MDM, did not have any significant effect on these surface markers and cytokine productions. Moreover, AZM increased IL-10 and CAM decreased IL-2 productions significantly, when naive T cells derived from spleen were co-cultured with DCs treated in advance with LPS and these macrolides. These findings suggest that 14-membered and 15-membered, but not 16-membered macrolides play as anti-inflammatory agents, at least in part, through modulating the functions of DCs. However, each macrolide affects them in different ways. PMID:17302905

  9. Development and validation of a reversed-phase HPLC method for simultaneous estimation of ambroxol hydrochloride and azithromycin in tablet dosage form.

    PubMed

    Shaikh, K A; Patil, S D; Devkhile, A B

    2008-12-15

    A simple, precise and accurate reversed-phase liquid chromatographic method has been developed for the simultaneous estimation of ambroxol hydrochloride and azithromycin in tablet formulations. The chromatographic separation was achieved on a Xterra RP18 (250 mm x 4.6 mm, 5 microm) analytical column. A Mixture of acetonitrile-dipotassium phosphate (30 mM) (50:50, v/v) (pH 9.0) was used as the mobile phase, at a flow rate of 1.7 ml/min and detector wavelength at 215 nm. The retention time of ambroxol and azithromycin was found to be 5.0 and 11.5 min, respectively. The validation of the proposed method was carried out for specificity, linearity, accuracy, precision, limit of detection, limit of quantitation and robustness. The linear dynamic ranges were from 30-180 to 250-1500 microg/ml for ambroxol hydrochloride and azithromycin, respectively. The percentage recovery obtained for ambroxol hydrochloride and azithromycin were 99.40 and 99.90%, respectively. Limit of detection and quantification for azithromycin were 0.8 and 2.3 microg/ml, for ambroxol hydrochloride 0.004 and 0.01 microg/ml, respectively. The developed method can be used for routine quality control analysis of titled drugs in combination in tablet formulation.

  10. Comparative trial of 3 days of azithromycin versus 10 days of clarithromycin in the treatment of children with acute otitis media with effusion.

    PubMed

    Arguedas, A; Loaiza, C; Rodriguez, F; Herrera, M L; Mohs, E

    1997-02-01

    The authors compared the efficacy, safety and tolerance of azithromycin and clarithromycin in pediatric patients with acute otitis media. A randomized, open clinical trial was performed comparing azithromycin and clarithromycin in children aged 6 months to 12 years of age with acute otitis media with effusion. Patients were allocated to azithromycin at 10 mg/kg once daily for 3 days or to clarithromycin at 15 mg/kg day divided into two equal doses for 10 days. Clinical examinations and tympanometric evaluations were performed at baseline, day 3-5, day 10-14, day 28-30 and day 50-60. Tympanocentesis fluid cultures were collected at enrollment and urine and blood samples were obtained at baseline and day 10-14. Of 100 patients enrolled, 97 were considered evaluable. The most common middle ear pathogens were Streptococcus pneumoniae (60%), Haemophilus influenzae (15%) and Staphylococcus aureus (13%). Fifty patients (100%) treated with azithromycin and 45 (95.7%) patients treated with clarithromycin had a satisfactory clinical response. Rates of persistence of middle ear effusion and possible drug related side effects were comparable. Based on the efficacy and safety results, azithromycin for 3 days and clarithromycin for 10 days are considered to represent an attractive alternative for the treatment of children with acute otitis media.

  11. Peak Plasma Concentration of Azithromycin and Treatment Responses in Mycobacterium avium Complex Lung Disease.

    PubMed

    Jeong, Byeong-Ho; Jeon, Kyeongman; Park, Hye Yun; Moon, Seong Mi; Kim, Su-Young; Lee, Soo-Youn; Shin, Sung Jae; Daley, Charles L; Koh, Won-Jung

    2016-10-01

    Macrolides, such as azithromycin (AZM) and clarithromycin, are the cornerstones of treatment for Mycobacterium avium complex lung disease (MAC-LD). Current guidelines recommend daily therapy with AZM for cavitary MAC-LD and intermittent therapy for noncavitary MAC-LD, but the effectiveness of these regimens has not been thoroughly investigated. This study evaluated associations between microbiological response and estimated peak plasma concentrations (Cmax) of AZM. The AZM Cmax was measured in patients receiving daily therapy (250 mg of AZM daily, n = 77) or intermittent therapy (500 mg of AZM three times weekly, n = 89) for MAC-LD and daily therapy for Mycobacterium abscessus complex LD (MABC-LD) (250 mg of AZM daily, n = 55). The AZM Cmax was lower with the daily regimen for MAC-LD (median, 0.24 μg/ml) than with the intermittent regimen for MAC-LD (median, 0.65 μg/ml; P < 0.001) or daily therapy for MABC-LD (median, 0.53 μg/ml; P < 0.001). After adjusting for confounding factors, AZM Cmax was independently associated with favorable microbiological responses in MAC-LD patients receiving a daily regimen (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 1.01 to 2.48; P = 0.044) but not an intermittent regimen (aOR, 0.85; 95% CI, 0.58 to 1.23, P = 0.379). With the daily AZM-based multidrug regimen for MAC-LD, a low AZM Cmax was common, whereas a higher AZM Cmax was associated with favorable microbiologic responses. The results also suggested that the addition of rifampin may lower AZM Cmax When a daily AZM-based multidrug regimen is used for treating severe MAC-LD, such as cavitary disease, the currently recommended AZM dose might be suboptimal. (This study has been registered at ClinicalTrials.gov under identifier NCT00970801.).

  12. [Efficacy and safety of azithromycin infusion in patients with mild or moderate community-acquired pneumonia].

    PubMed

    Noguchi, Shingo; Yatera, Kazuhiro; Kawanami, Toshinori; Yamasaki, Kei; Uchimura, Keigo; Hata, Ryosuke; Tachiwada, Takashi; Oda, Keishi; Hara, Kanako; Suzuki, Yu; Akata, Kentarou; Ogoshi, Takaaki; Tokuyama, Susumu; Inoue, Naoyuki; Nishida, Chinatsu; Orihashi, Takeshi; Yoshida, Yugo; Kawanami, Yukiko; Taura, Yusuke; Ishimoto, Hiroshi; Obata, Hideto; Tsuda, Toru; Yoshii, Chiharu; Mukae, Hiroshi

    2014-06-01

    Azithromycin (AZM) is one of 15-membered rings macrolide antibiotics with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria. So far, there had been no reports of the prospective studies evaluating efficacy and safety of AZM infusion in patients with mild or moderate community-acquired pneumonia (CAP). This study was conducted to evaluate prospectively the efficacy and safety of AZM in patients with mild or moderate CAP. AZM 500 mg was intravenously administered once daily, and the clinical efficacy were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-four patients were firstly registered, and eventually 61 and 62 patients were enrolled for the evaluation of clinical efficacy and safety of AZM, respectively. The efficacy of AZM in 61 patients evaluated was 88.5%. In addition, the efficacies of AZM in each pneumonia severity index by A-DROP system by the Japanese Respiratory Society (JRS) guideline in CAP were 85.2% in mild and 91.2% in moderate. Furthermore, the efficacy of AZM in each differentiation between suspicion of bacterial pneumonia and that of atypical pneumonia by JRS guideline in CAP were 91.7% in suspicion of atypical pneumonia, and its efficacy was high than that of bacterial pneumonia. Nineteen patients (20 cases; 15 with liver dysfunction, 4 with diarrhea, 1 with vascular pain) out of 62 patients were reported to have possible adverse effects of AZM. All of the patients with these adverse effects demonstrated mild dysfunction and continued AZM treatment, and these dysfunctions normalized soon after cessation of AZM. In conclusion, AZM is effective drug for patients with mild or moderate CAP, and we believe that it may be one of effective choice in the treatment of CAP patients who need hospitalization.

  13. Zika virus cell tropism in the developing human brain and inhibition by azithromycin

    PubMed Central

    Retallack, Hanna; Di Lullo, Elizabeth; Arias, Carolina; Knopp, Kristeene A.; Laurie, Matthew T.; Sandoval-Espinosa, Carmen; Mancia Leon, Walter R.; Krencik, Robert; Ullian, Erik M.; Spatazza, Julien; Pollen, Alex A.; Mandel-Brehm, Caleigh; Nowakowski, Tomasz J.; Kriegstein, Arnold R.; DeRisi, Joseph L.

    2016-01-01

    The rapid spread of Zika virus (ZIKV) and its association with abnormal brain development constitute a global health emergency. Congenital ZIKV infection produces a range of mild to severe pathologies, including microcephaly. To understand the pathophysiology of ZIKV infection, we used models of the developing brain that faithfully recapitulate the tissue architecture in early to midgestation. We identify the brain cell populations that are most susceptible to ZIKV infection in primary human tissue, provide evidence for a mechanism of viral entry, and show that a commonly used antibiotic protects cultured brain cells by reducing viral proliferation. In the brain, ZIKV preferentially infected neural stem cells, astrocytes, oligodendrocyte precursor cells, and microglia, whereas neurons were less susceptible to infection. These findings suggest mechanisms for microcephaly and other pathologic features of infants with congenital ZIKV infection that are not explained by neural stem cell infection alone, such as calcifications in the cortical plate. Furthermore, we find that blocking the glia-enriched putative viral entry receptor AXL reduced ZIKV infection of astrocytes in vitro, and genetic knockdown of AXL in a glial cell line nearly abolished infection. Finally, we evaluate 2,177 compounds, focusing on drugs safe in pregnancy. We show that the macrolide antibiotic azithromycin reduced viral proliferation and virus-induced cytopathic effects in glial cell lines and human astrocytes. Our characterization of infection in the developing human brain clarifies the pathogenesis of congenital ZIKV infection and provides the basis for investigating possible therapeutic strategies to safely alleviate or prevent the most severe consequences of the epidemic. PMID:27911847

  14. Novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus

    PubMed Central

    Liu, Xiaowei; Li, Zhan; Wang, Xiaodong; Chen, Yujuan; Wu, Fengbo; Men, Ke; Xu, Ting; Luo, Yan; Yang, Li

    2016-01-01

    Infections caused by multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), have become a public threat; therefore, development of new antimicrobial drugs or strategies is urgently required. In this study, a new antibacterial peptide DP7-C (Chol-suc-VQWRIRVAVIRK-NH2) and DP7-C-modified azithromycin (AZT)-loaded liposomes (LPs) are developed for the treatment of MRSA infection, and it was found that DP7-C inserted into the LP lipid bilayer not only functioned as a carrier to encapsulate the antibiotic AZT but also synergized the antibacterial effect of the encapsulated AZT. In vitro assays showed that DP7-C-modified LPs possessed sustained drug release profile and immune regulatory effect and did not show obvious cytotoxicity in mammal cells, but they did not possess direct antibacterial activity in vitro. In vivo studies revealed that DP7-C-modified LPs did not exhibit obvious side effects or toxicity in mice but were able to significantly reduce the bacterial counts in an MRSA-infectious mouse model and possessed high antibacterial activity. In particular, DP7-C-modified AZT-loaded LPs showed more positive therapeutic effects than either DP7-C-modified blank LPs or nonmodified AZT-loaded LPs treatment alone. Molecular mechanism studies demonstrated that DP7-C formulations effectively upregulated the production of anti-inflammatory cytokines and chemokines without inducing harmful immune response, suggesting that DP7-C was synergistic with AZT against the bacterial infection by activating the innate immune response. Most importantly, although DP7-C activated the innate immune response, it did not possess direct antibacterial activity in vitro, indicating that DP7-C did not possess the potential to induce bacteria resistance. The findings indicate that DP7-C-modified AZT-loaded LPs developed in this study have a great potential required for the clinical treatment of MRSA infections. PMID:28008253

  15. Relationship between Azithromycin Susceptibility and Administration Efficacy for Nontypeable Haemophilus influenzae Respiratory Infection

    PubMed Central

    Euba, Begoña; Moleres, Javier; Viadas, Cristina; Barberán, Montserrat; Caballero, Lucía; Grilló, María-Jesús; Bengoechea, José Antonio; de-Torres, Juan Pablo; Liñares, Josefina; Leiva, José

    2015-01-01

    Nontypeable Haemophilus influenzae (NTHI) is an opportunistic pathogen that is an important cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). COPD is an inflammatory disease of the airways, and exacerbations are acute inflammatory events superimposed on this background of chronic inflammation. Azithromycin (AZM) is a macrolide antibiotic with antibacterial and anti-inflammatory properties and a clinically proven potential for AECOPD prevention and management. Relationships between AZM efficacy and resistance by NTHI and between bactericidal and immunomodulatory effects on NTHI respiratory infection have not been addressed. In this study, we employed two pathogenic NTHI strains with different AZM susceptibilities (NTHI 375 [AZM susceptible] and NTHI 353 [AZM resistant]) to evaluate the prophylactic and therapeutic effects of AZM on the NTHI-host interplay. At the cellular level, AZM was bactericidal toward intracellular NTHI inside alveolar and bronchial epithelia and alveolar macrophages, and it enhanced NTHI phagocytosis by the latter cell type. These effects correlated with the strain MIC of AZM and the antibiotic dose. Additionally, the effect of AZM on NTHI infection was assessed in a mouse model of pulmonary infection. AZM showed both preventive and therapeutic efficacies by lowering NTHI 375 bacterial counts in lungs and bronchoalveolar lavage fluid (BALF) and by reducing histopathological inflammatory lesions in the upper and lower airways of mice. Conversely, AZM did not reduce bacterial loads in animals infected with NTHI 353, in which case a milder anti-inflammatory effect was also observed. Together, the results of this work link the bactericidal and anti-inflammatory effects of AZM and frame the efficacy of this antibiotic against NTHI respiratory infection. PMID:25712355

  16. Impact of Azithromycin on the Quorum Sensing-Controlled Proteome of Pseudomonas aeruginosa

    PubMed Central

    Swatton, J. E.; Davenport, P. W.; Maunders, E. A.; Griffin, J. L.; Lilley, K. S.; Welch, M.

    2016-01-01

    The macrolide antibiotic, azithromycin (AZM), has been reported to improve the clinical outcome of cystic fibrosis patients, many of whom are chronically-infected with Pseudomonas aeruginosa. However, the highest clinically-achievable concentrations of this drug are well-below the minimum inhibitory concentration for P. aeruginosa, raising the question of why AZM exhibits therapeutic activity. One possibility that has been raised by earlier studies is that AZM inhibits quorum sensing (QS) by P. aeruginosa. To explicitly test this hypothesis the changes brought about by AZM treatment need to be compared with those associated with specific QS mutants grown alongside in the same growth medium, but this has not been done. In this work, we used quantitative 2D-difference gel electrophoresis and 1H-NMR spectroscopy footprint analysis to examine whether a range of clinically-relevant AZM concentrations elicited proteomic and metabolomic changes in wild-type cultures that were similar to those seen in cultures of defined QS mutants. Consistent with earlier reports, over half of the AZM-induced spot changes on the 2D gels were found to affect QS-regulated proteins. However, AZM modulated very few protein spots overall (compared with QS) and collectively, these modulated proteins comprised only a small fraction (12–13%) of the global QS regulon. We conclude that AZM perturbs a sub-regulon of the QS system but does not block QS per se. Reinforcing this notion, we further show that AZM is capable of attenuating virulence factor production in another Gram-negative species that secretes copious quantities of exoenzymes (Serratia marcescens), even in the absence of a functional QS system. PMID:26808156

  17. Impact of azithromycin resistance mutations on the virulence and fitness of Chlamydia caviae in guinea pigs.

    PubMed

    Binet, Rachel; Bowlin, Anne K; Maurelli, Anthony T; Rank, Roger G

    2010-03-01

    Azithromycin (AZM) is a major drug used in the treatment and prophylaxis of infections caused by Chlamydia, yet no significant clinical resistance has been reported for these obligate intracellular bacteria. Nevertheless, spontaneous AZM resistance (Azm(r)) arose in vitro at frequencies ranging from 3 x 10(-8) to 8 x 10(-10) for clonal isolates of Chlamydia caviae, which is a natural pathogen of guinea pigs. Sequencing of the unique 23S rRNA gene copy in 44 independent Azm(r) isolates identified single mutations at position A(2058) or A(2059) (Escherichia coli numbering system). While SP(6)AZ(1) (A(2058)C) and SP(6)AZ(2) (A(2059)C) Azm(r) mutants showed growth defects in cell culture and were less pathogenic in the guinea pig ocular infection model than in the parent SP(6), the three isogenic C. caviae isolates grew equally well in the animal. On the other hand, coinoculation of the C. caviae parent strain with one of the Azm(r) strains was detrimental for the mutant strain. This apparent lack of association between pathology and bacterial load in vivo showed that virulence of the two Azm(r) mutants of C. caviae was attenuated. While chlamydial growth in vitro reflects the ability of the bacteria to multiply in permissive cells, survival in the host is a balance between cellular multiplication and clearance by the host immune system. The obligate intracellular nature of Chlamydia may therefore limit emergence of resistance in vivo due to the strength of the immune response induced by the wild-type antibiotic-sensitive bacteria at the time of antibiotic treatment.

  18. Microbiological and Clinical Effects of Sitafloxacin and Azithromycin in Periodontitis Patients Receiving Supportive Periodontal Therapy

    PubMed Central

    Okui, Takafumi; Ito, Harue; Nakajima, Mayuka; Honda, Tomoyuki; Shimada, Yasuko; Tabeta, Koichi; Akazawa, Kohei

    2016-01-01

    Sitafloxacin (STFX) is a newly developed quinolone that has robust antimicrobial activity against periodontopathic bacteria. We previously reported that oral administration of STFX during supportive periodontal therapy was as effective as conventional mechanical debridement under local anesthesia microbiologically and clinically for 3 months. The aim of the present study was to examine the short-term and long-term microbiological and clinical effects of systemic STFX and azithromycin (AZM) on active periodontal pockets during supportive periodontal therapy. Fifty-one patients receiving supportive periodontal therapy were randomly allocated to the STFX group (200 mg/day of STFX for 5 days) or the AZM group (500 mg/day of AZM for 3 days). The microbiological and clinical parameters were examined until 12 months after the systemic administration of each drug. The concentration of each drug in periodontal pockets and the antimicrobial susceptibility of clinical isolates were also analyzed. The proportions of red complex bacteria, i.e., Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, which are the representative periodontopathic bacteria, were significantly reduced at 1 month and remained lower at 12 months than those at baseline in both the STFX and AZM groups. Clinical parameters were significantly improved over the 12-month period in both groups. An increase in the MIC of AZM against clinical isolates was observed in the AZM group. These results indicate that monotherapy with systemic STFX and AZM might be an alternative treatment during supportive periodontal therapy in patients for whom invasive mechanical treatment is inappropriate. (This study has been registered with the University Hospital Medical Information Network-Clinical Trials Registry [UMIN-CTR] under registration number UMIN000007834.) PMID:26729495

  19. Killing of Streptococcus pneumoniae by azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin using drug minimum inhibitory concentrations and mutant prevention concentrations.

    PubMed

    Blondeau, J M; Shebelski, S D; Hesje, C K

    2015-06-01

    Streptococcus pneumoniae continues to be a significant respiratory pathogen, and increasing antimicrobial resistance compromises the use of β-lactam and macrolide antibiotics. Bacterial eradication impacts clinical outcome, and bacterial loads at the site of infection may fluctuate. Killing of two macrolide- and quinolone-susceptible clinical S. pneumoniae isolates by azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin against varying bacterial densities was determined using the measured minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC). For kill experiments, 10(6)-10(9) CFU/mL were exposed to the drug and were sampled at 0, 0.5, 1, 2, 3, 4, 6, 12 and 24 h following drug exposure. The log(10) reduction and percent reduction (kill) of viable cells was recorded. MICs and MPCs (mg/L) for azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin were 0.063-0.125/0.5-1, 0.031-0.063/0.25-0.5, 0.063/0.25-0.5, 0.008/0.016 and 0.031/0.25, respectively. Killing 10(6)-10(9) CFU/mL of bacteria by the drug MIC yielded incomplete killing, however log10 reductions occurred by 12 h and 24 h for all drugs. Exposure of 10(6)-10(9) CFU/mL to MPC drug concentrations resulted in the following log(10) reduction by 6h of drug exposure: azithromycin, 1.3-3.9; clarithromycin, 1.9-5.8; erythromycin, 0.8-4.7; telithromycin, 0.3-1.7; and gemifloxacin, 1.8-4.2. Bacterial loads at the site of infection may range from 10(6) to 10(9), and kill experiments utilising a higher bacterial inoculum provided a more accurate measure of antibiotic performance in high biomass situations. Killing was slower with telithromycin. Kill was greater and fastest with MPC versus MIC drug concentrations.

  20. Oral azithromycin given during labour decreases bacterial carriage in the mothers and their offspring: a double-blind randomized trial.

    PubMed

    Roca, A; Oluwalana, C; Bojang, A; Camara, B; Kampmann, B; Bailey, R; Demba, A; Bottomley, C; D'Alessandro, U

    2016-06-01

    Bacterial sepsis remains a leading cause of death among neonates with Staphylococcus aureus, group B streptococcus (GBS) and Streptococcus pneumoniae identified as the most common causative pathogens in Africa. Asymptomatic bacterial colonization is an intermediate step towards sepsis. We conducted a phase III, double-blind, placebo-controlled randomized trial to determine the impact of giving one oral dose of azithromycin to Gambian women in labour on the nasopharyngeal carriage of S. aureus, GBS or S. pneumoniae in the newborn at day 6 postpartum. Study participants were recruited in a health facility in western Gambia. They were followed for 8 weeks and samples were collected during the first 4 weeks. Between April 2013 and April 2014 we recruited 829 women who delivered 843 babies, including 13 stillbirths. Sixteen babies died during the follow-up period. No maternal deaths were observed. No serious adverse events related to the intervention were reported. According to the intent-to-treat analysis, prevalence of nasopharyngeal carriage of the bacteria of interest in the newborns at day 6 was lower in the intervention arm (28.3% versus 65.1% prevalence ratio 0.43; 95% CI 0.36-0.52, p <0.001). At the same time-point, prevalence of any bacteria in the mother was also lower in the azithromycin group (nasopharynx, 9.3% versus 40.0%, p <0.001; breast milk, 7.9% versus 21.6%, p <0.001; and the vaginal tract, 13.2% versus 24.2%, p <0.001). Differences between arms lasted for at least 4 weeks. Oral azithromycin given to women in labour decreased the carriage of bacteria of interest in mothers and newborns and may lower the risk of neonatal sepsis. Trial registrationClinicalTrials.gov Identifier NCT01800942.

  1. A Single Dose Oral Azithromycin versus Intramuscular Benzathine Penicillin for the Treatment of Yaws-A Randomized Non Inferiority Trial in Ghana

    PubMed Central

    2017-01-01

    Background Yaws is a treponemal infection that was almost eradicated fifty years ago; however, the disease has re-emerged in a number of countries including Ghana. A single-dose of intramuscular benzathine penicillin has been the mainstay of treatment for yaws. However, intramuscular injections are painful and pose safety and logistical constraints in the poor areas where yaws occurs. A single center randomized control trial (RCT) carried out in Papua New Guinea in 2012 demonstrated the efficacy of a single-dose of oral azithromycin for the treatment of yaws. In this study, we also compared the efficacy of a single oral dose of azithromycin as an alternative to intramuscular benzathine penicillin for the treatment of the disease in another geographic setting. Methodology We conducted an open-label, randomized non-inferiority trial in three neighboring yaws-endemic districts in Southern Ghana. Children aged 1–15 years with yaws lesions were assigned to receive either 30mg/kg of oral azithromycin or 50,000 units/kg of intramuscular benzathine penicillin. The primary end point was clinical cure rate, defined as a complete or partial resolution of lesions 3 weeks after treatment. The secondary endpoint was serological cure, defined as at least a 4-fold decline in baseline RPR titre 6 months after treatment. Non- inferiority of azithromycin treatment was determined if the upper bound limit of a 2 sided 95% CI was less than 10%. Findings The mean age of participants was 9.5 years (S.D.3.1, range: 1–15 years), 247(70%) were males. The clinical cure rates were 98.2% (95% CI: 96.2–100) in the azithromycin group and 96.9% (95% CI: 94.1–99.6) in the benzathine penicillin group. The serological cure rates at 6 months were 57.4% (95% CI: 49.9–64.9) in the azithromycin group and 49.1% (95% CI: 41.2–56.9) in the benzathine penicillin group, thus achieving the specified criteria for non-inferiority. Conclusions A single oral dose of azithromycin, at a dosage of 30mg

  2. Human serum activity of telithromycin, azithromycin and amoxicillin/clavulanate against common aerobic and anaerobic respiratory pathogens.

    PubMed

    Stein, Gary E; Schooley, Sharon; Tyrrell, Kerin L; Citron, Diane M; Goldstein, Ellie J C

    2007-01-01

    Telithromycin is a new ketolide antimicrobial with a good in vitro activity against both aerobic and anaerobic respiratory pathogens. In this study, we evaluated the antibacterial activity over time of telithromycin (800mg), azithromycin (500mg), and amoxicillin/clavulanate (875/125mg) in serum following single oral doses of these agents to 10 healthy subjects. Inhibitory and bactericidal titers were determined at 2, 6, 12, and 24h after each dose and the median titer was used to determine antibacterial activity. Against two azithromycin-resistant strains of Streptococcus pneumoniae, both telithromycin (MIC=0.25 and 0.5 microg/mL) and amoxicillin/clavulanate exhibited inhibitory and cidal activity for at least 6h. All three antibiotics provided prolonged (>or=12h) inhibitory activity against strains of Hemophilus influenzae (telithromycin MIC=4.0 microg/ml). Both telithromycin and amoxicillin/clavulanate exhibited rapid and prolonged inhibitory activity (>or=12h) against each of the anaerobes studied (Finegoldia [Peptostreptococcus] magna Peptostreptococcus micros, Prevotella bivia, and Prevotella melaninogenica). Moreover, both agents provided bactericidal activity against both Prevotella species. In this ex vivo pharmacodynamic study, we found that telithromycin provided rapid and prolonged antibacterial activity in serum against macrolide-resistant strains of S. pneumoniae, beta-lactamase-positive and -negative strains of H. influenzae, and common respiratory anaerobic pathogens. These findings suggest that telithromycin could have clinical utility in the treatment of community-acquired mixed aerobic-anaerobic respiratory tract infections, including chronic sinusitis and aspiration pneumonia.

  3. Expression comparison of azithromycin and clarithromycin in triple-therapy regimens for eradication of Helicobacter pylori in hemodialysis patients.

    PubMed

    Vafaeimanesh, Jamshid; Jalalzadeh, Mojgan; Nazarian, Morteza

    2014-01-01

    To compare a triple-therapy regimen based on change of antibiotic (azithromycin and clarithromycin) for the eradication of Helicobacter pylori in hemodialysis (HD) patients, we studied in a prospective, randomized, double-blinded clinical trial 39 patients who had dyspepsia and showed two positive results from the diagnostic tests of H. pylori infection including anti-H. pylori serology and stool antigen (HpSAg) and urease breath test (UBT). The patients were divided into two groups: Group-A received omeprazol 20 mg, amoxycilin 500 mg and clarithromycin 500 mg twice a day and Group-B received omeprazol 20 mg, amoxicillin 500 mg and azithromycin 250 mg twice a day. The adverse events and compliance with triple therapy were reviewed at one visit per week. Both groups were prescribed their medications for 14 days. Of the 39 patients, only 37 patients completed the treatment schedule (20 men and 19 women, with the mean being 59 years). Two patients died due to myocardial infarction before the start of treatment and were out of the study. The eradication rate of H. pylori, evaluated by negative results of UBT, was 82.4% in Group-A and 80% in Group-B (P-value = 1.0). The results of our study showed no significant difference of azitromycin versus claritromycin in the eradication of H. pylori infection in HD patients.

  4. Prevalence of Active and Latent Yaws in the Solomon Islands 18 Months after Azithromycin Mass Drug Administration for Trachoma

    PubMed Central

    Sokana, Oliver; Nachamkin, Eli; Puiahi, Elliot; Kilua, Georgina; Pillay, Allan; Bottomley, Christian; Solomon, Anthony W.; Mabey, David C.

    2016-01-01

    Introduction Both yaws and trachoma are endemic in the Pacific. Mass treatment with azithromycin is the mainstay of the WHO strategy for both the eradication of yaws and the elimination of trachoma as a public health problem, but the dose recommended for trachoma is lower than that for yaws. In countries where both diseases are endemic, there is a potential for synergy between yaws and trachoma control programs if mass treatment with the lower dose of azithromycin was shown to be effective for the treatment of yaws. In an earlier study, we demonstrated a profound reduction in the clinical and serological prevalence of yaws following a single round of mass treatment with azithromycin 20 mg/kg undertaken for the purposes of trachoma elimination. Methods This survey was conducted 18 months following a single round of azithromycin mass treatment in the same communities in which we had conducted our previous six-month follow-up survey. We examined children aged 1–14 years and took blood and lesion samples for yaws diagnosis using the Treponema pallidum particle agglutination assay (TPPA) and the non-treponemal Rapid Plasma Reagin (RPR) test. Results A total of 1,284 children were enrolled in the study. Amongst children aged 5–14 years, 223 had a positive TPPA (27.5%, 95% CI 13.6–47.7%). The TPPA seroprevalence amongst this age group did not differ significantly from either our pre-mass treatment survey or our initial follow-up survey. Thirty-five children had positive TPPA and positive RPR (4.3%, 95% CI 2.1–8.7%), and this did not differ significantly from our initial post-mass drug administration (MDA) follow-up survey (4.3% versus 3.5%, p = 0.43) but remained significantly lower than our initial pre-MDA survey (4.3% vs 21.7%, p <0.0001). Village-level MDA coverage was strongly associated with dual-seropositivity (p = 0.005). Amongst children aged 1–4 years, 16 had a positive TPPA (3.5%, 95% CI 1.6–7.1%). This did not differ significantly from the

  5. The effect of carbon dioxide on susceptibility testing of azithromycin, clarithromycin and roxithromycin against clinical isolates of Streptococcus pneumoniae and Streptococcus pyogenes by broth microdilution and the Etest: Artemis Project-first-phase study.

    PubMed

    Johnson, Jack; Bouchillon, Sam; Pontani, Dennis

    1999-06-01

    OBJECTIVE: To evaluate the effect of carbon dioxide on the susceptibility testing, using broth microdilution and the Etest (AB Biodisk, Solna, Sweden), of azithromycin, clarithromycin and roxithromycin against Streptococcus pneumoniae and Streptococcus pyogenes. METHODS: Fresh clinical isolates collected from 36 hospital laboratories in 12 countries were evaluated using the Etest in the presence of carbon dioxide. The isolates were retested under ambient conditions (absence of carbon dioxide) using broth microdilution and/or the Etest. RESULTS: Carbon dioxide falsely elevated azithromycin, clarithromycin and roxithromycin MIC90S for S. pneumoniae, determined by the Etest, approximately 12-fold. Also, the azithromycin MIC90 for S. pyogenes was increased fourfold; the effect was less marked for clarithromycin and roxithromycin. When isolates were retested in the absence of carbon dioxide, using the Etest or microdilution, susceptibilities to azithromycin were comparable to those to clarithromycin (S. pneumoniae, 93.4% versus 91.3%; S. pyogenes, 96.4% versus 95.8%). Both organisms were less susceptible to roxithromycin (S. pneumoniae, 71.3%; S. pyogenes, 85.7%). An internal standard control, consisting of 50 isolates each of S. pneumoniae, S. pyogenes and Haemophilus influenzae, confirmed that azithromycin susceptibility testing resulted in falsely elevated MICs. CONCLUSIONS: Carbon dioxide falsely elevated azithromycin MICs for S. pneumoniae and S. pyogenes, with an apparent reduction in susceptibility. When the in vitro activity of azithromycin and other macrolides against S. pneumoniae and S. pyogenes is being evaluated, awareness of the pH effect is essential.

  6. Topical azithromycin and clarithromycin inhibit acute and chronic skin inflammation in sensitized mice, with apparent selectivity for Th2-mediated processes in delayed-type hypersensitivity.

    PubMed

    Ivetić Tkalčević, Vanesa; Cužić, Snježana; Kramarić, Miroslava Dominis; Parnham, Michael J; Eraković Haber, Vesna

    2012-02-01

    Macrolide antibiotics inhibit the secretion of Th1 cytokines while their effects on the release of Th2 cytokines are variable. We investigated molecular and cellular markers of Th1- and Th2-mediated inflammatory mechanisms and the anti-inflammatory activity of azithromycin and clarithromycin in phorbol 12-myristate 13-acetate (PMA) and oxazolone (OXA)-induced skin inflammation. Dexamethasone (50 μg/ear), azithromycin, and clarithromycin (500 μg/ear) reduced TNF-α and interleukin (IL)-1β concentration in ear tissue by inhibiting inflammatory cell accumulation in PMA-induced inflammation. In OXA-induced early delayed-type hypersensitivity (DTH), the macrolides (2 mg/ear) and dexamethasone (25 μg/ear) reduced ear tissue inflammatory cell infiltration and secretion of IL-4 while clarithromycin also decreased IFN-γ concentration. Macrolides showed better activity when administered after the challenge. In OXA-induced chronic DTH, azithromycin (1 mg/ear) reduced the number of ear tissue mast cells and decreased the concentration of IL-4 in ear tissue and of immunoglobulin (Ig)E in serum. Clarithromycin (1 mg/ear) reduced serum IgE concentration, possibly by a mechanism independent of IL-4, while both macrolides attenuated mast cell degranulation. In conclusion, azithromycin and clarithromycin attenuate pro-inflammatory cytokine production and leukocyte infiltration during innate immune reactions, while selectively affecting Th2 rather than Th1 immunity in DTH reactions.

  7. Failure of oral antibiotic therapy, including azithromycin, in the treatment of a recurrent breast abscess caused by Salmonella enterica serotype Paratyphi A

    PubMed Central

    Fernando, Shelanah; Molland, Janice Gail; Gottlieb, Thomas

    2012-01-01

    We report a case of recurrent, multifocal Salmonella enterica serotype Paratyphi A breast abscesses, resistant to ciprofloxacin, which relapsed despite surgery, aspiration and multiple courses of antibiotics, including co-trimoxazole and azithromycin. The patient was cured after a prolonged course of intravenous ceftriaxone. PMID:23182142

  8. In vitro characterization of pH-sensitive azithromycin-loaded methoxy poly (ethylene glycol)-block-poly (aspartic acid-graft-imidazole) micelles.

    PubMed

    Teng, Fangfang; Deng, Peizong; Song, Zhimei; Zhou, Feilong; Feng, Runliang; Liu, Na

    2017-02-09

    In order to improve azithromycin's antibacterial activity in acidic medium, monomethoxy poly (ethylene glycol)-block-poly (aspartic acid-graft-imidazole) copolymer was synthesized through allylation, free radical addition, ring-opening polymerization and amidation reactions with methoxy poly (ethylene glycol) as raw material. Drug loading capacity and encapsulation efficiency of azithromycin-loaded micelles prepared via thin film hydration method were 11.58±0.86% and 96.06±1.93%, respectively. The drug-loaded micelles showed pH-dependent property in the respects of particle size, zeta potential at the range of pH 5.5-7.8. It could control drug in vitro release and demonstrate higher release rate at pH 6.0 than that at pH 7.4. In vitro antibacterial experiment indicated that the activity of azithromycin-loaded micelles against S. aureus was superior to free azithromycin in medium at both pH 6.0 and pH 7.4. Using fluorescein as substitute with pH-dependent fluorescence decrease property, laser confocal fluorescence microscopy analysis confirmed that cellular uptake of micelles was improved due to protonation of copolymer's imidazole groups at pH 6.0. The enhanced cellular uptake and release of drug caused its activity enhancement in acidic medium when compared with free drug. The micellar drug delivery system should be potential application in the field of bacterial infection treatment.

  9. Activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine compared with that of clarithromycin against multiplication of Mycobacterium avium complex within human macrophages.

    PubMed Central

    Perronne, C; Gikas, A; Truffot-Pernot, C; Grosset, J; Vilde, J L; Pocidalo, J J

    1991-01-01

    The activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine against two virulent strains of the Mycobacterium avium complex isolated from patients with AIDS were evaluated in a model of intracellular infection and were compared with that of clarithromycin. Human monocyte-derived macrophages were infected with the M. avium complex at day 6 of culture. The intracellular CFU was counted 60 min after inoculation. The intracellular and supernatant CFU was counted on days 4 and 7 after inoculation. The concentrations used, which were equal to peak levels in serum, were 10 micrograms of rifapentine per ml (MICs for the two strains, 4 and 16 micrograms/ml), 4 micrograms of clarithromycin per ml (MICs, 8 and 4 micrograms/ml), 1 microgram of azithromycin per ml (MICs, 32 and 16 micrograms/ml), 4 micrograms of temafloxacin per ml (MICs, 2 and 16 micrograms/ml), and 1 microgram of sparfloxacin per ml (MICs, 0.5 and 2 micrograms/ml). Compared with controls on day 7 after inoculation, clarithromycin (P less than 0.001), sparfloxacin (P less than 0.001), and azithromycin (P less than 0.001 for the first strain, P less than 0.02 for the second) slowed intracellular replication. Rifapentine (P less than 0.001) and temafloxacin (P less than 0.001) slowed intracellular replication of the first strain but not of the second strain. Azithromycin plus sparfloxacin was as effective as sparfloxacin alone. In this macrophage model, sparfloxacin or clarithromycin (difference not significant) exhibited a better efficacy than rifapentine, azithromycin, or temafloxacin against intracellular M. avium complex infection. PMID:1656860

  10. How Much Surface Coating of Hydrophobic Azithromycin Is Sufficient to Prevent Moisture-Induced Decrease in Aerosolisation of Hygroscopic Amorphous Colistin Powder?

    PubMed

    Zhou, Qi Tony; Loh, Zhi Hui; Yu, Jiaqi; Sun, Si-Ping; Gengenbach, Thomas; Denman, John A; Li, Jian; Chan, Hak-Kim

    2016-09-01

    Aerosolisation performance of hygroscopic particles of colistin could be compromised at elevated humidity due to increased capillary forces. Co-spray drying colistin with a hydrophobic drug is known to provide a protective coating on the composite particle surfaces against moisture-induced reduction in aerosolisation performance; however, the effects of component ratio on surface coating quality and powder aerosolisation at elevated relative humidities are unknown. In this study, we have systematically examined the effects of mass ratio of hydrophobic azithromycin on surface coating quality and aerosolisation performance of the co-spray dried composite particles. Four combination formulations with varying drug ratios were prepared by co-spray drying drug solutions. Both of the drugs in each combination formulation had similar in vitro deposition profiles, suggesting that each composite particle comprises two drugs in the designed mass ratio, which is supported by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) data. XPS and ToF-SIMS measurements also revealed that 50% by weight (or 35% by molecular fraction) of azithromycin in the formulation provided a near complete coating of 96.5% (molar fraction) on the composite particle surface, which is sufficient to prevent moisture-induced reduction in fine particle fraction (FPF)recovered and FPFemitted. Higher azithromycin content did not increase coating coverage, while contents of azithromycin lower than 20% w/w did not totally prevent the negative effects of humidity on aerosolisation performance. This study has highlighted that a critical amount of azithromycin is required to sufficiently coat the colistin particles for short-term protection against moisture.

  11. Prevalence of Trachoma in Car-Nicobar Island, India after Three Annual Rounds of Mass Drug Administration with Azithromycin

    PubMed Central

    Malhotra, Sumit; Vashist, Praveen; Gupta, Noopur; Kalaivani, Mani; Satpathy, Gita; Shah, Anita; Krishnan, Sujaya; Azad, Rajvardhan

    2016-01-01

    Background A high proportion of active trachoma infection in children of Car-Nicobar Island was reported through the Trachoma Rapid Assessment survey conducted in year 2010 by the same researchers. Annual mass drug treatment with azithromycin was administered from years 2010–12 to all individuals residing in this island for reducing the burden of active trachoma infection. A cross-sectional prevalence survey was conducted in the year 2013 to assess the post-treatment burden of trachoma in this population. Methods In the 15 randomly selected compact segments from each village of the island, children aged 1–9 years were examined for evidence of active trachoma infection and participants aged ten years and above were examined for trachomatous trichiasis and corneal opacity. Results A total of 809 children (1–9 years) and 2735 adults were examined. Coverage with azithromycin for all the three rounds was more than 80%. The prevalence of active trachoma infection in children aged 1–9 years old was 6.8% (95% CI 5.1, 8.5) and Trachomatous Trichiasis (TT) was 3.9% (95% CI 3.2, 4.6). The risk factors associated with active trachoma infection were older age and unclean faces. The risk factors associated with TT were older age and lower literacy level. Conclusion Trachoma has not been eliminated from Car-Nicobar Island in accordance to ‘Global Elimination of Trachoma, 2020’ guidelines. Sustained efforts and continuous surveillance admixed with adequate programmatic response is imperative for elimination of trachoma in the island. PMID:27391274

  12. Vibrio cholerae O1 with Reduced Susceptibility to Ciprofloxacin and Azithromycin Isolated from a Rural Coastal Area of Bangladesh

    PubMed Central

    Rashed, Shah M.; Hasan, Nur A.; Alam, Munirul; Sadique, Abdus; Sultana, Marzia; Hoq, Md. Mozammel; Sack, R. Bradley; Colwell, Rita R.; Huq, Anwar

    2017-01-01

    Cholera outbreaks occur each year in the remote coastal areas of Bangladesh and epidemiological surveillance and routine monitoring of cholera in these areas is challenging. In this study, a total of 97 Vibrio cholerae O1 isolates from Mathbaria, Bangladesh, collected during 2010 and 2014 were analyzed for phenotypic and genotypic traits, including antimicrobial susceptibility. Of the 97 isolates, 95 possessed CTX-phage mediated genes, ctxA, ace, and zot, and two lacked the cholera toxin gene, ctxA. Also both CTX+ and CTX− V. cholerae O1 isolated in this study carried rtxC, tcpAET, and hlyA. The classical cholera toxin gene, ctxB1, was detected in 87 isolates, while eight had ctxB7. Of 95 CTX+ V. cholerae O1, 90 contained rstRET and 5 had rstRCL. All isolates, except two, contained SXT related integrase intSXT. Resistance to penicillin, streptomycin, nalidixic acid, sulfamethoxazole-trimethoprim, erythromycin, and tetracycline varied between the years of study period. Most importantly, 93% of the V. cholerae O1 were multidrug resistant. Six different resistance profiles were observed, with resistance to streptomycin, nalidixic acid, tetracycline, and sulfamethoxazole-trimethoprim predominant every year. Ciprofloxacin and azithromycin MIC were 0.003–0.75 and 0.19–2.00 μg/ml, respectively, indicating reduced susceptibility to these antibiotics. Sixteen of the V. cholerae O1 isolates showed higher MIC for azithromycin (≥0.5 μg/ml) and were further examined for 10 macrolide resistance genes, erm(A), erm(B), erm(C), ere(A), ere(B), mph(A), mph(B), mph(D), mef(A), and msr(A) with none testing positive for the macrolide resistance genes. PMID:28270803

  13. In vitro effects of four macrolides (roxithromycin, spiramycin, azithromycin (CP-62,993), and A-56268) on Toxoplasma gondii

    SciTech Connect

    Chang, H.R.; Pechere, J.C.

    1988-04-01

    The effect of four macrolides against intracellular Toxoplasma gondii was determined in three different in vitro systems. Unactivated murine peritoneal macrophages were infected with the virulent RH strain of T. gondii. The activity of the macrolides was first measured with (/sup 3/H)uracil, which is incorporated by the parasite but not the host cell. The 50% inhibitory concentrations (IC50s) and 95% confidence limits were calculated at 54 (38 to 73), 140 (98 to 201), 147 (101 to 214), and 246 (187 to 325) micron for roxithromycin, azithromycin (CP-62,993), A-56268, and spiramycin, respectively. Inhibition of Toxoplasma growth was confirmed by microscopic examination of the infected macrophages after treatment with roxithromycin. Compared with untreated controls, roxithromycin concentrations near the IC50s decreased the number of infected cells, the number of tachyzoites per vacuole, and the number of cells containing rosettes (i.e., clusters of more than eight tachyzoites). After treatment with the four macrolides, tachyzoites were released from the macrophages and subcultured in HeLa cells, which are nonprofessional phagocytes, to assess the viability of the remaining parasites. This showed that the macrolides at concentrations corresponding to four times their 90% inhibitory concentrations (IC90s) had no significant killing effect. At 8 times the IC90, roxithromycin showed an incomplete killing effect, similar to that of the combination of pyrimethamine (0.41 microM)-sulfadiazine (99.42 microM). All macrolides tested showed inhibitory effects against intracellular T. gondii, but amounts of azithromycin and A-56268 corresponding to the IC90 appeared to be toxic against the host macrophages, which might have had nonspecific activity against Toxoplasma metabolism.

  14. Azithromycin vs. Placebo for the Clinical Outcome in Campylobacter concisus Diarrhoea in Adults: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial

    PubMed Central

    Nielsen, Hans Linde; Kirk, Karina Frahm; Bodilsen, Jacob; Ejlertsen, Tove; Nielsen, Henrik

    2016-01-01

    Campylobacter concisus has been associated with prolonged mild diarrhoea, but investigations regarding the efficacy of antimicrobial treatment have not been reported previously. We initiated a phase 3, single-centre, randomized, double-blinded, placebo-controlled study comparing the efficacy of 500 mg once-daily dose of azithromycin with a 500 mg once-daily dose of placebo for three days, for the treatment of C. concisus diarrhoea in adult patients with a follow-up period of ten days. If symptoms persisted at day ten, the patient was offered cross-over study treatment of three days and another ten-day follow-up period. The primary efficacy endpoint was the clinical response, defined as time to cessation of diarrhoea (<3 stools/day or reversal of accompanying symptoms). Our estimated sample size was 100 patients. We investigated a total of 10,036 diarrheic stool samples from 7,089 adult patients. Five-hundred and eighty-eight C. concisus positive patients were assessed for eligibility, of which 559 were excluded prior to randomization. The three main reasons for exclusion were duration of diarrhoea longer than 21 days (n = 124), previous antibiotic treatment (n = 113), and co-pathogens in stools (n = 87). Therefore, 24 patients completed the trial with either azithromycin (n = 12) or placebo (n = 12). Both groups presented symptoms of mild, prolonged diarrhoea with a mean duration of 18 days (95% CI: 16–19). One person in the azithromycin group and four from the placebo group chose to continue with crossover medication after the initial ten-day period. In the azithromycin group, there was a mean of seven days (95% CI: 5–9) to clinical cure and for the placebo group it was ten days (95% CI: 6–14) (OR—3 (95% CI: -7–1). We observed no differences in all examined outcomes between azithromycin treatment and placebo. However, due to unforeseen recruitment difficulties we did not reach our estimated sample size of 100 patients and statistical power to conclude on

  15. In Vitro Susceptibilities of Bordetella pertussis and Bordetella parapertussis to Two Ketolides (HMR 3004 and HMR 3647), Four Macrolides (Azithromycin, Clarithromycin, Erythromycin A, and Roxithromycin), and Two Ansamycins (Rifampin and Rifapentine)

    PubMed Central

    Hoppe, Jörg E.; Bryskier, André

    1998-01-01

    When tested by agar dilution on Mueller-Hinton agar supplemented with 5% horse blood, the ketolides HMR 3004 and HMR 3647 were slightly more active (MIC at which 90% of the isolates were inhibited [MIC90], 0.03 μg/ml) against Bordetella pertussis than azithromycin, clarithromycin, erythromycin A, and roxithromycin. Azithromycin (MIC90, 0.06 μg/ml) was the most active compound against B. parapertussis. Rifampin and rifapentine were considerably less active. PMID:9559823

  16. Quantitative analysis of gentamicin, azithromycin, telithromycin, ciprofloxacin, moxifloxacin, and oritavancin (LY333328) activities against intracellular Staphylococcus aureus in mouse J774 macrophages.

    PubMed

    Seral, Cristina; Van Bambeke, Françoise; Tulkens, Paul M

    2003-07-01

    Using J774 macrophages, the intracellular activities of gentamicin, azithromycin, telithromycin, ciprofloxacin, moxifloxacin, and oritavancin (LY333328) against Staphylococcus aureus (strain ATCC 25923) have been quantitatively assessed in a 24-h model. S. aureus was positively localized in phagolysosomes by confocal and electron microscopy, and extracellular growth was prevented with 0.5 mg of gentamicin/liter (1x MIC) in controls. When tested at extracellular concentrations equivalent to their maximum concentrations in human serum, all antibiotics except azithromycin caused a significant reduction of the postphagocytosis inoculum within 24 h, albeit to markedly different extents (telithromycin [2 mg/liter], 0.60 log; ciprofloxacin [4.3 mg/liter], 0.81 log; gentamicin [18 mg/liter], 1.21 log; moxifloxacin [4 mg/liter], 1.51 log; oritavancin [25 mg/liter], 3.49 log). Intracellular activities were not systematically related to drug accumulation (apparent cellular-to-extracellular concentration ratios in infected cells: ciprofloxacin, 3.2; gentamicin, 6.8; telithromycin, 8.7; moxifloxacin, 13.4; azithromycin, 50; oritavancin, 348). Intracellular activity was not directly correlated to extracellular activity as measured in broth. Conditions of pH 5 (i.e., mimicking that of phagolysosomes) markedly reduced the activity of gentamicin, azithromycin, and telithromycin (>or=32 x) and fairly extensively reduced that of ciprofloxacin and moxifloxacin (>or=4 x) but did not affect oritavancin activity. We conclude that the cellular accumulation of antibiotics is not the only parameter to take into account for intracellular activity but that local environmental conditions (such as pH) and other factors can also prove critical.

  17. Septic arthritis of the hip in a Cambodian child caused by multidrug-resistant Salmonella enterica serovar Typhi with intermediate susceptibility to ciprofloxacin treated with ceftriaxone and azithromycin.

    PubMed

    Pocock, J M; Khun, P A; Moore, C E; Vuthy, S; Stoesser, N; Parry, C M

    2014-08-01

    Septic arthritis is a rare complication of typhoid fever. A 12-year-old boy without pre-existing disease attended a paediatric hospital in Cambodia with fever and left hip pain. A hip synovial fluid aspirate grew multidrug-resistant Salmonella enterica ser. Typhi with intermediate susceptibility to ciprofloxacin. Arthrotomy, 2 weeks of intravenous ceftriaxone and 4 weeks of oral azithromycin led to resolution of symptoms. The optimum management of septic arthritis in drug-resistant typhoid is undefined.

  18. Single-dose (30 mg/kg) azithromycin compared with 10-day amoxicillin/clavulanate for the treatment of uncomplicated acute otitis media: a double-blind, placebo-controlled, randomized clinical trial☆

    PubMed Central

    Block, Stan L; Arrieta, Antonio; Seibel, Matthew; McLinn, Samuel; Eppes, Stephen; Murphy, Mary J

    2003-01-01

    Background: The long half-life of azithromycin allows for single-dose oral therapy for acute otitis media (AOM). Objective: This study was designed to compare the efficacy and tolerability of single-dose azithromycin with 10-day, twice-daily amoxicillin/clavulanate for the treatment of new-onset, uncomplicated AOM in children. Methods: Children aged 6 months to 12 years with new-onset AOM were randomly assigned to receive either a single 30-mg/kg dose of azithromycin or standard-dose amoxicillin/clavulanate (45 mg/kg administered BID for 10 days) in a double-blind, double-placebo, multicenter clinical trial. The diagnosis of AOM was based on specific clinical signs and symptoms, and was confirmed by pneumatic otoscopy and acoustic reflectometry (level ≥3). Clinical response was assessed on days 12–16 and 28–32. Results: Mean (SD) age of children receiving azithromycin (n = 173) or amoxicillin/clavulanate (n = 173) was 2.7 (2.3) years and 3.4 (2.8) years, respectively, with 43% and 36% ≤2 years of age. Most (53.2%) of the children were boys, and most (51.2%) were white. Clinical success rates (intent-to-treat) for azithromycin and amoxicillin/clavulanate, respectively, were 87% and 88% (95% CI, −9.2 to 6.5) on day 12–16 and 75% and 75% (95% CI, −10.2 to 10.5) on day 28–32. The incidences of treatment-related adverse events for azithromycin and amoxicillin/clavulanate were 16.8% and 22.5%, respectively. Corresponding rates of diarrhea were 6.4% and 12.7%, respectively. Vomiting, which was generally mild, occurred in 7 children in each group. One azithromycin patient and 5 amoxicillin/clavulanate patients discontinued treatment because of adverse events. The compliance rate for azithromycin was significantly higher than that for amoxicillin/clavulanate (99% vs 83%; P<0.001). Conclusions: In this trial comparing the efficacy of single-dose azithromycin (30 mg/kg) with twice-daily amoxicillin/clavulanate (45 mg/kg) for the treatment of new

  19. Therapeutic efficacy of azithromycin, clarithromycin, minocycline and tosufloxacin against macrolide-resistant and macrolide-sensitive Mycoplasma pneumoniae pneumonia in pediatric patients

    PubMed Central

    Koseki, Naoko; Kaiho, Miki; Ariga, Tadashi; Kikuta, Hideaki; Togashi, Takehiro; Oba, Koji; Morita, Keisuke; Nagano, Naoko; Nakanishi, Masanori; Hara, Kazuya; Hazama, Kyosuke; Watanabe, Toru; Yamanaka, Tatsuru; Sasaki, Satoshi; Furuyama, Hideto; Shibata, Mutsuo; Shida, Satoru; Ishizaka, Akihito; Tabata, Yuichi; Aoyagi, Hayato; Naito, Hiroyuki; Yoshioka, Mikio; Horino, Atsuko; Kenri, Tsuyoshi

    2017-01-01

    Objective To clarify therapeutic effects of azithromycin, clarithromycin, minocycline and tosufloxacin against macrolide-resistant Mycoplasma pneumoniae (MRMP) pneumonia and against macrolide-sensitive Mycoplasma pneumoniae (MSMP) pneumonia in pediatric patients. Methods A prospective, multicenter observational study was conducted from July 2013 to August 2015. The therapeutic effects of azithromycin, clarithromycin, minocycline and tosufloxacin were evaluated in 59 patients with pneumonia caused by MRMP and in 50 patients with pneumonia caused by MSMP. In vitro activities of antimicrobial agents against isolates of Mycoplasma pneumoniae were also measured. Results Mean durations of fever following commencement of treatment in patients infected with MRMP and MSMP were 5.2 and 1.9 days, respectively (log-rank test, P < 0.0001). Among patients infected with MRMP, mean durations of fever were 4.6, 5.5, 1.0 and 7.5 days for patients treated with azithromycin, clarithromycin, minocycline and tosufloxacin, respectively (log-rank test, P < 0.0001). Among patients infected with MSMP, mean durations of fever were 2.5, 1.7, 0.9 and 4.3 days for patients treated with azithromycin, clarithromycin, minocycline and tosufloxacin, respectively (log-rank test, P = 0.0162). The MIC90s of azithromycin and clarithromycin among the 27 isolates of MRMP were 64 and 256 μg/ml, respectively, and those among the 23 isolates of MSMP were <0.000125 and 0.001 μg/ml, respectively. The MIC90s of minocycline and tosufloxacin among the 27 isolates of MRMP were 1.0 and 0.25 μg/ml, respectively, and those among the 23 isolates of MSMP were 1.0 and 0.5 μg/ml, respectively. Conclusion Both minocycline and tosufloxacin showed good in vitro activities against MRMP. Minocycline, but not tosufloxacin, shortened the duration of fever in pediatric patients infected with MRMP compared to the duration of fever in patients treated with macrolides. PMID:28288170

  20. The efficacy of oral azithromycin in clearing ocular chlamydia: mathematical modeling from a community-randomized trachoma trial.

    PubMed

    Liu, Fengchen; Porco, Travis C; Mkocha, Harran A; Muñoz, Beatriz; Ray, Kathryn J; Bailey, Robin L; Lietman, Thomas M; West, Sheila K

    2014-03-01

    Mass oral azithromycin distributions have dramatically reduced the prevalence of the ocular strains of chlamydia that cause trachoma. Assessing efficacy of the antibiotic in an individual is important in planning trachoma elimination. However, the efficacy is difficult to estimate, because post-treatment laboratory testing may be complicated by nonviable organisms or reinfection. Here, we monitored ocular chlamydial infection twice a year in pre-school children in 32 communities as part of a cluster-randomized clinical trial in Tanzania (prevalence in children was lowered from 22.0% to 4.7% after 3-year of annual treatment). We used a mathematical transmission model to estimate the prevalence of infection immediately after treatment, and found the effective field efficacy of antibiotic in an individual to be 67.6% (95% CI: 56.5-75.1%) in this setting. Sensitivity analyses suggested that these results were not dependent on specific assumptions about the duration of infection. We found no evidence of decreased efficacy during the course of the trial. We estimated an 89% chance of elimination after 10 years of annual treatment with 95% coverage.

  1. Genomic Epidemiology and Molecular Resistance Mechanisms of Azithromycin-Resistant Neisseria gonorrhoeae in Canada from 1997 to 2014

    PubMed Central

    Demczuk, Walter; Martin, Irene; Peterson, Shelley; Bharat, Amrita; Van Domselaar, Gary; Graham, Morag; Lefebvre, Brigitte; Allen, Vanessa; Hoang, Linda; Tyrrell, Greg; Horsman, Greg; Wylie, John; Haldane, David; Archibald, Chris; Wong, Tom; Unemo, Magnus

    2016-01-01

    The emergence of Neisseria gonorrhoeae strains with decreased susceptibility to cephalosporins and azithromycin (AZM) resistance (AZMr) represents a public health threat of untreatable gonorrhea infections. Genomic epidemiology through whole-genome sequencing was used to describe the emergence, dissemination, and spread of AZMr strains. The genomes of 213 AZMr and 23 AZM-susceptible N. gonorrhoeae isolates collected in Canada from 1989 to 2014 were sequenced. Core single nucleotide polymorphism (SNP) phylogenomic analysis resolved 246 isolates into 13 lineages. High-level AZMr (MICs ≥ 256 μg/ml) was found in 5 phylogenetically diverse isolates, all of which possessed the A2059G mutation (Escherichia coli numbering) in all four 23S rRNA alleles. One isolate with high-level AZMr collected in 2009 concurrently had decreased susceptibility to ceftriaxone (MIC = 0.125 μg/ml). An increase in the number of 23S rRNA alleles with the C2611T mutations (E. coli numbering) conferred low to moderate levels of AZMr (MICs = 2 to 4 and 8 to 32 μg/ml, respectively). Low-level AZMr was also associated with mtrR promoter mutations, including the −35A deletion and the presence of Neisseria meningitidis-like sequences. Geographic and temporal phylogenetic clustering indicates that emergent AZMr strains arise independently and can then rapidly expand clonally in a region through local sexual networks. PMID:26935729

  2. The efficacy of oral azithromycin in clearing ocular chlamydia: Mathematical modeling from a community-randomized trachoma trial

    PubMed Central

    Liu, Fengchen; Porco, Travis C.; Mkocha, Harran A.; Muñoz, Beatriz; Ray, Kathryn J.; Bailey, Robin L; Lietman, Thomas M.; West, Sheila K.

    2015-01-01

    Mass oral azithromycin distributions have dramatically reduced the prevalence of the ocular strains of chlamydia that cause trachoma. Assessing efficacy of the antibiotic in an individual is important in planning trachoma elimination. However, the efficacy is difficult to estimate, because post-treatment laboratory testing may be complicated by nonviable organisms or reinfection. Here, we monitored ocular chlamydial infection twice a year in pre-school children in 32 communities as part of a cluster-randomized clinical trial in Tanzania (prevalence in children was lowered from 22.0% to 4.7% after 3-year of annual treatment). We used a mathematical transmission model to estimate the prevalence of infection immediately after treatment, and found the effective field efficacy of antibiotic in an individual to be 67.6% (95% CI: 56.5–75.1%) in this setting. Sensitivity analyses suggested that these results were not dependent on specific assumptions about the duration of infection. We found no evidence of decreased efficacy during the course of the trial. We estimated an 89% chance of elimination after 10 years of annual treatment with 95% coverage. PMID:24593917

  3. Dexamethasone suppression test

    MedlinePlus

    DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medication. Afterward, your blood is drawn ...

  4. Notes from the Field: Outbreaks of Shigella sonnei Infection with Decreased Susceptibility to Azithromycin Among Men Who Have Sex with Men - Chicago and Metropolitan Minneapolis-St. Paul, 2014.

    PubMed

    Bowen, Anna; Eikmeier, Dana; Talley, Pamela; Siston, Alicia; Smith, Shamika; Hurd, Jacqueline; Smith, Kirk; Leano, Fe; Bicknese, Amelia; Norton, J Corbin; Campbell, Davina

    2015-06-05

    Increasing rates of shigellosis among adult males, particularly men who have sex with men (MSM), have been documented in the United States, Canada, and Europe, and MSM appear to be at greater risk for infection with shigellae that are not susceptible to ciprofloxacin or azithromycin. Azithromycin is the first-line empiric antimicrobial treatment for shigellosis among children and is a second-line treatment among adults. Isolates collected in 2014 in two U.S. cities from outbreaks of shigellosis displayed highly similar pulsed-field gel electrophoresis (PFGE) patterns and decreased susceptibility to azithromycin (DSA). This report summarizes and compares the findings from investigations of the two outbreaks, which occurred among MSM in metropolitan Minneapolis-St. Paul, Minnesota, and Chicago, Illinois.

  5. Effects of azithromycin, metronidazole, amoxicillin, and metronidazole plus amoxicillin on an in vitro polymicrobial subgingival biofilm model.

    PubMed

    Soares, Geisla M S; Teles, Flavia; Starr, Jacqueline R; Feres, Magda; Patel, Michele; Martin, Lynn; Teles, Ricardo

    2015-05-01

    Chronic periodontitis is one of the most prevalent human diseases and is caused by dysbiosis of the subgingival microbiota. Treatment involves primarily mechanical disruption of subgingival biofilms and, in certain cases, adjunctive use of systemic antibiotic therapy. In vitro biofilm models have been developed to study antimicrobial agents targeting subgingival species. However, these models accommodate a limited number of taxa, lack reproducibility, and have low throughput. We aimed to develop an in vitro multispecies biofilm model that mimics subgingival plaque, to test antimicrobial agents. Biofilms were cultivated using the Calgary Biofilm Device and were exposed to amoxicillin (AMX), metronidazole (MTZ), azithromycin (AZM), and AMX-MTZ at four different concentrations for 12, 24, or 36 h. Chlorhexidine (CHX) (0.12%) was used as the positive control. The compositions of the biofilms were analyzed by checkerboard DNA-DNA hybridization, and the percent reduction in biofilm metabolic activity was determined using 2,3,5-triphenyltetrazolium chloride and spectrophotometry. Thirty-five of the 40 species used in the inoculum were consistently recovered from the resulting in vitro biofilms. After 36 h of exposure at the 1:27 dilution, AMX-MTZ reduced metabolic activity 11% less than CHX (q = 0.0207) but 54% more than AMX (q = 0.0031), 72% more than MTZ (q = 0.0031), and 67% more than AZM (q = 0.0008). Preliminary evidence of a synergistic interaction between AMX and MTZ was also observed. In summary, we developed reproducible biofilms with 35 subgingival bacterial species, and our results suggested that the combination of AMX and MTZ had greater antimicrobial effects on these in vitro multispecies biofilms than expected on the basis of the independent effects of the drugs.

  6. Maternal Intravenous Administration of Azithromycin Results in Significant Fetal Uptake in a Sheep Model of Second Trimester Pregnancy

    PubMed Central

    Miura, Yuichiro; Payne, Matthew S.; Jobe, Alan H.; Kallapur, Suhas G.; Saito, Masatoshi; Stock, Sarah J.; Spiller, O. Brad; Ireland, Demelza J.; Yaegashi, Nobuo; Clarke, Michael; Hahne, Dorothee; Rodger, Jennifer; Keelan, Jeffrey A.; Newnham, John P.

    2014-01-01

    Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks of gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation age-approriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intra-amniotic AZ dose or repeated maternal intravenous (i.v.) AZ doses would safely yield therapeutic levels of AZ in an 80-day-gestation (term is 150 days) ovine fetus. Fifty sheep carrying single pregnancies at 80 days gestation were randomized to receive either: (i) a single intra-amniotic AZ administration or (ii) maternal intravenous AZ administration every 12 h. Amniotic fluid, maternal plasma, and fetal AZ concentrations were determined over a 5-day treatment regimen. Markers of liver injury and amniotic fluid inflammation were measured to assess fetal injury in response to drug exposure. A single intra-amniotic administration yielded significant AZ accumulation in the amniotic fluid and fetal lung. In contrast, repeated maternal intravenous administrations achieved high levels of AZ accumulation in the fetal lung and liver and a statistically significant increase in the fetal plasma drug concentration at 120 h. There was no evidence of fetal injury in response to drug exposure. These data suggest that (i) repeated maternal i.v. AZ dosing yields substantial fetal tissue uptake, although fetal plasma drug levels remain low; (ii) transfer of AZ from the amniotic fluid is less than transplacental transfer; and (iii) exposure to high concentrations of AZ did not elicit overt changes in fetal white blood cell counts, amniotic fluid monocyte chemoattractant protein 1 concentrations, or hepatotoxicity, all consistent with an absence of fetal injury. PMID:25155606

  7. Effect of azithromycin on gingival overgrowth induced by cyclosporine A + nifedipine combination therapy: A morphometric analysis in rats

    PubMed Central

    Ratre, Madhu Singh; Mehta, Dhoom Singh

    2016-01-01

    Background: Drug-induced gingival overgrowth (DIGO) is a well-known adverse effect of cyclosporine A (CsA) and nifedipine (Nf) therapy. The aim of the present morphometric study was to evaluate the effect of azithromycin (Azi) on the combined GO in rats induced by CsA + Nf combination. Materials and Methods: Thirty Sprague-Dawley male rats were randomly divided equally into three groups. Group 1 (control) received olive oil only; Group 2 received a combination of CsA and Nf in olive oil throughout the study period; Group 3 received CsA + Nf combination therapy, and Azi was added for 1 week in the 5th week. All the drugs were delivered by oral route. Impressions of the mandibular central incisal regions were taken, and study models were prepared at baseline and biweekly up to the 8 weeks. Statistical analysis was done by one-way analysis of variance and intergroup comparisons were made using Tukey's post hoc analysis. Results: Significant GO was evident in Group 2 and Group 3 rats when compared to Group 1. However, in Group 3 (Azi), GO was observed up to the 4th week, but a significant decrease in GO was noticed during 6–8th week after the administration of Azi in 5th week. Conclusion: Azi is an effective drug in the remission of DIGO induced by combined therapy of CsA + Nf and thereby can be considered as a useful therapeutic regimen in minimizing the DIGO in transplant patients. PMID:28298821

  8. Azithromycin pharmacokinetics in the serum and its distribution to the skin in healthy dogs and dogs with pyoderma.

    PubMed

    Zur, Gila; Soback, Stefan; Weiss, Yfat; Perry, Elad; Lavy, Eran; Britzi, Malka

    2014-04-01

    Serum and skin tissue azithromycin (AZM) concentrations were analysed in healthy and pyoderma affected dogs to determine AZM pharmacokinetics and to establish the effect of disease on AZM skin disposition. AZM was administered orally to two groups of healthy dogs: (1) at 7.02 mg/kg (n=7) and (2) at 11.2mg/kg (n=9). A crossover design was used on five of them. Seven dogs with pyoderma were treated with AZM at 10.7 mg/kg. The two groups of healthy dogs received AZM once daily over three consecutive days and dogs with pyoderma received the same treatment repeated twice with an interval of 1 week. AZM concentrations were determined by liquid chromatography-tandem mass spectrometry. AZM was rapidly absorbed and slowly excreted. In healthy dogs, maximum serum concentrations appeared 2h after administration and were (mean ± standard deviation) 0.60 ± 0.25 μg/mL and 1.03 ± 0.43 μg/mL, and the half-lives were 49.9 ± 5.10 and 51.9 ± 6.69 h for doses of 7.02 and 11.2mg/kg, respectively. Clearance (CL0-24/F) was similar in both dosing groups (1.24 ± 0.24 and 1.29 ± 0.24 L/h/kg) and the respective mean residence time (MRT0-24) was 11.1 ± 0.8 and 8.4 ± 2.2h. The skin concentration in healthy dogs was 3.5-6.5 and 5.0-12.0 times higher than the corresponding serum concentration after the two doses and increased after the cessation of AZM administration. The ratio increased significantly in inflamed tissue (9.5-26.2).

  9. Effects of Azithromycin, Metronidazole, Amoxicillin, and Metronidazole plus Amoxicillin on an In Vitro Polymicrobial Subgingival Biofilm Model

    PubMed Central

    Teles, Flavia; Starr, Jacqueline R.; Feres, Magda; Patel, Michele; Martin, Lynn

    2015-01-01

    Chronic periodontitis is one of the most prevalent human diseases and is caused by dysbiosis of the subgingival microbiota. Treatment involves primarily mechanical disruption of subgingival biofilms and, in certain cases, adjunctive use of systemic antibiotic therapy. In vitro biofilm models have been developed to study antimicrobial agents targeting subgingival species. However, these models accommodate a limited number of taxa, lack reproducibility, and have low throughput. We aimed to develop an in vitro multispecies biofilm model that mimics subgingival plaque, to test antimicrobial agents. Biofilms were cultivated using the Calgary Biofilm Device and were exposed to amoxicillin (AMX), metronidazole (MTZ), azithromycin (AZM), and AMX-MTZ at four different concentrations for 12, 24, or 36 h. Chlorhexidine (CHX) (0.12%) was used as the positive control. The compositions of the biofilms were analyzed by checkerboard DNA-DNA hybridization, and the percent reduction in biofilm metabolic activity was determined using 2,3,5-triphenyltetrazolium chloride and spectrophotometry. Thirty-five of the 40 species used in the inoculum were consistently recovered from the resulting in vitro biofilms. After 36 h of exposure at the 1:27 dilution, AMX-MTZ reduced metabolic activity 11% less than CHX (q = 0.0207) but 54% more than AMX (q = 0.0031), 72% more than MTZ (q = 0.0031), and 67% more than AZM (q = 0.0008). Preliminary evidence of a synergistic interaction between AMX and MTZ was also observed. In summary, we developed reproducible biofilms with 35 subgingival bacterial species, and our results suggested that the combination of AMX and MTZ had greater antimicrobial effects on these in vitro multispecies biofilms than expected on the basis of the independent effects of the drugs. PMID:25733510

  10. Development of a Population Pharmacokinetic Model To Describe Azithromycin Whole-Blood and Plasma Concentrations over Time in Healthy Subjects

    PubMed Central

    Anic-Milic, T.; Oreskovic, K.; Padovan, J.; Brouwer, K. L. R.; Zuo, P.; Schmith, V. D.

    2013-01-01

    Azithromycin (AZI), a broad-spectrum antibiotic, accumulates in polymorphonuclear cells and peripheral blood mononuclear cells. The distribution of AZI in proinflammatory cells may be important to the anti-inflammatory properties. Previous studies have described plasma AZI pharmacokinetics. The objective of this study was to describe the pharmacokinetics of AZI in whole blood (concentration in whole blood [Cb]) and plasma (concentration in plasma [Cp]) of healthy subjects. In this study, 12 subjects received AZI (500 mg once a day for 3 days). AZI Cb and Cp were quantified in serial samples collected up to 3 weeks after the last dose and analyzed using noncompartmental and compartmental methods. After the last dose, Cb was greater than Cp. Importantly, Cb, but not Cp, was quantifiable in all but one subject at 3 weeks. The blood area under the curve during a 24-h dosing interval (AUC24) was ∼2-fold greater than the plasma AUC24, but simulations suggested that Cb was not at steady state by day 3. Upon exploration of numerous models, an empirical 3-compartment model adequately described Cp and Cb, but Cp was somewhat underestimated. Intercompartmental clearance (CL; likely representing cells) was lower than apparent oral CL (18 versus 118 liters/h). Plasma, peripheral, and cell compartmental volumes were 439 liters, 2,980 liters, and 3,084 liters, respectively. Interindividual variability in CL was low (26.2%), while the volume of distribution variability was high (107%). This is the first report to describe AZI Cb in healthy subjects, the distribution parameters between Cp and Cb, and AZI retention in blood for up to 3 weeks following 3 daily doses. The model can be used to predict Cb from Cp for AZI under various dosing regimens. (This study has been registered at ClinicalTrials.gov under registration no. NCT01026064.) PMID:23629714

  11. The comparison of single-dose ceftriaxone, five-day azithromycin, and ten-day amoxicillin/clavulanate for the treatment of children with acute otitis media.

    PubMed

    Biner, Betül; Celtik, Coşkun; Oner, Naci; Küçükuğurluoğlu, Yasemin; Güzel, Ahmet; Yildirim, Cetin; Adali, Mustafa Kemal

    2007-01-01

    The aim of the study was to evaluate the efficacy of short-course antimicrobial therapies [single intramuscular dose of ceftriaxone (50 mg/kg, not exceeding 1 g), 5 days of azithromycin (10 mg/kg on day 1, then 5 mg/kg daily on days 2-5) and the traditional 10-day course of amoxicillin/clavulanate (90/6.4 mg/kg/day in 2 doses)] in children with acute otitis media (AOM). The study was conducted as a prospective, comparative, open randomized trial between February 2001 and April 2003, and 104 children were enrolled, with a mean age of 3.8 (2.3) years. The clinical and otoscopic assessments of the children were made on days 0, 3, 11 and 30 after admission, and tympanometry was performed on day 30. The patients were diagnosed and followed with a scoring system. Clinical success was achieved in 29/34 patients (85.3%) in the ceftriaxone group, 27/31 patients (87.1%) in the azithromycin group and 34/39 children (87.2%) in the amoxicillin/clavulanate group. The rate of persistence of middle-ear fluid did not differ between the three groups (p>0.05). During the one-month period, no recurrent case was observed. The most common drug-related adverse effects were associated with the gastrointestinal system. In conclusion, for the treatment of children with AOM, the clinical success of single-dose intramuscular ceftriaxone and of five-day azithromycin treatments was comparable to that of the traditional 10-day therapy with high-dose amoxicillin/clavulanate.

  12. The Belgian trial with azithromycin for acute COPD exacerbations requiring hospitalization: an investigator-initiated study protocol for a multicenter, randomized, double-blind, placebo-controlled trial

    PubMed Central

    Vermeersch, Kristina; Gabrovska, Maria; Deslypere, Griet; Demedts, Ingel K; Slabbynck, Hans; Aumann, Joseph; Ninane, Vincent; Verleden, Geert M; Troosters, Thierry; Bogaerts, Kris; Brusselle, Guy G; Janssens, Wim

    2016-01-01

    Background Long-term use of macrolide antibiotics is effective to prevent exacerbations in chronic obstructive pulmonary disease (COPD). As risks and side effects of long-term intervention outweigh the benefits in the general COPD population, the optimal dose, duration of treatment, and target population are yet to be defined. Hospitalization for an acute exacerbation (AE) of COPD may offer a targeted risk group and an obvious risk period for studying macrolide interventions. Methods/design Patients with COPD, hospitalized for an AE, who have a smoking history of ≥10 pack-years and had ≥1 exacerbation in the previous year will be enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (NCT02135354). On top of a standardized treatment of systemic corticosteroids and antibiotics, subjects will be randomized to receive either azithromycin or placebo during 3 months, at an uploading dose of 500 mg once a day for 3 days, followed by a maintenance dose of 250 mg once every 2 days. The primary endpoint is the time-to-treatment failure during the treatment phase (ie, from the moment of randomization until the end of intervention). Treatment failure is a novel composite endpoint defined as either death, the admission to intensive care or the requirement of additional systemic steroids or new antibiotics for respiratory reasons, or the diagnosis of a new AE after discharge. Discussion We investigate whether azithromycin initiated at the onset of a severe exacerbation, with a limited duration and at a low dose, might be effective and safe in the highest risk period during and immediately after the acute event. If proven effective and safe, this targeted approach may improve the treatment of severe AEs and redirect the preventive use of azithromycin in COPD to a temporary intervention in the subgroup with the highest unmet needs. PMID:27099485

  13. Azithromycin and spiramycin induce anti-inflammatory response in human trophoblastic (BeWo) cells infected by Toxoplasma gondii but are able to control infection.

    PubMed

    Franco, P S; Gomes, A O; Barbosa, B F; Angeloni, M B; Silva, N M; Teixeira-Carvalho, A; Martins-Filho, O A; Silva, D A O; Mineo, J R; Ferro, E A V

    2011-11-01

    Toxoplasma gondii is an important pathogen which may cause fetal infection if primary infection. Our previous studies have used human choriocarcinoma trophoblastic cells (BeWo cell line) as experimental model of T. gondii infection involving placental microenvironment. This study aimed to examine the effects of azithromycin and spiramycin against T. gondii infection in BeWo cells. Cells were treated with different concentrations of the macrolide antibiotics and analyzed first for cell viability using thiazolyl blue tetrazole (MTT) assay. As cell viability was significantly decreased with drug concentrations higher than 400 μg/mL, the concentration range used in further experiments was from 50 to 400 μg/mL. The number of infected cells and intracellular replication of T. gondii decreased after treatment with each drug. The infection induced up-regulation of the macrophage migration inhibitory factor (MIF), which was also enhanced in infected cells after treatment with azithromycin, but not with spiramycin. Analysis of the cytokine profile showed increase TNF-α, IL-10 and IL-4 production, but decreased IFN-γ levels, were detected in infected cells and treated with each drug. In conclusion, treatment of human trophoblastic BeWo cells with with azithromycin or spiramycin is able to control the infection and replication of T. gondii. In addition, treatment with these macrolides, especially with azityromycin induces an anti-inflammatory response and high MIF production, which can be important for the establishment and maintenance of a viable pregnancy during T. gondii infection.

  14. Efficacy and safety of azithromycin 1 g once daily for 3 days in the treatment of community-acquired pneumonia: an open-label randomised comparison with amoxicillin-clavulanate 875/125 mg twice daily for 7 days.

    PubMed

    Paris, R; Confalonieri, M; Dal Negro, R; Ligia, G P; Mos, L; Todisco, T; Rastelli, V; Perna, G; Cepparulo, M

    2008-02-01

    This randomised, open-label, non-inferiority study was designed to demonstrate that a 3-day course of oral azithromycin 1 g once daily was at least as effective as a standard 7-day course of oral amoxicillin-clavulanate 875/125 mg twice daily in the treatment of outpatients with community-acquired pneumonia (Fine class I and II). In total, 267 patients with clinically and radiologically confirmed community-acquired pneumonia were randomly assigned to receive either the azithromycin (n=136) or the amoxicillin-clavulanate (n=131) regimen. At screening, 60/136 (58.8%) and 61/131 (62.9%) respectively had at least one pathogen identified by sputum culture, PCR, or serology. The primary endpoint was the clinical response in the intent-to-treat population at the end of therapy (day 8 to 12). Clinical success rates were 126/136 (92.6%) for azithromycin and 122/131 (93.1%) for amoxicillin-clavulanate (treatment difference: - 0.48%; 95% confidence interval: - 5.66%; 4.69%). Clinical and radiological success rates at follow-up (day 22-26) were consistent with the end of therapy results, no patient reporting clinical relapse. Bacteriological success rates at the end of therapy were 32/35 (91.4%) for azithromycin and 30/33 (90.9%) for amoxicillin-clavulanate (treatment difference: 0.52%; 95% confidence interval - 10.81%; 11.85%). Both treatment regimens were well tolerated: the overall incidence of adverse events was 34/136 (25.0%) for azithromycin and 22/132 (16.7%) for amoxicillin-clavulanate. In both treatment groups, the most commonly reported events were gastrointestinal symptoms. Azithromycin 1g once daily for 3 days is at least as effective as amoxicillin-clavulanate 875/125 mg twice daily for 7 days in the treatment of adult patients with community-acquired pneumonia.

  15. Fire Suppression and Response

    NASA Technical Reports Server (NTRS)

    Ruff, Gary A.

    2004-01-01

    This report is concerned with the following topics regarding fire suppression:What is the relative effectiveness of candidate suppressants to extinguish a representative fire in reduced gravity, including high-O2 mole fraction, low -pressure environments? What are the relative advantages and disadvantages of physically acting and chemically-acting agents in spacecraft fire suppression? What are the O2 mole fraction and absolute pressure below which a fire cannot exist? What effect does gas-phase radiation play in the overall fire and post-fire environments? Are the candidate suppressants effective to extinguish fires on practical solid fuels? What is required to suppress non-flaming fires (smoldering and deep seated fires) in reduced gravity? How can idealized space experiment results be applied to a practical fire scenario? What is the optimal agent deployment strategy for space fire suppression?

  16. A Cross-Sectional Study of ‘Yaws’ in Districts of Ghana Which Have Previously Undertaken Azithromycin Mass Drug Administration for Trachoma Control

    PubMed Central

    Ghinai, Rosanna; El-Duah, Philip; Chi, Kai-Hua; Pillay, Allan; Solomon, Anthony W.; Bailey, Robin L.; Agana, Nsiire; Mabey, David C. W.; Chen, Cheng-Yen

    2015-01-01

    Yaws, caused by Treponema pallidum ssp. pertenue, is reportedly endemic in Ghana. Mass distribution of azithromycin is now the cornerstone of the WHO yaws eradication campaign. Mass distribution of azithromycin at a lower target dose was previously undertaken in two regions of Ghana for the control of trachoma. Ongoing reporting of yaws raises the possibility that resistance may have emerged in T. pallidum pertenue, or that alternative infections may be responsible for some of the reported cases. We conducted a cross-sectional survey in thirty communities in two districts of Ghana where MDA for trachoma had previously been conducted. Children aged 5–17 years with ulcerative lesions compatible with yaws were enrolled. Samples for treponemal serology and lesion PCR were collected from all children. 90 children with 98 lesions were enrolled. Syphilis serology was negative in all of them. PCR for T. pallidum ssp pertenue was negative in all children, but Haemophilus ducreyi DNA was detected in 9 lesions. In these communities, previously treated for trachoma, we found no evidence of ongoing transmission of yaws. H. ducreyi was associated with a proportion of skin lesions, but the majority of lesions remain unexplained. Integration of diagnostic testing into both pre and post-MDA surveillance systems is required to better inform yaws control programmes. PMID:25632942

  17. Combination therapy with ampicillin and azithromycin in an experimental pneumococcal pneumonia is bactericidal and effective in down regulating inflammation in mice

    PubMed Central

    2014-01-01

    Objectives Emergence of multidrug resistance among Streptococcus pneumoniae (SP), has limited the available options used to treat infections caused by this organism. The objective of this study was to compare the role of monotherapy and combination therapy with ampicillin (AMP) and azithromycin (AZM) in eradicating bacterial burden and down regulating lung inflammation in a murine experimental pneumococcal infection model. Methods Balb/C mice were infected with 106 CFU of SP. Treatments with intravenous ampicillin (200 mg/kg) and azithromycin (50 mg/kg) either alone or in combination was initiated 18 h post infection, animals were sacrificed from 0 – 6 h after initiation of treatment. AMP and AZM were quantified in serum by microbiological assay. Levels of TNF-α, IFN-γ IL-6, and IL-10 in serum and in lungs, along with myeloperoxidase, inflammatory cell count in broncho alveolar lavage fluid, COX-2 and histopathological changes in lungs were estimated. Results Combination therapy down regulated lung inflammation and accelerated bacterial clearance. This approach also significantly decreased TNF-α, IFN-γ, IL-6 and increased IL-10 level in serum and lungs along with decreased myeloperoxidase, pulmonary vascular permeability, inflammatory cell numbers and COX-2 levels in lungs. Conclusions Combinatorial therapy resulted in comparable bactericidal activity against the multi-drug resistant isolate and may represent an alternative dosing strategy, which may help to alleviate problems with pneumococcal pneumonia. PMID:24565171

  18. Comparative in vitro activities of azithromycin, Bay y 3118, levofloxacin, sparfloxacin, and 11 other oral antimicrobial agents against 194 aerobic and anaerobic bite wound isolates.

    PubMed Central

    Goldstein, E J; Nesbit, C A; Citron, D M

    1995-01-01

    The activities of sparfloxacin, levofloxacin, Bay y 3118, azithromycin, cefprozil, loracarbef, and nine other oral antimicrobial agents against 194 aerobic and anaerobic clinical bite wound isolates were determined by the agar dilution method. Sparfloxacin, levofloxacin, and Bay y 3118 were active against all aerobic isolates (MICs at which 90% of the isolates are inhibited [MIC90], < or = 1.0 microgram/ml for sparfloxacin and levofloxacin and 0.1 microgram/ml for Bay y 3118) and many anaerobic isolates, with the exception of the fusobacteria. Azithromycin was more active than erythromycin by 1 to 2 dilutions against many aerobes, including Pasteurella multocida and Eikenella corrodens, and by 2 to 4 dilutions against anaerobic isolates. Cefprozil was more active (MIC90, < or = 1 microgram/ml) than loracarbef (MIC90, < or = 4 micrograms/ml) against aerobic gram-positive isolates, but both had poor activity (MIC90, > or = 16 micrograms/ml) against peptostreptococci. Both cefprozil and loracarbef had MIC90s of < or = 0.5 micrograms/ml against P. multocida. PMID:7625795

  19. A cross-sectional study of 'yaws' in districts of Ghana which have previously undertaken azithromycin mass drug administration for trachoma control.

    PubMed

    Ghinai, Rosanna; El-Duah, Philip; Chi, Kai-Hua; Pillay, Allan; Solomon, Anthony W; Bailey, Robin L; Agana, Nsiire; Mabey, David C W; Chen, Cheng-Yen; Adu-Sarkodie, Yaw; Marks, Michael

    2015-01-01

    Yaws, caused by Treponema pallidum ssp. pertenue, is reportedly endemic in Ghana. Mass distribution of azithromycin is now the cornerstone of the WHO yaws eradication campaign. Mass distribution of azithromycin at a lower target dose was previously undertaken in two regions of Ghana for the control of trachoma. Ongoing reporting of yaws raises the possibility that resistance may have emerged in T. pallidum pertenue, or that alternative infections may be responsible for some of the reported cases. We conducted a cross-sectional survey in thirty communities in two districts of Ghana where MDA for trachoma had previously been conducted. Children aged 5-17 years with ulcerative lesions compatible with yaws were enrolled. Samples for treponemal serology and lesion PCR were collected from all children. 90 children with 98 lesions were enrolled. Syphilis serology was negative in all of them. PCR for T. pallidum ssp pertenue was negative in all children, but Haemophilus ducreyi DNA was detected in 9 lesions. In these communities, previously treated for trachoma, we found no evidence of ongoing transmission of yaws. H. ducreyi was associated with a proportion of skin lesions, but the majority of lesions remain unexplained. Integration of diagnostic testing into both pre and post-MDA surveillance systems is required to better inform yaws control programmes.

  20. Hail suppression and society.

    PubMed

    Changnon, S A; Farhar, B C; Swanson, E R

    1978-04-28

    An interdisciplinary assessment of hail suppression in the past, present, and future has shown it to be currently scientifically uncertain but a potentially beneficial future technology. An established suppression technology would be widely adopted in the Great Plains, providing benefits to agriculture and secondarily to the American consumer. Development of a reliable technology will require a sizable longterm federal commitment to atmospheric and social research. Subcritical funding would be a mistake. Orderly future usage of hail suppression, with its scientific complexities and regional character, will necessitate development of governmental regulations, evaluation procedures, interstate arrangements, and means for compensating those who lose from modification.

  1. Growth hormone suppression test

    MedlinePlus

    GH suppression test; Glucose loading test; Acromegaly - blood test; Gigantism - blood test ... At least 3 blood samples are taken. The test is done in the following way: The first blood sample is collected between 6 ...

  2. Jet Noise Suppression

    NASA Technical Reports Server (NTRS)

    Gliebe, P. R.; Brausch, J. F.; Majjigi, R. K.; Lee, R.

    1991-01-01

    The objectives of this chapter are to review and summarize the jet noise suppression technology, to provide a physical and theoretical model to explain the measured jet noise suppression characteristics of different concepts, and to provide a set of guidelines for evolving jet noise suppression designs. The underlying principle for all jet noise suppression devices is to enhance rapid mixing (i.e., diffusion) of the jet plume by geometric and aerothermodynamic means. In the case of supersonic jets, the shock-cell broadband noise reduction is effectively accomplished by the elimination or mitigation of the shock-cell structure. So far, the diffusion concepts have predominantly concentrated on jet momentum and energy (kinetic and thermal) diffusion, in that order, and have yielded better noise reduction than the simple conical nozzles. A critical technology issue that needs resolution is the effect of flight on the noise suppression potential of mechanical suppressor nozzles. A more thorough investigation of this mechanism is necessary for the successful development and design of an acceptable noise suppression device for future high-speed civil transports.

  3. Differential inhibition of activity, activation and gene expression of MMP-9 in THP-1 cells by azithromycin and minocycline versus bortezomib: A comparative study

    PubMed Central

    Knoops, Sofie; Aldinucci Buzzo, João L.; Boon, Lise; Martens, Erik; Opdenakker, Ghislain; Kolaczkowska, Elzbieta

    2017-01-01

    Gelatinase B or matrix metalloproteinase-9 (MMP-9) (EC 3.4.24.35) is increased in inflammatory processes and cancer, and is associated with disease progression. In part, this is due to MMP-9-mediated degradation of extracellular matrix, facilitating influx of leukocytes into inflamed tissues and invasion or metastasis of cancer cells. MMP-9 is produced as proMMP-9 and its propeptide is subsequently removed by other proteases to generate proteolytically active MMP-9. The significance of MMP-9 in pathologies triggered the development of specific inhibitors of this protease. However, clinical trials with synthetic inhibitors of MMPs in the fight against cancer were disappointing. Reports on active compounds which inhibit MMP-9 should be carefully examined in this regard. In a considerable set of recent publications, two antibiotics (minocycline and azythromycin) and the proteasome inhibitor bortezomib, used in cancers, were reported to inhibit MMP-9 at different stages of its expression, activation or activity. The current study was undertaken to compare and to verify the impact of these compounds on MMP-9. With exception of minocycline at high concentrations (>100 μM), the compounds did not affect processing of proMMP-9 into MMP-9, nor did they affect direct MMP-9 gelatinolytic activity. In contrast, azithromycin specifically reduced MMP-9 mRNA and protein levels without affecting NF-κB in endotoxin-challenged monocytic THP-1 cells. Bortezomib, although being highly toxic, had no MMP-9-specific effects but significantly upregulated cyclooxygenase-2 (COX-2) activity and PGE2 levels. Overall, our study clarified that azithromycin decreased the levels of MMP-9 by reduction of gene and protein expression while minocycline inhibits proteolytic activity at high concentrations. PMID:28369077

  4. Explosion suppression system

    DOEpatents

    Sapko, Michael J.; Cortese, Robert A.

    1992-01-01

    An explosion suppression system and triggering apparatus therefor are provided for quenching gas and dust explosions. An electrically actuated suppression mechanism which dispenses an extinguishing agent into the path ahead of the propagating flame is actuated by a triggering device which is light powered. This triggering device is located upstream of the propagating flame and converts light from the flame to an electrical actuation signal. A pressure arming device electrically connects the triggering device to the suppression device only when the explosion is sensed by a further characteristic thereof beside the flame such as the pioneer pressure wave. The light powered triggering device includes a solar panel which is disposed in the path of the explosion and oriented between horizontally downward and vertical. Testing mechanisms are also preferably provided to test the operation of the solar panel and detonator as well as the pressure arming mechanism.

  5. The suppression of enhanced bitterness intensity of macrolide dry syrup mixed with an acidic powder.

    PubMed

    Ishizaka, Toshihiko; Okada, Sachie; Takemoto, Eri; Tokuyama, Emi; Tsuji, Eriko; Mukai, Junji; Uchida, Takahiro

    2007-10-01

    The aim of the present study was to identify a medicine which strongly enhanced the bitterness of clarithromycin dry syrup (CAMD) when administered concomitantly and to develop a method to suppress this enhanced bitterness. The bitterness enhancement was evaluated not only by gustatory sensation tests but also using pH and taste sensor measurements of the mixed sample. A remarkable bitterness enhancement was found when CAMD was mixed with the acidic powder L-carbocysteine. The acidic pH (pH 3.40) of the suspension made from these two preparations, seemed to be due to enhanced release of clarithromycin caused by the dissolution of the alkaline polymer film-coating. Several methods for preventing this bitterness enhancement were investigated. Neither increasing the volume of water taken with the mixture, nor changing the ratio of CAMD:L-carbocysteine in the mixture, were effective in reducing the bitterness intensity of the CAMD/L-carbocysteine mixture. The best way to achieve taste masking was to first administer CAMD mixed with chocolate jelly, which has a neutral pH, followed by the L-carbocysteine suspension. Similar results were obtained for the bitterness suppression of azithromycin fine granules with L-carbocysteine. The chocolate jelly will be useful for taste masking of bitter macrolide drug formulations, when they need to be administered together with acidic drug formulations.

  6. Sensory suppression during feeding

    PubMed Central

    Foo, H.; Mason, Peggy

    2005-01-01

    Feeding is essential for survival, whereas withdrawal and escape reactions are fundamentally protective. These critical behaviors can compete for an animal's resources when an acutely painful stimulus affects the animal during feeding. One solution to the feeding-withdrawal conflict is to optimize feeding by suppressing pain. We examined whether rats continue to feed when challenged with a painful stimulus. During feeding, motor withdrawal responses to noxious paw heat either did not occur or were greatly delayed. To investigate the neural basis of sensory suppression accompanying feeding, we recorded from brainstem pain-modulatory neurons involved in the descending control of pain transmission. During feeding, pain-facilitatory ON cells were inhibited and pain-inhibitory OFF cells were excited. When a nonpainful somatosensory stimulus preactivated ON cells and preinhibited OFF cells, rats interrupted eating to react to painful stimuli. Inactivation of the brainstem region containing ON and OFF cells also blocked pain suppression during eating, demonstrating that brainstem pain-modulatory neurons suppress motor reactions to external stimulation during homeostatic behaviors. PMID:16275919

  7. Learning motion discrimination with suppressed and un-suppressed MT.

    PubMed

    Thompson, Benjamin; Liu, Zili

    2006-06-01

    Perceptual learning of motion direction discrimination is generally thought to rely on the middle temporal area of the brain (MT/V5). A recent study investigating learning of motion discrimination when MT was psychophysically suppressed found that learning was possible with suppressed MT, but only when the task was sufficiently easy [Lu, H., Qian, N., Liu, Z. (2004). Learning motion discrimination with suppressed MT. Vision Research 44, 1817-1825]. We investigated whether this effect was indeed due to MT suppression or whether it could be explained by task difficulty alone. By comparing learning of motion discrimination when MT was suppressed vs. un-suppressed, at different task difficulties, we found that task difficulty alone could not explain the effects. At the highest difficulty, learning was not possible with suppressed MT, confirming [Lu, H., Qian, N., Liu, Z. (2004). Learning motion discrimination with suppressed MT. Vision Research 44, 1817-1825]. In comparison, learning was possible with un-suppressed MT at the same difficulty level. At the intermediate task difficulty, there was a clear learning disadvantage when MT was suppressed. Only for the easiest level of difficulty, did learning become equally possible for both suppressed and un-suppressed conditions. These findings suggest that MT plays an important role in learning to discriminate relatively fine differences in motion direction.

  8. Pressure suppression containment system

    DOEpatents

    Gluntz, D.M.; Townsend, H.E.

    1994-03-15

    A pressure suppression containment system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and a gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The wetwell pool includes a plenum for receiving the non-condensable gas carried with steam from the drywell following a loss-of-coolant-accident (LOCA). The wetwell plenum is vented to a plenum above the GDCS pool following the LOCA for suppressing pressure rise within the containment vessel. A method of operation includes channeling steam released into the drywell following the LOCA into the wetwell pool for cooling along with the non-condensable gas carried therewith. The GDCS pool is then drained by gravity, and the wetwell plenum is vented into the GDCS plenum for channeling the non-condensable gas thereto. 6 figures.

  9. Pressure suppression containment system

    DOEpatents

    Gluntz, Douglas M.; Townsend, Harold E.

    1994-03-15

    A pressure suppression containment system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and a gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The wetwell pool includes a plenum for receiving the non-condensable gas carried with steam from the drywell following a loss-of coolant-accident (LOCA). The wetwell plenum is vented to a plenum above the GDCS pool following the LOCA for suppressing pressure rise within the containment vessel. A method of operation includes channeling steam released into the drywell following the LOCA into the wetwell pool for cooling along with the non-condensable gas carried therewith. The GDCS pool is then drained by gravity, and the wetwell plenum is vented into the GDCS plenum for channeling the non-condensable gas thereto.

  10. Drug Insight: appetite suppressants.

    PubMed

    Bray, George A

    2005-02-01

    The term 'appetite suppressant' is used to denote drugs that act primarily on the neurochemical transmitters of the central nervous system to reduce food intake. In addition to drugs that release or mimic the effect of norepinephrine (noradrenaline), this could include drugs that inhibit: reuptake of norepinephrine or 5-hydroxytryptamine (also known as serotonin); bind to the gamma-aminobutyric acid receptors or the cannabinoid receptors; and some peptides that reduce food intake. The sympathomimetic drugs phentermine, diethylpropion, benzphetamine, and phendimetrazine--so named because they mimic many effects of norepinephrine--are only approved in a few countries, and then only for short-term use. Sibutramine, a norepinephrine-5-hydroxytryptamine reuptake inhibitor, is approved for long-term use. Several new mechanisms for drug action are under investigation. Appetite suppressants should be viewed as useful adjuncts to diet and physical activity and might help selected patients to achieve and maintain weight loss.

  11. Quantitative determination of the macrolide antibiotics erythromycin, roxithromycin, azithromycin and clarithromycin in human serum by high-performance liquid chromatography using pre-column derivatization with 9-fluorenylmethyloxycarbonyl chloride and fluorescence detection.

    PubMed

    Sastre Toraño, J; Guchelaar, H J

    1998-12-11

    A validated, highly sensitive and precise high-performance liquid chromatographic (HPLC) method for the determination of the macrolides erythromycin, azithromycin, clarithromycin and roxithromycin in human serum is described. A diethyl ether extract, obtained from serum using a saturated sodium carbonate solution, was treated with 9-fluorenylmethyl-oxycarbonyl chloride (FMOC-Cl) for 40 min at 40 degrees C and chromatographed on a base-deactivated octadecyl column, maintained at 50 degrees C during elution, using an eluent composed of acetonitrile-hydrogenphosphate buffer, pH 7.5, with 0.125% triethylamine (3:2, v/v). Fluorescence detection was used at an excitation wavelength of 255 nm and an emission wavelength of 315 nm. Erythromycin, clarithromycin, roxithromycin and azithromycin were found to have retention times of 8.8, 15.7, 17.1 and 20.7 min, respectively. Recoveries ranging from 93 to 104% were found with reproducibility coefficients of variation of 1.1-5%. Mean correlation coefficients of 0.9997, 0.9998, 0.9996 and 0.9994 were found for the linear calibration curves (n = 2) of erythromycin (0.320-16.1 mg/l), roxithromycin (3.24-19.4 mg/l), clarithromycin (0.190-19.4 mg/l) and azithromycin (0.0988-4.94 mg/l), respectively.

  12. Tactile suppression of displacement.

    PubMed

    Ziat, Mounia; Hayward, Vincent; Chapman, C Elaine; Ernst, Marc O; Lenay, Charles

    2010-10-01

    In vision, the discovery of the phenomenon of saccadic suppression of displacement has made important contributions to the understanding of the stable world problem. Here, we report a similar phenomenon in the tactile modality. When scanning a single Braille dot with two fingers of the same hand, participants were asked to decide whether the dot was stationary or whether it was displaced from one location to another. The stimulus was produced by refreshable Braille devices that have dots that can be swiftly raised and recessed. In some conditions, the dot was stationary. In others, a displacement was created by monitoring the participant's finger position and by switching the dot activation when it was not touched by either finger. The dot displacement was of either 2.5 mm or 5 mm. We found that in certain cases, displaced dots were felt to be stationary. If the displacement was orthogonal to the finger movements, tactile suppression occurred effectively when it was of 2.5 mm, but when the displacement was of 5 mm, the participants easily detected it. If the displacement was medial-lateral, the suppression effect occurred as well, but less often when the apparent movement of the dot opposed the movement of the finger. In such cases, the stimulus appeared sooner than when the brain could predict it from finger movement, supporting a predictive rather than a postdictive differential processing hypothesis.

  13. Next generation fire suppressants

    NASA Technical Reports Server (NTRS)

    Brown, Jerry A.

    1995-01-01

    Spectrex, Inc., located in Cedar Grove, NJ is a manufacturer of fire detection and suppression equipment. Spectrex is one of the original pioneers in high speed fire detection and suppression systems for combat vehicles. Spectrex has installed fire suppressions systems in thousands of combat vehicles and ships throughout the world. Additionally, they manufacture flame explosion detectors, ship damage control systems, and optical gas and vapor detectors. The culmination of several years of research and development has recently produced an innovative electro-optical continuous monitoring systems called SharpEye 20/20I IR(sup 3) and SAFEYE that provide fast and reliable gas, vapor, aerosol, flame, and explosion detection. SharpEye 20/20I IR(sup 3) is a self-contained triple spectrum flame detector which scans for oscillating IR radiation (1 to 10 Hz) in the spectral bands ranging from 4.0 to 5.0 microns and uses programmed algorithms to check the ratio and correlation of data received by the three sensors to make the system highly immune to false alarms. It is extremely sensitive as it can detect a 1 x 1 square foot gasoline pan fire at 200 feet in less than 3 seconds. The sensitivity is user programmable, offering 4 ranges of detection. SAFEYE is comprised of a selected number of multispectral ban microprocessors controlled detectors which are in communication with one or more radiation sources that is projected along a 600 feet optical path. The signals from the selected narrow bands are processed and analyzed by highly sophisticated algorithms. It is ideal for high risk, remote, large areas such as petroleum and chemical manufacturing sites, waste dumps, aircraft cargo bays, and ship compartments. The SAFEYE will perform direct readings of the presence or rate of rise of concentrations of gases, vapors, or aerosols at the range of parts per million and provide alarms at various set points at different levels of concentrations.

  14. Anti-bacterial performance of azithromycin nanoparticles as colloidal drug delivery system against different gram-negative and gram-positive bacteria

    PubMed Central

    Azhdarzadeh, Morteza; Lotfipour, Farzaneh; Zakeri-Milani, Parvin; Mohammadi, Ghobad; Valizadeh, Hadi

    2012-01-01

    Purpose: Azithromycin (AZI) is a new macrolide antibiotic with a better activity against intracellular gram negative bacteria in comparison with Erythromycin. The purpose of this research was to prepare AZI nanoparticles (NPs) using PLGA polymer and to compare the effectiveness of prepared nanoparticles with untreated AZI solution. Methods: AZI NPs were prepared by Modified Quasi-Emulsion Solvent Diffusion method. The antibacterial activities of prepared NPs in comparison with AZI solution were assayed against indicator bacteria of Escherichia coli (PTCC 1330), Haemophilus influenzae (PTCC 1623) and Streptococcus pneumoniae (PTCC 1240) using agar well diffusion. Inhibition zone diameters (IZD) of nano-formulation were compared to the corresponding untreated AZI. Mean Inhibitory Concentration (MIC) values of AZI were also determined using serial dilution method in nutrient broth medium. Results: Mean IZD of nano-formulations for all indicator bacteria were significantly higher than that of untreated AZI (P<0.01). The enhanced antibacterial efficacy was more dominant in the gram positive species. The MIC values of NPs against the tested bacteria were reduced 8 times in comparison to those of untreated AZI. Conclusion: These results indicated an improved potency of AZI NPs which could be attributed to the modified surface characteristics as well as increased drug adsorption and uptake. PMID:24312766

  15. Facile synthesis of the necklace-like graphene oxide-multi-walled carbon nanotube nanohybrid and its application in electrochemical sensing of azithromycin.

    PubMed

    Zhang, Kaixin; Lu, Limin; Wen, Yangping; Xu, Jingkun; Duan, Xuemin; Zhang, Long; Hu, Dufen; Nie, Tao

    2013-07-17

    A novel electrochemical platform was designed for the determination of Azithromycin (Azi), a widely used macrolide antibiotic, by combining the hydrophilic properties of graphene oxide (GO) and the excellent electronic and antifouling properties of multi-walled carbon nanotubes (MWCNTs). Stable MWCNTs aqueous dispersion has been prepared using GO nano-sheets as surfactant and the obtained GO-MWCNTs nanohybrid was characterized by UV-vis spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, transmission electron microscopy and electrochemical impedance spectroscopy, which confirmed that GO nano-sheets were attached onto the wall of MWCNTs to form a necklace-like structure. Electrochemical results obviously reveal that the oxidation peak currents of Azi obtained at the GC electrode modified with GO-MWCNTs hybrid are much higher than those at the MWCNTs/GC, GO/GC and bare GC electrodes. Under optimized conditions, the anodic peak current was linear to the concentration of Azi in the range from 0.1 to 10 μM with the detection limit of 0.07 μM. To further validate its possible application, the proposed method was successfully used for the determination of Azi in pharmaceutical formulations with satisfactory results.

  16. Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried microparticulate/nanoparticulate antibiotic dry powders of tobramycin and azithromycin for pulmonary inhalation aerosol delivery.

    PubMed

    Li, Xiaojian; Vogt, Frederick G; Hayes, Don; Mansour, Heidi M

    2014-02-14

    The purpose of this study was to systematically design pure antibiotic drug dry powder inhalers (DPIs) for targeted antibiotic pulmonary delivery in the treatment of pulmonary infections and comprehensively correlate the physicochemical properties in the solid-state and spray-drying conditions effects on aerosol dispersion performance as dry powder inhalers (DPIs). The two rationally chosen model antibiotic drugs, tobramycin (TOB) and azithromycin (AZI), represent two different antibiotic drug classes of aminoglycosides and macrolides, respectively. The particle size distributions were narrow, unimodal, and in the microparticulate/nanoparticulate size range. The SD particles possessed relatively spherical particle morphology, smooth surface morphology, low residual water content, and the absence of long-range molecular order. The emitted dose (ED%), fine particle fraction (FPF%) and respirable fraction (RF%) were all excellent. The MMAD values were in the inhalable range (<10 μm) with smaller MMAD values for SD AZI powders in contrast to SD TOB powders. Positive linear correlations were observed between the aerosol dispersion performance parameter of FPF with increasing spray-drying pump rates and also with the difference between thermal parameters expressed as Tg-To (i.e. the difference between the glass transition temperature and outlet temperature) for SD AZI powders. The aerosol dispersion performance for SD TOB appeared to be influenced by its high water vapor sorption behavior (hygroscopicity) and pump rates or To. Aerosol dispersion performance of SD powders were distinct for both antibiotic drug aerosol systems and also between different pump rates for each system.

  17. A new on-line, in-tube pre-column derivatization technique for high performance liquid chromatographic determination of azithromycin in human serum.

    PubMed

    Bahrami, Gholamreza; Mohammadi, Bahareh

    2006-01-18

    Pre-column derivatization methods for high performance liquid chromatographic assay of specific pharmaceutical agents using 9-fluorenylmethyl chloroformate (FMOC-Cl) have received special attention because highly fluorescent and stable adducts are provided by these methods. However, unlike the post-column on-line techniques, long derivatization time is needed and the reaction cannot be well controlled. A new, sensitive and fast pre-column on-line derivatization technique coupled with high-performance liquid chromatography using FMOC-Cl as labeling agent is described and validated for determination of azithromycin in human serum. After extraction of the drug from serum, the residue was reconstituted in mixture of acetonitrile-phosphate buffer (3:1, v/v; pH 8.5) and directly injected onto the chromatographic system. Continuous on-line derivatization and analysis of the compounds were successfully performed using in-tube elution of FMOC-Cl. The total time needed for derivatization and chromatographic analysis of the drug was 13 min. The assay was reliable and reproducible, with limit of quantification of 10 ng/ml. The described technique may offer significant advantages over existing off-line derivatization methods using FMOC-Cl.

  18. Azithromycin Synergizes with Cationic Antimicrobial Peptides to Exert Bactericidal and Therapeutic Activity Against Highly Multidrug-Resistant Gram-Negative Bacterial Pathogens

    PubMed Central

    Lin, Leo; Nonejuie, Poochit; Munguia, Jason; Hollands, Andrew; Olson, Joshua; Dam, Quang; Kumaraswamy, Monika; Rivera, Heriberto; Corriden, Ross; Rohde, Manfred; Hensler, Mary E.; Burkart, Michael D.; Pogliano, Joe; Sakoulas, George; Nizet, Victor

    2015-01-01

    Antibiotic resistance poses an increasingly grave threat to the public health. Of pressing concern, rapid spread of carbapenem-resistance among multidrug-resistant (MDR) Gram-negative rods (GNR) is associated with few treatment options and high mortality rates. Current antibiotic susceptibility testing guiding patient management is performed in a standardized manner, identifying minimum inhibitory concentrations (MIC) in bacteriologic media, but ignoring host immune factors. Lacking activity in standard MIC testing, azithromycin (AZM), the most commonly prescribed antibiotic in the U.S., is never recommended for MDR GNR infection. Here we report a potent bactericidal action of AZM against MDR carbapenem-resistant isolates of Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. This pharmaceutical activity is associated with enhanced AZM cell penetration in eukaryotic tissue culture media and striking multi-log-fold synergies with host cathelicidin antimicrobial peptide LL-37 or the last line antibiotic colistin. Finally, AZM monotherapy exerts clear therapeutic effects in murine models of MDR GNR infection. Our results suggest that AZM, currently ignored as a treatment option, could benefit patients with MDR GNR infections, especially in combination with colistin. PMID:26288841

  19. Suppression subtractive hybridization.

    PubMed

    Ghorbel, Mohamed T; Murphy, David

    2011-01-01

    Comparing two RNA populations that differ from the effects of a single independent variable, such as a drug treatment or a specific genetic defect, can establish differences in the abundance of specific transcripts that vary in a population dependent manner. There are different methods for identifying differentially expressed genes. These methods include microarray, Serial Analysis of Gene Expression (SAGE), and quantitative Reverse-Transcriptase Polymerase Chain Reaction (qRT-PCR). Herein, the protocol describes an easy and cost-effective alternative that does not require prior knowledge of the transcriptomes under examination. It is specifically relevant when low levels of RNA starting material are available. This protocol describes the use of Switching Mechanism At RNA Termini Polymerase Chain Reaction (SMART-PCR) to amplify cDNA from small amounts of RNA. The amplified cDNA populations under comparison are then subjected to Suppression Subtractive Hybridization (SSH-PCR). SSH-PCR is a technique that couples subtractive hybridization with suppression PCR to selectively amplify fragments of differentially expressed genes. The resulting products are cDNA populations enriched for significantly overrepresented transcripts in either of the two input RNAs. These cDNA populations can then be cloned to generate subtracted cDNA library. Microarrays made with clones from the subtracted forward and reverse cDNA libraries are then screened for differentially expressed genes using targets generated from tester and driver total RNAs.

  20. Pharmacology of appetite suppression.

    PubMed

    Halford, J C; Blundell, J E

    2000-01-01

    Despite a rising worldwide epidemic of obesity there is currently only a very small number of anti-obesity drugs available to manage the problem. Large numbers of differing pharmacological agents reliably produce a reduction in food intake when administered acutely to animals, and when administered chronically they result in a significant decrease in body mass. Behavioural analysis of drug-induced anorexia in animals demonstrates that various compounds profoundly effect feeding behaviour in differing ways. This indicates the variety of mechanisms by which pharmacological agents can induce changes in food intake, body weight and eventually body composition. Some of the same drugs produce decreases in food intake and weight loss in humans. Some of these drugs do so by modifying the functioning of the appetite system as measured by subjective changes in feelings of hunger and fullness (indices of satiety). Such drugs can be considered as "appetite suppressants" with clinical potential as anti-obesity agents. Other drugs induce changes in food intake and body weight through various physiological mechanisms inducing feelings of nausea or even by side effect related malaise. Of the drugs considered suitable candidates for appetite suppressants are agents which act via peripherally satiety peptide systems (such as CCK, Bombesin/GRP, Enterostatin and GLP-1), or alter the CNS levels of various hypothalamic neuropeptides (NPY, Galanin, Orexin and Melanocortins) or levels of the key CNS appetite monoamine neurotransmitters such as serotonin (5-HT) and noradrenaline (NA). Recently, the hormone leptin has been regarded as a hormonal signal linking adipose tissue status with a number of key central nervous system circuits. The peptide itself stimulates leptin receptors and it links with POMC and MC-4 receptors. These receptors may also provide drug targets for the control of appetite. Any changes induced by a potential appetite suppressant should be considered in terms of the (i

  1. Pressure suppression system

    DOEpatents

    Gluntz, Douglas M.

    1994-01-01

    A pressure suppression system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and an enclosed gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The GDCS pool includes a plenum for receiving through an inlet the non-condensable gas carried with steam from the drywell following a loss-of-coolant accident (LOCA). A condenser is disposed in the GDCS plenum for condensing the steam channeled therein and to trap the non-condensable gas therein. A method of operation includes draining the GDCS pool following the LOCA and channeling steam released into the drywell following the LOCA into the GDCS plenum for cooling along with the non-condensable gas carried therewith for trapping the gas therein.

  2. ZERO SUPPRESSION FOR RECORDERS

    DOEpatents

    Fort, W.G.S.

    1958-12-30

    A zero-suppression circuit for self-balancing recorder instruments is presented. The essential elements of the circuit include a converter-amplifier having two inputs, one for a reference voltage and the other for the signal voltage under analysis, and a servomotor with two control windings, one coupled to the a-c output of the converter-amplifier and the other receiving a reference input. Each input circuit to the converter-amplifier has a variable potentiometer and the sliders of the potentiometer are ganged together for movement by the servoinotor. The particular noveity of the circuit resides in the selection of resistance values for the potentiometer and a resistor in series with the potentiometer of the signal circuit to ensure the full value of signal voltage variation is impressed on a recorder mechanism driven by servomotor.

  3. Pressure suppression system

    DOEpatents

    Gluntz, D.M.

    1994-10-04

    A pressure suppression system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and an enclosed gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The GDCS pool includes a plenum for receiving through an inlet the non-condensable gas carried with steam from the drywell following a loss-of-coolant accident (LOCA). A condenser is disposed in the GDCS plenum for condensing the steam channeled therein and to trap the non-condensable gas therein. A method of operation includes draining the GDCS pool following the LOCA and channeling steam released into the drywell following the LOCA into the GDCS plenum for cooling along with the non-condensable gas carried therewith for trapping the gas therein. 3 figs.

  4. Ultrasonic Frost Suppression

    NASA Astrophysics Data System (ADS)

    Adachi, Kazunari; Saiki, Kazushi; Sato, Hiroki; Ito, Takahiro

    2003-02-01

    The authors have observed the accumulation of frost on the surface of a rectangular aluminum alloy (duralumin) plate flexurally vibrating at approximately 37 kHz in an atmosphere of almost 100% relative humidity at 2°C. The plate surface, which had been prepolished with abrasive slurry for maintaining its average surface roughness of about 100 nm, was refrigerated at a temperature of -20°C with cold carbon-dioxide gas as coolant. Experiments have been conducted with and without fine silver oxide powder spread on the plate surface so as to examine the effect of artificial ice crystal nuclei. Ultrasonic vibrations with an amplitude of 3.4 μm (rms) are found to suppress frost accumulation by approximately 60%. The phenomenon cannot be ascribed directly to the heat generation caused by high-amplitude vibration, but may have a complex mechanical and/or acoustical effect on small ice crystals.

  5. Factors influencing dust suppressant effectiveness

    SciTech Connect

    Copeland, C.R.; Eisele, T.C.; Chesney, D.J.; Kawatra, S.K.

    2008-11-15

    Water sprays are a common method used to reduce particulate matter (PM) emissions. Various factors such as wettability, surface area coverage, fine particle engulfment rates, interparticle adhesion forces, suppressant penetration and suppressant longevity have all been suggested as critical factors in achieving effective PM control. However, it has not been established which of these factors are the most important. Experimental work indicated that suppressant penetration is the most critical of these factors. The length of time after application that suppressants were effective was also improved by using hygroscopic reagents that retained moisture to prevent evaporation. Maximizing suppressant penetration and improving suppressant longevity led to an average 86% reduction in PM10 concentrations in laboratory dust tower tests.

  6. The site of saccadic suppression.

    PubMed

    Thilo, Kai V; Santoro, Loredana; Walsh, Vincent; Blakemore, Colin

    2004-01-01

    During rapid eye movements, or saccades, stable vision is maintained by active reduction of visual sensitivity. The site of this saccadic suppression remains uncertain. Here we show that phosphenes--small illusory visual perceptions--induced by transcranial magnetic stimulation (TMS) to the human occipital cortex are immune to saccadic suppression, whereas phosphenes induced by retinal stimulation are not, thus providing direct physiological evidence that saccadic suppression occurs between the retina and the occipital visual cortex.

  7. Fabrication of a Selective and Sensitive Sensor Based on Molecularly Imprinted Polymer/Acetylene Black for the Determination of Azithromycin in Pharmaceuticals and Biological Samples

    PubMed Central

    Zhou, Tingting; Tao, Yun; Jin, Hua; Song, Bin; Jing, Tao; Luo, Dan; Zhou, Yusun; Zhou, Yikai; Lee, Yong-Ill; Mei, Surong

    2016-01-01

    A new selective and sensitive sensor based on molecularly imprinted polymer/acetylene black (MIP/AB) was developed for the determination of azithromycin (AZM) in pharmaceuticals and biological samples. The MIP of AZM was synthesized by precipitation polymerization. MIP and AB were then respectively introduced as selective and sensitive elements for the preparation of MIP/AB-modified carbon paste (MIP/ABP) electrode. The performance of the obtained sensor was estimated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques. Compared with non-molecularly imprinted polymer (NIP) electrodes, NIP/ABP electrodes, and MIP-modified carbon paste electrodes, MIP/ABP electrode exhibited excellent current response toward AZM. The prepared sensor also exhibited good selectivity for AZM in comparison with structurally similar compounds. The effect of electrode composition, extraction parameters, and electrolyte conditions on the current response of the sensor was investigated. Under the optimized conditions, the prepared sensor showed two dynamic linear ranges of 1.0 × 10−7 mol L−1 to 2.0 × 10−6 mol L−1 and 2.0 × 10−6 mol L−1 to 2.0 × 10−5 mol L−1, with a limit of detection of 1.1 × 10−8 mol L−1. These predominant properties ensured that the sensor exhibits excellent reliability for detecting AZM in pharmaceuticals and biological fluids without the assistance of any separation techniques. The results were validated by the high-performance liquid chromatography–tandem mass spectrometry method. PMID:26820753

  8. Randomised, double-blind, placebo-controlled trial with azithromycin selects for anti-inflammatory microbial metabolites in the emphysematous lung

    PubMed Central

    Segal, Leopoldo N; Clemente, Jose C; Wu, Benjamin G; Wikoff, William R; Gao, Zhan; Li, Yonghua; Ko, Jane P; Rom, William N; Blaser, Martin J; Weiden, Michael D

    2017-01-01

    Introduction Azithromycin (AZM) reduces pulmonary inflammation and exacerbations in patients with COPD having emphysema. The antimicrobial effects of AZM on the lower airway microbiome are not known and may contribute to its beneficial effects. Here we tested whether AZM treatment affects the lung microbiome and bacterial metabolites that might contribute to changes in levels of inflammatory cytokines in the airways. Methods 20 smokers (current or ex-smokers) with emphysema were randomised to receive AZM 250 mg or placebo daily for 8 weeks. Bronchoalveolar lavage (BAL) was performed at baseline and after treatment. Measurements performed in acellular BAL fluid included 16S rRNA gene sequences and quantity; 39 cytokines, chemokines and growth factors and 119 identified metabolites. The response to lipopolysaccharide (LPS) by alveolar macrophages after ex-vivo treatment with AZM or bacterial metabolites was assessed. Results Compared with placebo, AZM did not alter bacterial burden but reduced α-diversity, decreasing 11 low abundance taxa, none of which are classical pulmonary pathogens. Compared with placebo, AZM treatment led to reduced in-vivo levels of chemokine (C-X-C) ligand 1 (CXCL1), tumour necrosis factor (TNF)-α, interleukin (IL)-13 and IL-12p40 in BAL, but increased bacterial metabolites including glycolic acid, indol-3-acetate and linoleic acid. Glycolic acid and indol-3-acetate, but not AZM, blunted ex-vivo LPS-induced alveolar macrophage generation of CXCL1, TNF-α, IL-13 and IL-12p40. Conclusion AZM treatment altered both lung microbiota and metabolome, affecting anti-inflammatory bacterial metabolites that may contribute to its therapeutic effects. Trial registration number NCT02557958. PMID:27486204

  9. STRV Cryocooler Tip Motion Suppression

    NASA Technical Reports Server (NTRS)

    Glaser, R.; Ross, R. G., Jr.; Johnson, D. L.

    1994-01-01

    The Space Technology Research Vehicle (STRV-1b) scheduled to fly at the beginning of June 1994, has a cryocooler vibration suppression experiment aboard doing motion suppression of the tip of the coldfinger. STRV-1b is a bread box sized satellite to be launched on the next flight of the Ariane-4.

  10. An Alternative to Thought Suppression?

    ERIC Educational Resources Information Center

    Boice, Robert

    2012-01-01

    Comments on the original article, "Setting free the bears: Escape from thought suppression," by D. M. Wegner (see record 2011-25622-008). While Wegner supposed that we might have to learn to live with bad thoughts, the present author discusses the use of imagination and guided imagery as an alternative to forced thought suppression.

  11. Inducing amnesia through systemic suppression

    PubMed Central

    Hulbert, Justin C.; Henson, Richard N.; Anderson, Michael C.

    2016-01-01

    Hippocampal damage profoundly disrupts the ability to store new memories of life events. Amnesic windows might also occur in healthy people due to disturbed hippocampal function arising during mental processes that systemically reduce hippocampal activity. Intentionally suppressing memory retrieval (retrieval stopping) reduces hippocampal activity via control mechanisms mediated by the lateral prefrontal cortex. Here we show that when people suppress retrieval given a reminder of an unwanted memory, they are considerably more likely to forget unrelated experiences from periods surrounding suppression. This amnesic shadow follows a dose-response function, becomes more pronounced after practice suppressing retrieval, exhibits characteristics indicating disturbed hippocampal function, and is predicted by reduced hippocampal activity. These findings indicate that stopping retrieval engages a suppression mechanism that broadly compromises hippocampal processes and that hippocampal stabilization processes can be interrupted strategically. Cognitively triggered amnesia constitutes an unrecognized forgetting process that may account for otherwise unexplained memory lapses following trauma. PMID:26977589

  12. Painful consequences of anger suppression.

    PubMed

    Quartana, Phillip J; Burns, John W

    2007-05-01

    The authors experimentally examined the effects of anger suppression on pain perception. On the basis of ironic process theory, they proposed that efforts to suppress experiential or expressive components of anger may paradoxically enhance cognitive accessibility of anger-related thoughts and feelings, thereby contaminating perception of succeeding pain in an anger-congruent manner. Participants were randomly assigned to nonsuppression or experiential or expressive suppression conditions during mental arithmetic with or without harassment. A cold-pressor task followed. Results revealed that participants instructed to suppress experiential or expressive components of emotion during harassment not only reported the greatest pain levels, but also rated the anger-specific dimensions of pain uniquely strong. Results suggest that attempts to suppress anger may amplify pain sensitivity by ironically augmenting perception of the irritating and frustrating qualities of pain.

  13. Suppressive activity of macrolide antibiotics on nitric oxide production by lipopolysaccharide stimulation in mice.

    PubMed Central

    Terao, Hajime; Asano, Kazuhito; Kanai, Ken-ichi; Kyo, Yoshiyuki; Watanabe, So; Hisamitsu, Tadashi; Suzaki, Harumi

    2003-01-01

    BACKGROUND: Low-dose and long-term administration of macrolide antibiotics into patients with chronic airway inflammatory diseases could favorably modify their clinical conditions. However, the therapeutic mode of action of macrolides is not well understood. Free oxygen radicals, including nitric oxide (NO), are well recognized as the important final effector molecules in the development and the maintenance of inflammatory diseases. PURPOSE: The influence of macrolide antibiotics on NO generation was examined in vivo. METHODS: Male ICR mice, 5 weeks of age, were orally administered with either roxithromycin, clarithromycin, azithromycin or josamycin once a day for 2-4 weeks. The mice were then injected intraperitoneally with 5.0 mg/kg lipopolysaccharide (LPS) and the plasma NO level was examined 6 h later. RESULTS: Although pre-treatment of mice with macrolide antibiotics for 2 weeks scarcely affected NO generation by LPS injection, the administration of macrolide antibiotics, except for josamycin, for 4 weeks significantly inhibited LPS-induced NO generation. The data in the present study also showed that pre-treatment of mice with macrolide antibiotics for 4 weeks significantly suppresses not only production of pro-inflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha, but also inducible nitric oxide synthase mRNA expressions, which are enhanced by LPS injection. CONCLUSION: These results strongly suggest that suppressive activity of macrolide antibiotics on NO generation in response to LPS stimulation in vivo may, in part, account for the clinical efficacy of macrolides on chronic inflammatory diseases. PMID:14514469

  14. Simple suppression of radiation damping.

    PubMed

    Khitrin, A K; Jerschow, Alexej

    2012-12-01

    Radiation damping is known to cause line-broadening and frequency shifts of strong resonances in NMR spectra. While several techniques exist for the suppression of these effects, many require specialized hardware, or are only compatible with the presence of few strong resonances. We describe a simple pulse sequence for radiation damping suppression in spectra with many strong resonances. The sequence can be used as-is to generate simple spectra or as a signal excitation part in more advanced experiments.

  15. In Vitro Anti-inflammatory and Antimicrobial Activities of Azithromycin After Loaded in Chitosan- and Tween 20-Based Oil-in-Water Macroemulsion for Acne Management.

    PubMed

    Shunmugaperumal, Tamilvanan; Kaur, Varinder

    2016-06-01

    The objectives of the current investigation are (1) to prepare and characterize (particle size, surface charge (potential zeta), surface morphology by transmission electron microscopy, drug content, and drug release) the azithromycin (AZM, 100 mg)-loaded oil-in-water (o/w) macroemulsion, (2) to assess the toxicity of macroemulsion with or without AZM using RBC lysis test in comparison with AZM in phosphate buffer solution of pH 7.4, (3) to compare the in vitro antimicrobial activity (in Escherichia coli using zone inhibition assay) of AZM-loaded macroemulsion with its aqueous solution, and (4) to assess the in vitro anti-inflammatory effect (using egg albumin denaturation bioassay) of the AZM-loaded macroemulsion in comparison with diclofenac sodium in phosphate buffer solution of pH 7.4. The AZM-loaded macroemulsion possessed the dispersed oil droplets with a mean diameter value of 52.40 ± 1.55 μm. A reversal in the zeta potential value from negative (-2.16 ± 0.75 mV) to positive (+6.52 ± 0.96 mV) was noticed when AZM was added into the macroemulsion. At a 1:5 dilution ratio, 2.06 ± 0.03 mg of drug was released from macroemulsion followed by 1.01 ± 0.01 and 0.25 ± 0.08 mg, respectively, for 1:10 and 1:40 dilution ratios. Antimicrobial activity maintenance and significant reduction of RBC lysis property were noticed for AZM after loaded in the macroemulsion. However, an increment in the absorbance values for emulsion-treated samples in comparison to the control samples was noticed in the anti-inflammatory test. This speculates the potential of the AZM-loaded emulsion to manage inflammatory conditions produced at Acne vulgaris.

  16. Maternal Intravenous Treatment with either Azithromycin or Solithromycin Clears Ureaplasma parvum from the Amniotic Fluid in an Ovine Model of Intrauterine Infection

    PubMed Central

    Miura, Yuichiro; Payne, Matthew S.; Keelan, Jeffrey A.; Noe, Andres; Carter, Sean; Watts, Rory; Spiller, Owen B.; Jobe, Alan H.; Kallapur, Suhas G.; Saito, Masatoshi; Stock, Sarah J.; Newnham, John P.

    2014-01-01

    Intrauterine infection with Ureaplasma spp. is strongly associated with preterm birth and adverse neonatal outcomes. We assessed whether combined intraamniotic (IA) and maternal intravenous (IV) treatment with one of two candidate antibiotics, azithromycin (AZ) or solithromycin (SOLI), would eradicate intrauterine Ureaplasma parvum infection in a sheep model of pregnancy. Sheep with singleton pregnancies received an IA injection of U. parvum serovar 3 at 85 days of gestational age (GA). At 120 days of GA, animals (n = 5 to 8/group) received one of the following treatments: (i) maternal IV SOLI with a single IA injection of vehicle (IV SOLI only); (ii) maternal IV SOLI with a single IA injection of SOLI (IV+IA SOLI); (iii) maternal IV AZ and a single IA injection of vehicle (IV AZ only); (iv) maternal IV AZ and a single IA injection of AZ (IV+IA AZ); or (v) maternal IV and single IA injection of vehicle (control). Lambs were surgically delivered at 125 days of GA. Treatment efficacies were assessed by U. parvum culture, quantitative PCR, enzyme-linked immunosorbent assay, and histopathology. Amniotic fluid (AF) from all control animals contained culturable U. parvum. AF, lung, and chorioamnion from all AZ- or SOLI-treated animals (IV only or IV plus IA) were negative for culturable U. parvum. Relative to the results for the control, the levels of expression of interleukin 1β (IL-1β), IL-6, IL-8, and monocyte chemoattractant protein 2 (MCP-2) in fetal skin were significantly decreased in the IV SOLI-only group, the MCP-1 protein concentration in the amniotic fluid was significantly increased in the IV+IA SOLI group, and there was no significant difference in the histological inflammation scoring of lung or chorioamnion among the five groups. In the present study, treatment with either AZ or SOLI (IV only or IV+IA) effectively eradicated macrolide-sensitive U. parvum from the AF. There was no discernible difference in antibiotic therapy efficacy between IV-only and

  17. Suppressed Charmed B Decay

    SciTech Connect

    Snoek, Hella Leonie

    2009-06-02

    This thesis describes the measurement of the branching fractions of the suppressed charmed B0 → D*- a0+ decays and the non-resonant B0 → D*- ηπ+ decays in approximately 230 million Υ(4S) → B$\\bar{B}$ events. The data have been collected with the BABAR detector at the PEP-II B factory at the Stanford Linear Accelerator Center in California. Theoretical predictions of the branching fraction of the B0 → D*- a{sub 0}+ decays show large QCD model dependent uncertainties. Non-factorizing terms, in the naive factorization model, that can be calculated by QCD factorizing models have a large impact on the branching fraction of these decay modes. The predictions of the branching fractions are of the order of 10-6. The measurement of the branching fraction gives more insight into the theoretical models. In general a better understanding of QCD models will be necessary to conduct weak interaction physics at the next level. The presence of CP violation in electroweak interactions allows the differentiation between matter and antimatter in the laws of physics. In the Standard Model, CP violation is incorporated in the CKM matrix that describes the weak interaction between quarks. Relations amongst the CKM matrix elements are used to present the two relevant parameters as the apex of a triangle (Unitarity Triangle) in a complex plane. The over-constraining of the CKM triangle by experimental measurements is an important test of the Standard Model. At this moment no stringent direct measurements of the CKM angle γ, one of the interior angles of the Unitarity Triangle, are available. The measurement of the angle γ can be performed using the decays of neutral B mesons. The B0 → D*- a0+ decay is sensitive to the angle γ and, in comparison to the current decays that are being employed, could significantly

  18. The amphetamine appetite suppressant saga.

    PubMed

    2004-02-01

    (1) In 1999, all amphetamine derivatives still sold in France as appetite suppressants were withdrawn from the market because of serious cardiovascular adverse effects. Sibutramine, marketed in France since 2001, is closely related to this group of drugs. (2) The adverse effects shared by these drugs are mainly neuropsychiatric (due to a psychostimulant action) and cardiovascular (arterial hypertension and tachycardia). (3) More specific cardiovascular adverse effects, such as pulmonary hypertension and severe cardiac valve damage, emerged after several years of use. The first reports date back to the 1960s. (4) The pulmonary hypertension associated with appetite suppressants can be fatal or necessitate transplantation. (5) Cardiac valve damage due to appetite suppressants is generally irreversible and sometimes requires surgery.

  19. Visual Surround Suppression in Schizophrenia

    PubMed Central

    Tibber, Marc S.; Anderson, Elaine J.; Bobin, Tracy; Antonova, Elena; Seabright, Alice; Wright, Bernice; Carlin, Patricia; Shergill, Sukhwinder S.; Dakin, Steven C.

    2013-01-01

    Compared to unaffected observers patients with schizophrenia (SZ) show characteristic differences in visual perception, including a reduced susceptibility to the influence of context on judgments of contrast – a manifestation of weaker surround suppression (SS). To examine the generality of this phenomenon we measured the ability of 24 individuals with SZ to judge the luminance, contrast, orientation, and size of targets embedded in contextual surrounds that would typically influence the target’s appearance. Individuals with SZ demonstrated weaker SS compared to matched controls for stimuli defined by contrast or size, but not for those defined by luminance or orientation. As perceived luminance is thought to be regulated at the earliest stages of visual processing our findings are consistent with a suppression deficit that is predominantly cortical in origin. In addition, we propose that preserved orientation SS in SZ may reflect the sparing of broadly tuned mechanisms of suppression. We attempt to reconcile these data with findings from previous studies. PMID:23450069

  20. Noise suppressing capillary separation system

    DOEpatents

    Yeung, Edward S.; Xue, Yongjun

    1996-07-30

    A noise-suppressing capillary separation system for detecting the real-time presence or concentration of an analyte in a sample is provided. The system contains a capillary separation means through which the analyte is moved, a coherent light source that generates a beam which is split into a reference beam and a sample beam that irradiate the capillary, and a detector for detecting the reference beam and the sample beam light that transmits through the capillary. The laser beam is of a wavelength effective to be absorbed by a chromophore in the capillary. The system includes a noise suppressing system to improve performance and accuracy without signal averaging or multiple scans.

  1. Conditioned suppression, punishment, and aversion

    NASA Technical Reports Server (NTRS)

    Orme-Johnson, D. W.; Yarczower, M.

    1974-01-01

    The aversive action of visual stimuli was studied in two groups of pigeons which received response-contingent or noncontingent electric shocks in cages with translucent response keys. Presentation of grain for 3 sec, contingent on key pecking, was the visual stimulus associated with conditioned punishment or suppression. The responses of the pigeons in three different experiments are compared.

  2. Noise suppressing capillary separation system

    DOEpatents

    Yeung, E.S.; Xue, Y.

    1996-07-30

    A noise-suppressing capillary separation system for detecting the real-time presence or concentration of an analyte in a sample is provided. The system contains a capillary separation means through which the analyte is moved, a coherent light source that generates a beam which is split into a reference beam and a sample beam that irradiate the capillary, and a detector for detecting the reference beam and the sample beam light that transmits through the capillary. The laser beam is of a wavelength effective to be absorbed by a chromophore in the capillary. The system includes a noise suppressing system to improve performance and accuracy without signal averaging or multiple scans. 13 figs.

  3. Suppression of operant vs consummatory behavior.

    PubMed

    DeCosta, M J; Ayres, J J

    1971-07-01

    The magnitude and variability of conditioned suppression of bar pressing and dipper licking were compared. In two steady-state experiments, suppression of bar pressing was more profound and more stable from day to day. The two measures of suppression were uncorrelated as indexed by Pearson product-moment correlation coefficients computed for adjacent trials. Correlations within measures (internal consistency) were somewhat higher for the bar-press system except when a high proportion of rats completely suppressed on one of the correlated trials. In a transient state experiment in which possible adventitious punishment of both response systems was eliminated, suppression of bar pressing was again more profound and considerably slower to extinguish.

  4. Fire suppression and detection equipment

    SciTech Connect

    E.E. Bates

    2006-01-15

    Inspection and testing guidelines go beyond the 'Code of Federal Regulation'. Title 30 of the US Code of Federal Regulations (30 CFR) contains requirements and references to national standards for inspection, testing and maintenance of fire suppression and detection equipment for mine operators. However, federal requirements have not kept pace with national standards and best practices. The article lists National Fire Protection (NFPA) standards that are referenced by the US Mine Safety and Health Administration (MSHA) in 30 CFR. It then discusses other NFPA Standards excluded from 30 CFR and explains the NFPA standard development process. 2 refs., 3 tabs., 5 photos.

  5. Menstrual suppression in special circumstances.

    PubMed

    Kirkham, Yolanda A; Ornstein, Melanie P; Aggarwal, Anjali; McQuillan, Sarah; Allen, Lisa; Millar, Debra; Dalziel, Nancy; Gascon, Suzy; Hakim, Julie; Ryckman, Julie; Spitzer, Rachel; Van Eyk, Nancy

    2014-10-01

    Objectif : Offrir, aux fournisseurs de soins de santé, un document de consensus canadien comptant des recommandations pour ce qui est de la suppression menstruelle chez les patientes qui font face à des obstacles physiques et/ou cognitifs ou chez les patientes qui font l’objet d’un traitement contre le cancer et pour lesquelles les règles pourraient exercer un effet délétère sur la santé. Options : Le présent document analyse les options disponibles aux fins de la suppression menstruelle, les indications, les contre-indications et les effets indésirables (tant immédiats qu’à long terme) propres à cette dernière, et les explorations et le monitorage nécessaires tout au long de la suppression. Issues : Les cliniciens seront mieux renseignés au sujet des options et des indications propres à la suppression menstruelle chez les patientes qui présentent des déficiences cognitives et/ou physiques et chez les patientes qui font l’objet d’une chimiothérapie, d’une radiothérapie ou d’autres traitements contre le cancer. Résultats : La littérature publiée a été récupérée par l’intermédiaire de recherches menées dans Medline, EMBASE, OVID et The Cochrane Library au moyen d’un vocabulaire contrôlé et de mots clés appropriés (p. ex. « heavy menstrual bleeding », « menstrual suppression », « chemotherapy/radiation », « cognitive disability », « physical disability », « learning disability »). Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés, aux études observationnelles et aux études pilotes. Aucune restriction n’a été imposée en matière de langue ou de date. Les recherches ont été mises à jour de façon régulière et du nouveau matériel a été intégré à la directive clinique jusqu’en septembre 2013. La littérature grise (non publiée) a été identifiée par l’intermédiaire de recherches menées dans les sites Web d

  6. Orientation-tuned suppression in binocular rivalry reveals general and specific components of rivalry suppression.

    PubMed

    Stuit, Sjoerd M; Cass, John; Paffen, Chris L E; Alais, David

    2009-10-16

    During binocular rivalry (BR), conflicting monocular images are alternately suppressed from awareness. During suppression of an image, contrast sensitivity for probes is reduced by approximately 0.3-0.5 log units relative to when the image is in perceptual dominance. Previous studies on rivalry suppression have led to controversies concerning the nature and extent of suppression during BR. We tested for feature-specific suppression using orthogonal rivaling gratings and measuring contrast sensitivity to small grating probes at a range of orientations in a 2AFC orientation discrimination task. Results indicate that suppression is not uniform across orientations: suppression was much greater for orientations close to that of the suppressed grating. The higher suppression was specific to a narrow range around the suppressed rival grating, with a tuning similar to V1 orientation bandwidths. A similar experiment tested for spatial frequency tuning and found that suppression was stronger for frequencies close to that of the suppressed grating. Interestingly, no tuned suppression was observed when a flicker-and-swap paradigm was used, suggesting that tuned suppression occurs only for lower-level, interocular rivalry. Together, the results suggest there are two components to rivalry suppression: a general feature-invariant component and an additional component specifically tuned to the rivaling features.

  7. Suppressed epidemics in multirelational networks

    NASA Astrophysics Data System (ADS)

    Xu, Elvis H. W.; Wang, Wei; Xu, C.; Tang, Ming; Do, Younghae; Hui, P. M.

    2015-08-01

    A two-state epidemic model in networks with links mimicking two kinds of relationships between connected nodes is introduced. Links of weights w1 and w0 occur with probabilities p and 1 -p , respectively. The fraction of infected nodes ρ (p ) shows a nonmonotonic behavior, with ρ drops with p for small p and increases for large p . For small to moderate w1/w0 ratios, ρ (p ) exhibits a minimum that signifies an optimal suppression. For large w1/w0 ratios, the suppression leads to an absorbing phase consisting only of healthy nodes within a range pL≤p ≤pR , and an active phase with mixed infected and healthy nodes for p pR . A mean field theory that ignores spatial correlation is shown to give qualitative agreement and capture all the key features. A physical picture that emphasizes the intricate interplay between infections via w0 links and within clusters formed by nodes carrying the w1 links is presented. The absorbing state at large w1/w0 ratios results when the clusters are big enough to disrupt the spread via w0 links and yet small enough to avoid an epidemic within the clusters. A theory that uses the possible local environments of a node as variables is formulated. The theory gives results in good agreement with simulation results, thereby showing the necessity of including longer spatial correlations.

  8. Water Mist fire suppression experiment

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Water Mist commercial research program is scheduled to fly an investigation on STS-107 in 2002. This investigation will be flown as an Experimental Mounting Structure (EMS) insert into the updated Combustion Module (CM-2), a sophisticated combustion chamber plus diagnostic equipment. (The investigation hardware is shown here mounted in a non-flight frame similar to the EMS.) Water Mist is a commercial research program by the Center for Commercial Applications of Combustion in Space (CCACS), a NASA Commercial Space Center located at the Colorado School of Mines, in Golden, CO and Industry Partner Environmental Engineering Concepts. The program is focused on developing water mist as a replacement for bromine-based chemical fire suppression agents (halons). By conducting the experiments in microgravity, interference from convection currents is minimized and fundamental knowledge can be gained. This knowledge is incorporated into models, which can be used to simulate a variety of physical environments. The immediate objective of the project is to study the effect of a fine water mist on a laminar propagating flame generated in a propane-air mixture at various equivalence ratios. The effects of droplet size and concentration on the speed of the flame front is used as a measure of the effectiveness of fire suppression in this highly controlled experimental environment.

  9. Detection of Anorectal and Cervicovaginal Chlamydia Trachomatis Infections following Azithromycin Treatment: Prospective Cohort Study with Multiple Time-Sequential Measures of rRNA, DNA, Quantitative Load and Symptoms

    PubMed Central

    Dukers-Muijrers, Nicole H. T. M.; Speksnijder, Arjen G. C. L.; Morré, Servaas A.; Wolffs, Petra F. G.; van der Sande, Marianne A. B.; Brink, Antoinette A. T. P.; van den Broek, Ingrid V. F.; Werner, Marita I. L. S.; Hoebe, Christian J. P. A.

    2013-01-01

    Background Determination of Chlamydia trachomatis (Ct) treatment success is hampered by current assessment methods, which involve a single post-treatment measurement only. Therefore, we evaluated Ct detection by applying multiple laboratory measures on time-sequential post-treatment samples. Methods A prospective cohort study was established with azithromycin-treated (1000 mg) Ct patients (44 cervicovaginal and 15 anorectal cases). Each patient provided 18 self-taken samples pre-treatment and for 8 weeks post-treatment (response: 96%; 1,016 samples). Samples were tested for 16S rRNA (TMA), bacterial load (quantitative PCR; Chlamydia plasmid DNA) and type (serovar and multilocus sequence typing). Covariates (including behavior, pre-treatment load, anatomic site, symptoms, age, and menstruation) were tested for their potential association with positivity and load at 3–8 weeks using regression analyses controlling for repeated measures. Findings By day 9, Ct positivity decreased to 20% and the median load to 0.3 inclusion-forming units (IFU) per ml (pre-treatment: 170 IFU/ml). Of the 35 cases who reported no sex, sex with a treated partner or safe sex with a new partner, 40% had detection, i.e. one or more positive samples from 3–8 weeks (same Ct type over time), indicating possible antimicrobial treatment failure. Cases showed intermittent positive detection and the number of positive samples was higher in anorectal cases than in cervicovaginal cases. The highest observed bacterial load between 3–8 weeks post-treatment was 313 IFU/ml, yet the majority (65%) of positive samples showed a load of ≤2 IFU/ml. Pre-treatment load was found to be associated with later load in anorectal cases. Conclusions A single test at 3–8 weeks post-treatment frequently misses Ct. Detection reveals intermittent low loads, with an unknown risk of later complications or transmission. These findings warrant critical re-evaluation of the clinical management of single dose

  10. Parasitological Clearance Rates and Drug Concentrations of a Fixed Dose Combination of Azithromycin-Chloroquine in Asymptomatic Pregnant Women with Plasmodium Falciparum Parasitemia: An Open-Label, Non-Comparative Study in Sub-Saharan Africa

    PubMed Central

    Phiri, Kamija; Kimani, Joshua; Mtove, George A.; Zhao, Qinying; Rojo, Ricardo; Robbins, Jeffery; Duparc, Stephan; Ayoub, Ayman; Vandenbroucke, Pol

    2016-01-01

    Background Malaria remains one of the most important causes of morbidity and mortality in pregnant women and their newborn babies in sub-Saharan Africa. Intermittent preventive treatment in pregnancy (IPTp) is recommended by the World Health Organization (WHO) to reduce the burden of disease and improve maternal and neonatal survival and general health. Due to the growing resistance to sulfadoxine-pyrimethamine (SP), the current WHO-recommended drug for IPTp, identification of new and effective drugs is an urgent priority. Methods and Findings This was an open-label, non-comparative study (NCT01103713) in 5 countries in East and sub-Saharan Africa (Benin, Kenya, Malawi, Tanzania, and Uganda) to assess parasitological response and drug concentrations of a single, 3-day course of four tablets of a fixed-dose combination of azithromycin-chloroquine (AZCQ) 250/155 mg given during the second or third trimester to women with asymptomatic Plasmodium falciparum parasitemia in their first or second pregnancy. Parasitemia was determined by microscopy and molecular genotyping was performed to characterize parasites relative to the baseline infection. Weekly follow-up visits took place until day 42 after first dose and additional follow-up occurred after delivery. Systemic concentrations of azithromycin (AZ), chloroquine (CQ), and the CQ metabolite, desethyl CQ (DECQ) were evaluated at Day 0 (pre-dose), at Day 2 (pre-dose, 2 and 8 hours) and randomly at Days 7 and 14. Systemic concentrations of CQ and DECQ were also measured randomly at Day 21 and Day 28. In total, 404 women were screened for eligibility and 168 were treated, 155 of whom completed the study. PCR-adjusted parasitological response in the modified intent-to-treat population at day 28 (the primary efficacy endpoint) was estimated by the Kaplan-Meier method as 99.35% (95% confidence interval [CI]: 97.76, 100.00). PCR-adjusted parasitological response remained high at day 42 (95.19%; 95% CI: 91.35, 99.03). In

  11. A randomized, double-masked, parallel-group, comparative study to evaluate the clinical efficacy and safety of 1% azithromycin–0.1% dexamethasone combination compared to 1% azithromycin alone, 0.1% dexamethasone alone, and vehicle in the treatment of subjects with blepharitis

    PubMed Central

    Hosseini, Kamran; Lindstrom, Richard L; Foulks, Gary; Nichols, Kelly K

    2016-01-01

    Purpose To evaluate the clinical efficacy and safety of a 1% azithromycin–0.1% dexamethasone combination in DuraSite (“combination”) compared to 0.1% dexamethasone in DuraSite, 1% azithromycin in DuraSite, and vehicle in the treatment of subjects with blepharitis. Materials and methods This was a Phase III, double-masked, vehicle-controlled, four-arm study in which 907 subjects with blepharitis were randomized to combination (n=305), 0.1% dexamethasone (n=298), 1% azithromycin (n=155), or vehicle (n=149). Ten study visits were scheduled: screening visit, days 1 and 4 (dosing phase) and 15, and months 1–6 (follow-up phase). On day 1, subjects applied one drop of the study drug to the eyelid of the inflamed eye(s) twice daily, and continued with twice-daily dosing for 14 days. After completing 14 days of dosing, subjects were followed for 6 months for efficacy and safety. Results A total of 57 subjects (6.3%) had complete clinical resolution at day 15: 25 (8.2%), 17 (5.7%), 8 (5.2%), and 7 (4.7%) subjects in the combination-, 0.1% dexamethasone-, 1% azithromycin-, and vehicle-treatment groups, respectively. The combination was superior to 1% azithromycin and vehicle alone, but not to 0.1% dexamethasone alone. Mean composite (total) clinical sign and symptom scores improved in all four treatment groups during the post-treatment evaluation phase for the intent-to-treat population, but outcomes were superior when a drop containing 0.1% dexamethasone was utilized. Clinical response was noted as early as day 4, and persisted as long as 6 months. Most adverse events were considered mild in severity and not related to the study drug. Conclusion A higher percentage of subjects in the combination group achieved complete clinical resolution of the signs and symptoms of blepharitis at day 15 than with 1% azithromycin and vehicle, but outcomes were similar to treatment with 0.1% dexamethasone alone. The combination was well tolerated. PMID:27570444

  12. How to suppress undesired synchronization.

    PubMed

    Louzada, V H P; Araújo, N A M; Andrade, J S; Herrmann, H J

    2012-01-01

    Examples of synchronization can be found in a wide range of phenomena such as neurons firing, lasers cascades, chemical reactions, and opinion formation. However, in many situations the formation of a coherent state is not pleasant and should be mitigated. For example, the onset of synchronization can be the root of epileptic seizures, traffic congestion in networks, and the collapse of constructions. Here we propose the use of contrarians to suppress undesired synchronization. We perform a comparative study of different strategies, either requiring local or total knowledge, and show that the most efficient one solely requires local information. Our results also reveal that, even when the distribution of neighboring interactions is narrow, significant improvement is observed when contrarians sit at the highly connected elements. The same qualitative results are obtained for artificially generated networks and two real ones, namely, the Routers of the Internet and a neuronal network.

  13. Elastic Suppression of Viscous Fingering

    NASA Astrophysics Data System (ADS)

    Peng, Gunnar; Lister, John

    2016-11-01

    Consider peeling an elastic tape or beam away from a rigid base to which it is stuck by a film of viscous liquid. The peeling motion requires air to invade the viscous liquid and is thus susceptible to the Saffman-Taylor fingering instability. We analyse the fundamental travelling-wave solution and show that the advancing air-liquid interface remains linearly stable at higher capillary numbers than in a standard Hele-Shaw cell. A short-wavelength expansion yields an analytical expression for the growth rate which is valid for all unstable modes throughout the parameter space, allowing us to identify and quantify four distinct physical mechanisms that each help suppress the instability. Applying our method to the experiments by Pihler-Puzovic et al. (2012) reveals that the radial geometry and time-variation stabilize the system further.

  14. How to suppress undesired synchronization

    PubMed Central

    Louzada, V. H. P.; Araújo, N. A. M.; Andrade, J. S.; Herrmann, H. J.

    2012-01-01

    Examples of synchronization can be found in a wide range of phenomena such as neurons firing, lasers cascades, chemical reactions, and opinion formation. However, in many situations the formation of a coherent state is not pleasant and should be mitigated. For example, the onset of synchronization can be the root of epileptic seizures, traffic congestion in networks, and the collapse of constructions. Here we propose the use of contrarians to suppress undesired synchronization. We perform a comparative study of different strategies, either requiring local or total knowledge, and show that the most efficient one solely requires local information. Our results also reveal that, even when the distribution of neighboring interactions is narrow, significant improvement is observed when contrarians sit at the highly connected elements. The same qualitative results are obtained for artificially generated networks and two real ones, namely, the Routers of the Internet and a neuronal network. PMID:22993685

  15. Tactile stimulation can suppress visual perception

    PubMed Central

    Ide, Masakazu; Hidaka, Souta

    2013-01-01

    An input (e.g., airplane takeoff sound) to a sensory modality can suppress the percept of another input (e.g., talking voices of neighbors) of the same modality. This perceptual suppression effect is evidence that neural responses to different inputs closely interact with each other in the brain. While recent studies suggest that close interactions also occur across sensory modalities, crossmodal perceptual suppression effect has not yet been reported. Here, we demonstrate that tactile stimulation can suppress the percept of visual stimuli: Visual orientation discrimination performance was degraded when a tactile vibration was applied to the observer's index finger of hands. We also demonstrated that this tactile suppression effect on visual perception occurred primarily when the tactile and visual information were spatially and temporally consistent. The current findings would indicate that neural signals could closely and directly interact with each other, sufficient to induce the perceptual suppression effect, even across sensory modalities. PMID:24336391

  16. Tactile stimulation can suppress visual perception.

    PubMed

    Ide, Masakazu; Hidaka, Souta

    2013-12-13

    An input (e.g., airplane takeoff sound) to a sensory modality can suppress the percept of another input (e.g., talking voices of neighbors) of the same modality. This perceptual suppression effect is evidence that neural responses to different inputs closely interact with each other in the brain. While recent studies suggest that close interactions also occur across sensory modalities, crossmodal perceptual suppression effect has not yet been reported. Here, we demonstrate that tactile stimulation can suppress the percept of visual stimuli: Visual orientation discrimination performance was degraded when a tactile vibration was applied to the observer's index finger of hands. We also demonstrated that this tactile suppression effect on visual perception occurred primarily when the tactile and visual information were spatially and temporally consistent. The current findings would indicate that neural signals could closely and directly interact with each other, sufficient to induce the perceptual suppression effect, even across sensory modalities.

  17. MEK5 suppresses osteoblastic differentiation

    SciTech Connect

    Kaneshiro, Shoichi; Otsuki, Dai; Yoshida, Kiyoshi; Yoshikawa, Hideki; Higuchi, Chikahisa

    2015-07-31

    Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase (MAPK) family and is activated by its upstream kinase, MAPK kinase 5 (MEK5), which is a member of the MEK family. Although the role of MEK5 has been investigated in several fields, little is known about its role in osteoblastic differentiation. In this study, we have demonstrated the role of MEK5 in osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells and bone marrow stromal ST2 cells. We found that treatment with BIX02189, an inhibitor of MEK5, increased alkaline phosphatase (ALP) activity and the gene expression of ALP, osteocalcin (OCN) and osterix, as well as it enhanced the calcification of the extracellular matrix. Moreover, osteoblastic cell proliferation decreased at a concentration of greater than 0.5 μM. In addition, knockdown of MEK5 using siRNA induced an increase in ALP activity and in the gene expression of ALP, OCN, and osterix. In contrast, overexpression of wild-type MEK5 decreased ALP activity and attenuated osteoblastic differentiation markers including ALP, OCN and osterix, but promoted cell proliferation. In summary, our results indicated that MEK5 suppressed the osteoblastic differentiation, but promoted osteoblastic cell proliferation. These results implied that MEK5 may play a pivotal role in cell signaling to modulate the differentiation and proliferation of osteoblasts. Thus, inhibition of MEK5 signaling in osteoblasts may be of potential use in the treatment of osteoporosis. - Highlights: • MEK5 inhibitor BIX02189 suppresses proliferation of osteoblasts. • MEK5 knockdown and MEK5 inhibitor promote differentiation of osteoblasts. • MEK5 overexpression inhibits differentiation of osteoblasts.

  18. Two Techniques For Suppressing Vibrations In Structures

    NASA Technical Reports Server (NTRS)

    Chen, Gun-Shing; Garba, John A.; Wada, Ben K.

    1991-01-01

    Two techniques intended to be used together to suppress vibrations in large, complicated truss structure involve combination of active and passive damping. Based on bridge feedback and criterion for placement of actuators. Research continues to develop system using these and other techniques to suppress vibrations in, and help control shape of, truss structure in outer space that supports precise, segmented reflector of communication antenna. On Earth, developmental techniques applicable to suppression of vibrations in bridges and tall buildings.

  19. Acoustic Suppression Systems and Related Methods

    NASA Technical Reports Server (NTRS)

    Kolaini, Ali R. (Inventor); Kern, Dennis L. (Inventor)

    2013-01-01

    An acoustic suppression system for absorbing and/or scattering acoustic energy comprising a plurality of acoustic targets in a containment is described, the acoustic targets configured to have resonance frequencies allowing the targets to be excited by incoming acoustic waves, the resonance frequencies being adjustable to suppress acoustic energy in a set frequency range. Methods for fabricating and implementing the acoustic suppression system are also provided.

  20. ISS Update: Burning and Suppression of Solids

    NASA Video Gallery

    ISS Update Commentator Pat Ryan interviews Paul Ferkul, Principal Investigator for the Burning and Suppression of Solids (BASS) experiment, about performing combustion experiments in microgravity. ...

  1. Issues in Numerical Simulation of Fire Suppression

    SciTech Connect

    Tieszen, S.R.; Lopez, A.R.

    1999-04-12

    This paper outlines general physical and computational issues associated with performing numerical simulation of fire suppression. Fire suppression encompasses a broad range of chemistry and physics over a large range of time and length scales. The authors discuss the dominant physical/chemical processes important to fire suppression that must be captured by a fire suppression model to be of engineering usefulness. First-principles solutions are not possible due to computational limitations, even with the new generation of tera-flop computers. A basic strategy combining computational fluid dynamics (CFD) simulation techniques with sub-grid model approximations for processes that have length scales unresolvable by gridding is presented.

  2. Bone suppression technique for chest radiographs

    NASA Astrophysics Data System (ADS)

    Huo, Zhimin; Xu, Fan; Zhang, Jane; Zhao, Hui; Hobbs, Susan K.; Wandtke, John C.; Sykes, Anne-Marie; Paul, Narinder; Foos, David

    2014-03-01

    High-contrast bone structures are a major noise contributor in chest radiographic images. A signal of interest in a chest radiograph could be either partially or completely obscured or "overshadowed" by the highly contrasted bone structures in its surrounding. Thus, removing the bone structures, especially the posterior rib and clavicle structures, is highly desirable to increase the visibility of soft tissue density. We developed an innovative technology that offers a solution to suppress bone structures, including posterior ribs and clavicles, on conventional and portable chest X-ray images. The bone-suppression image processing technology includes five major steps: 1) lung segmentation, 2) rib and clavicle structure detection, 3) rib and clavicle edge detection, 4) rib and clavicle profile estimation, and 5) suppression based on the estimated profiles. The bone-suppression software outputs an image with both the rib and clavicle structures suppressed. The rib suppression performance was evaluated on 491 images. On average, 83.06% (±6.59%) of the rib structures on a standard chest image were suppressed based on the comparison of computer-identified rib areas against hand-drawn rib areas, which is equivalent to about an average of one rib that is still visible on a rib-suppressed image based on a visual assessment. Reader studies were performed to evaluate reader performance in detecting lung nodules and pneumothoraces with and without a bone-suppression companion view. Results from reader studies indicated that the bone-suppression technology significantly improved radiologists' performance in the detection of CT-confirmed possible nodules and pneumothoraces on chest radiographs. The results also showed that radiologists were more confident in making diagnoses regarding the presence or absence of an abnormality after rib-suppressed companion views were presented

  3. Attentional selection by distractor suppression.

    PubMed

    Caputo, G; Guerra, S

    1998-03-01

    Selective attention was studied in displays containing singletons popping out for their odd form or color. The target was defined as the form-singleton, the distractor as the color-singleton. The task was to discriminate the length of a longer line inside the target. Target-distractor similarity was controlled using a threshold measurement as dependent variable in experiments in which distractor presence vs absence, bottom-up vs top-down selection (through knowledge of target features), and target-distractor distance were manipulated. The results in the bottom-up condition showed that length threshold was elevated when a distractor was present and that this elevation progressively increased as the number of distractors was increased from one to two. This set-size effect was not accounted by the hypothesis that selective attention intervenes only at the stage of decision before response. Selective attention produced a suppressive surround in which discriminability of neighboring objects was strongly reduced, and a larger surround in which discriminability was reduced by an approximately constant amount. Different results were found in the top-down condition in which target discriminability was unaffected by distractor presence and no effect of target-distractor distance was found. On the other hand, response times in both bottom-up and top-down conditions were slower the shorter the target-distractor distance was. On the basis of the experimental results, selective attention is a parallel process of spatial filtering at an intermediate processing level operating after objects have been segmented. This filtering stage explores high level interactions between objects taking control on combinatorial explosion by operating over only a limited spatial extent: it picks out a selected object and inhibits the neighboring objects; then, non-selected objects are suppressed across the overall image. When no feature-based selection is available in the current behavior, this

  4. New approaches to hard bubble suppression

    NASA Technical Reports Server (NTRS)

    Henry, R. D.; Besser, P. J.; Warren, R. G.; Whitcomb, E. C.

    1973-01-01

    Description of a new double-layer method for the suppression of hard bubbles that is more versatile than previously reported suppression techniques. It is shown that it may be possible to prevent hard bubble generation without recourse to exchange coupling of multilayer films.

  5. Growth suppression caused by corticosteroid eye drops.

    PubMed

    Wolthers, Ole D

    2011-01-01

    Scarce data on systemic activity of corticosteroid eye drops are available in children. Two weeks treatment with fluorometholone eye drops in a case series of five children caused growth suppression detected by knemometry. The suppression had no impact on height growth during the following year.

  6. Suppressive soils: back on the radar screen

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Suppressive soils are those in which a pathogen does not establish or persist, establishes but causes little or no damage, or establishes and causes disease for a while but thereafter the disease is less important, although the pathogen may persist in the soil (Weller, 2002). ‘General suppression,’ ...

  7. Ferromagnetic resonance probe liftoff suppression apparatus

    DOEpatents

    Davis, Thomas J.; Tomeraasen, Paul L.

    1985-01-01

    A liftoff suppression apparatus utilizing a liftoff sensing coil to sense the amount a ferromagnetic resonance probe lifts off the test surface during flaw detection and utilizing the liftoff signal to modulate the probe's field modulating coil to suppress the liftoff effects.

  8. Polypyrrole actuators for tremor suppression

    NASA Astrophysics Data System (ADS)

    Skaarup, Steen; Mogensen, Naja; Bay, Lasse; West, Keld

    2003-07-01

    Neurological tremor affecting limbs can be divided into at least 6 different types with frequencies ranging from 2 to about 20 Hz. In order to alleviate the symptoms by suppressing the tremor, sensing and actuation systems able to perform at these frequencies are needed. Electroactive polymers exemplify "soft actuator" technology that may be especially suitable for use in conjunction with human limbs. The electrochemical and mechanical properties of polypyrrole dodecyl benzene sulphonate actuator films have been studied with this application in mind. The results show that the time constants for the change of length and for the stiffness change are significantly different; the stiffness change being about 10 times faster. Both force measurements and Electrochemical Quartz Crystal Microbalance measurements indicate that the actuation process is complex and involves at least two different processes. The EQCM results make it possible to formulate a hypothesis for the two different time constants: Sodium ions enter the polymer correlated with a fast mass change that probably involves a few (~4) strongly bound water molecules as well. On further reduction, about 10 additional water molecules enter the polymer in a slower process driven by osmotic pressure. Earlier work has tended to focus on achieving the maximum length change, therefore taking the time needed to include all processes. However, since the slower process described above is associated with the lowest strength of the actuator, concentrating on the faster stiffness change results in only a small reduction in the work done by the actuator. This may make actuation at higher frequencies feasible.

  9. Multicopy Suppression Underpins Metabolic Evolvability

    PubMed Central

    Patrick, Wayne M.; Quandt, Erik M.; Swartzlander, Dan B.; Matsumura, Ichiro

    2009-01-01

    Our understanding of the origins of new metabolic functions is based upon anecdotal genetic and biochemical evidence. Some auxotrophies can be suppressed by overexpressing substrate-ambiguous enzymes (i.e., those that catalyze the same chemical transformation on different substrates). Other enzymes exhibit weak but detectable catalytic promiscuity in vitro (i.e., they catalyze different transformations on similar substrates). Cells adapt to novel environments through the evolution of these secondary activities, but neither their chemical natures nor their frequencies of occurrence have been characterized en bloc. Here, we systematically identified multifunctional genes within the Escherichia coli genome. We screened 104 single-gene knockout strains and discovered that many (20%) of these auxotrophs were rescued by the overexpression of at least one noncognate E. coli gene. The deleted gene and its suppressor were generally unrelated, suggesting that promiscuity is a product of contingency. This genome-wide survey demonstrates that multifunctional genes are common and illustrates the mechanistic diversity by which their products enhance metabolic robustness and evolvability. PMID:17884825

  10. Transport suppression by shear reduction

    NASA Astrophysics Data System (ADS)

    Martinell, Julio; Del-Castillo-Negrete, Diego

    2009-11-01

    The relationship between transport and shear is a problem of considerable interest to magnetically confined plasmas. It is well known that there are cases in which an increase of flow shear can lead to a reduction of turbulent transport. However, this is not a generic result, and there are transport problems in which the opposite is the case. In particular, as originally discussed in Ref. footnotetextdel-Castillo-Negrete and Morrison, Phys. Fluids A 5, 948 (1993), barriers to chaotic transport typically form in regions of vanishing shear. This property, which is generic to the so-called non-twist Hamiltonian systems footnotetextdel-Castillo-Negrete, Greene, and Morrison, Physica D 91, 1 (1996), explains the observed resilience of transport barriers in non-monotonic zonal flows in plasmas and fluids and the robustness of shearless magnetic surfaces in reverse shear configurations. Here we study the role of finite Larmor radius (FLR) effects on the suppression of chaotic transport by shear reduction in a simplified model. Following Ref. footnotetextdel-Castillo-Negrete, Phys. Plasmas, 7, 1702 (2000) we consider a model consisting of a superposition of drift waves and a non-monotonic zonal flow. The FLR effects are incorporated by gyroaveraging the E xB velocity, and transport is studied by following the evolution of ensembles of test particles.

  11. Impacts of suppressing guide on information spreading

    NASA Astrophysics Data System (ADS)

    Xu, Jinghong; Zhang, Lin; Ma, Baojun; Wu, Ye

    2016-02-01

    It is quite common that guides are introduced to suppress the information spreading in modern society for different purposes. In this paper, an agent-based model is established to quantitatively analyze the impacts of suppressing guides on information spreading. We find that the spreading threshold depends on the attractiveness of the information and the topology of the social network with no suppressing guides at all. Usually, one would expect that the existence of suppressing guides in the spreading procedure may result in less diffusion of information within the overall network. However, we find that sometimes the opposite is true: the manipulating nodes of suppressing guides may lead to more extensive information spreading when there are audiences with the reversal mind. These results can provide valuable theoretical references to public opinion guidance on various information, e.g., rumor or news spreading.

  12. Burst suppression probability algorithms: state-space methods for tracking EEG burst suppression

    NASA Astrophysics Data System (ADS)

    Chemali, Jessica; Ching, ShiNung; Purdon, Patrick L.; Solt, Ken; Brown, Emery N.

    2013-10-01

    Objective. Burst suppression is an electroencephalogram pattern in which bursts of electrical activity alternate with an isoelectric state. This pattern is commonly seen in states of severely reduced brain activity such as profound general anesthesia, anoxic brain injuries, hypothermia and certain developmental disorders. Devising accurate, reliable ways to quantify burst suppression is an important clinical and research problem. Although thresholding and segmentation algorithms readily identify burst suppression periods, analysis algorithms require long intervals of data to characterize burst suppression at a given time and provide no framework for statistical inference. Approach. We introduce the concept of the burst suppression probability (BSP) to define the brain's instantaneous propensity of being in the suppressed state. To conduct dynamic analyses of burst suppression we propose a state-space model in which the observation process is a binomial model and the state equation is a Gaussian random walk. We estimate the model using an approximate expectation maximization algorithm and illustrate its application in the analysis of rodent burst suppression recordings under general anesthesia and a patient during induction of controlled hypothermia. Main result. The BSP algorithms track burst suppression on a second-to-second time scale, and make possible formal statistical comparisons of burst suppression at different times. Significance. The state-space approach suggests a principled and informative way to analyze burst suppression that can be used to monitor, and eventually to control, the brain states of patients in the operating room and in the intensive care unit.

  13. Mutual Suppression: Comment on Paulhus et Al. (2004)

    ERIC Educational Resources Information Center

    Nickerson, Carol

    2008-01-01

    Paulhus, Robins, Trzesniewski, and Tracy ("Multivariate Behavioral Research," 2004, 39, 305-328) suggested that the three types of two-predictor suppression situations--classical suppression, cooperative suppression, and net suppression--can all be considered special cases of mutual suppression, in that the magnitude of each of the two…

  14. Psychopathology and Thought Suppression: A Quantitative Review

    PubMed Central

    Magee, Joshua C.; Harden, K. Paige; Teachman, Bethany A.

    2012-01-01

    Recent theories of psychopathology have suggested that thought suppression intensifies the persistence of intrusive thoughts, and proposed that difficulty with thought suppression may differ between groups with and without psychopathology. The current meta-analytic review evaluates empirical evidence for difficulty with thought suppression as a function of the presence and specific type of psychopathology. Based on theoretical proposals from the psychopathology literature, diagnosed and analogue samples were expected to show greater recurrence of intrusive thoughts during thought suppression attempts than non-clinical samples. However, results showed no overall differences in the recurrence of thoughts due to thought suppression between groups with and without psychopathology. There was, nevertheless, variation in the recurrence of thoughts across different forms of psychopathology, including relatively less recurrence during thought suppression for samples with symptoms of Obsessive-Compulsive Disorder, compared to non-clinical samples. However, these differences were typically small and provided only mixed support for existing theories. Implications for cognitive theories of intrusive thoughts are discussed, including proposed mechanisms underlying thought suppression. PMID:22388007

  15. Suppression effects in feature-based attention

    PubMed Central

    Wang, Yixue; Miller, James; Liu, Taosheng

    2015-01-01

    Attending to a feature enhances visual processing of that feature, but it is less clear what occurs to unattended features. Single-unit recording studies in middle temporal (MT) have shown that neuronal modulation is a monotonic function of the difference between the attended and neuron's preferred direction. Such a relationship should predict a monotonic suppressive effect in psychophysical performance. However, past research on suppressive effects of feature-based attention has remained inconclusive. We investigated the suppressive effect for motion direction, orientation, and color in three experiments. We asked participants to detect a weak signal among noise and provided a partially valid feature cue to manipulate attention. We measured performance as a function of the offset between the cued and signal feature. We also included neutral trials where no feature cues were presented to provide a baseline measure of performance. Across three experiments, we consistently observed enhancement effects when the target feature and cued feature coincided and suppression effects when the target feature deviated from the cued feature. The exact profile of suppression was different across feature dimensions: Whereas the profile for direction exhibited a “rebound” effect, the profiles for orientation and color were monotonic. These results demonstrate that unattended features are suppressed during feature-based attention, but the exact suppression profile depends on the specific feature. Overall, the results are largely consistent with neurophysiological data and support the feature-similarity gain model of attention. PMID:26067533

  16. Azithromycin-Ciprofloxacin-Impregnated Urinary Catheters Avert Bacterial Colonization, Biofilm Formation, and Inflammation in a Murine Model of Foreign-Body-Associated Urinary Tract Infections Caused by Pseudomonas aeruginosa.

    PubMed

    Saini, Hina; Vadekeetil, Anitha; Chhibber, Sanjay; Harjai, Kusum

    2017-03-01

    Pseudomonas aeruginosa is a multifaceted pathogen causing a variety of biofilm-mediated infections, including catheter-associated urinary tract infections (CAUTIs). The high prevalence of CAUTIs in hospitals, their clinical manifestations, such as urethritis, cystitis, pyelonephritis, meningitis, urosepsis, and death, and the associated economic challenges underscore the need for management of these infections. Biomaterial modification of urinary catheters with two drugs seems an interesting approach to combat CAUTIs by inhibiting biofilm. Previously, we demonstrated the in vitro efficacy of urinary catheters impregnated with azithromycin (AZM) and ciprofloxacin (CIP) against P. aeruginosa Here, we report how these coated catheters impact the course of CAUTI induced by P. aeruginosa in a murine model. CAUTI was established in female LACA mice with uncoated or AZM-CIP-coated silicone implants in the bladder, followed by transurethral inoculation of 10(8) CFU/ml of biofilm cells of P. aeruginosa PAO1. AZM-CIP-coated implants (i) prevented biofilm formation on the implant's surface (P ≤ 0.01), (ii) restricted bacterial colonization in the bladder and kidney (P < 0.0001), (iii) averted bacteriuria (P < 0.0001), and (iv) exhibited no major histopathological changes for 28 days in comparison to uncoated implants, which showed persistent CAUTI. Antibiotic implants also overcame implant-mediated inflammation, as characterized by trivial levels of inflammatory markers such as malondialdehyde (P < 0.001), myeloperoxidase (P < 0.05), reactive oxygen species (P ≤ 0.001), and reactive nitrogen intermediates (P < 0.01) in comparison to those in uncoated implants. Further, AZM-CIP-coated implants showed immunomodulation by manipulating the release of inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-10 to the benefit of the host. Overall, the study demonstrates long-term in vivo effectiveness of AZM-CIP-impregnated catheters, which may

  17. Impact of Intermittent Preventive Treatment in Pregnancy with Azithromycin-Containing Regimens on Maternal Nasopharyngeal Carriage and Antibiotic Sensitivity of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus: a Cross-Sectional Survey at Delivery

    PubMed Central

    Unger, Holger W.; Aho, Celestine; Ome-Kaius, Maria; Wangnapi, Regina A.; Umbers, Alexandra J.; Jack, Wanda; Lafana, Alice; Michael, Audrey; Hanieh, Sarah; Siba, Peter; Mueller, Ivo; Greenhill, Andrew R.

    2015-01-01

    Sulfadoxine-pyrimethamine (SP) plus azithromycin (AZ) (SPAZ) has the potential for intermittent preventive treatment of malaria in pregnancy (IPTp), but its use could increase circulation of antibiotic-resistant bacteria associated with severe pediatric infections. We evaluated the effect of monthly SPAZ-IPTp compared to a single course of SP plus chloroquine (SPCQ) on maternal nasopharyngeal carriage and antibiotic susceptibility of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus at delivery among 854 women participating in a randomized controlled trial in Papua New Guinea. Serotyping was performed, and antibiotic susceptibility was evaluated by disk diffusion and Etest. Potential risk factors for carriage were examined. Nasopharyngeal carriage at delivery of S. pneumoniae (SPAZ, 7.2% [30/418], versus SPCQ, 19.3% [84/436]; P < 0.001) and H. influenzae (2.9% [12/418] versus 6.0% [26/436], P = 0.028), but not S. aureus, was significantly reduced among women who had received SPAZ-IPTp. The number of macrolide-resistant pneumococcal isolates was small but increased in the SPAZ group (13.3% [4/30], versus SPCQ, 2.2% [2/91]; P = 0.033). The proportions of isolates with serotypes covered by the 13-valent pneumococcal conjugate vaccine were similar (SPAZ, 10.3% [3/29], versus SPCQ, 17.6% [16/91]; P = 0.352). Although macrolide-resistant isolates were rare, they were more commonly detected in women who had received SPAZ-IPTp, despite the significant reduction of maternal carriage of S. pneumoniae and H. influenzae observed in this group. Future studies on SPAZ-IPTp should evaluate carriage and persistence of macrolide-resistant S. pneumoniae and other pathogenic bacteria in both mothers and infants and assess the clinical significance of their circulation. PMID:25673788

  18. Integrin endosomal signalling suppresses anoikis

    PubMed Central

    Alanko, Jonna; Mai, Anja; Jacquemet, Guillaume; Schauer, Kristine; Kaukonen, Riina; Saari, Markku; Goud, Bruno; Ivaska, Johanna

    2016-01-01

    to enhanced signalling of co-trafficked receptor tyrosine kinases10, 11 it has remained unclear whether endocytosed active integrins signal in endosomes. Here, we demonstrate that integrin signalling is not restricted to focal adhesions as previously described and that endocytosis is necessary for full ECM-induced, integrin mediated ERK, AKT and FAK signalling. We find that FAK binds directly to and can become activated on purified endosomes. Moreover, the FERM-domain of FAK is able to bind purified integrin containing endosomes, suggesting the potential for integrin signalling complexes to assemble on endosomes after internalization of active integrins. Importantly, FAK is required for anchorage-independent growth and suppression of anoikis 12. Integrin endosomal signalling correlates with reduced anoikis sensitivity in normal cells and anchorage-independent growth and metastasis in breast cancer cells. PMID:26436690

  19. Effects of tic suppression: ability to suppress, rebound, negative reinforcement, and habituation to the premonitory urge.

    PubMed

    Specht, Matt W; Woods, Douglas W; Nicotra, Cassandra M; Kelly, Laura M; Ricketts, Emily J; Conelea, Christine A; Grados, Marco A; Ostrander, Rick S; Walkup, John T

    2013-01-01

    The comprehensive behavioral intervention for tics (CBIT) represents a safe, effective non-pharmacological treatment for Tourette's disorder that remains underutilized as a treatment option. Contributing factors include the perceived negative consequences of tic suppression and the lack of a means through which suppression results in symptom improvement. Participants (n = 12) included youth ages 10-17 years with moderate-to-marked tic severity and noticeable premonitory urges who met Tourette's or chronic tic disorder criteria. Tic frequency and urge rating data were collected during an alternating sequence of tic freely or reinforced tic suppression periods. Even without specific instructions regarding how to suppress tics, youth experienced a significant, robust (72%), stable reduction in tic frequency under extended periods (40 min) of contingently reinforced tic suppression in contrast to periods of time when tics were ignored. Following periods of prolonged suppression, tic frequency returned to pre-suppression levels. Urge ratings did not show the expected increase during the initial periods of tic suppression, nor a subsequent decline in urge ratings during prolonged, effective tic suppression. Results suggest that environments conducive to tic suppression result in reduced tic frequency without adverse consequences. Additionally, premonitory urges, underrepresented in the literature, may represent an important enduring etiological consideration in the development and maintenance of tic disorders.

  20. Suppression of immune response to Listeria monocytogenes: mechanism(s) of immune complex suppression.

    PubMed Central

    Virgin, H W; Wittenberg, G F; Bancroft, G J; Unanue, E R

    1985-01-01

    We have investigated possible mechanisms underlying immune complex suppression of resistance to Listeria monocytogenes. Inhibition of resistance was found when immune complexes were formed in vivo in immune mice or in nonimmune mice adoptively transferred with specific antibody. Suppression was also found when nonimmune mice were injected with immune complexes preformed in vitro. We investigated the role of complement by decomplementing mice with cobra venom factor purified by high-pressure liquid chromatography. Complete depletion of serum C3 did not eliminate immune complex suppression of resistance to L. monocytogenes, suggesting that complement activation is not required for immune complex suppression. Infection-induced changes in the surface phenotype and functional properties of macrophages from normal and immune complex-suppressed mice were also investigated. Macrophage expression of both H-2K and Ia molecules increased during the response of normal mice to L. monocytogenes. However, these changes were not found in immune complex-suppressed mice. In contrast, membrane interleukin 1 expression was increased in macrophages from suppressed mice compared with macrophages from normal mice. Macrophages from L. monocytogenes-infected normal and immune complex-suppressed mice expressed cytotoxicity against tumor cells in vitro. We conclude that immune complexes do not inhibit resistance to L. monocytogenes by activation of complement or decreasing macrophage cytotoxic activity. Rather, defects in Ia expression by macrophages from suppressed mice might be one component responsible for immune complex suppression of resistance to L. monocytogenes. PMID:3932204

  1. Suppression factors in diffractive photoproduction of dijets

    NASA Astrophysics Data System (ADS)

    Klasen, Michael; Kramer, Gustav

    2010-11-01

    Now that new publications of H1 data for the diffractive photoproduction of dijets, which overlap with the earlier published H1 data and the recently published data of the ZEUS collaboration, have appeared, we have recalculated the cross sections for this process in next-to-leading order (NLO) of perturbative QCD to see whether they can be interpreted consistently. The results of these calculations are compared to the data of both collaborations. We find that the NLO cross sections disagree with the data, showing that factorization breaking occurs at that order. If direct and resolved contributions are both suppressed by the same amount, the global suppression factor depends on the transverse-energy cut. However, by suppressing only the resolved contribution, also reasonably good agreement with all the data is found with a suppression factor independent of the transverse-energy cut.

  2. METHOD OF SUPPRESSING GASTROINTESTINAL UREASE ACTIVITY

    DOEpatents

    Visek, W.J.

    1963-04-23

    This patent shows a method of increasing the growth rate of chicks. Certain diacyl substituted ureas such as alloxan, murexide, and barbituric acid are added to their feed, thereby suppressing gastrointestinal urease activity and thus promoting growth. (AEC)

  3. Suppression as a stereotype control strategy.

    PubMed

    Monteith, M J; Sherman, J W; Devine, P G

    1998-01-01

    Recent research reveals that efforts to suppress stereotypic thoughts can backfire and produce a rebound effect, such that stereotypic thinking increases to a level that is even greater than if no attempt at stereotype control was initially exercised (e.g., Macrae, Bodenhausen, Milne, & Jetten, 1994). The primary goal of this article is to present an in-depth theoretical analysis of stereotype suppression that identifies numerous potential moderators of the effect of stereotype suppression on the likelihood of subsequent rebound. Our analysis of stereotype suppression focuses on two broad issues: the influence of level of prejudice and the influence of processing goals on the activation versus application of stereotypes. Although stereotype rebound occurs under some circumstances, we suggest that a complete understanding of this phenomenon requires consideration of the full array of possible moderating influences.

  4. Marihuana smoking suppresses luteinizing hormone in women.

    PubMed

    Mendelson, J H; Mello, N K; Ellingboe, J; Skupny, A S; Lex, B W; Griffin, M

    1986-06-01

    Smoking a single 1-g marihuana cigarette containing 1.8% delta 9-tetrahydrocannabinol induced a 30% suppression of plasma luteinizing hormone levels (P less than .02) in women during the luteal phase of the menstrual cycle. After marihuana placebo cigarette smoking, no luteinizing hormone suppression was observed in the same women under double-blind conditions. Marihuana may have adverse effects upon reproductive function during the luteal phase of the menstrual cycle as a consequence of gonadotropin inhibition.

  5. Investigation of refracting flows for acoustic suppression

    NASA Technical Reports Server (NTRS)

    Sloan, D.; Purves, R. B.; Farquhar, B. W.

    1977-01-01

    An experimental investigation to determine the possibility of using refracting flows for the suppression of aircraft inlet noise is described. Observations of wave refraction in duct flows and measurements of the increase in effectiveness of acoustic linings due to refraction have suggested methods for the design of engine inlet ducts which can either suppress noise internally or direct it to where it causes less annoyance.

  6. Flame Suppression Agent, System and Uses

    NASA Technical Reports Server (NTRS)

    Parrish, Clyde F. (Inventor)

    2013-01-01

    Aqueous droplets encapsulated in a flame retardant polymer are useful in suppressing combustion. Upon exposure to a flame, the encapsulated aqueous droplets rupture and vaporize, removing heat and displacing oxygen to retard the combustion process. The polymer encapsulant, through decomposition, may further add free radicals to the combustion atmosphere, thereby further retarding the combustion process. The encapsulated aqueous droplets may be used as a replacement to halon, water mist and dry powder flame suppression systems.

  7. Measurement of myeloid cell immune suppressive activity.

    PubMed

    Dolcetti, Luigi; Peranzoni, Elisa; Bronte, Vincenzo

    2010-11-01

    This unit presents simple methods to assess the immunosuppressive properties of immunoregulatory cells of myeloid origin, such as myeloid-derived suppressor cells (MDSCs), both in vitro and in vivo. These methods are general and could be adapted to test the impact of different suppressive populations on T cell activation, proliferation, and cytotoxic activity; moreover they could be useful to assess the influence exerted on immune suppressive pathways by genetic modifications, chemical inhibitors, and drugs.

  8. Method for Transducer Transient Suppression. I. Theory

    DTIC Science & Technology

    1992-09-01

    Vol. 92, No. 3, September 1992 Method for transducer transient suppression. I: Theory Jean C. Piquette Naval Research Laboratory. Underwater Sound...TITLE AND SUBTITLE 5. FUNDING NUMBERS Method for transducer transient suppression. I: Theo:y PE - 61153N TA - RROII-08-42 WU - DN220-161 6. AUTHOR(S) Jean...STATEMENT 12b. DISTRIBUTION CODE Approved for public release; distribution unlimited. 13. ABSTRACT (Maximum 200 words) The problem of driving a transducer in

  9. Noise suppression in surface microseismic data

    USGS Publications Warehouse

    Forghani-Arani, Farnoush; Batzle, Mike; Behura, Jyoti; Willis, Mark; Haines, Seth S.; Davidson, Michael

    2012-01-01

    We introduce a passive noise suppression technique, based on the τ − p transform. In the τ − p domain, one can separate microseismic events from surface noise based on distinct characteristics that are not visible in the time-offset domain. By applying the inverse τ − p transform to the separated microseismic event, we suppress the surface noise in the data. Our technique significantly improves the signal-to-noise ratios of the microseismic events and is superior to existing techniques for passive noise suppression in the sense that it preserves the waveform. We introduce a passive noise suppression technique, based on the τ − p transform. In the τ − p domain, one can separate microseismic events from surface noise based on distinct characteristics that are not visible in the time-offset domain. By applying the inverse τ − p transform to the separated microseismic event, we suppress the surface noise in the data. Our technique significantly improves the signal-to-noise ratios of the microseismic events and is superior to existing techniques for passive noise suppression in the sense that it preserves the waveform.

  10. Suppression sours sacrifice: emotional and relational costs of suppressing emotions in romantic relationships.

    PubMed

    Impett, Emily A; Kogan, Aleksandr; English, Tammy; John, Oliver; Oveis, Christopher; Gordon, Amie M; Keltner, Dacher

    2012-06-01

    What happens when people suppress their emotions when they sacrifice for a romantic partner? This multimethod study investigates how suppressing emotions during sacrifice shapes affective and relationship outcomes. In Part 1, dating couples came into the laboratory to discuss important romantic relationship sacrifices. Suppressing emotions was associated with emotional costs for the partner discussing his or her sacrifice. In Part 2, couples participated in a 14-day daily experience study. Within-person increases in emotional suppression during daily sacrifice were associated with decreases in emotional well-being and relationship quality as reported by both members of romantic dyads. In Part 3, suppression predicted decreases in relationship satisfaction and increases in thoughts about breaking up with a romantic partner 3 months later. In the first two parts of the study, authenticity mediated the costly effects of suppression. Implications for research on close relationships and emotion regulation are discussed.

  11. The temporal frequency tuning of continuous flash suppression reveals peak suppression at very low frequencies

    PubMed Central

    Han, Shui’er; Lunghi, Claudia; Alais, David

    2016-01-01

    Continuous flash suppression (CFS) is a psychophysical technique where a rapidly changing Mondrian pattern viewed by one eye suppresses the target in the other eye for several seconds. Despite the widespread use of CFS to study unconscious visual processes, the temporal tuning of CFS suppression is currently unknown. In the present study we used spatiotemporally filtered dynamic noise as masking stimuli to probe the temporal characteristics of CFS. Surprisingly, we find that suppression in CFS peaks very prominently at approximately 1 Hz, well below the rates typically used in CFS studies (10 Hz or more). As well as a strong bias to low temporal frequencies, CFS suppression is greater for high spatial frequencies and increases with increasing masker contrast, indicating involvement of parvocellular/ventral mechanisms in the suppression process. These results are reminiscent of binocular rivalry, and unifies two phenomenon previously thought to require different explanations. PMID:27767078

  12. Feature-based attention modulates surround suppression

    PubMed Central

    Flevaris, Anastasia V.; Murray, Scott O.

    2015-01-01

    Stimuli appearing in the surround of the classical receptive field (CRF) can reduce neuronal firing and perceived contrast of a preferred stimulus in the CRF, a phenomenon referred to as surround suppression. Suppression is greatest when the surrounding stimulus has the same orientation and spatial frequency (SF) as the central target. Although spatial attention has been shown to influence surround suppression, the effects of feature-based attention have yet to be characterized. Using behavioral contrast adaptation in humans, we examined center-surround interactions between SF and orientation, and asked whether attending to one feature dimension versus the other influenced suppression. A center-surround triplet comprised of a central target Gabor and two flanking Gabors were used for adaptation. The flankers could have the same SF and orientation as the target, or differ in one or both of the feature dimensions. Contrast thresholds were measured for the target before and after adapting to center-surround triplets, and postadaptation thresholds were taken as an indirect measure of surround suppression. Both feature dimensions contributed to surround suppression and did not summate. Moreover, when center and surround had the same feature value in one dimension (e.g., same orientation) but had different values in the other dimension (e.g., different SF), there was more suppression when attention was directed to the feature dimension that matched between center and surround than when attention was directed to the feature dimension that differed. These results demonstrate that feature-based attention can influence center-surround interactions by enhancing the effects of the attended dimension. PMID:25630380

  13. CONDITIONS FOR CSR MICROBUNCHING GAIN SUPPRESSION

    SciTech Connect

    Tsai, Cheng Ying; Douglas, David R.; Li, Rui; Tennant, Christopher D.; di Mitri, Simone

    2016-05-01

    The coherent synchrotron radiation (CSR) of a high brightness electron beam traversing a series of dipoles, such as transport arcs, may result in phase space degradation. On one hand, the CSR can perturb electron transverse motion in dispersive regions along the beamline, causing emittance growth. On the other hand, the CSR effect on the longitudinal beam dynamics could result in microbunching gain enhancement. For transport arcs, several schemes have been proposed* to suppress the CSR-induced emittance growth. Similarly, several scenarios have been introduced** to suppress CSR-induced microbunching gain, which however mostly aim for linac-based machines. In this paper we try to provide sufficient conditions for suppression of CSR-induced microbunching gain along a transport arc, analogous to*. Several example lattices are presented, with the relevant microbunching analyses carried out by our semi-analytical Vlasov solver***. The simulation results show that lattices satisfying the proposed conditions indeed have microbunching gain suppressed. We expect this analysis can shed light on lattice design approach that could suppress the CSR-induced microbunching gain.

  14. Suppression of branches in Eucalyptus trees.

    PubMed

    Senthalir, P; Sharanya, S; Paramathma, M

    2004-06-01

    The effect of neem oil, which acts as a suckericide in tobacco, on branch suppression in Eucalyptus tereticornis was assessed to help maximize stem biomass. Lateral branches of selected trees were pruned, and neem oil solutions at concentrations of either 80%, 40%, 20%, 10%, or 0% (untreated control) were applied to leaf axils of the pruned branches. Regeneration of branches was suppressed, and the magnitude of suppression was proportional to the concentration of neem oil. Compared to the control, the percentage reduction in branching at 80% neem oil was 41.6%. When regenerated branches were repruned and neem oil applied at either 100%, 80%, or 0% (control), the regenerating ability of these branches was severely repressed by 78% at 100% neem oil relative to the control. Apical shoots were also topped and treated at either 100% or 0% (control) neem oil to identify the principal suppressive component in neem oil. The principal component azadirachtin was tested at 375, 750, 1500, 3125, 6250, 12 500, 25 000, 50 000, and 100 000 ppm and 0 ppm as the control. Reduction in the coppicing shoot was as high as 85%. Azadirachtin was responsible for the suppression. By pruning the lateral branches with neem oil, wasteful consumption of photosynthates can be precluded and the stem biomass maximized.

  15. Tactical Checkpoint: Hail/Warn Suppress/Stop (Poster)

    DTIC Science & Technology

    2010-11-15

    distractor , optical suppression , human behavior, checkpoint, ambient light, driver suppression , human experimentation, light, paintball, obscuration...HAIL/WARN AND - SUPPRESS /STOP Poster Presented at the 2010 Directed Energies Professional Society Meeting, 15-19 November 2010. 5a. CONTRACT NUMBER...warning to a driver that is approaching a checkpoint. The laser, MCNC light, and the windshield obscuration were evaluated for their suppression

  16. Appetite suppressants and valvular heart disease.

    PubMed

    Weissman, N J

    2001-04-01

    The association between valvular heart disease and diet pills was discovered several years ago in a small cohort of patients. Subsequent uncontrolled surveys and reports suggested a prevalence of cardiac abnormalities as high as 30%. These results led to widespread concern by millions of appetite suppressant users and the withdrawal of both fenfluramine and dexfenfluramine from the market. Through this review of the literature, it becomes apparent that we have better defined the association between valvular heart disease and appetite suppressants; nonetheless, many questions and controversies remain. Most large scale, multicenter, controlled studies have shown that a prevalence of significant valve regurgitation is between 2 and 12% and that the likelihood of disease increases with increasing dose and/or duration of appetite suppressant use, but several other issues, such as the mechanism of action, remain unanswered.

  17. Wing rock suppression using forebody vortex control

    NASA Technical Reports Server (NTRS)

    Ng, T. T.; Ong, L. Y.; Suarez, C. J.; Malcolm, G. N.

    1991-01-01

    Static and free-to-roll tests were conducted in a water tunnel with a configuration that consisted of a highly-slender forebody and 78-deg sweep delta wings. Flow visualization was performed and the roll angle histories were obtained. The fluid mechanisms governing the wing rock of this configuration were identified. Different means of suppressing wing rock by controlling the forebody vortices using small blowing jets were also explored. Steady blowing was found to be capable of suppressing wing rock, but significant vortex asymmetries had to be induced at the same time. On the other hand, alternating pulsed blowing on the left and right sides of the forebody was demonstrated to be potentially an effective means of suppressing wing rock and eliminating large asymmetric moments at high angles of attack.

  18. Implicitly learned suppression of irrelevant spatial locations.

    PubMed

    Leber, Andrew B; Gwinn, Rachael E; Hong, Yoolim; O'Toole, Ryan J

    2016-12-01

    How do we ignore a salient, irrelevant stimulus whose location is predictable? A variety of studies using instructional manipulations have shown that participants possess the capacity to exert location-based suppression. However, for the visual search challenges we face in daily life, we are not often provided explicit instructions and are unlikely to consciously deliberate on what our best strategy might be. Instead, we might rely on our past experience-in the form of implicit learning-to exert strategic control. In this paper, we tested whether implicit learning could drive spatial suppression. In Experiment 1, participants searched displays in which one location contained a target, while another contained a salient distractor. An arrow cue pointed to the target location with 70 % validity. Also, unbeknownst to the participants, the same arrow cue predicted the distractor location with 70 % validity. Results showed facilitated RTs to the predicted target location, confirming target enhancement. Critically, distractor interference was reduced at the predicted distractor location, revealing that participants used spatial suppression. Further, we found that participants had no explicit knowledge of the cue-distractor contingencies, confirming that the learning was implicit. In Experiment 2, to seek further evidence for suppression, we modified the task to include occasional masked probes following the arrow cue; we found worse probe identification accuracy at the predicted distractor location than control locations, providing converging evidence that observers spatially suppressed the predicted distractor locations. These results reveal an ecologically desirable mechanism of suppression, which functions without the need for conscious knowledge or externally guided instructions.

  19. Large-Scale Identification and Analysis of Suppressive Drug Interactions

    PubMed Central

    Cokol, Murat; Weinstein, Zohar B.; Yilancioglu, Kaan; Tasan, Murat; Doak, Allison; Cansever, Dilay; Mutlu, Beste; Li, Siyang; Rodriguez-Esteban, Raul; Akhmedov, Murodzhon; Guvenek, Aysegul; Cokol, Melike; Cetiner, Selim; Giaever, Guri; Iossifov, Ivan; Nislow, Corey; Shoichet, Brian; Roth, Frederick P.

    2014-01-01

    SUMMARY One drug may suppress the effects of another. Although knowledge of drug suppression is vital to avoid efficacy-reducing drug interactions or discover countermeasures for chemical toxins, drug-drug suppression relationships have not been systematically mapped. Here, we analyze the growth response of Saccharomyces cerevisiae to anti-fungal compound (“drug”) pairs. Among 440 ordered drug pairs, we identified 94 suppressive drug interactions. Using only pairs not selected on the basis of their suppression behavior, we provide an estimate of the prevalence of suppressive interactions between anti-fungal compounds as 17%. Analysis of the drug suppression network suggested that Bromopyruvate is a frequently suppressive drug and Staurosporine is a frequently suppressed drug. We investigated potential explanations for suppressive drug interactions, including chemogenomic analysis, coaggregation, and pH effects, allowing us to explain the interaction tendencies of Bromopyruvate. PMID:24704506

  20. Vibration Isolation, Suppression, Steering, and Pointing (VISSP)

    NASA Technical Reports Server (NTRS)

    Wada, Ben K.; Rahman, Zahidul; Kedikian, Roland

    1996-01-01

    The design of a six degree of freedom flight vibration isolation suppression and steering (VISS) subsystem for a mid-wave infrared camera on the top of a spacecraft is presented. The development of a long stroke piezoelectric, redundant, compact, low stiffness and power efficient actuator is summarized. A subsystem that could be built and validated for flight within 15 months was investigated. The goals of the VISS are 20 dB vibration isolation above 2 Hz, 15 dB vibration suppression of disturbances at about 60 Hz and 120 Hz, and +/- 0.3 deg steering at 2 Hz and 4 Hz.

  1. Active Suppression Of Vibrations On Aircraft Structures

    NASA Technical Reports Server (NTRS)

    Maestrello, Lucio

    1995-01-01

    Method of active suppression of nonlinear and nonstationary vibrations developed to reduce sonic fatigue and interior noise in high-speed aircraft. Structure of aircraft exhibits periodic, chaotic, and random vibrations when forced by high-intensity sound from jet engines, shock waves, turbulence, and separated flows. Method of suppressing vibrations involves feedback control: Strain gauges or other sensors mounted in paths of propagation of vibrations on structure sense vibrations; outputs of sensors processed into control signal applied to actuator mounted on structure, inducing compensatory forces.

  2. Immune suppressive mechanisms in the tumor microenvironment.

    PubMed

    Munn, David H; Bronte, Vincenzo

    2016-04-01

    Effective immunotherapy, whether by checkpoint blockade or adoptive cell therapy, is limited in most patients by a key barrier: the immunosuppressive tumor microenvironment. Suppression of tumor-specific T cells is orchestrated by the activity of a variety of stromal myeloid and lymphoid cells. These often display inducible suppressive mechanisms that are triggered by the same anti-tumor inflammatory response that the immunotherapy intends to create. Therefore, a more comprehensive understanding of how the immunosuppressive milieu develops and persists is critical in order to harness the full power of immunotherapy of cancer.

  3. Corticosteroids and Immune Suppressive Therapies in Horses.

    PubMed

    Leclere, Mathilde

    2017-04-01

    Immune suppressive therapies target exaggerated and deleterious responses of the immune system. Triggered by exogenous or endogenous factors, these improper responses can lead to immune or inflammatory manifestations, such as urticaria, equine asthma, or autoimmune and immune-mediated diseases. Glucocorticoids are the most commonly used immune suppressive drugs and the only ones supported by robust evidence of clinical efficacy in equine medicine. In some conditions, combining glucocorticoids with other pharmacologic and nonpharmacologic treatments, such as azathioprine, antihistamine, bronchodilators, environmental management, or desensitization, can help to decrease dosages and associated side effects.

  4. Suppressive competition: how sounds may cheat sight.

    PubMed

    Kayser, Christoph; Remedios, Ryan

    2012-02-23

    In this issue of Neuron, Iurilli et al. (2012) demonstrate that auditory cortex activation directly engages local GABAergic circuits in V1 to induce sound-driven hyperpolarizations in layer 2/3 and layer 6 pyramidal neurons. Thereby, sounds can directly suppress V1 activity and visual driven behavior.

  5. Suppression Situations in Multiple Linear Regression

    ERIC Educational Resources Information Center

    Shieh, Gwowen

    2006-01-01

    This article proposes alternative expressions for the two most prevailing definitions of suppression without resorting to the standardized regression modeling. The formulation provides a simple basis for the examination of their relationship. For the two-predictor regression, the author demonstrates that the previous results in the literature are…

  6. Characterization of Immune Suppression Induced by Polyribonucleotides.

    DTIC Science & Technology

    1985-12-01

    RD-0162 482 CHARACTERIZATION OF IMMUNE SUPPRESSION INDUCED Y v i POLYRIDONUCLEOTIDES(U) MINNESOTA UNIV DULUTH DEPT OF MEDICAL MICROBIOLOGY AND...Polyribonucleotides by Marilyn J. Odean and Arthur G. Johnson Dept. of Medical Microbiology /Immunology University of Minnesota-Duluth 55812 DTICS ELECTE DEC 18

  7. Active suppression after involuntary capture of attention.

    PubMed

    Sawaki, Risa; Luck, Steven J

    2013-04-01

    After attention has been involuntarily captured by a distractor, how is it reoriented toward a target? One possibility is that attention to the distractor passively fades over time, allowing the target to become attended. Another possibility is that the captured location is actively suppressed so that attention can be directed toward the target location. The present study investigated this issue with event-related potentials (ERPs), focusing on the N2pc component (a neural measure of attentional deployment) and the Pd component (a neural measure of attentional suppression). Observers identified a color-defined target in a search array, which was preceded by a task-irrelevant cue array. When the cue array contained an item that matched the target color, this item captured attention (as measured both behaviorally and with the N2pc component). This capture of attention was followed by active suppression (indexed by the Pd component), and this was then followed by a reorienting of attention toward the target in the search array (indexed by the N2pc component). These findings indicate that the involuntary capture of attention by a distractor is followed by an active suppression process that presumably facilitates the subsequent voluntary orienting of attention to the target.

  8. Sound-suppressing structure with thermal relief

    NASA Technical Reports Server (NTRS)

    Nash, D. O.; Holowach, J. (Inventor)

    1978-01-01

    Sound-suppressing structure comprising stacked acoustic panels wherein the inner high frequency panel is mounted for thermal expansion with respect to the outer low frequency panel is discussed. Slip joints eliminate the potential for thermal stresses, and a thermal expansion gap between the panels provides for additional relative thermal growth while reducing heat convection into the low frequency panel.

  9. Suppressed Carrier Synchronizers for ISI Channels

    NASA Technical Reports Server (NTRS)

    Hinedi, Sami M.; Simon, Marvin K.

    1996-01-01

    We demonstrate a class of suppressed carrier synchronization loops that are motivated by MAP estimation theory and in the presence of ISI outperform the conventional I-Q loop which is designed on the basis of zero ISI (wideband assumption). The measure of comparison used is the so-called.

  10. Radio science measurements with suppressed carrier

    NASA Astrophysics Data System (ADS)

    Asmar, S.; Divsalar, D.; Oudrhiri, K.; Hamkins, J.

    Radio Science started when it became apparent with early deep space missions that occultations by planetary atmospheres would affect the quality of radio communications. Since then the atmospheric properties and other aspects of planetary science, solar science, and fundamental physics were studied by scientists. Radio Science data was always extracted from a received pure residual carrier (without data modulation). For some missions, it is very desirable to obtain Radio Science data from a suppressed carrier modulation. In this paper we propose a method to extract Radio Science data when a coded suppressed carrier modulation is used in deep space communications. The type of modulation can be BPSK, QPSK, OQPSK, MPSK or even GMSK. However we concentrate mostly on BPSK modulation. The proposed method for suppressed carrier simply tries to wipe out data that acts as an interference for Radio Science measurements. In order to measure the estimation errors in amplitude and phase of the Radio Science data we use the Cramer-Rao bound (CRB). The CRB for suppressed carrier modulation with non-ideal data wiping is then compared with residual carrier modulation under the same noise condition. The method of derivation of the CRB for non-ideal data wiping is an innovative method that is presented here. Some numerical results are provided for a coded system.

  11. Radio Science Measurements with Suppressed Carrier

    NASA Technical Reports Server (NTRS)

    Asmar, Sami; Divsalar, Dariush; Oudrhiri, Kamal

    2013-01-01

    Radio Science started when it became apparent with early Solar missions that occultations by planetary atmospheres would affect the quality of radio communications. Since then the atmospheric properties and other aspects of planetary science, solar science, and fundamental physics were studied by scientists. Radio Science data was always extracted from a received pure residual carrier (without data modulation). For some missions, it is very desirable to obtain Radio Science data from a suppressed carrier modulation. In this paper we propose a method to extract Radio Science data when a coded suppressed carrier modulation is used in deep space communications. Type of modulation can be BPSK, QPSK, OQPSK, MPSK or even GMSK. However we concentrate mostly on BPSK modulation. The proposed method for suppressed carrier simply tries to wipe out data that acts as an interference for Radio Science measurements. In order to measure the estimation errors in amplitude and phase of the Radio Science data we use Cramer-Rao bound (CRB). The CRB for the suppressed carrier modulation with non-ideal data wiping is then compared with residual carrier modulation under the same noise condition. The method of derivation of CRB for non-ideal data wiping is an innovative method that presented here. Some numerical results are provided for coded system.

  12. Government Doublethink: Protection or Suppression in Information.

    ERIC Educational Resources Information Center

    Drake, Miriam A.

    2003-01-01

    Discusses regulations and actions related to government withholding, suppressing, and altering information since September 11, 2001. Topics include conflicting goals of an informed citizenry versus national security, science and technology progress versus protection of sensitive information, and public health versus ideology; political pressure;…

  13. Collective suppression of linewidths in circuit QED.

    PubMed

    Nissen, Felix; Fink, Johannes M; Mlynek, Jonas A; Wallraff, Andreas; Keeling, Jonathan

    2013-05-17

    We report the experimental observation and a theoretical explanation of collective suppression of linewidths for multiple superconducting qubits coupled to a good cavity. This demonstrates how strong qubit-cavity coupling can significantly modify the dephasing and dissipation processes that might be expected for individual qubits, and can potentially improve coherence times in many-body circuit QED.

  14. Spacecraft Fire Suppression: Testing and Evaluation

    NASA Technical Reports Server (NTRS)

    Abbud-Madrid, Angel; McKinnon, J. Thomas; Delplanque, Jean-Pierre; Kailasanath, Kazhikathra; Gokoglu, Suleyman; Wu, Ming-Shin

    2004-01-01

    The objective of this project is the testing and evaluation of the effectiveness of a variety of fire suppressants and fire-response techniques that will be used in the next generation of spacecraft (Crew Exploration Vehicle, CEV) and planetary habitats. From the many lessons learned in the last 40 years of space travel, there is common agreement in the spacecraft fire safety community that a new fire suppression system will be needed for the various types of fire threats anticipated in new space vehicles and habitats. To date, there is no single fire extinguishing system that can address all possible fire situations in a spacecraft in an effective, reliable, clean, and safe way. The testing conducted under this investigation will not only validate the various numerical models that are currently being developed, but it will provide new design standards on fire suppression that can then be applied to the next generation of spacecraft extinguishment systems. The test program will provide validation of scaling methods by conducting small, medium, and large scale fires. A variety of suppression methods will be tested, such as water mist, carbon dioxide, and nitrogen with single and multiple injection points and direct or distributed agent deployment. These injection methods cover the current ISS fire suppression method of a portable hand-held fire extinguisher spraying through a port in a rack and also next generation spacecraft units that may have a multi-point suppression delivery system built into the design. Consideration will be given to the need of a crew to clean-up the agent and recharge the extinguishers in flight in a long-duration mission. The fire suppression methods mentioned above will be used to extinguish several fire scenarios that have been identified as the most relevant to spaceflight, such as overheated wires, cable bundles, and circuit boards, as well as burning cloth and paper. Further testing will be conducted in which obstructions and

  15. Benchmark enclosure fire suppression experiments - phase 1 test report.

    SciTech Connect

    Figueroa, Victor G.; Nichols, Robert Thomas; Blanchat, Thomas K.

    2007-06-01

    A series of fire benchmark water suppression tests were performed that may provide guidance for dispersal systems for the protection of high value assets. The test results provide boundary and temporal data necessary for water spray suppression model development and validation. A review of fire suppression in presented for both gaseous suppression and water mist fire suppression. The experimental setup and procedure for gathering water suppression performance data are shown. Characteristics of the nozzles used in the testing are presented. Results of the experiments are discussed.

  16. Overcoming fixation with repeated memory suppression.

    PubMed

    Angello, Genna; Storm, Benjamin C; Smith, Steven M

    2015-01-01

    Fixation (blocks to memories or ideas) can be alleviated not only by encouraging productive work towards a solution, but, as the present experiments show, by reducing counterproductive work. Two experiments examined relief from fixation in a word-fragment completion task. Blockers, orthographically similar negative primes (e.g., ANALOGY), blocked solutions to word fragments (e.g., A_L_ _GY) in both experiments. After priming, but before the fragment completion test, participants repeatedly suppressed half of the blockers using the Think/No-Think paradigm, which results in memory inhibition. Inhibiting blockers did not alleviate fixation in Experiment 1 when conscious recollection of negative primes was not encouraged on the fragment completion test. In Experiment 2, however, when participants were encouraged to remember negative primes at fragment completion, relief from fixation was observed. Repeated suppression may nullify fixation effects, and promote creative thinking, particularly when fixation is caused by conscious recollection of counterproductive information.

  17. Glucose Suppresses Biological Ferroelectricity in Aortic Elastin

    NASA Astrophysics Data System (ADS)

    Liu, Yuanming; Wang, Yunjie; Chow, Ming-Jay; Chen, Nataly Q.; Ma, Feiyue; Zhang, Yanhang; Li, Jiangyu

    2013-04-01

    Elastin is an intriguing extracellular matrix protein present in all connective tissues of vertebrates, rendering essential elasticity to connective tissues subjected to repeated physiological stresses. Using piezoresponse force microscopy, we show that the polarity of aortic elastin is switchable by an electrical field, which may be associated with the recently discovered biological ferroelectricity in the aorta. More interestingly, it is discovered that the switching in aortic elastin is largely suppressed by glucose treatment, which appears to freeze the internal asymmetric polar structures of elastin, making it much harder to switch, or suppressing the switching completely. Such loss of ferroelectricity could have important physiological and pathological implications from aging to arteriosclerosis that are closely related to glycation of elastin.

  18. Suppression of Eimeria tenella sporulation by disinfectants.

    PubMed

    You, Myung-Jo

    2014-08-01

    The disinfectant effects (DEs) of 10 types of chemicals, defined by their ability to destroy or inhibit oocysts and consequently prevent sporulation of Eimeria tenella field isolate, were evaluated in vitro. Correct species assignments and sample purities were confirmed by the singular internal transcribed spacer (ITS)-PCR analysis. A total of 18 treatments were performed, and the disinfection suppression levels were 75.9% for 39% benzene + 22% xylene (1:10 dilution), 85.5% for 30% cresol soup (1:1 dilution), and 91.7% for 99.9% acetic acid (1:2 dilution) group. The results indicate that acetic acid, cresol soup, and benzene+xylene are good candidates for suppression of E. tenella oocyst sporulation.

  19. Suppressing photochemical reactions with quantized light fields

    NASA Astrophysics Data System (ADS)

    Galego, Javier; Garcia-Vidal, Francisco J.; Feist, Johannes

    2016-12-01

    Photoisomerization, that is, a photochemical reaction leading to a change of molecular structure after absorption of a photon, can have detrimental effects such as leading to DNA damage under solar irradiation, or as a limiting factor for the efficiency of solar cells. Here, we show that strong coupling of organic molecules to a confined light mode can be used to strongly suppress photoisomerization, as well as other photochemical reactions, and thus convert molecules that normally show fast photodegradation into photostable forms. We find this to be especially efficient in the case of collective strong coupling, where the distribution of a single excitation over many molecules and the light mode leads to a collective protection effect that almost completely suppresses the photochemical reaction.

  20. Active flutter suppression using dipole filters

    NASA Technical Reports Server (NTRS)

    Srinathkumar, S.; Waszak, Martin R.

    1992-01-01

    By using traditional control concepts of gain root locus, the active suppression of a flutter mode of a flexible wing is examined. It is shown that the attraction of the unstable mode towards a critical system zero determines the degree to which the flutter mode can be stabilized. For control situations where the critical zero is adversely placed in the complex plane, a novel compensation scheme called a 'Dipole' filter is proposed. This filter ensures that the flutter mode is stabilized with acceptable control energy. The control strategy is illustrated by designing flutter suppression laws for an active flexible wing (AFW) wind-tunnel model, where minimal control effort solutions are mandated by control rate saturation problems caused by wind-tunnel turbulence.

  1. Suppressing photochemical reactions with quantized light fields

    PubMed Central

    Galego, Javier; Garcia-Vidal, Francisco J.; Feist, Johannes

    2016-01-01

    Photoisomerization, that is, a photochemical reaction leading to a change of molecular structure after absorption of a photon, can have detrimental effects such as leading to DNA damage under solar irradiation, or as a limiting factor for the efficiency of solar cells. Here, we show that strong coupling of organic molecules to a confined light mode can be used to strongly suppress photoisomerization, as well as other photochemical reactions, and thus convert molecules that normally show fast photodegradation into photostable forms. We find this to be especially efficient in the case of collective strong coupling, where the distribution of a single excitation over many molecules and the light mode leads to a collective protection effect that almost completely suppresses the photochemical reaction. PMID:27941754

  2. Sleep deprivation suppresses aggression in Drosophila

    PubMed Central

    Kayser, Matthew S; Mainwaring, Benjamin; Yue, Zhifeng; Sehgal, Amita

    2015-01-01

    Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness. DOI: http://dx.doi.org/10.7554/eLife.07643.001 PMID:26216041

  3. Appetite suppressants and valvular heart disease.

    PubMed

    Seghatol, Frank F; Rigolin, Vera H

    2002-09-01

    Appetite suppressants fenfluramine, dexfenfluramine, and phentermine have been used alone or in combination as an alternative to diet and surgery in the management of obesity. This therapy was halted in 1997 after reports of valvular lesions affecting almost one third of patients treated with these drugs. Fortunately, most cases of appetite suppressant-related valve disease are mild or moderate and rarely required valve repair or replacement. Follow-up studies have suggested improvement in valvulopathy after discontinuation of the treatment. The mechanism of valve disease induced by these drugs is speculative and may be related to their serotonergic effects. Echocardiographic features are similar to carcinoid heart disease and valvulopathy associated with ergot use. Most cases require only follow-up and endocarditis prophylaxis; surgery is rarely needed.

  4. System for Suppressing Vibration in Turbomachine Components

    NASA Technical Reports Server (NTRS)

    Morrison, Carlos R. (Inventor); Provenza, Andrew J. (Inventor); Choi, Benjamin B. (Inventor); Bakhle, Milind A. (Inventor); Min, James B (Inventor); Stefko, George L. (Inventor); Kussmann, John A (Inventor); Fougere, Alan J (Inventor)

    2013-01-01

    Disclosed is a system for suppressing vibration and noise mitigation in structures such as blades in turbomachinery. The system includes flexible piezoelectric patches which are secured on or imbedded in turbomachinery blades which, in one embodiment, comprises eight (8) fan blades. The system further includes a capacitor plate coupler and a power transfer apparatus, which may both be arranged into one assembly, that respectively transfer data and power. Each of the capacitive plate coupler and power transfer apparatus is configured so that one part is attached to a fixed member while another part is attached to a rotatable member with an air gap there between. The system still further includes a processor that has 16 channels, eight of which serve as sensor channels, and the remaining eight, serving as actuation channels. The processor collects and analyzes the sensor signals and, in turn, outputs corrective signals for vibration/noise suppression of the turbine blades.

  5. Immersion diuresis without expected suppression of vasopressin

    NASA Technical Reports Server (NTRS)

    Keil, L. C.; Silver, J. E.; Wong, N.; Spaul, W. A.; Greenleaf, J. E.; Kravik, S. E.

    1984-01-01

    There is a shift of blood from the lower parts of the body to the thoracic circulation during bed rest, water immersion, and presumably during weightlessness. On earth, this central fluid shift is associated with a profound diuresis. However, the mechanism involved is not yet well understood. The present investigation is concerned with measurements regarding the plasma vasopressin, fluid, electrolyte, and plasma renin activity (PRA) responses in subjects with normal preimmersion plasma vasopressin (PVP) concentration. In the conducted experiments, PRA was suppressed significantly at 30 min of immersion and had declined by 74 percent by the end of the experiment. On the basis of previously obtained results, it appears that sodium excretion during immersion may be independent of aldosterone action. Experimental results indicate that PVP is not suppressed by water immersion in normally hydrated subjects and that other factors may be responsible for the diuresis.

  6. Abnormal Grain Growth Suppression in Aluminum Alloys

    NASA Technical Reports Server (NTRS)

    Hales, Stephen J. (Inventor); Claytor, Harold Dale (Inventor); Alexa, Joel A. (Inventor)

    2015-01-01

    The present invention provides a process for suppressing abnormal grain growth in friction stir welded aluminum alloys by inserting an intermediate annealing treatment ("IAT") after the welding step on the article. The IAT may be followed by a solution heat treatment (SHT) on the article under effectively high solution heat treatment conditions. In at least some embodiments, a deformation step is conducted on the article under effective spin-forming deformation conditions or under effective superplastic deformation conditions. The invention further provides a welded article having suppressed abnormal grain growth, prepared by the process above. Preferably the article is characterized with greater than about 90% reduction in area fraction abnormal grain growth in any friction-stir-welded nugget.

  7. Adaptive Suppression of Noise in Voice Communications

    NASA Technical Reports Server (NTRS)

    Kozel, David; DeVault, James A.; Birr, Richard B.

    2003-01-01

    A subsystem for the adaptive suppression of noise in a voice communication system effects a high level of reduction of noise that enters the system through microphones. The subsystem includes a digital signal processor (DSP) plus circuitry that implements voice-recognition and spectral- manipulation techniques. The development of the adaptive noise-suppression subsystem was prompted by the following considerations: During processing of the space shuttle at Kennedy Space Center, voice communications among test team members have been significantly impaired in several instances because some test participants have had to communicate from locations with high ambient noise levels. Ear protection for the personnel involved is commercially available and is used in such situations. However, commercially available noise-canceling microphones do not provide sufficient reduction of noise that enters through microphones and thus becomes transmitted on outbound communication links.

  8. Adaptive Modal Identification for Flutter Suppression Control

    NASA Technical Reports Server (NTRS)

    Nguyen, Nhan T.; Drew, Michael; Swei, Sean S.

    2016-01-01

    In this paper, we will develop an adaptive modal identification method for identifying the frequencies and damping of a flutter mode based on model-reference adaptive control (MRAC) and least-squares methods. The least-squares parameter estimation will achieve parameter convergence in the presence of persistent excitation whereas the MRAC parameter estimation does not guarantee parameter convergence. Two adaptive flutter suppression control approaches are developed: one based on MRAC and the other based on the least-squares method. The MRAC flutter suppression control is designed as an integral part of the parameter estimation where the feedback signal is used to estimate the modal information. On the other hand, the separation principle of control and estimation is applied to the least-squares method. The least-squares modal identification is used to perform parameter estimation.

  9. PUMA Suppresses Intestinal Tumorigenesis in Mice

    PubMed Central

    Qiu, Wei; Carson-Walter, Eleanor B.; Kuan, Shih Fan; Zhang, Lin; Yu, Jian

    2010-01-01

    Defective apoptosis contributes to tumorigenesis, although the critical molecular targets remain to be fully characterized. PUMA, a BH3-only protein essential for p53-dependent apoptosis, has been shown to suppress lymphomagenesis. In this study, we investigated the role of PUMA in intestinal tumorigenesis using two animal models. In the azoxymethane (AOM)/dextran sulfate sodium salt model, PUMA deficiency increased the multiplicity and size of colon tumors but reduced the frequency of β-catenin hotspot mutations. The absence of PUMA led to a significantly elevated incidence of precursor lesions induced by AOM. AOM was found to induce p53-dependent PUMA expression and PUMA-dependent apoptosis in the colonic crypts and stem cell compartment. Furthermore, PUMA deficiency significantly enhanced the formation of spontaneous macroadenomas and microadenomas in the distal small intestine and colon of APCMin/+ mice. These results show an essential role of PUMA-mediated apoptosis in suppressing intestinal tumorigenesis in mice. PMID:19491259

  10. Efficacy and Safety of Azithromycin-Chloroquine versus Sulfadoxine-Pyrimethamine for Intermittent Preventive Treatment of Plasmodium falciparum Malaria Infection in Pregnant Women in Africa: An Open-Label, Randomized Trial

    PubMed Central

    Kimani, Joshua; Phiri, Kamija; Kamiza, Steve; Duparc, Stephan; Ayoub, Ayman; Rojo, Ricardo; Robbins, Jeffery; Orrico, Russell; Vandenbroucke, Pol

    2016-01-01

    Background The World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) in African regions with moderate to high malaria transmission. However, growing resistance to SP threatens the effectiveness of IPTp-SP, and alternative drugs are needed. This study tested the efficacy, tolerability, and safety of a fixed-dose combination azithromycin-chloroquine (AZCQ; 250 mg AZ/155 mg CQ base) for IPTp relative to IPTp-SP. Methods and Findings A randomized, Phase 3, open-label, multi-center study was conducted in sub-Saharan Africa (Benin, Kenya, Malawi, Tanzania, and Uganda) between October 2010 and November 2013. Pregnant women received 3 IPTp courses with AZCQ (each course: 1,000/620 mg AZCQ QD for 3 days) or SP (each course 1,500/75 mg SP QD for 1 day) at 4- to 8-week intervals during the second and third trimester. Long-lasting insecticide-treated bednets were also provided at enrollment. Study participants were followed up until day 28 post delivery (time window: day 28–42). The primary endpoint was the proportion of participants with sub-optimal pregnancy outcomes (a composite endpoint comprising live-borne neonates with low birth weight [LBW, <2,500 g], premature birth [<37 weeks], still birth [>28 weeks], abortion [≤28 weeks], lost to follow-up prior to observation of pregnancy outcome, or missing birth weight). The study was terminated early after recruitment of 2,891 of the planned 5,044 participants, due to futility observed in a pre-specified 35% interim analysis. In the final intent-to-treat dataset, 378/1,445 (26.2%) participants in the AZCQ and 342/1,445 (23.7%) in the SP group had sub-optimal pregnancy outcomes, with an estimated risk ratio (RR) of 1.11 (95% CI: 0.97, 1.25; p = 0.12). There was no significant difference in the incidence of LBW between treatment groups (57/1138 [5.0%] in the AZCQ group, 68/1188 [5.7%] in the SP group, RR 0.87 [95% CI: 0.62, 1.23]; p = 0.44). IPTp

  11. Effect of weighting on time sidelobe suppression

    NASA Technical Reports Server (NTRS)

    Dicenzo, A.

    1978-01-01

    Weighting simulations in the time domain were considered to shape the time-compressed pulse waveform. The digital input radar data were 32 bit I,Q, and simulated data from a point target, imaged by a Seasat-A type system. Weighting functions tested include stepped-amplitude distributions, (with 1 through 5 steps), and the cosine-squared plus pedestal distribution. Effects treated include mainlobe ratio, signal to noise ratio, and nearest sidelobe suppression.

  12. Analysis and Evaluation of Suppressive Shields

    DTIC Science & Technology

    1977-06-01

    resistance of the shield to fragment penetration, and 7. attenuation of thermal effects by the shield . Other aspects of the design include problems of entry...propellant, 2. methods to predict the thermal environment outside of a suppressive shield , 3. comparisons between measured and predicted pressures... SHIELDS by P. A. Co- x P. S. Westine CD J. J. Kulesz L.LJ E. D. Espurza c-.- January 1978 SOUTHWEST RESEARCH INSTITUTE Post Office Drawer 28510, 6220

  13. Investigation of refracting flows for acoustic suppression

    NASA Technical Reports Server (NTRS)

    Sloan, D.; Purves, R. B.; Farquhar, B. W.

    1977-01-01

    An experimental program to determine the possibility of using refracting flows for the suppression of aircraft inlet noise has been completed. Observations of wave behavior in accelerating duct flows have suggested that acoustic wave refraction could be used to direct inlet noise away from the ground upward to where it causes less annoyance. Measurements have also shown that acoustic wave refraction can cause large improvements in the effectiveness of acoustic lining material.

  14. Currently available cough suppressants for chronic cough.

    PubMed

    Chung, Kian Fan

    2008-01-01

    Chronic cough is a common symptom but only a fraction of patients seek medical attention. Addressing the causes of chronic cough may lead to control of cough; however, this approach is not always successful since there is a certain degree of failure even when the cause(s) of cough are adequately treated; in idiopathic cough, there is no cause to treat. Persistent cough may be associated with deterioration of quality of life, and treatment with cough suppressants is indicated. Currently available cough suppressants include the centrally acting opioids such as morphine, codeine, and dextromethorphan. Peripherally acting antitussives include moguisteine and levodropropizine. Early studies report success in reducing cough in patients with chronic bronchitis or COPD; however, a carefully conducted study showed no effect of codeine on cough of COPD. Success with these cough suppressants can be achieved at high doses that are associated with side effects. Slow-release morphine has been reported to be useful in controlling intractable cough with good tolerance to constipation and drowsiness. There have been case reports of the success of centrally acting drugs such as amitryptiline, paroxetine, gabapentin, and carbamezepine in chronic cough. New opioids such as nociceptin or antagonists of TRPV1 may turn out to be more effective. Efficacy of cough suppressants must be tested in double-blind randomised trials using validated measures of cough in patients with chronic cough not responding to specific treatments. Patients with chronic cough are in desperate need of effective antitussives that can be used either on demand or on a long-term basis.

  15. [Cancer immunotherapy. Importance of overcoming immune suppression].

    PubMed

    Malvicini, Mariana; Puchulo, Guillermo; Matar, Pablo; Mazzolini, Guillermo

    2010-01-01

    Increasing evidence indicates that the immune system is involved in the control of tumor progression. Effective antitumor immune response depends on the interaction between several components of the immune system, including antigen-presenting cells and different T cell subsets. However, tumor cells develop a number of mechanisms to escape recognition and elimination by the immune system. In this review we discuss these mechanisms and address possible therapeutic approaches to overcome the immune suppression generated by tumors.

  16. Fire suppression in human-crew spacecraft

    NASA Technical Reports Server (NTRS)

    Friedman, Robert; Dietrich, Daniel L.

    1991-01-01

    Fire extinguishment agents range from water and foam in early-design spacecraft (Halon 1301 in the present Shuttle) to carbon dioxide proposed for the Space Station Freedom. The major challenge to spacecraft fire extinguishment design and operations is from the micro-gravity environment, which minimizes natural convection and profoundly influences combustion and extinguishing agent effectiveness, dispersal, and post-fire cleanup. Discussed here are extinguishment in microgravity, fire-suppression problems anticipated in future spacecraft, and research needs and opportunities.

  17. FGF Suppresses Poldip2 Expression in Osteoblasts.

    PubMed

    Katsumura, Sakie; Izu, Yayoi; Yamada, Takayuki; Griendling, Kathy; Harada, Kiyoshi; Noda, Masaki; Ezura, Yoichi

    2016-12-05

    Osteoporosis is one of the most prevalent ageing-associated diseases that are soaring in the modern world. Although various aspects of the disease have been investigated to understand the bases of osteoporosis, the pathophysiological mechanisms underlying bone loss is still incompletely understood. Poldip2 is a molecule that has been shown to be involved in cell migration of vascular cells and angiogenesis. However, expression of Poldip2 and its regulation in bone cells were not known. Therefore, we examined the Poldip2 mRNA expression and the effects of bone regulators on the Poldip2 expression in osteoblasts. We found that Poldip2 mRNA is expressed in osteoblastic MC3T3-E1 cells. As FGF controls osteoblasts and angiogenesis, FGF regulation was investigated in these cells. FGF suppressed the expression of Poldip2 in MC3T3-E1 cells in a time dependent manner. Protein synthesis inhibitor but not transcription inhibitor reduced the FGF effects on Poldip2 gene expression in MC3T3-E1 cells. As for bone-related hormones, dexamethasone was found to enhance the expression of Poldip2 in osteoblastic MC3T3-E1 cells whereas FGF still suppressed such dexamethasone effects. With respect to function, knockdown of Poldip2 by siRNA suppressed the migration of MC3T3-E1 cells. Poldip2 was also expressed in the primary cultures of osteoblast-enriched cells and FGF also suppressed its expression. Finally, Poldip2 was expressed in femoral bone in vivo and its levels were increased in aged mice compared to young adult mice. These data indicate that Poldip2 is expressed in osteoblastic cells and is one of the targets of FGF. J. Cell. Biochem. 9999: 1-8, 2017. © 2016 Wiley Periodicals, Inc.

  18. Suppression of Ostwald Ripening by Chemical Reactions

    NASA Astrophysics Data System (ADS)

    Zwicker, David; Hyman, Anthony A.; Jülicher, Frank

    2015-03-01

    Emulsions consisting of droplets immersed in a fluid are typically unstable and coarsen over time. One important coarsening process is Ostwald ripening, which is driven by the surface tension of the droplets. Ostwald ripening must thus be suppressed to stabilize emulsions, e.g. to control the properties of pharmaceuticals, food, or cosmetics. Suppression of Ostwald ripening is also important in biological cells, which contain stable liquid-like compartments, e.g. germ granules, Cajal-bodies, and centrosomes. Such systems are often driven away from equilibrium by chemical reactions and can thus be called active emulsions. Here, we show that non-equilibrium chemical reactions can suppress Ostwald Ripening, leading to stable, monodisperse emulsions. We derive analytical approximations of the typical droplet size, droplet count, and time scale of the dynamics from a coarse-grained description of the droplet dynamics. We also compare these results to numerical simulations of the continuous concentration fields. Generally, we thus show how chemical reactions can be used to stabilize emulsions and to control their properties in technology and nature.

  19. Suppressing bullfrog larvae with carbon dioxide

    USGS Publications Warehouse

    Gross, Jackson A.; Ray, Andrew; Sepulveda, Adam J.; Watten, Barnaby J.; Densmore, Christine L.; Layhee, Megan J.; Mark Abbey-Lambert,; ,

    2014-01-01

    Current management strategies for the control and suppression of the American Bullfrog (Lithobates catesbeianus = Rana catesbeiana Shaw) and other invasive amphibians have had minimal effect on their abundance and distribution. This study evaluates the effects of carbon dioxide (CO2) on pre- and prometamorphic Bullfrog larvae. Bullfrogs are a model organism for evaluating potential suppression agents because they are a successful invader worldwide. From experimental trials we estimated that the 24-h 50% and 99% lethal concentration (LC50 and LC99) values for Bullfrog larvae were 371 and 549 mg CO2/L, respectively. Overall, larvae that succumbed to experimental conditions had a lower body condition index than those that survived. We also documented sublethal changes in blood chemistry during prolonged exposure to elevated CO2. Specifically, blood pH decreased by more than 0.5 pH units after 9 h of exposure and both blood partial pressure of CO2 (pCO2) and blood glucose increased. These findings suggest that CO2 treatments can be lethal to Bullfrog larvae under controlled laboratory conditions. We believe this work represents the necessary foundation for further consideration of CO2 as a potential suppression agent for one of the most harmful invaders to freshwater ecosystems.

  20. Hypergravity suppresses bone resorption in ovariectomized rats

    NASA Astrophysics Data System (ADS)

    Ikawa, Tesshu; Kawaguchi, Amu; Okabe, Takahiro; Ninomiya, Tadashi; Nakamichi, Yuko; Nakamura, Midori; Uehara, Shunsuke; Nakamura, Hiroaki; Udagawa, Nobuyuki; Takahashi, Naoyuki; Nakamura, Hiroaki; Wakitani, Shigeyuki

    2011-04-01

    The effects of gravity on bone metabolism are unclear, and little has been reported about the effects of hypergravity on the mature skeleton. Since low gravity has been shown to decrease bone volume, we hypothesized that hypergravity increases bone volume. To clarify this hypothesis, adult female rats were ovariectomized and exposed to hypergravity (2.9G) using a centrifugation system. The rats were killed 28 days after the start of loading, and the distal femoral metaphysis of the rats was studied. Bone architecture was assessed by micro-computed tomography (micro-CT) and bone mineral density was measured using peripheral quantitative CT (pQCT). Hypergravity increased the trabecular bone volume of ovariectomized rats. Histomorphometric analyses revealed that hypergravity suppressed both bone formation and resorption and increased bone volume in ovariectomized rats. Further, the cell morphology, activity, proliferation, and differentiation of osteoclasts and osteoblasts exposed to hypergravity were evaluated in vitro. Hypergravity inhibited actin ring formation in mature osteoclasts, which suggested that the osteoclast activity was suppressed. However, hypergravity had no effect on osteoblasts. These results suggest that hypergravity can stimulate an increase in bone volume by suppressing bone resorption in ovariectomized rats.

  1. Neural Networks for Mindfulness and Emotion Suppression.

    PubMed

    Murakami, Hiroki; Katsunuma, Ruri; Oba, Kentaro; Terasawa, Yuri; Motomura, Yuki; Mishima, Kazuo; Moriguchi, Yoshiya

    2015-01-01

    Mindfulness, an attentive non-judgmental focus on "here and now" experiences, has been incorporated into various cognitive behavioral therapy approaches and beneficial effects have been demonstrated. Recently, mindfulness has also been identified as a potentially effective emotion regulation strategy. On the other hand, emotion suppression, which refers to trying to avoid or escape from experiencing and being aware of one's own emotions, has been identified as a potentially maladaptive strategy. Previous studies suggest that both strategies can decrease affective responses to emotional stimuli. They would, however, be expected to provide regulation through different top-down modulation systems. The present study was aimed at elucidating the different neural systems underlying emotion regulation via mindfulness and emotion suppression approaches. Twenty-one healthy participants used the two types of strategy in response to emotional visual stimuli while functional magnetic resonance imaging was conducted. Both strategies attenuated amygdala responses to emotional triggers, but the pathways to regulation differed across the two. A mindful approach appears to regulate amygdala functioning via functional connectivity from the medial prefrontal cortex, while suppression uses connectivity with other regions, including the dorsolateral prefrontal cortex. Thus, the two types of emotion regulation recruit different top-down modulation processes localized at prefrontal areas. These different pathways are discussed.

  2. Surface state transport suppression in topological insulators

    NASA Astrophysics Data System (ADS)

    Reijnders, Anjan A.; Tian, Y.; Pohl, G.; Kivlichan, I. D.; Zhao, S. Y. Frank; Kim, Y.-J.; Jia, S.; Cava, R. J.; Kwok, D. C.; Lee, N.; Cheong, S. W.; Burch, Kenneth S.

    2013-03-01

    An unresolved question in experimental research on topological insulators (TI) is the suppression mechanism of a TI's surface state transport. While room temperature ARPES studies reveal clear evidence of surface states, their observation in transport measurements is limited to low temperatures. A better understanding of this suppression is of fundamental interest, and crucial for pushing the boundary of device applications towards room-temperature operation. In this talk, we report the temperature dependent optical properties of the topological insulator Bi2Te2Se (BTS), obtained by infrared spectroscopy and ellipsometry, probing surface and bulk states simultaneously. We see clear evidence of coherent surface state transport at low temperature and find that electron-phonon coupling causes the gradual suppression of surface state transport as temperature rises to 43K. In the bulk, electron-phonon coupling enables the emergence of an indirect band gap transition, which peaks at 43K, and is limited by thermal ionization of the bulk valance band above 43K. For comparison with other resistive TIs, we also discuss the optical properties to BiSbSe2Te. Financially supported by NSERC CRSNG, Ontario Research Fund, Canadian Foundation for Innovation, Prins Bernhard Cultuurfonds, NSF

  3. Atomic clocks with suppressed blackbody radiation shift.

    PubMed

    Yudin, V I; Taichenachev, A V; Okhapkin, M V; Bagayev, S N; Tamm, Chr; Peik, E; Huntemann, N; Mehlstäubler, T E; Riehle, F

    2011-07-15

    We develop a concept of atomic clocks where the blackbody radiation shift and its fluctuations can be suppressed by 1-3 orders of magnitude independent of the environmental temperature. The suppression is based on the fact that in a system with two accessible clock transitions (with frequencies ν1 and ν2) which are exposed to the same thermal environment, there exists a "synthetic" frequency ν(syn) ∝ (ν1 - ε12ν2) largely immune to the blackbody radiation shift. For example, in the case of 171Yb+ it is possible to create a synthetic-frequency-based clock in which the fractional blackbody radiation shift can be suppressed to the level of 10(-18) in a broad interval near room temperature (300±15  K). We also propose a realization of our method with the use of an optical frequency comb generator stabilized to both frequencies ν1 and ν2, where the frequency ν(syn) is generated as one of the components of the comb spectrum.

  4. Hippocampal leptin suppresses methamphetamine-induced hyperlocomotion.

    PubMed

    Nishio, Masahiro; Watanabe, Yasuhiro

    2010-10-01

    Leptin is an anorexigenic peptide which is synthesized in white adipose tissue. The actions of leptin are mediated by the leptin receptor which is abundantly localized in the hypothalamus and is involved in energy regulation and balance. Recently, there has been evidence suggesting that the leptin receptor is also present in the hippocampus and may be involved with hippocampal excitability and long-term depression. To investigate the physiological function of leptin signalling in the hippocampus, we studied the effects of leptin on methamphetamine-induced ambulatory hyperactivity by utilizing intra-hippocampal infusion (i.h.) in mice. Our results show that the infusion of leptin (5 ng each bilaterally i.h.) does not affect the basal ambulatory activity but significantly suppresses methamphetamine-induced ambulatory hyperactivity as compared to saline-infused controls. Interestingly, higher dose of leptin increases the suppression of the methamphetamine-induced ambulatory hyperactivity. The i.h. infusion of leptin did not activate the JAK-STAT pathway, which is the cellular signalling pathway through which leptin acts in the hypothalamus. The infusion of leptin also did not affect activation of p42/44 MAPK which is known to be another leptin-induced signalling pathway in the brain. These results demonstrate that leptin has a novel potential suppressive effect on methamphetamine-induced hyperlocomotion and also suggest that there must be an alternative pathway in the hippocampus through which leptin signalling is being mediated.

  5. Suppression of Marangoni Convection in Float Zones

    NASA Technical Reports Server (NTRS)

    Dressler, R. F.

    1985-01-01

    The basic purpose of this program is to demonstrate by means of an Earth-based 1-g experiment that the undesirable Marangoni (surface tension) convection can be suppressed or significantly reduced by means of gas jets directed tangentially to the free surface of the liquid in a float zone. These jets will establish the tangential shear stress field over the surface which must be adjusted to equal the counter-stress resultant of the Marangoni shear stress which causes the convection. For proposed materials processing in space (o-g), particularly of important, highly reactive semiconductor materials, e.g., silicon, microgravity will virtually eliminate the unwanted thermal-buoyancy convection in the liquid silicon, but will have no effect in reducing the Marangoni convection. Unless this can be sufficiently suppressed by other means, there may be no significant advantages to the proposed space processing of reactive semiconductors. Although some inert gas such as argon must be used for the corrosive liquid silicon, the Earth-based experiment uses air jets and various transparent oils, since the basic principle involved is the same. The first float zone is enclosed in a very small rectangular box with a quasi-planar free surface. Stable Marangoni convection has been achieved and velocities measured photographically. The air jet system with variable velocity and temperature is under construction. Three independent parameters must be optimized to attain maximum suppression: the gas velocity, angle of attack, and gas temperature.

  6. Glucocorticoids suppress bone formation via the osteoclast.

    PubMed

    Kim, Hyun-Ju; Zhao, Haibo; Kitaura, Hideki; Bhattacharyya, Sandip; Brewer, Judson A; Muglia, Louis J; Ross, F Patrick; Teitelbaum, Steven L

    2006-08-01

    The pathogenesis of glucocorticoid-induced (GC-induced) bone loss is unclear. For example, osteoblast apoptosis is enhanced by GCs in vivo, but they stimulate bone formation in vitro. This conundrum suggests that an intermediary cell transmits a component of the bone-suppressive effects of GCs to osteoblasts in the intact animal. Bone remodeling is characterized by tethering of the activities of osteoclasts and osteoblasts. Hence, the osteoclast is a potential modulator of the effect of GCs on osteoblasts. To define the direct impact of GCs on bone-resorptive cells, we compared the effects of dexamethasone (DEX) on WT osteoclasts with those derived from mice with disruption of the GC receptor in osteoclast lineage cells (GRoc-/- mice). While the steroid prolonged longevity of osteoclasts, their bone-degrading capacity was suppressed. The inhibitory effect of DEX on bone resorption reflects failure of osteoclasts to organize their cytoskeleton in response to M-CSF. DEX specifically arrested M-CSF activation of RhoA, Rac, and Vav3, each of which regulate the osteoclast cytoskeleton. In all circumstances GRoc-/- mice were spared the impact of DEX on osteoclasts and their precursors. Consistent with osteoclasts modulating the osteoblast-suppressive effect of DEX, GRoc-/- mice are protected from the steroid's inhibition of bone formation.

  7. Conditionals, Context, and the Suppression Effect.

    PubMed

    Cariani, Fabrizio; Rips, Lance J

    2016-02-01

    Modus ponens is the argument from premises of the form If A, then B and A to the conclusion B (e.g., from If it rained, Alicia got wet and It rained to Alicia got wet). Nearly all participants agree that the modus ponens conclusion logically follows when the argument appears in this Basic form. However, adding a further premise (e.g., If she forgot her umbrella, Alicia got wet) can lower participants' rate of agreement-an effect called suppression. We propose a theory of suppression that draws on contemporary ideas about conditional sentences in linguistics and philosophy. Semantically, the theory assumes that people interpret an indicative conditional as a context-sensitive strict conditional: true if and only if its consequent is true in each of a contextually determined set of situations in which its antecedent is true. Pragmatically, the theory claims that context changes in response to new assertions, including new conditional premises. Thus, the conclusion of a modus ponens argument may no longer be accepted in the changed context. Psychologically, the theory describes people as capable of reasoning about broad classes of possible situations, ordered by typicality, without having to reason about individual possible worlds. The theory accounts for the main suppression phenomena, and it generates some novel predictions that new experiments confirm.

  8. BAER suppression during posterior fossa dural opening

    PubMed Central

    Shields, Christopher B.; Shields, Lisa B. E.; Jiang, Yi Dan; Yao, Tom; Zhang, Yi Ping; Sun, David A.

    2015-01-01

    Background: Intraoperative monitoring with brainstem auditory evoked responses (BAER) provides an early warning signal of potential neurological injury and may avert tissue damage to the auditory pathway or brainstem. Unexplained loss of the BAER signal in the operating room may present a dilemma to the neurosurgeon. Methods: This paper documents two patients who displayed a unique mechanism of suppression of the BAER apparent within minutes following dural opening for resection of a posterior fossa meningioma. Results: In two patients with anterior cerebellopontine angle and clival meningiomas, there was a significant deterioration of the BAER soon after durotomy but prior to cerebellar retraction and tumor removal. Intracranial structures in the posterior fossa lying between the tumor and dural opening were shifted posteriorly after durotomy. Conclusion: We hypothesized that the cochlear nerve and vessels entering the acoustic meatus were compressed or stretched when subjected to tissue shift. This movement caused cochlear nerve dysfunction that resulted in BAER suppression. BAER was partially restored after the tumor was decompressed, dura repaired, and bone replaced. BAER was not suppressed following durotomy for removal of a meningioma lying posterior to the cochlear complex. Insight into the mechanisms of durotomy-induced BAER inhibition would allay the neurosurgeon's anxiety during the operation. PMID:25883849

  9. System and method for suppressing sublimation using opacified aerogel

    NASA Technical Reports Server (NTRS)

    Sakamoto, Jeff S. (Inventor); Snyder, G. Jeffrey (Inventor); Calliat, Thierry (Inventor); Fleurial, Jean-Pierre (Inventor); Jones, Steven M. (Inventor); Palk, Jong-Ah (Inventor)

    2008-01-01

    The present invention relates to a castable, aerogel-based, ultra-low thermal conductivity opacified insulation to suppress sublimation. More specifically, the present invention relates to an aerogel opacified with various opacifying or reflecting constituents to suppress sublimation and provide thermal insulation in thermoelectric modules. The opacifying constituent can be graded within the aerogel for increased sublimation suppression, and the density of the aerogel can similarly be graded to achieve optimal thermal insulation and sublimation suppression.

  10. Coating Thermoelectric Devices To Suppress Sublimation

    NASA Technical Reports Server (NTRS)

    Sakamoto, Jeffrey; Caillat, Thierry; Fleurial, Jean-Pierre; Snyder, G. Jeffrey

    2007-01-01

    A technique for suppressing sublimation of key elements from skutterudite compounds in advanced thermoelectric devices has been demonstrated. The essence of the technique is to cover what would otherwise be the exposed skutterudite surface of such a device with a thin, continuous film of a chemically and physically compatible metal. Although similar to other sublimation-suppression techniques, this technique has been specifically tailored for application to skutterudite antimonides. The primary cause of deterioration of most thermoelectric materials is thermal decomposition or sublimation - one or more elements sublime from the hot side of a thermoelectric couple, changing the stoichiometry of the device. Examples of elements that sublime from their respective thermoelectric materials are Ge from SiGe, Te from Pb/Te, and now Sb from skutterudite antimonides. The skutterudite antimonides of primary interest are CoSb3 [electron-donor (n) type] and CeFe(3-x)Co(x)Sb12 [electron-acceptor (p) type]. When these compounds are subjected to typical operating conditions [temperature of 700 C and pressure <10(exp -5) torr (0.0013 Pa)], Sb sublimes from their surfaces, with the result that Sb depletion layers form and advance toward their interiors. As the depletion layer advances in a given device, the change in stoichiometry diminishes the thermal-to-electric conversion efficiency of the device. The problem, then, is to prevent sublimation, or at least reduce it to an acceptably low level. In preparation for an experiment on suppression of sublimation, a specimen of CoSb3 was tightly wrapped in a foil of niobium, which was selected for its chemical stability. In the experiment, the wrapped specimen was heated to a temperature of 700 C in a vacuum of residual pressure <10(exp -5) torr (0.0013 Pa), then cooled and sectioned. Examination of the sectioned specimen revealed that no depletion layer had formed, indicating the niobium foil prevented sublimation of antimony at 700 C

  11. Unsuppressible Repetition Suppression and exemplar-specific Expectation Suppression in the Fusiform Face Area.

    PubMed

    Pajani, Auréliane; Kouider, Sid; Roux, Paul; de Gardelle, Vincent

    2017-12-01

    Recent work casts Repetition Suppression (RS), i.e. the reduced neural response to repeated stimuli, as the consequence of reduced surprise for repeated inputs. This research, along with other studies documenting Expectation Suppression, i.e. reduced responses to expected stimuli, emphasizes the role of expectations and predictive codes in perception. Here, we use fMRI to further characterize the nature of predictive signals in the human brain. Prior to scanning, participants were implicitly exposed to associations within face pairs. Critically, we found that this resulted in exemplar-specific Expectation Suppression in the fusiform face-sensitive area (FFA): individual faces that could be predicted from the associations elicited reduced FFA responses, as compared to unpredictable faces. Thus, predictive signals in the FFA are specific to face exemplars, and not only generic to the category of face stimuli. In addition, we show that under such circumstances, the occurrence of surprising repetitions did not trigger enhanced brain responses, as had been recently hypothesized, but still suppressed responses, suggesting that repetition suppression might be partly 'unsuppressible'. Repetition effects cannot be fully modulated by expectations, which supports the recent view that expectation and repetition effects rest on partially independent mechanisms. Altogether, our study sheds light on the nature of expectation signals along the perceptual system.

  12. Repetition suppression and expectation suppression are dissociable in time in early auditory evoked fields.

    PubMed

    Todorovic, Ana; de Lange, Floris P

    2012-09-26

    Repetition of a stimulus, as well as valid expectation that a stimulus will occur, both attenuate the neural response to it. These effects, repetition suppression and expectation suppression, are typically confounded in paradigms in which the nonrepeated stimulus is also relatively rare (e.g., in oddball blocks of mismatch negativity paradigms, or in repetition suppression paradigms with multiple repetitions before an alternation). However, recent hierarchical models of sensory processing inspire the hypothesis that the two might be separable in time, with repetition suppression occurring earlier, as a consequence of local transition probabilities, and suppression by expectation occurring later, as a consequence of learnt statistical regularities. Here we test this hypothesis in an auditory experiment by orthogonally manipulating stimulus repetition and stimulus expectation and, using magnetoencephalography, measuring the neural response over time in human subjects. We found that stimulus repetition (but not stimulus expectation) attenuates the early auditory response (40-60 ms), while stimulus expectation (but not stimulus repetition) attenuates the subsequent, intermediate stage of auditory processing (100-200 ms). These findings are well in line with hierarchical predictive coding models, which posit sequential stages of prediction error resolution, contingent on the level at which the hypothesis is generated.

  13. Infection with Theiler's murine encephalomyelitis virus directly induces proinflammatory cytokines in primary astrocytes via NF-kappaB activation: potential role for the initiation of demyelinating disease.

    PubMed

    Palma, JoAnn P; Kwon, Daeho; Clipstone, Neil A; Kim, Byung S

    2003-06-01

    Theiler's virus infection in the central nervous system (CNS) induces a demyelinating disease very similar to human multiple sclerosis. We have assessed cytokine gene activation upon Theiler's murine encephalomyelitis virus (TMEV) infection and potential mechanisms in order to delineate the early events in viral infection that lead to immune-mediated demyelinating disease. Infection of SJL/J primary astrocyte cultures induces selective proinflammatory cytokine genes (interleukin-12p40 [IL-12p40], IL-1, IL-6, tumor necrosis factor alpha, and beta interferon [IFN-beta]) important in the innate immune response to infection. We find that TMEV-induced cytokine gene expression is mediated by the NF-kappaB pathway based on the early nuclear NF-kappaB translocation and suppression of cytokine activation in the presence of specific inhibitors of the NF-kappaB pathway. Further studies show this to be partly independent of dsRNA-dependent protein kinase (PKR) and IFN-alpha/beta pathways. Altogether, these results demonstrate that infection of astrocytes and other CNS-resident cells by TMEV provides the early NF-kappaB-mediated signals that directly activate various proinflammatory cytokine genes involved in the initiation and amplification of inflammatory responses in the CNS known to be critical for the development of immune-mediated demyelination.

  14. Effects of tumor necrosis factor alpha on host immune response in chronic persistent tuberculosis: possible role for limiting pathology.

    PubMed

    Mohan, V P; Scanga, C A; Yu, K; Scott, H M; Tanaka, K E; Tsang, E; Tsai, M M; Flynn, J L; Chan, J

    2001-03-01

    Reactivation of latent tuberculosis contributes significantly to the incidence of disease caused by Mycobacterium tuberculosis. The mechanisms involved in the containment of latent tuberculosis are poorly understood. Using the low-dose model of persistent murine tuberculosis in conjunction with MP6-XT22, a monoclonal antibody that functionally neutralizes tumor necrosis factor alpha (TNF-alpha), we examined the effects of TNF-alpha on the immunological response of the host in both persistent and reactivated tuberculous infections. The results confirm an essential role for TNF-alpha in the containment of persistent tuberculosis. TNF-alpha neutralization resulted in fatal reactivation of persistent tuberculosis characterized by a moderately increased tissue bacillary burden and severe pulmonic histopathological deterioration that was associated with changes indicative of squamous metaplasia and fluid accumulation in the alveolar space. Analysis of pulmonic gene and protein expression of mice in the low-dose model revealed that nitric oxide synthase was attenuated during MP6-XT22-induced reactivation, but was not totally suppressed. Interleukin-12p40 and gamma interferon gene expression in TNF-alpha-neutralized mice was similar to that in control mice. In contrast, interleukin-10 expression was augmented in the TNF-alpha-neutralized mice. In summary, results of this study suggest that TNF-alpha plays an essential role in preventing reactivation of persistent tuberculosis, modulates the pulmonic expression of specific immunologic factors, and limits the pathological response of the host.

  15. Individual Differences in Spontaneous Expressive Suppression Predict Amygdala Responses to Fearful Stimuli: The Role of Suppression Priming

    PubMed Central

    Chen, Shengdong; Deng, Zhongyan; Xu, Yin; Long, Quanshan; Yang, Jiemin; Yuan, Jiajin

    2017-01-01

    Though the spontaneous emotion regulation has received long discussions, few studies have explored the regulatory effects of spontaneous expressive suppression in neural activations, especially in collectivistic cultural context. The functional magnetic resonance imaging (fMRI) study aimed to examine whether individual differences in the tendency to use suppression are correlated with amygdala responses to negative situations when individuals are unconsciously primed with expressive suppression. Twenty-three healthy Chinese undergraduates completed an fMRI paradigm involving fear processing, and a synonym matching task was added to prime participants with the unconscious (automatic) expressive suppression goal. Participants completed measures of typical emotion regulation use (reappraisal and suppression), trait anxiety, and neuroticism. Results indicated that only in emotion suppression prime condition, greater use of suppression in everyday life was related to decreased amygdala activity. These associations were not attributable to variation in trait anxiety, neuroticism, or the habitual use of reappraisal. These findings suggest that in collectivistic cultural settings, individual differences in expressive suppression do not alter fear-related neural activation during suppression-irrelevant context. However, unconscious suppression priming facilitates the manifestation of individual differences in the neural consequence of expressive suppression, as reflected by the priming-specific decrease of emotional subcortical activations with more use of expressive suppression. PMID:28197108

  16. UAV visual signature suppression via adaptive materials

    NASA Astrophysics Data System (ADS)

    Barrett, Ron; Melkert, Joris

    2005-05-01

    Visual signature suppression (VSS) methods for several classes of aircraft from WWII on are examined and historically summarized. This study shows that for some classes of uninhabited aerial vehicles (UAVs), primary mission threats do not stem from infrared or radar signatures, but from the amount that an aircraft visually stands out against the sky. The paper shows that such visual mismatch can often jeopardize mission success and/or induce the destruction of the entire aircraft. A psycho-physioptical study was conducted to establish the definition and benchmarks of a Visual Cross Section (VCS) for airborne objects. This study was centered on combining the effects of size, shape, color and luminosity or effective illumance (EI) of a given aircraft to arrive at a VCS. A series of tests were conducted with a 6.6ft (2m) UAV which was fitted with optically adaptive electroluminescent sheets at altitudes of up to 1000 ft (300m). It was shown that with proper tailoring of the color and luminosity, the VCS of the aircraft dropped from more than 4,200cm2 to less than 1.8cm2 at 100m (the observed lower limit of the 20-20 human eye in this study). In laypersons terms this indicated that the UAV essentially "disappeared". This study concludes with an assessment of the weight and volume impact of such a Visual Suppression System (VSS) on the UAV, showing that VCS levels on this class UAV can be suppressed to below 1.8cm2 for aircraft gross weight penalties of only 9.8%.

  17. Revisiting mu suppression in autism spectrum disorder.

    PubMed

    Dumas, Guillaume; Soussignan, Robert; Hugueville, Laurent; Martinerie, Jacques; Nadel, Jacqueline

    2014-10-17

    Two aspects of the EEG literature lead us to revisit mu suppression in Autism Spectrum Disorder (ASD). First and despite the fact that the mu rhythm can be functionally segregated in two discrete sub-bands, 8-10 Hz and 10-12/13 Hz, mu-suppression in ASD has been analyzed as a homogeneous phenomenon covering the 8-13 Hz frequency. Second and although alpha-like activity is usually found across the entire scalp, ASD studies of action observation have focused on the central electrodes (C3/C4). The present study was aimed at testing on the whole brain the hypothesis of a functional dissociation of mu and alpha responses to the observation of human actions in ASD according to bandwidths. Electroencephalographic (EEG) mu and alpha responses to execution and observation of hand gestures were recorded on the whole scalp in high functioning subjects with ASD and typical subjects. When two bandwidths of the alpha-mu 8-13 Hz were distinguished, a different mu response to observation appeared for subjects with ASD in the upper sub-band over the sensorimotor cortex, whilst the lower sub-band responded similarly in the two groups. Source reconstructions demonstrated that this effect was related to a joint mu-suppression deficit over the occipito-parietal regions and an increase over the frontal regions. These findings suggest peculiarities in top-down response modulation in ASD and question the claim of a global dysfunction of the MNS in autism. This research also advocates for the use of finer grained analyses at both spatial and spectral levels for future directions in neurophysiological accounts of autism.

  18. Cough Suppressant and Pharmacologic Protussive Therapy

    PubMed Central

    Bolser, Donald C.

    2011-01-01

    Background Cough-suppressant therapy, previously termed nonspecific antitussive therapy, incorporates the use of pharmacologic agents with mucolytic effects and/or inhibitory effects on the cough reflex itself. The intent of this type of therapy is to reduce the frequency and/or intensity of coughing on a short-term basis. Methods Data for this review were obtained from several National Library of Medicine (PubMed) searches (from 1960 to 2004), which were performed between May and September 2004, of the literature published in the English language, limited to human studies, using combinations of the search terms “cough,” “double-blind placebo-controlled,” “antitussive,” “mucolytic,” “cough clearance,” “common cold,” “protussive,” “guaifenesin,” “glycerol,” and “zinc.” Results Mucolytic agents are not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Peripheral and central antitussive agents can be useful in patients with chronic bronchitis, but can have little efficacy in patients with cough due to upper respiratory infection. Some protussive agents are effective in increasing cough clearance, but their long-term effectiveness has not been established. DNase is not effective as a protussive agent in patients with cystic fibrosis. Inhaled mannitol is acutely effective in this patient population, but its therapeutic potential must be investigated further. Conclusions These findings suggest that suppressant therapy is most effective when used for the short-term reduction of coughing. Relatively few drugs are effective as cough suppressants. PMID:16428717

  19. Weed Suppression by Seven Clover Species

    SciTech Connect

    Ross, Shirley M.; King, Jane R.; Izaurralde, R Cesar C.; O'Donovan, John T.

    2001-01-01

    Used as cover crops, clover species may differ in their ability to suppress weed growth. Field trials were conducted in Alberta, Canada to measure the growth of brown mustard [Brassica juncea (L.) Czern.], in mowed and nonmowed production, as influenced by alsike (Trifolium hybridum L.), balansa [T. michelianum Savi var. balansae (Boiss.) Azn.], berseem (T. alexandrinum L.), crimson [T. incarnatum (Boiss.) Azn.], berseem (T. alexandrinum L.), crimson (T. incarnatum L.), Persian (T. resupinatum L.), red (T. pratense L.), and white Dutch (T. repens L.) clover and fall rye (Secale cereale L.). In 1997, clovers reduced mustard biomass in nonmowed treatments by 29% on a high- fertility soil (Typic Cryoboroll) at Edmonton and by 57% on a low- fertility soil (Typic Cryoboralf) at Breton. At Edmonton, nonmowed mustard biomass was reduced by alsike and berseem clover in 1996 and by alsike, balansa, berseem, and crimson clover in 1997. At Breton, all seven clover species suppressed weed biomass. A negative correlation was noted among clover and mustard biomass at Edmonton but not at Breton. The effects of mowing varied with location, timing, and species. Mowing was beneficial to crop/weed proportion at Edmonton but not at Breton. Mowing at early flowering of mustard large-seeded legumes and sweetclover (Melilotus offici) produced greater benefit than mowing at late flowering. With early mowing, all clover species suppressed mustard growth at Edmonton. Clovers reduced mustard regrowth (g plant21 ) and the number of mustard plants producing regrowth. The characteristics of berseem clover (upright growth, long stems, high biomass, and late flowering) would support its use as a cover crop or forage in north-central Alberta.

  20. Suppression of erythropoiesis by dietary nitrate

    PubMed Central

    Ashmore, Tom; Fernandez, Bernadette O.; Evans, Colin E.; Huang, Yun; Branco-Price, Cristina; Griffin, Julian L.; Johnson, Randall S.; Feelisch, Martin; Murray, Andrew J.

    2015-01-01

    In mammals, hypoxia-triggered erythropoietin release increases red blood cell mass to meet tissue oxygen demands. Using male Wistar rats, we unmask a previously unrecognized regulatory pathway of erythropoiesis involving suppressor control by the NO metabolite and ubiquitous dietary component nitrate. We find that circulating hemoglobin levels are modulated by nitrate at concentrations achievable by dietary intervention under normoxic and hypoxic conditions; a moderate dose of nitrate administered via the drinking water (7 mg NaNO3/kg body weight/d) lowered hemoglobin concentration and hematocrit after 6 d compared with nonsupplemented/NaCl-supplemented controls. The underlying mechanism is suppression of hepatic erythropoietin expression associated with the downregulation of tissue hypoxia markers, suggesting increased pO2. At higher nitrate doses, however, a partial reversal of this effect occurred; this was accompanied by increased renal erythropoietin expression and stabilization of hypoxia-inducible factors, likely brought about by the relative anemia. Thus, hepatic and renal hypoxia-sensing pathways act in concert to modulate hemoglobin in response to nitrate, converging at an optimal minimal hemoglobin concentration appropriate to the environmental/physiologic situation. Suppression of hepatic erythropoietin expression by nitrate may thus act to decrease blood viscosity while matching oxygen supply to demand, whereas renal oxygen sensing could act as a brake, averting a potentially detrimental fall in hematocrit.—Ashmore, T., Fernandez, B. O., Evans, C. E., Huang, Y., Branco-Price, C., Griffin, J. L., Johnson, R. S., Feelisch, M., Murray, A. J. Suppression of erythropoiesis by dietary nitrate. PMID:25422368

  1. Chaos suppression in gas-solid fluidization.

    PubMed

    Pence, Deborah V.; Beasley, Donald E.

    1998-06-01

    Fluidization in granular materials occurs primarily as a result of a dynamic balance between gravitational forces and forces resulting from the flow of a fluid through a bed of discrete particles. For systems where the fluidizing medium and the particles have significantly different densities, density wave instabilities create local pockets of very high void fraction termed bubbles. The fluidization regime is termed the bubbling regime. Such a system is appropriately termed a self-excited nonlinear system. The present study examines chaos suppression resulting from an opposing oscillatory flow in gas-solid fluidization. Time series data representing local, instantaneous pressure were acquired at the surface of a horizontal cylinder submerged in a bubbling fluidized bed. The particles had a weight mean diameter of 345 &mgr;m and a narrow size distribution. The state of fluidization corresponded to the bubbling regime and total air flow rates employed in the present study ranged from 10% to 40% greater than that required for minimum fluidization. The behavior of time-varying local pressure in fluidized beds in the absence of a secondary flow is consistent with deterministic chaos. Kolmogorov entropy estimates from local, instantaneous pressure suggest that the degree of chaotic behavior can be substantially suppressed by the presence of an opposing, oscillatory secondary flow. Pressure signals clearly show a "phase-locking" phenomenon coincident with the imposed frequency. In the present study, the greatest degree of suppression occurred for operating conditions with low primary and secondary flow rates, and a secondary flow oscillation frequency of 15 Hz. (c) 1998 American Institute of Physics.

  2. Cosmic Coincidences: Investigations for Neutron Background Suppression

    PubMed Central

    Heimbach, Craig R.

    2007-01-01

    Two experimental investigations were made in order to reduce background counts in neutron detectors. Each investigation relied upon the fact that neutron background is largely due to cosmic ray interactions with the air and ground. The first attempt was to look at neutron arrival times. Neutron events close in time were taken to have been of a common origin due to cosmic rays. The second investigation was similar, but based on coincident neutron/muon events. The investigations showed only a small effect, not practical for the suppression of neutron background. PMID:27110457

  3. Cosmic Coincidences: Investigations for Neutron Background Suppression.

    PubMed

    Heimbach, Craig R

    2007-01-01

    Two experimental investigations were made in order to reduce background counts in neutron detectors. Each investigation relied upon the fact that neutron background is largely due to cosmic ray interactions with the air and ground. The first attempt was to look at neutron arrival times. Neutron events close in time were taken to have been of a common origin due to cosmic rays. The second investigation was similar, but based on coincident neutron/muon events. The investigations showed only a small effect, not practical for the suppression of neutron background.

  4. Suppression of range sidelobes in bistatic radars

    NASA Astrophysics Data System (ADS)

    McCue, J. J. G.

    1980-03-01

    A bistatic radar is considered in which linear-FM pulses are employed to obtain the needed range resolution while using a long pulse. Range sidelobes of the pulse received over the direct path from the transmitter tend to interfere with the return from the target. It is shown that conventional weighting schemes give little or no suppression of some of the range sidelobes of a linear-FM rectangular pulse passed through a matched filter. This is explained by the irregular spacing of the sidelobes in the pulse when it passes through the matched filter.

  5. Suppressed $B_s$ decays at CDF

    SciTech Connect

    Dorigo, Mirco

    2011-05-01

    We review three recent results of the CDF collaboration on B{sub s}{sup 0} suppressed decays: the first search for CP-violation in the B{sub s}{sup 0} {yields} {phi}{phi} decay, where two CP-violating asymmetries expected to be zero in the Standard Model are measured, and the observation and the branching ratio measurements of B{sub s}{sup 0} {yields} J/{Psi} f{sub 0}(980) and B{sub s}{sup 0} {yields} J/{Psi} K{sup (*)} decays.

  6. Method for suppressing noise in measurements

    NASA Technical Reports Server (NTRS)

    Carson, Paul J. (Inventor); Madsen, Louis A. (Inventor); Leskowitz, Garett M. (Inventor); Weitekamp, Daniel P. (Inventor)

    2000-01-01

    Techniques of combining separate but correlated measurements to form a second-order or higher order correlation function to suppress the effects of noise in the initial condition of a system capable of retaining memory of an initial state of the system with a characteristic relaxation time. At least two separate measurements are obtained from the system. The temporal separation between the two separate measurements is preferably comparable to or less than the characteristic relaxation time and is adjusted to allow for a correlation between two measurements.

  7. Suppressing Electron Cloud in Future Linear Colliders

    SciTech Connect

    Pivi, M; Kirby, R.E.; Raubenheimer, T.O.; Le Pimpec, F.; /PSI, Villigen

    2005-05-27

    Any accelerator circulating positively charged beams can suffer from a build-up of an electron cloud (EC) in the beam pipe. The cloud develops through ionization of residual gases, synchrotron radiation and secondary electron emission and, when severe, can cause instability, emittance blow-up or loss of the circulating beam. The electron cloud is potentially a luminosity limiting effect for both the Large Hadron Collider (LHC) and the International Linear Collider (ILC). For the ILC positron damping ring, the development of the electron cloud must be suppressed. This paper discusses the state-of-the-art of the ongoing SLAC and international R&D program to study potential remedies.

  8. Orientation-tuned surround suppression in mouse visual cortex.

    PubMed

    Self, Matthew W; Lorteije, Jeannette A M; Vangeneugden, Joris; van Beest, Enny H; Grigore, Mihaela E; Levelt, Christiaan N; Heimel, J Alexander; Roelfsema, Pieter R

    2014-07-09

    The firing rates of neurons in primary visual cortex (V1) are suppressed by large stimuli, an effect known as surround suppression. In cats and monkeys, the strength of suppression is sensitive to orientation; responses to regions containing uniform orientations are more suppressed than those containing orientation contrast. This effect is thought to be important for scene segmentation, but the underlying neural mechanisms are poorly understood. We asked whether it is possible to study these mechanisms in the visual cortex of mice, because of recent advances in technology for studying the cortical circuitry in mice. It is unknown whether neurons in mouse V1 are sensitive to orientation contrast. We measured the orientation selectivity of surround suppression in the different layers of mouse V1. We found strong surround suppression in layer 4 and the superficial layers, part of which was orientation tuned: iso-oriented surrounds caused more suppression than cross-oriented surrounds. Surround suppression was delayed relative to the visual response and orientation-tuned suppression was delayed further, suggesting two separate suppressive mechanisms. Previous studies proposed that surround suppression depends on the activity of inhibitory somatostatin-positive interneurons in the superficial layers. To test the involvement of the superficial layers we topically applied lidocaine. Silencing of the superficial layers did not prevent orientation-tuned suppression in layer 4. These results show that neurons in mouse V1, which lacks orientation columns, show orientation-dependent surround suppression in layer 4 and the superficial layers and that surround suppression in layer 4 does not require contributions from neurons in the superficial layers.

  9. Suppression of Ostwald ripening in active emulsions

    NASA Astrophysics Data System (ADS)

    Zwicker, David; Hyman, Anthony A.; Jülicher, Frank

    2015-07-01

    Emulsions consisting of droplets immersed in a fluid are typically unstable since they coarsen over time. One important coarsening process is Ostwald ripening, which is driven by the surface tension of the droplets. Stability of emulsions is relevant not only in complex fluids but also in biological cells, which contain liquidlike compartments, e.g., germ granules, Cajal bodies, and centrosomes. Such cellular systems are driven away from equilibrium, e.g., by chemical reactions, and thus can be called active emulsions. In this paper, we study such active emulsions by developing a coarse-grained description of the droplet dynamics, which we analyze for two different chemical reaction schemes. We first consider the simple case of first-order reactions, which leads to stable, monodisperse emulsions in which Ostwald ripening is suppressed within a range of chemical reaction rates. We then consider autocatalytic droplets, which catalyze the production of their own droplet material. Spontaneous nucleation of autocatalytic droplets is strongly suppressed and their emulsions are typically unstable. We show that autocatalytic droplets can be nucleated reliably and their emulsions stabilized by the help of chemically active cores, which catalyze the production of droplet material. In summary, different reaction schemes and catalytic cores can be used to stabilize emulsions and to control their properties.

  10. Jet noise suppression by porous plug nozzles

    NASA Technical Reports Server (NTRS)

    Bauer, A. B.; Kibens, V.; Wlezien, R. W.

    1982-01-01

    Jet noise suppression data presented earlier by Maestrello for porous plug nozzles were supplemented by the testing of a family of nozzles having an equivalent throat diameter of 11.77 cm. Two circular reference nozzles and eight plug nozzles having radius ratios of either 0.53 or 0.80 were tested at total pressure ratios of 1.60 to 4.00. Data were taken both with and without a forward motion or coannular flow jet, and some tests were made with a heated jet. Jet thrust was measured. The data were analyzed to show the effects of suppressor geometry on nozzle propulsive efficiency and jet noise. Aerodynamic testing of the nozzles was carried out in order to study the physical features that lead to the noise suppression. The aerodynamic flow phenomena were examined by the use of high speed shadowgraph cinematography, still shadowgraphs, extensive static pressure probe measurements, and two component laser Doppler velocimeter studies. The different measurement techniques correlated well with each other and demonstrated that the porous plug changes the shock cell structure of a standard nozzle into a series of smaller, periodic cell structures without strong shock waves. These structures become smaller in dimension and have reduced pressure variations as either the plug diameter or the porosity is increased, changes that also reduce the jet noise and decrease thrust efficiency.

  11. Inhibition of saccades elicits attentional suppression.

    PubMed

    Dhawan, Saurabh; Deubel, Heiner; Jonikaitis, Donatas

    2013-05-17

    Visuospatial attention has been shown to have a central role in planning and generation of saccades but what role, if any, it plays in inhibition of saccades remains unclear. In this study, we used an oculomotor delayed match- or nonmatch-to-sample task in which a cued location has to be encoded and memorized for one of two very different goals-to plan a saccade to it or to avoid making a saccade to it. We measured the spatial allocation of attention during the delay and found that while marking a location as a future saccade target resulted in an attentional benefit at that location, marking it as forbidden to saccades led to an attentional cost. Additionally, saccade trajectories were found to deviate away more from the "don't look" location than from a saccade-irrelevant distractor confirming greater inhibition of an actively forbidden location in oculomotor programming. Our finding that attention is suppressed at locations forbidden to saccades confirms and complements the claim of a selective and obligatory coupling between saccades and attention-saccades at the memorized location could neither be planned nor suppressed independent of a corresponding effect on attentional performance.

  12. Suppression of erythropoiesis by dietary nitrate.

    PubMed

    Ashmore, Tom; Fernandez, Bernadette O; Evans, Colin E; Huang, Yun; Branco-Price, Cristina; Griffin, Julian L; Johnson, Randall S; Feelisch, Martin; Murray, Andrew J

    2015-03-01

    In mammals, hypoxia-triggered erythropoietin release increases red blood cell mass to meet tissue oxygen demands. Using male Wistar rats, we unmask a previously unrecognized regulatory pathway of erythropoiesis involving suppressor control by the NO metabolite and ubiquitous dietary component nitrate. We find that circulating hemoglobin levels are modulated by nitrate at concentrations achievable by dietary intervention under normoxic and hypoxic conditions; a moderate dose of nitrate administered via the drinking water (7 mg NaNO3/kg body weight/d) lowered hemoglobin concentration and hematocrit after 6 d compared with nonsupplemented/NaCl-supplemented controls. The underlying mechanism is suppression of hepatic erythropoietin expression associated with the downregulation of tissue hypoxia markers, suggesting increased pO2. At higher nitrate doses, however, a partial reversal of this effect occurred; this was accompanied by increased renal erythropoietin expression and stabilization of hypoxia-inducible factors, likely brought about by the relative anemia. Thus, hepatic and renal hypoxia-sensing pathways act in concert to modulate hemoglobin in response to nitrate, converging at an optimal minimal hemoglobin concentration appropriate to the environmental/physiologic situation. Suppression of hepatic erythropoietin expression by nitrate may thus act to decrease blood viscosity while matching oxygen supply to demand, whereas renal oxygen sensing could act as a brake, averting a potentially detrimental fall in hematocrit.

  13. Antisense RNA suppression of peroxidase gene expression

    SciTech Connect

    Lagrimini, L.M.; Bradford, S.; De Leon, F.D. )

    1989-04-01

    The 5{prime} half the anionic peroxidase cDNA of tobacco was inserted into a CaMV 35S promoter/terminator expression cassette in the antisense configuration. This was inserted into the Agrobacterium-mediated plant transformation vector pCIBIO which includes kanamycin selection, transformed into two species of tobacco (N. tabacum and M. sylvestris), and plants were subsequently regenerated on kanamycin. Transgenic plants were analyzed for peroxidase expression and found to have 3-5 fold lower levels of peroxidase than wild-type plants. Isoelectric focusing demonstrated that the antisense RNA only suppressed the anionic peroxidase. Wound-induced peroxidase expression was found not to be affected by the antisense RNA. Northern blots show a greater than 5 fold suppression of anionic peroxidase mRNA in leaf tissue, and the antisense RNA was expressed at a level 2 fold over the endogenous mRNA. Plants were self-pollinated and F1 plants showed normal segregation. N. sylvestris transgenic plants with the lowest level of peroxidase are epinastic, and preliminary results indicate elevated auxin levels. Excised pith tissue from both species of transgenic plants rapidly collapse when exposed to air, while pith tissue from wild-type plants showed little change when exposed to air. Further characterization of these phenotypes is currently being made.

  14. Phase noise suppression through parametric filtering

    NASA Astrophysics Data System (ADS)

    Cassella, Cristian; Strachan, Scott; Shaw, Steven W.; Piazza, Gianluca

    2017-02-01

    In this work, we introduce and experimentally demonstrate a parametric phase noise suppression technique, which we call "parametric phase noise filtering." This technique is based on the use of a solid-state parametric amplifier operating in its instability region and included in a non-autonomous feedback loop connected at the output of a noisy oscillator. We demonstrate that such a system behaves as a parametrically driven Duffing resonator and can operate at special points where it becomes largely immune to the phase fluctuations that affect the oscillator output signal. A prototype of a parametric phase noise filter (PFIL) was designed and fabricated to operate in the very-high-frequency range. The PFIL prototype allowed us to significantly reduce the phase noise at the output of a commercial signal generator operating around 220 MHz. Noise reduction of 16 dB (40×) and 13 dB (20×) were obtained, respectively, at 1 and 10 kHz offsets from the carrier frequency. The demonstration of this phase noise suppression technique opens up scenarios in the development of passive and low-cost phase noise cancellation circuits for any application demanding high quality frequency generation.

  15. Inhibition of SIRT2 suppresses hepatic fibrosis.

    PubMed

    Arteaga, Maribel; Shang, Na; Ding, Xianzhong; Yong, Sherri; Cotler, Scott J; Denning, Mitchell F; Shimamura, Takashi; Breslin, Peter; Lüscher, Bernhard; Qiu, Wei

    2016-06-01

    Liver fibrosis can progress to cirrhosis and result in serious complications of liver disease. The pathogenesis of liver fibrosis involves the activation of hepatic stellate cells (HSCs), the underlying mechanisms of which are not fully known. Emerging evidence suggests that the classic histone deacetylases play a role in liver fibrosis, but the role of another subfamily of histone deacetylases, the sirtuins, in the development of hepatic fibrosis remains unknown. In this study, we found that blocking the activity of sirtuin 2 (SIRT2) by using inhibitors or shRNAs significantly suppressed fibrogenic gene expression in HSCs. We further demonstrated that inhibition of SIRT2 results in the degradation of c-MYC, which is important for HSC activation. In addition, we discovered that inhibition of SIRT2 suppresses the phosphorylation of ERK, which is critical for the stabilization of c-MYC. Moreover, we found that Sirt2 deficiency attenuates the hepatic fibrosis induced by carbon tetrachloride (CCl4) and thioacetamide (TAA). Furthermore, we showed that SIRT2, p-ERK, and c-MYC proteins are all overexpressed in human hepatic fibrotic tissues. These data suggest a critical role for the SIRT2/ERK/c-MYC axis in promoting hepatic fibrogenesis. Inhibition of the SIRT2/ERK/c-MYC axis represents a novel strategy to prevent and to potentially treat liver fibrosis and cirrhosis.

  16. Suppression of soil nitrification by plants.

    PubMed

    Subbarao, Guntur Venkata; Yoshihashi, Tadashi; Worthington, Margaret; Nakahara, Kazuhiko; Ando, Yasuo; Sahrawat, Kanwar Lal; Rao, Idupulapati Madhusudhana; Lata, Jean-Christophe; Kishii, Masahiro; Braun, Hans-Joachim

    2015-04-01

    Nitrification, the biological oxidation of ammonium to nitrate, weakens the soil's ability to retain N and facilitates N-losses from production agriculture through nitrate-leaching and denitrification. This process has a profound influence on what form of mineral-N is absorbed, used by plants, and retained in the soil, or lost to the environment, which in turn affects N-cycling, N-use efficiency (NUE) and ecosystem health and services. As reactive-N is often the most limiting in natural ecosystems, plants have acquired a range of mechanisms that suppress soil-nitrifier activity to limit N-losses via N-leaching and denitrification. Plants' ability to produce and release nitrification inhibitors from roots and suppress soil-nitrifier activity is termed 'biological nitrification inhibition' (BNI). With recent developments in methodology for in-situ measurement of nitrification inhibition, it is now possible to characterize BNI function in plants. This review assesses the current status of our understanding of the production and release of biological nitrification inhibitors (BNIs) and their potential in improving NUE in agriculture. A suite of genetic, soil and environmental factors regulate BNI activity in plants. BNI-function can be genetically exploited to improve the BNI-capacity of major food- and feed-crops to develop next-generation production systems with reduced nitrification and N2O emission rates to benefit both agriculture and the environment. The feasibility of such an approach is discussed based on the progresses made.

  17. Suppression pheromone and cockroach rank formation

    NASA Astrophysics Data System (ADS)

    Kou, Rong; Chang, Huan-Wen; Chen, Shu-Chun; Ho, Hsiao-Yung

    2009-06-01

    Although agonistic behaviors in the male lobster cockroach ( Nauphoeta cinerea) are well known, the formation of an unstable hierarchy has long been a puzzle. In this study, we investigate how the unstable dominance hierarchy in N. cinerea is maintained via a pheromone signaling system. In agonistic interactions, aggressive posture (AP) is an important behavioral index of aggression. This study showed that, during the formation of a governing hierarchy, thousands of nanograms of 3-hydroxy-2-butanone (3H-2B) were released by the AP-adopting dominant in the first encounter fight, then during the early domination period and that this release of 3H-2B was related to rank maintenance, but not to rank establishment. For rank maintenance, 3H-2B functioned as a suppression pheromone, which suppressed the fighting capability of rivals and kept them in a submissive state. During the period of rank maintenance, as the dominant male gradually decreased his 3H-2B release, the fighting ability of the subordinate gradually developed, as shown by the increasing odds of a subordinate adopting an AP (OSAP). The OSAP was negatively correlated with the amount of 3H-2B released by the dominant and positively correlated with the number of domination days. The same OSAP could be achieved earlier by reducing the amount of 3H-2B released by the dominant indicates that whether the subordinate adopts an offensive strategy depends on what the dominant is doing.

  18. Suppression of Dopamine Neurons Mediates Reward

    PubMed Central

    Yamagata, Nobuhiro; Abe, Ayako; Tanimoto, Hiromu

    2016-01-01

    Massive activation of dopamine neurons is critical for natural reward and drug abuse. In contrast, the significance of their spontaneous activity remains elusive. In Drosophila melanogaster, depolarization of the protocerebral anterior medial (PAM) cluster dopamine neurons en masse signals reward to the mushroom body (MB) and drives appetitive memory. Focusing on the functional heterogeneity of PAM cluster neurons, we identified that a single class of PAM neurons, PAM-γ3, mediates sugar reward by suppressing their own activity. PAM-γ3 is selectively required for appetitive olfactory learning, while activation of these neurons in turn induces aversive memory. Ongoing activity of PAM-γ3 gets suppressed upon sugar ingestion. Strikingly, transient inactivation of basal PAM-γ3 activity can substitute for reward and induces appetitive memory. Furthermore, we identified the satiety-signaling neuropeptide Allatostatin A (AstA) as a key mediator that conveys inhibitory input onto PAM-γ3. Our results suggest the significance of basal dopamine release in reward signaling and reveal a circuit mechanism for negative regulation. PMID:27997541

  19. Wireless Inductive Power Device Suppresses Blade Vibrations

    NASA Technical Reports Server (NTRS)

    Morrison, Carlos R.; Provenza, Andrew J.; Choi, Benjamin B.; Bakhle, Milind A.; Min, James B.; Stefko, George L.; Duffy, Kirsten P.; Fougers, Alan J.

    2011-01-01

    Vibration in turbomachinery can cause blade failures and leads to the use of heavier, thicker blades that result in lower aerodynamic efficiency and increased noise. Metal and/or composite fatigue in the blades of jet engines has resulted in blade destruction and loss of lives. Techniques for suppressing low-frequency blade vibration, such as gtuned circuit resistive dissipation of vibratory energy, h or simply "passive damping," can require electronics incorporating coils of unwieldy dimensions and adding unwanted weight to the rotor. Other approaches, using vibration-dampening devices or damping material, could add undesirable weight to the blades or hub, making them less efficient. A wireless inductive power device (WIPD) was designed, fabricated, and developed for use in the NASA Glenn's "Dynamic Spin Rig" (DSR) facility. The DSR is used to simulate the functionality of turbomachinery. The relatively small and lightweight device [10 lb (approx.=4.5 kg)] replaces the existing venerable and bulky slip-ring. The goal is the eventual integration of this technology into actual turbomachinery such as jet engines or electric power generators, wherein the device will facilitate the suppression of potentially destructive vibrations in fan blades. This technology obviates slip rings, which require cooling and can prove unreliable or be problematic over time. The WIPD consists of two parts: a remote element, which is positioned on the rotor and provides up to 100 W of electrical power to thin, lightweight piezoelectric patches strategically placed on/in fan blades; and a stationary base unit that wirelessly communicates with the remote unit. The base unit supplies inductive power, and also acts as an input and output corridor for wireless measurement, and active control command to the remote unit. Efficient engine operation necessitates minimal disturbance to the gas flow across the turbine blades in any effort to moderate blade vibration. This innovation makes it

  20. Detection and Description of Soils with Specific Nematode Suppressiveness

    PubMed Central

    Westphal, Andreas

    2005-01-01

    Soils with specific suppressiveness to plant-parasitic nematodes are of interest to define the mechanisms that regulate population density. Suppressive soils prevent nematodes from establishing and from causing disease, and they diminish disease severity after initial nematode damage in continuous culturing of a host. A range of non-specific and specific soil treatments, followed by infestation with a target nematode, have been employed to identify nematode-suppressive soils. Biocidal treatments, soil transfer tests, and baiting approaches together with observations of the plant-parasitic nematode in the root zone of susceptible host plants have improved the understanding of nematode-suppressive soils. Techniques to demonstrate specific soil suppressiveness against plant-parasitic nematodes are compared in this review. The overlap of studies on soil suppressiveness with recent advances in soil health and quality is briefly discussed. The emphasis is on methods (or criteria) used to detect and identify soils that maintain specific soil suppressiveness to plant-parasitic nematodes. While biocidal treatments can detect general and specific soil suppressiveness, soil transfer studies, by definition, apply only to specific soil suppressiveness. Finally, potential strategies to exploit suppressive soils are presented. PMID:19262851

  1. Exploiting Symmetry for Quantum Error Suppression

    NASA Astrophysics Data System (ADS)

    Nam, Yunseong; Blümel, Reinhold

    2016-05-01

    In light of recent experimental progress in quantum computing, the time is ripe to discuss quantum computer hardware optimization. Taking the digital/analog hybrid nature of quantum computers into account, choosing a proper processor architecture for a given quantum algorithm becomes crucial in making quantum computing a practical reality. As a first step in this direction, we investigate the robustness of quantum adders with respect to naturally occurring hardware defects and errors. In particular, we compare the robustness of the ripple-carry adder to that of the quantum Fourier adder. We show that, surprisingly, when used in Shor's algorithm, the quantum Fourier adder may well be more robust than the ripple-carry adder. We present a noise suppression scheme, called symmetric noise, applicable to the quantum Fourier architecture, that, measured in terms of fidelity, results in an order-of-magnitude performance boost.

  2. Circuit protection devices for transient suppression

    NASA Technical Reports Server (NTRS)

    Childers, Richard

    1991-01-01

    The Electromer Corporation has developed a series of transient voltage suppression components based on a patented, specially formulated PolyClamp (trademark) material. PolyClamp components are a new class of transient voltage surge suppressors that extend the range of protection offered by transients protectors. The PolyClamp transient surge suppressors provide low capacitance, high energy capability, and packaging flexibility. A wide variety of applications can be protected. A tube and ferrule configuration was designed to be used with MIL/Aerospace style connectors and is designed to meet the applicable environmental, mechanical, and electrical requirements as defined by the United States and European defence standards performance requirements. Here, PolyClamp is compared with current transient surge suppressors. Typical performance and design are discussed.

  3. Axionic suppression of plasma wakefield acceleration

    NASA Astrophysics Data System (ADS)

    Burton, D. A.; Noble, A.; Walton, T. J.

    2016-09-01

    Contemporary attempts to explain the existence of ultra-high energy cosmic rays using plasma-based wakefield acceleration deliberately avoid non-standard model particle physics. However, such proposals exploit some of the most extreme environments in the Universe and it is conceivable that hypothetical particles outside the standard model have significant implications for the effectiveness of the acceleration process. Axions solve the strong CP problem and provide one of the most important candidates for cold dark matter, and their potential significance in the present context should not be overlooked. Our analysis of the field equations describing a plasma augmented with axions uncovers a dramatic axion-induced suppression of the energy gained by a test particle in the wakefield driven by a particle bunch, or an intense pulse of electromagnetic radiation, propagating at ultra-relativistic speeds within the strongest magnetic fields in the Universe.

  4. Inhibiting macrophage proliferation suppresses atherosclerotic plaque inflammation.

    PubMed

    Tang, Jun; Lobatto, Mark E; Hassing, Laurien; van der Staay, Susanne; van Rijs, Sarian M; Calcagno, Claudia; Braza, Mounia S; Baxter, Samantha; Fay, Francois; Sanchez-Gaytan, Brenda L; Duivenvoorden, Raphaël; Sager, Hendrik; Astudillo, Yaritzy M; Leong, Wei; Ramachandran, Sarayu; Storm, Gert; Pérez-Medina, Carlos; Reiner, Thomas; Cormode, David P; Strijkers, Gustav J; Stroes, Erik S G; Swirski, Filip K; Nahrendorf, Matthias; Fisher, Edward A; Fayad, Zahi A; Mulder, Willem J M

    2015-04-01

    Inflammation drives atherosclerotic plaque progression and rupture, and is a compelling therapeutic target. Consequently, attenuating inflammation by reducing local macrophage accumulation is an appealing approach. This can potentially be accomplished by either blocking blood monocyte recruitment to the plaque or increasing macrophage apoptosis and emigration. Because macrophage proliferation was recently shown to dominate macrophage accumulation in advanced plaques, locally inhibiting macrophage proliferation may reduce plaque inflammation and produce long-term therapeutic benefits. To test this hypothesis, we used nanoparticle-based delivery of simvastatin to inhibit plaque macrophage proliferation in apolipoprotein E deficient mice (Apoe(-/-) ) with advanced atherosclerotic plaques. This resulted in rapid reduction of plaque inflammation and favorable phenotype remodeling. We then combined this short-term nanoparticle intervention with an eight-week oral statin treatment, and this regimen rapidly reduced and continuously suppressed plaque inflammation. Our results demonstrate that pharmacologically inhibiting local macrophage proliferation can effectively treat inflammation in atherosclerosis.

  5. Inhibiting macrophage proliferation suppresses atherosclerotic plaque inflammation

    PubMed Central

    Tang, Jun; Lobatto, Mark E.; Hassing, Laurien; van der Staay, Susanne; van Rijs, Sarian M.; Calcagno, Claudia; Braza, Mounia S.; Baxter, Samantha; Fay, Francois; Sanchez-Gaytan, Brenda L.; Duivenvoorden, Raphaël; Sager, Hendrik B.; Astudillo, Yaritzy M.; Leong, Wei; Ramachandran, Sarayu; Storm, Gert; Pérez-Medina, Carlos; Reiner, Thomas; Cormode, David P.; Strijkers, Gustav J.; Stroes, Erik S. G.; Swirski, Filip K.; Nahrendorf, Matthias; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

    2015-01-01

    Inflammation drives atherosclerotic plaque progression and rupture, and is a compelling therapeutic target. Consequently, attenuating inflammation by reducing local macrophage accumulation is an appealing approach. This can potentially be accomplished by either blocking blood monocyte recruitment to the plaque or increasing macrophage apoptosis and emigration. Because macrophage proliferation was recently shown to dominate macrophage accumulation in advanced plaques, locally inhibiting macrophage proliferation may reduce plaque inflammation and produce long-term therapeutic benefits. To test this hypothesis, we used nanoparticle-based delivery of simvastatin to inhibit plaque macrophage proliferation in apolipoprotein E–deficient mice (Apoe−/−) with advanced atherosclerotic plaques. This resulted in the rapid reduction of plaque inflammation and favorable phenotype remodeling. We then combined this short-term nanoparticle intervention with an 8-week oral statin treatment, and this regimen rapidly reduced and continuously suppressed plaque inflammation. Our results demonstrate that pharmacologically inhibiting local macrophage proliferation can effectively treat inflammation in atherosclerosis. PMID:26295063

  6. Eigenspace techniques for active flutter suppression

    NASA Technical Reports Server (NTRS)

    Garrard, William L.; Liebst, Bradley S.; Farm, Jerome A.

    1987-01-01

    The use of eigenspace techniques for the design of an active flutter suppression system for a hypothetical research drone is discussed. One leading edge and two trailing edge aerodynamic control surfaces and four sensors (accelerometers) are available for each wing. Full state control laws are designed by selecting feedback gains which place closed loop eigenvalues and shape closed loop eigenvectors so as to stabilize wing flutter and reduce gust loads at the wing root while yielding accepatable robustness and satisfying constrains on rms control surface activity. These controllers are realized by state estimators designed using an eigenvalue placement/eigenvector shaping technique which results in recovery of the full state loop transfer characteristics. The resulting feedback compensators are shown to perform almost as well as the full state designs. They also exhibit acceptable performance in situations in which the failure of an actuator is simulated.

  7. Pulse compression and prepulse suppression apparatus

    DOEpatents

    Dane, Clifford B.; Hackel, Lloyd A.; George, Edward V.; Miller, John L.; Krupke, William F.

    1993-01-01

    A pulse compression and prepulse suppression apparatus (10) for time compressing the output of a laser (14). A pump pulse (46) is separated from a seed pulse (48) by a first polarized beam splitter (20) according to the orientation of a half wave plate (18). The seed pulse (48) is directed into an SBS oscillator (44) by two plane mirrors (22, 26) and a corner mirror (24), the corner mirror (24) being movable to adjust timing. The pump pulse (46) is directed into an SBS amplifier 34 wherein SBS occurs. The seed pulse (48), having been propagated from the SBS oscillator (44), is then directed through the SBS amplifier (34) wherein it sweeps the energy of the pump pulse (46) out of the SBS amplifier (34) and is simultaneously compressed, and the time compressed pump pulse (46) is emitted as a pulse output (52). A second polarized beam splitter (38) directs any undepleted pump pulse 58 away from the SBS oscillator (44).

  8. Pulse compression and prepulse suppression apparatus

    DOEpatents

    Dane, C.B.; Hackel, L.A.; George, E.V.; Miller, J.L.; Krupke, W.F.

    1993-11-09

    A pulse compression and prepulse suppression apparatus (10) for time compressing the output of a laser (14). A pump pulse (46) is separated from a seed pulse (48) by a first polarized beam splitter (20) according to the orientation of a half wave plate (18). The seed pulse (48) is directed into an SBS oscillator (44) by two plane mirrors (22, 26) and a corner mirror (24), the corner mirror (24) being movable to adjust timing. The pump pulse (46) is directed into an SBS amplifier 34 wherein SBS occurs. The seed pulse (48), having been propagated from the SBS oscillator (44), is then directed through the SBS amplifier (34) wherein it sweeps the energy of the pump pulse (46) out of the SBS amplifier (34) and is simultaneously compressed, and the time compressed pump pulse (46) is emitted as a pulse output (52). A second polarized beam splitter (38) directs any undepleted pump pulse 58 away from the SBS oscillator (44).

  9. Vibration suppression in a large space structure

    NASA Technical Reports Server (NTRS)

    Narendra, Kumpati S.

    1988-01-01

    The Yale University Center for Systems Science and the NASA Johnson Space Center collaborated in a study of vibration suppression in a large space structure during the period January 1985 to August 1987. The research proposal submitted by the Center to NASA concerned disturbance isolation in flexible space structures. The general objective of the proposal was to create within the Center a critical mass of expertise on problems related to the dynamics and control of large flexible space structures. A specific objective was to formulate both passive and active control strategies for the disturbance isolation problem. Both objectives were achieved during the period of the contract. While an extensive literature exists on the control of flexible space structures, it is generally acknowledged that many important questions remain open at even a fundamental level. Hence, instead of studying grossly simplified models of complex structural systems, it was decided as a first step to confine attention to detailed and thorough analyses of simple structures.

  10. Desferrioxamine suppresses Plasmodium falciparum in Aotus monkeys.

    PubMed

    Pollack, S; Rossan, R N; Davidson, D E; Escajadillo, A

    1987-02-01

    Clinical observation has suggested that iron deficiency may be protective in malaria, and we have found that desferrioxamine (DF), an iron-specific chelating agent, inhibited Plasmodium falciparum growth in vitro. It was difficult to be confident that DF would be effective in an intact animal, however, because continuous exposure to DF was required in vitro and, in vivo, DF is rapidly excreted. Also, the in vitro effect of DF was overcome by addition of iron to the culture and in vivo there are potentially high local iron concentrations when iron is absorbed from the diet or released from reticuloendothelial cells. We now show that DF given by constant subcutaneous infusion does suppress parasitemia in P. falciparum-infected Aotus monkeys.

  11. Reverse wave suppression in unstable ring resonator

    NASA Astrophysics Data System (ADS)

    Mirels, H.; Chodzko, R. A.; Bernard, J. M.; Giedt, R. R.; Coffer, J. G.

    1984-12-01

    Criteria for effective reverse-wave suppression (RWS) in CW and pulsed unstable ring lasers with inhomogeneously broadened media are determined theoretically, and the performance of a CW HF linear ring resonator (Chodzko et al., 1976) and of two configurations of a pulsed CO2 annular beam-rotation/internal-axicon (BRIA) resonator (Bullock et al., 1979) without and with an RWS mirror is evaluated experimentally. In the CW laser, the average forward-wave (FW) and RW power values are shown to be 61 and 39 W without RWS and 110 and 2.7 W with RWS, corresponding to a FW/RW power ratio of 41; in the pulsed BRIA lasers, power ratios of about 20 are achieved, but the RWS effectiveness is found to be highly sensitive to RWS-mirror and cavity misalignment. Graphs, drawings, tables, and photographs of typical waveforms are included.

  12. Passive runaway electron suppression in tokamak disruptions

    SciTech Connect

    Smith, H. M.; Helander, P.

    2013-07-15

    Runaway electrons created in disruptions pose a serious problem for tokamaks with large current. It would be desirable to have a runaway electron suppression method which is passive, i.e., a method that does not rely on an uncertain disruption prediction system. One option is to let the large electric field inherent in the disruption drive helical currents in the wall. This would create ergodic regions in the plasma and increase the runaway losses. Whether these regions appear at a suitable time and place to affect the formation of the runaway beam depends on disruption parameters, such as electron temperature and density. We find that it is difficult to ergodize the central plasma before a beam of runaway current has formed. However, the ergodic outer region will make the Ohmic current profile contract, which can lead to instabilities that yield large runaway electron losses.

  13. Upsilon suppression in the QGP at the LHC

    NASA Astrophysics Data System (ADS)

    Wolschin, Georg

    2016-12-01

    The suppression of ϒ-mesons in the hot quark-gluon medium in PbPb collisions is accounted for in a model that encompasses gluodissociation, collisional damping, screening, and reduced feed-down. Theoretical results for centrality-dependent suppression factors of the ϒ (1 S) and ϒ (2 S) states are compared with CMS data. The measured ground state suppression is well represented, but discrepancies between data and model persist for peripheral ϒ (2 S)-events that require additional suppression mechanisms. The pT-dependence of the suppression is discussed and a prediction for the centrality-dependent ϒ (1 S) suppression in 5.02 TeV PbPb is made.

  14. An appetite suppressant from Hoodia species.

    PubMed

    van Heerden, Fanie R; Marthinus Horak, R; Maharaj, Vinesh J; Vleggaar, Robert; Senabe, Jeremiah V; Gunning, Philip J

    2007-10-01

    Studies conducted at the Council for Scientific and Industrial Research (CSIR, South Africa) identified extracts from Hoodia species, in particular Hoodia pilifera and Hoodia gordonii, as possessing appetite suppressing properties. Two pregnane glycosides were isolated by fractionation of the dried stems of H. gordonii. Their structures were determined as 3beta-[beta-D-thevetopyranosyl-(1-->4)-beta-D- cymaropyranosyl-(1-->4)-beta-D-cymaropyranosyloxy]-12beta-tigloyloxy-14beta-hydroxypregn-5-en-20-one (1) and 3beta-[beta-D-cymaropyranosyl-(1-->4)-beta-D-6-thevetopyranosyl-(1-->4)-beta-D-cymaropyranosyl-(1-->4)-beta-D-cymaropyranosyloxy]-12beta-tigloyloxy-14beta-hydroxypregn-5-en-20-one (2) on the basis of spectroscopic studies and conversion to known compounds. Compounds 1 and 2 were also isolated from H. pilifera. Compound 1 was tested for its appetite suppressant properties in rats by oral gavage at 6.25-50 mg/kg and the results showed that all doses resulted in a decrease of food consumption over an eight day period and a body mass decrease when compared to the control sample receiving only the vehicle. In a comparative study against a fenfluramine control sample, compound 1 resulted in a reduction in food intake over the study period, with a concomitant overall decrease in body weight while fenfluramine resulted in a small decrease in food intake, but an increase in body weight (though less than control group) over the same period of time.

  15. Suppressive effects of ketamine on macrophage functions

    SciTech Connect

    Chang Yi; Chen, T.-L.; Sheu, J.-R.; Chen, R.-M. . E-mail: rmchen@tmu.edu.tw

    2005-04-01

    Ketamine is an intravenous anesthetic agent. Clinically, induction of anesthesia with ketamine can cause immunosuppression. Macrophages play important roles in host defense. In this study, we attempted to evaluate the effects of ketamine on macrophage functions and its possible mechanism using mouse macrophage-like Raw 264.7 cells as the experimental model. Exposure of macrophages to 10 and 100 {mu}M ketamine, which correspond to 0.1 and 1 times the clinically relevant concentration, for 1, 6, and 24 h had no effect on cell viability or lactate dehydrogenase release. When the administered concentration reached 1000 {mu}M, ketamine caused a release of lactate dehydrogenase and cell death. Ketamine, at 10 and 100 {mu}M, did not affect the chemotactic activity of macrophages. Administration of 1000 {mu}M ketamine in macrophages resulted in a decrease in cell migration. Treatment of macrophages with ketamine reduced phagocytic activities. The oxidative ability of macrophages was suppressed by ketamine. Treatment with lipopolysaccharide induced TNF-{alpha}, IL-1{beta}, and IL-6 mRNA in macrophages. Administration of ketamine alone did not influence TNF-{alpha}, IL-1{beta}, or IL-6 mRNA production. Meanwhile, cotreatment with ketamine and lipopolysaccharide significantly inhibited lipopolysaccharide-induced TNF-{alpha}, IL-1{beta}, and IL-6 mRNA levels. Exposure to ketamine led to a decrease in the mitochondrial membrane potential. However, the activity of mitochondrial complex I NADH dehydrogenase was not affected by ketamine. This study shows that a clinically relevant concentration of ketamine (100 {mu}M) can suppress macrophage function of phagocytosis, its oxidative ability, and inflammatory cytokine production possibly via reduction of the mitochondrial membrane potential instead of direct cellular toxicity.

  16. SUPPRESSION OF STAR FORMATION IN NGC 1266

    SciTech Connect

    Alatalo, Katherine; Lanz, Lauranne; Bitsakis, Theodoros; Appleton, Philip N.; Ogle, Patrick M.; Lacy, Mark; Lonsdale, Carol J.; Nyland, Kristina; Meier, David S.; Cales, Sabrina L.; Chang, Philip; Davis, Timothy A.; De Zeeuw, P. T.; Martín, Sergio

    2015-01-01

    NGC 1266 is a nearby lenticular galaxy that harbors a massive outflow of molecular gas powered by the mechanical energy of an active galactic nucleus (AGN). It has been speculated that such outflows hinder star formation (SF) in their host galaxies, providing a form of feedback to the process of galaxy formation. Previous studies, however, indicated that only jets from extremely rare, high-power quasars or radio galaxies could impart significant feedback on their hosts. Here we present detailed observations of the gas and dust continuum of NGC 1266 at millimeter wavelengths. Our observations show that molecular gas is being driven out of the nuclear region at M-dot {sub out}≈110 M{sub ⊙} yr{sup –1}, of which the vast majority cannot escape the nucleus. Only 2 M {sub ☉} yr{sup –1} is actually capable of escaping the galaxy. Most of the molecular gas that remains is very inefficient at forming stars. The far-infrared emission is dominated by an ultra-compact (≲ 50 pc) source that could either be powered by an AGN or by an ultra-compact starburst. The ratio of the SF surface density (Σ{sub SFR}) to the gas surface density (Σ{sub H{sub 2}}) indicates that SF is suppressed by a factor of ≈50 compared to normal star-forming galaxies if all gas is forming stars, and ≈150 for the outskirt (98%) dense molecular gas if the central region is powered by an ultra-compact starburst. The AGN-driven bulk outflow could account for this extreme suppression by hindering the fragmentation and gravitational collapse necessary to form stars through a process of turbulent injection. This result suggests that even relatively common, low-power AGNs are able to alter the evolution of their host galaxies as their black holes grow onto the M-σ relation.

  17. Suppression of human spermatogenesis by testosterone implants.

    PubMed

    Handelsman, D J; Conway, A J; Boylan, L M

    1992-11-01

    Hormonally induced azoospermia is an effective, reversible form of male contraception; however, some men treated with weekly im testosterone enanthate (TE) injections fail to become azoospermic. As weekly injections cause widely fluctuating and supraphysiological testosterone levels, we tested the hypothesis that more stable, physiological testosterone levels would consistently produce azoospermia. Using a depot testosterone formulation which provides stable, physiological range testosterone levels for up to 6 months, we studied nine men before and after insertion of six 200 mg testosterone implants under the abdominal wall skin and compared the results with 38 men treated in a previous study with weekly im injections of 200 mg TE. Testosterone implants suppressed sperm output to near-azoospermia between the second to fourth postimplant months returning to normal by the sixth postimplant month. The fall in sperm output at the first month was greater after testosterone implants than TE injections (58% vs. 17%, P = 0.011) but similar proportions of men became azoospermic (5/9 vs. 25/38) or severely oligozoospermic (< 1 million/ml; 9/9 vs. 37/38). Plasma testosterone and estradiol levels remained mostly within the eugonadal range after implants but were markedly supraphysiological during TE injections. Both treatments suppressed immunoreactive LH and FSH to undetectable levels by ultrasensitive fluoroimmunoassay. Sex hormone-binding globulin levels were decreased and PRL levels increased by TE injections but neither was changed by testosterone implants. Prostate-specific antigen demonstrated a small rise of marginal significance (P = 0.065) after testosterone implants. Fewer men experienced acne after implants (0/9 vs. 25/38, p = 0.0004). Therefore a depot testosterone preparation with quasi-zero-order release demonstrates higher dose efficiency with similar (but not uniform) efficacy at inducing azoospermia but may cause fewer androgenic side-effects than weekly TE

  18. Range sidelobe suppression in wideband phased array radars

    NASA Astrophysics Data System (ADS)

    Belcher, Melvin L., Jr.; Moss, Karen M.

    The authors delineate some considerations in achieving RSL (range sidelobe) suppression in wideband phased arrays. Attention is given to wideband radar characteristics suppression of spurious signals, and sources of wideband RSLs. It is suggested that the parallelism associated with the transmitter and antenna paths should mitigate associated uncorrelated time-varying error modulation. The exciter can be a major RSL contributor unless spurious signal suppression with the SSBM (single sideband modulator) is emphasized in design and calibration procedures.

  19. Proof Testing of a Candidate Category 3 Suppressive Shield

    DTIC Science & Technology

    1976-08-01

    Susquehanna Instruments ST-2 piezoelectric transducers were used to measure blast pressure external to the shield at ground level. The ST-2...Calibration of Side-on Blast Pressure Measurements 12 Category 3 Suppressive Shield Explosive Containment Tests, Instrumental Details 13 Category...3 Suppressive Shield Test Bl-1 Side-on Blast Pressure Measurements 27 Categroy 3 Suppressive Shield Tests B2-1 and B2-2 Side-on Blast Pressure

  20. Suppression of Density Fluctuations in a Quantum Degenerate Fermi Gas

    SciTech Connect

    Sanner, Christian; Su, Edward J.; Keshet, Aviv; Gommers, Ralf; Shin, Yong-il; Huang Wujie; Ketterle, Wolfgang

    2010-07-23

    We study density profiles of an ideal Fermi gas and observe Pauli suppression of density fluctuations (atom shot noise) for cold clouds deep in the quantum degenerate regime. Strong suppression is observed for probe volumes containing more than 10 000 atoms. Measuring the level of suppression provides sensitive thermometry at low temperatures. After this method of sensitive noise measurements has been validated with an ideal Fermi gas, it can now be applied to characterize phase transitions in strongly correlated many-body systems.

  1. Tactical Checkpoint: Hail/Warn Suppress/Stop (Briefing Charts)

    DTIC Science & Technology

    2010-11-15

    U.S. Army Research, Development and Engineering Command Tactical Checkpoint: Hail/Warn Suppress /Stop Target Behavioral Response Laboratory... SUPPRESS /STOP Presented at the 2010 Directed Energies Professional Society Meeting, 15-19 November 2010. 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c...driver that is approaching a checkpoint. The laser, MCNC light, and the windshield obscuration were evaluated for their suppression capabilities (ability

  2. Methods for suppressing isomerization of olefin metathesis products

    DOEpatents

    Firth, Bruce E.; Kirk, Sharon E.; Gavaskar, Vasudeo S.

    2015-09-22

    A method for suppressing isomerization of an olefin metathesis product produced in a metathesis reaction includes adding an isomerization suppression agent to a mixture that includes the olefin metathesis product and residual metathesis catalyst from the metathesis reaction under conditions that are sufficient to passivate at least a portion of the residual metathesis catalyst. The isomerization suppression agent is phosphorous acid, a phosphorous acid ester, phosphinic acid, a phosphinic acid ester or combinations thereof. Methods of refining natural oils are described.

  3. Optimal Tuning for Disturbance Suppression Mechanism for Model Predictive Control

    NASA Astrophysics Data System (ADS)

    Tange, Yoshio; Nakazawa, Chikashi

    Disturbance suppression is one of most required performances in process control. We recently proposed a new disturbance suppression mechanism applicable for model predictive control in order to enhance disturbance suppression performance for ramp-like disturbances. The proposed method utilized the prediction error of controlled values and generates a disturbance compensation signal by a constant gain feedback. In this paper, we propose an improved version of the disturbance suppression mechanism by applying a low-pass filter and parameter tuning methods by which we can make the mechanism more tolerant to various disturbances such as ramp, step, and other supposable ones. We also show numerical simulation results with an oil distillation tower plant.

  4. To suppress, or not to suppress? That is repression: controlling intrusive thoughts in addictive behaviour.

    PubMed

    Moss, Antony C; Erskine, James A K; Albery, Ian P; Allen, James Richard; Georgiou, George J

    2015-05-01

    Research to understand how individuals cope with intrusive negative or threatening thoughts suggests a variety of different cognitive strategies aimed at thought control. In this review, two of these strategies--thought suppression and repressive coping--are discussed in the context of addictive behaviour. Thought suppression involves conscious, volitional attempts to expel a thought from awareness, whereas repressive coping, which involves the avoidance of thoughts without the corresponding conscious intention, appears to be a far more automated process. Whilst there has been an emerging body of research exploring the role of thought suppression in addictive behaviour, there remains a dearth of research which has considered the role of repressive coping in the development of, and recovery from, addiction. Based on a review of the literature, and a discussion of the supposed mechanisms which underpin these strategies for exercising mental control, a conceptual model is proposed which posits a potential common mechanism. This model makes a number of predictions which require exploration in future research to fully understand the cognitive strategies utilised by individuals to control intrusive thoughts related to their addictive behaviour.

  5. Chronic Juvenile Delinquency and the "Suppression Effect": An Exploratory Study.

    ERIC Educational Resources Information Center

    Fraser, Mark; Norman, Michael

    1988-01-01

    Notes that fear of apprehension and punishment have been reported to suppress juvenile crime. Discusses suppression effect in regard to the correlates of chronic juvenile delinquency and exploratory evidence that youth who commit large volume of crime do not fear sanctions imposed by juvenile court any more than youth who commit only one offense…

  6. Social hierarchy and depression: the role of emotion suppression.

    PubMed

    Langner, Carrie A; Epel, Elissa S; Matthews, Karen A; Moskowitz, Judith T; Adler, Nancy E

    2012-01-01

    Position in the social hierarchy is a major determinant of health outcomes. We examined the associations between aspects of social hierarchy and depressive symptoms with a specific focus on one potential psychological mechanism: emotion suppression. Suppressing negative emotion has mental health costs, but individuals with low social power and low social status may use these strategies to avoid conflict. Study 1 assessed perceived social power, tendency to suppress negative emotion, and depressive symptoms in a community sample of women. Low social power was related to greater depressive symptoms, and this relationship was partially mediated by emotion suppression. Study 2 examined education as a proxy for social hierarchy position, anger suppression, and depressive symptoms in a national, longitudinal cohort study (The coronary artery risk development in young adults [CARDIA] study; Cutter et al., 1991). Much as in study 1, low education levels were correlated with greater depressive symptoms, and this relationship was partially mediated by anger suppression. Further, suppression mediated the relationship between low education and subsequent depression up to 15 years later. These findings support the theory that social hierarchy affects mental health in part through a process of emotion suppression.

  7. 48 CFR 452.236-78 - Fire Suppression and Liability.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Fire Suppression and... Fire Suppression and Liability. As prescribed in § 436.578, the following clause may be inserted in contracts awarded for Integrated Resource Service Contracts (IRSC) awarded for the Forest Service....

  8. Preliminary Evidence for Reduced Auditory Lateral Suppression in Schizophrenia

    PubMed Central

    Ramage, Erin. M.; Weintraub, David M.; Vogel, Sally J.; Sutton, Griffin P.; Ringdahl, Erik N.; Allen, Daniel N.; Snyder, Joel S.

    2014-01-01

    Background Well-documented auditory processing deficits such as impaired frequency discrimination and reduced suppression of auditory brain responses in schizophrenia (SZ) may contribute to abnormal auditory functioning in everyday life. Lateral suppression of non-stimulated neurons by stimulated neurons has not been extensively assessed in SZ and likely plays an important role in precise encoding of sounds. Therefore, this study evaluated whether lateral suppression of activity in auditory cortex is impaired in SZ. Methods SZ participants and control participants watched a silent movie with subtitles while listening to trials composed of a 0.5 s control stimulus (CS), a 3 s filtered masking noise (FN), and a 0.5 s test stimulus (TS). The CS and TS were identical on each trial and had energy corresponding to the high energy (recurrent suppression) or low energy (lateral suppression) portions of the FN. Event-related potentials were recorded and suppression was measured as the amplitude change between CS and TS. Results Peak amplitudes of the auditory P2 component (160–260 ms) showed reduced lateral but not recurrent suppression in SZ participants. Conclusions Reduced lateral suppression in SZ participants may lead to overlap of neuronal populations representing different auditory stimuli. Such imprecise neural representations may contribute to the difficulties SZ participants have in discriminating complex stimuli in everyday life. PMID:25583249

  9. Thought Suppression and Meaning in Life: A Longitudinal Investigation

    ERIC Educational Resources Information Center

    Krause, Neal

    2007-01-01

    The purpose of this study is to see if older adults who experience problems with thought suppression tend to encounter greater difficulty deriving a sense of meaning in life. Data from a longitudinal nationwide survey of older people (N = 988) indicate that greater difficulty with thought suppression is associated with a decline in meaning over…

  10. Eye Contact Facilitates Awareness of Faces during Interocular Suppression

    ERIC Educational Resources Information Center

    Stein, Timo; Senju, Atsushi; Peelen, Marius V.; Sterzer, Philipp

    2011-01-01

    Eye contact captures attention and receives prioritized visual processing. Here we asked whether eye contact might be processed outside conscious awareness. Faces with direct and averted gaze were rendered invisible using interocular suppression. In two experiments we found that faces with direct gaze overcame such suppression more rapidly than…

  11. POTENTIAL ENVIRONMENTAL IMPACTS OF DUST SUPPRESSANTS: "ADVOIDING ANOTHER TIMES BEACH"

    EPA Science Inventory

    In the past decade, there has been an increased use of chemical dust suppressants such as i water, salts, asphalt emulsion, vegetable oils, molasses, synthetic polymers, mulches, and lignin 1 products. Dust suppressants abate dust by changing the physical properties of the soil s...

  12. 30 CFR 75.1107 - Fire suppression devices.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... approved by the Secretary shall be used in the hydraulic systems of such equipment. Such fluids shall be used in the hydraulic systems of other underground equipment unless fire suppression devices meeting... Fire-Resistant Hydraulic Fluids on Underground Equipment § 75.1107 Fire suppression devices. On...

  13. 30 CFR 75.1107 - Fire suppression devices.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... approved by the Secretary shall be used in the hydraulic systems of such equipment. Such fluids shall be used in the hydraulic systems of other underground equipment unless fire suppression devices meeting... Fire-Resistant Hydraulic Fluids on Underground Equipment § 75.1107 Fire suppression devices. On...

  14. 14 CFR 460.13 - Smoke detection and fire suppression.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Smoke detection and fire suppression. 460.13 Section 460.13 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION... Crew § 460.13 Smoke detection and fire suppression. An operator or crew must have the ability to...

  15. 14 CFR 460.13 - Smoke detection and fire suppression.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Smoke detection and fire suppression. 460.13 Section 460.13 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION... Crew § 460.13 Smoke detection and fire suppression. An operator or crew must have the ability to...

  16. Suppression of ultrafast supercontinuum generation in a salivary protein.

    PubMed

    Santhosh, Chidangil; Dharmadhikari, Aditya K; Alti, Kamlesh; Dharmadhikari, Jayashree A; Mathur, Deepak

    2007-01-01

    The first studies of the propagation of ultrafast (<45 fs) pulses of intense infrared light through protein media reveal that supercontinuum (white light) generation is severely suppressed in the presence of the protein alpha-amylase, a potential stress marker in human saliva. The continuum suppression capacity is attributed to the electron scavenging property of the protein.

  17. Social Hierarchy and Depression: The Role of Emotion Suppression

    PubMed Central

    Langner, Carrie A.; Epel, Elissa; Matthews, Karen; Moskowitz, Judith T.; Adler, Nancy

    2017-01-01

    Position in the social hierarchy is a major determinant of health outcomes. We examined the associations between aspects of social hierarchy and depressive symptoms with a specific focus on one potential psychological mechanism: emotion suppression. Suppressing negative emotion has mental health costs, but individuals with low social power and low social status may use these strategies to avoid conflict. Study 1 assessed perceived social power, tendency to suppress negative emotion, and depressive symptoms in a community sample of women. Low social power was related to greater depressive symptoms, and this relationship was partially mediated by emotion suppression. Study 2 examined education as a proxy for social hierarchy position, anger suppression, and depressive symptoms in a national, longitudinal cohort study (The Coronary Artery Risk Development in Young Adults (CARDIA) study). Similar to Study 1, low education levels were correlated with greater depressive symptoms, and this relationship was partially mediated by anger suppression. Further, suppression mediated the relationship between low education and subsequent depression up to 15 years later. These findings support the theory that social hierarchy affects mental health in part through a process of emotion suppression. PMID:22808688

  18. Suppressive mechanisms in visual motion processing: from perception to intelligence

    PubMed Central

    Tadin, Duje

    2015-01-01

    Perception operates on an immense amount of incoming information that greatly exceeds the brain's processing capacity. Because of this fundamental limitation, the ability to suppress irrelevant information is a key determinant of perceptual efficiency. Here, I will review a series of studies investigating suppressive mechanisms in visual motion processing, namely perceptual suppression of large, background-like motions. These spatial suppression mechanisms are adaptive, operating only when sensory inputs are sufficiently robust to guarantee visibility. Converging correlational and causal evidence links these behavioral results with inhibitory center-surround mechanisms, namely those in cortical area MT. Spatial suppression is abnormally weak in several special populations, including the elderly and those with schizophrenia—a deficit that is evidenced by better-than-normal direction discriminations of large moving stimuli. Theoretical work shows that this abnormal weakening of spatial suppression should result in motion segregation deficits, but direct behavioral support of this hypothesis is lacking. Finally, I will argue that the ability to suppress information is a fundamental neural process that applies not only to perception but also to cognition in general. Supporting this argument, I will discuss recent research that shows individual differences in spatial suppression of motion signals strongly predict individual variations in IQ scores. PMID:26299386

  19. Ejector Noise Suppression with Auxiliary Jet Injection

    NASA Technical Reports Server (NTRS)

    Berman, Charles H.; Andersen, Otto P., Jr.

    1997-01-01

    An experimental program to reduce aircraft jet turbulence noise investigated the interaction of small auxiliary jets with a larger main jet. Significant reductions in the far field jet noise were obtained over a range of auxiliary jet pressures and flow rates when used in conjunction with an acoustically lined ejector. While the concept is similar to that of conventional ejector suppressors that use mechanical mixing devices, the present approach should improve thrust and lead to lower weight and less complex noise suppression systems since no hardware needs to be located in the main jet flow. A variety of auxiliary jet and ejector configurations and operating conditions were studied. The best conditions tested produced peak to peak noise reductions ranging from 11 to 16 dB, depending on measurement angle, for auxiliary jet mass flows that were 6.6% of the main jet flow with ejectors that were 8 times the main jet diameter in length. Much larger reductions in noise were found at the original peak frequencies of the unsuppressed jet over a range of far field measurement angles.

  20. Harnessing Regulatory T cells to Suppress Asthma

    PubMed Central

    Thorburn, Alison N.; Hansbro, Philip M.

    2010-01-01

    Regulatory T cells (Tregs) play an essential role in maintaining the homeostatic balance of immune responses. Asthma is an inflammatory condition of the airways that is driven by dysregulated immune responses toward normally innocuous antigens. Individuals with asthma have fewer and less functional Tregs, which may lead to uncontrolled effector cell responses and promote proasthmatic responses of T helper type 2, T helper 17, natural killer T, antigen-presenting, and B cells. Tregs have the capacity to either directly or indirectly suppress these responses. Hence, the induced expansion of functional Tregs in predisposed or individuals with asthma is a potential approach for the prevention and treatment of asthma. Infection by a number of micro-organisms has been associated with reduced prevalence of asthma, and many infectious agents have been shown to induce Tregs and reduce allergic airways disease in mouse models. The translation of the regulatory and therapeutic properties of infectious agents for use in asthma requires the identification of key modulatory components and the development and trial of effective immunoregulatory therapies. Further translational and clinical research is required for the induction of Tregs to be harnessed as a therapeutic strategy for asthma. PMID:20097830

  1. A Mathematical Model for Suppression Subtractive Hybridization

    PubMed Central

    Gadgil, Chetan; Rink, Anette; Beattie, Craig

    2002-01-01

    Suppression subtractive hybridization (SSH) is frequently used to unearth differentially expressed genes on a whole-genome scale. Its versatility is based on combining cDNA library subtraction and normalization, which allows the isolation of sequences of varying degrees of abundance and differential expression. SSH is a complex process with many adjustable parameters that affect the outcome of gene isolation.We present a mathematical model of SSH based on DNA hybridization kinetics for assessing the effect of various parameters to facilitate its optimization. We derive an equation for the probability that a particular differentially expressed species is successfully isolated and use this to quantify the effect of the following parameters related to the cDNA sample: (a) mRNA abundance; (b) partial sequence complementarity to other species; and (3) degree of differential expression. We also evaluate the effect of parameters related to the process, including: (a) reaction times; and (b) extent of driver excess used in the two hybridization reactions. The optimum set of process parameters for successful isolation of differentially expressed species depends on transcript abundance. We show that the reaction conditions have a significant effect on the occurrence of false-positives and formulate strategies to isolate specific subsets of differentially expressed genes. We also quantify the effect of non-specific hybridization on the false-positive results and present strategies for spiking cDNA sequences to address this problem. PMID:18629052

  2. Method for suppressing noise in measurements

    NASA Technical Reports Server (NTRS)

    Carson, Paul L. (Inventor); Madsen, Louis A. (Inventor); Leskowitz, Garett M. (Inventor); Weitekamp, Daniel P. (Inventor)

    2000-01-01

    Methods for suppressing noise in measurements by correlating functions based on at least two different measurements of a system at two different times. In one embodiment, a measurement operation is performed on at least a portion of a system that has a memory. A property of the system is measured during a first measurement period to produce a first response indicative of a first state of the system. Then the property of the system is measured during a second measurement period to produce a second response indicative of a second state of the system. The second measurement is performed after an evolution duration subsequent to the first measurement period when the system still retains a degree of memory of an aspect of the first state. Next, a first function of the first response is combined with a second function of the second response to form a second-order correlation function. Information of the system is then extracted from the second-order correlation function.

  3. 't Hooft suppression and holographic entropy

    NASA Astrophysics Data System (ADS)

    Kelly, William R.; Kuns, Kevin; Marolf, Donald

    2015-10-01

    Recent works have related the bulk first law of black hole mechanics to the first law of entanglement in a dual CFT. These are first order relations, and receive corrections for finite changes. In particular, the latter is naively expected to be accurate only for small changes in the quantum state. But when Newton's constant is small relative to the AdS scale, the former holds to good approximation even for classical perturbations that contain many quanta. This suggests that — for appropriate states — corrections to the first law of entanglement are suppressed by powers of N in CFTs whose correlators satisfy 't Hooft large- N power counting. We take first steps toward verifying that this is so by studying the large- N structure of the entropy of spatial regions for a class of CFT states motivate dby those created from the vacuum by acting with real-time single-trace sources. We show that 1 /N counting matches bulk predictions, though we require the effect of the source on the modular hamiltonian to be non-singular. The magnitude of our sources is ɛ N with ɛ fixed-but-small as N → ∞. Our results also provide a perturbative derivation — without relying on the replica trick — of the subleading Faulkner-Lewkowycz-Maldacena correction to the Ryu-Takayagi and Hubeny-Rangamani-Takayanagi conjectures at all orders in 1 /N.

  4. Contrast, induction, facilitation, suppression, and conservation1

    PubMed Central

    Allison, James

    1976-01-01

    Ten rats received all of their water in daily 1-hr sessions. Following a baseline phase in which lever and water spout were freely available throughout each session, subjects were trained to press the lever for water on mixed schedules composed of two alternating components. Each component gave access to water for a fixed cumulation of drinking time every time the rat cumulated a fixed amount of lever-pressing time. Changes in one component produced contrast and induction effects, both positive and negative, with respect to both lever pressing and drinking in the unchanged component. All schedules facilitated lever pressing relative to baseline. All schedules suppressed drinking relative to baseline, even though contingency sessions allowed ample time to perform the baseline amount of drinking. The entire pattern of results was predicted in quantitative detail by assuming that the total amount of a dimension apportioned to lever pressing and drinking is conserved between baseline and contingency sessions. Conservation theory was shown to predict several effects produced by simple fixed-ratio schedules, and was compared favorably with probability-differential (Premack, 1971) and response-deprivation (Timberlake and Allison, 1974) theory. PMID:16811902

  5. Ribavirin efficiently suppresses porcine nidovirus replication.

    PubMed

    Kim, Youngnam; Lee, Changhee

    2013-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine epidemic diarrhea virus (PEDV) are porcine nidoviruses that represent emerging viral pathogens causing heavy economic impacts on the swine industry. Although ribavirin is a well-known antiviral drug against a broad range of both DNA and RNA viruses in vitro, its inhibitory effect and mechanism of action on porcine nidovirus replication remains to be elucidated. Therefore, the present study was conducted to determine whether ribavirin suppresses porcine nidovirus infection. Our results demonstrated that ribavirin treatment dose-dependently inhibited the replication of both nidoviruses. The antiviral activity of ribavirin on porcine nidovirus replication was found to be primarily exerted at early times post-infection. Treatment with ribavirin resulted in marked reduction of viral genomic and subgenomic RNA synthesis, viral protein expression, and progeny virus production in a dose-dependent manner. Investigations into the mechanism of action of ribavirin against PRRSV and PEDV revealed that the addition of guanosine to the ribavirin treatment significantly reversed the antiviral effects, suggesting that depletion of the intracellular GTP pool by inhibiting IMP dehydrogenase may be essential for ribavirin activity. Further sequencing analysis showed that the mutation frequency in ribavirin-treated cells was similar to that in untreated cells, indicating that ribavirin did not induce error-prone replication. Taken together, our data indicate that ribavirin might not only be a good therapeutic agent against porcine nidovirus, but also a potential candidate to be evaluated against other human and animal coronaviruses.

  6. Clutter suppression interferometry system design and processing

    NASA Astrophysics Data System (ADS)

    Knight, Chad; Deming, Ross; Gunther, Jake

    2015-05-01

    Clutter suppression interferometry (CSI) has received extensive attention due to its multi-modal capability to detect slow-moving targets, and concurrently form high-resolution synthetic aperture radar (SAR) images from the same data. The ability to continuously augment SAR images with geo-located ground moving target indicators (GMTI) provides valuable real-time situational awareness that is important for many applications. CSI can be accomplished with minimal hardware and processing resources. This makes CSI a natural candidate for applications where size, weight and power (SWaP) are constrained, such as unmanned aerial vehicles (UAVs) and small satellites. This paper will discuss the theory for optimal CSI system configuration focusing on sparse time-varying transmit and receive array manifold due to SWaP considerations. The underlying signal model will be presented and discussed as well as the potential benefits that a sparse time-varying transmit receive manifold provides. The high-level processing objectives will be detailed and examined on simulated data. Then actual SAR data collected with the Space Dynamic Laboratory (SDL) FlexSAR radar system will be analyzed. The simulated data contrasted with actual SAR data helps illustrate the challenges and limitations found in practice vs. theory. A new novel approach incorporating sparse signal processing is discussed that has the potential to reduce false- alarm rates and improve detections.

  7. The SSM with Suppressed SUSY Charge

    NASA Astrophysics Data System (ADS)

    Dixon, John A.

    2016-10-01

    The concept of Suppressed SUSY Charge, introduced in a recent Letter, is used here to assemble a new version of the SSM. This new SSM has no need for Squarks or Sleptons. It does not need spontaneous breaking of SUSY, so that the cosmological constant problem does not arise (at least at tree level). It mimics the usual non-supersymmetric Standard Model very well, and the absence of large flavour changing neutral currents is natural. There is no need for a hidden sector, or a messenger sector, or explicit 'soft' breaking of SUSY. Spontaneous Gauge Symmetry Breaking from SU (3) × SU (2) × U (1) to SU (3) × U (1) in the model assembled here implies the existence of two new very heavy Higgs Bosons with mass 13.4 TeV, slightly smaller than the energy of the LHC at 14 TeV. There is also a curious set of Gauginos and Higgsinos which have exactly the same masses as the Higgs and Gauge Bosons. These do not couple to the Quarks and Leptons, except through the Higgs and Gauge Bosons. As it stands, this model probably gives rise to too many W+ decays to be consistent with experiment. The Feynman loop expansion of this theory also needs further examination.

  8. Heavy quarkonium suppression in a fireball

    SciTech Connect

    Escobedo, Miguel Ángel

    2016-01-22

    The dissociation of heavy quarkonium seen in heavy-ion collisions is a phenomena that allows to extract information of the produced thermal medium. This was believed to be due to the screening of the static potential but recently perturbative computations and some lattice studies have pointed out the possibility of having an imaginary part of the potential that would also contribute to dissociation. In recent years a program to study heavy quarkonium with the use of non-relativistic effective field theories (EFTs) has been started, this allows to make the computations in a more systematic way by defining a more suitable power counting and making it more difficult to miss necessary resummations. However until now these studies have been done assuming thermal equilibrium. In this work we will discuss what happens in the EFT formalism when heavy quarkonium is in a medium that is not in thermal equilibrium and what is the expected suppression when a medium with a time dependent effective temperature that follows Bjorken evolution is considered. This will be done adapting previous results from different temperature regimes.

  9. Growth suppression in the Trichuris dysentery syndrome.

    PubMed

    Cooper, E S; Bundy, D A; MacDonald, T T; Golden, M H

    1990-04-01

    The Trichuris Dysentery Syndrome (Ramsey, 1962) is an insidious, chronic condition which has clinical features similar to Crohn's ileocolitis and ulcerative colitis, diseases similarly associated with growth retardation. The attained heights and weights of 19 children at the time of diagnosis of intens, -2.4 Standard Deviation (Z) scores from the Tanner-Whitehouse median with weight, adjusted for height-age, -1.3 Z. We present data on the growth velocities of 11 of the children in the half-year following worm expulsion by mebendazole. These children returned to their home environments without food supplementation or close follow-up, but showed an average height velocity of +5.5 Z and weight velocity (for height-age) of +2.4 Z. Of 8 children with unequivocal height spurts only 3 had any weight spurt. We suggest that the pattern of catch-up growth points to the existence of some specific link between allergy or inflammation in the lower intestinal tract and suppression of linear growth, rather than to stunting due to general deprivation and undernutrition.

  10. Evolution of cancer suppression as revealed by mammalian comparative genomics.

    PubMed

    Tollis, Marc; Schiffman, Joshua D; Boddy, Amy M

    2017-02-02

    Cancer suppression is an important feature in the evolution of large and long-lived animals. While some tumor suppression pathways are conserved among all multicellular organisms, others mechanisms of cancer resistance are uniquely lineage specific. Comparative genomics has become a powerful tool to discover these unique and shared molecular adaptations in respect to cancer suppression. These findings may one day be translated to human patients through evolutionary medicine. Here, we will review theory and methods of comparative cancer genomics and highlight major findings of cancer suppression across mammals. Our current knowledge of cancer genomics suggests that more efficient DNA repair and higher sensitivity to DNA damage may be the key to tumor suppression in large or long-lived mammals.

  11. Active flutter suppression - Control system design and experimental validation

    NASA Technical Reports Server (NTRS)

    Waszak, Martin R.; Srinathkumar, S.

    1991-01-01

    The synthesis and experimental validation of an active flutter suppression controller for the Active Flexible Wing wind-tunnel model is presented. The design is accomplished with traditional root locus and Nyquist methods using interactive computer graphics tools and with extensive use of simulation-based analysis. The design approach uses a fundamental understanding of the flutter mechanism to formulate a simple controller structure to meet stringent design specifications. Experimentally, the flutter suppression controller succeeded in simultaneous suppression of two flutter modes, significantly increasing the flutter dynamic pressure despite errors in flutter dynamic pressure and flutter frequency in the mathematical model. The flutter suppression controller was also successfully operated in combination with a roll maneuver controller to perform flutter suppression during rapid rolling maneuvers.

  12. Physical work causes suppression of ovarian function in women.

    PubMed Central

    Jasieńska, G; Ellison, P T

    1998-01-01

    The suppression of reproductive function is known to occur in women engaging in activities that require high energetic expenses, such as sport participation and subsistence work. It is still unclear, however, if reproductive suppression is a response to high levels of energy expenditure, or only to the resulting state of negative energy balance. To our knowledge, this study provides the first evidence that work-related energy expenditure alone, without associated negative energy balance, can lead to the suppression of reproductive function in women. We document suppression of ovarian function expressed as lowered salivary progesterone levels in women from an agricultural community who work hard, but remain in neutral energy balance. We propose two alternative evolutionary explanations (the 'pre-emptive ovarian suppression' hypothesis and the 'constrained down-regulation' hypothesis) for the observed results. PMID:9802241

  13. An electrophysiological assessment of distractor suppression in visual search tasks.

    PubMed

    Mazza, Veronica; Turatto, Massimo; Caramazza, Alfonso

    2009-07-01

    We investigated whether the N2pc is unequivocally linked to distractor-suppression mechanisms, as is commonly assumed. According to the distractor-suppression account of the N2pc, no suppression, and thus no N2pc, should occur when homogeneous distractors help in selecting the target, such as when the target feature is unpredictable. Participants performed a simple detection or a finer discrimination on a singleton target, which had either a variable or a constant color. Contrary to the distractor-suppression account, an N2pc was present for both the variable and the constant conditions, and for both tasks. Additionally, target feature consistency correlated with earlier N2pc onsets relative to variable blocks. Both results indicate that the N2pc is not unequivocally linked to distractor-suppression mechanisms, but may index mechanisms involved in identifying and localizing relevant stimuli through enhancement of their features.

  14. Attenuating social affective learning effects with Memory Suppression manipulations.

    PubMed

    Molet, Mikael; Kosinski, Thierry; Craddock, Paul; Miguez, Gonzalo; Mash, Lisa E; Miller, Ralph R

    2016-02-01

    People can form opinions of other individuals based on information about their good or bad behavior. The present study investigated whether this affective learning might depend on memory links formed between initially neutral people and valenced information. First, participants viewed neutral faces paired with sentences describing prosocial or antisocial behaviors. Second, memory suppression manipulations with the potential to aid in the forgetting of valenced information were administered. Using the Think/No think paradigm, the effectiveness of four different suppression instructions was compared: Unguided Suppression, Guided Suppression, Distraction, and Thought Substitution. Overall, all the tasks appreciably reduced affective learning based on prosocial information, but only the Guided Suppression and Thought Substitution tasks reduced affective learning based on antisocial information. These results suggest that weakening the putative memory link between initially neutral people and valenced information can decrease the effect of learned associations on the evaluation of other people. We interpreted this as indicative that social affective learning may rely on declarative memories.

  15. Suppression of Antigen-Specific Lymphocyte Activation in Simulated Microgravity

    NASA Technical Reports Server (NTRS)

    Cooper, David; Pride, Michael W.; Brown, Eric L.; Risin, Diana; Pellis, Neal R.

    1999-01-01

    Various parameters of immune suppression are observed in astronauts during and after spaceflight, and in isolated immune cells in true and simulated microgravity. Specifically, polyclonal activation of T cells is severely suppressed in true and simulated microgravity. These recent findings with various polyclonal activators suggests a suppression of oligoclonal lymphocyte activation in microgravity. We utilized rotating wall vessel (RWV) bioreactors that simulate aspects of microgravity for cell cultures to analyze three models of antigen-specific activation. A mixed-lymphocyte reaction (MLR), as a model for a primary immune response; a tetanus toxoid (TT) response and a B. burgdorferi (Bb) response, as models of a secondary immune response, were all suppressed in the RWV bioreactor. Our findings confirm that the suppression of activation observed with polyclonal models also encompasses oligoclonal antigen-specific activation.

  16. Cytokine treatment of macrophage suppression of T cell activation.

    PubMed

    Silberman, Daniel; Bucknum, Amanda; Kozlowski, Megan; Matlack, Robin; Riggs, James

    2010-01-01

    High Mphi:T cell ratios suppress the immune response to the retroviral superantigen Mls by IFNgamma-triggered production of the arg- and trp-consuming enzymes iNOS and IDO. Attempts to reverse suppression by treatment with pro-inflammatory cytokines revealed that IL-6 improved the T cell response to Mls and the pro-hematopoietic cyokines IL-3 and GM-CSF increased suppression. GM-CSF treatment increased Mphi expression of CD80, a ligand for the immune suppressive B7H1 and CTLA-4 receptors. These results illustrate potential strategies for reversing the suppression of cell-mediated immunity characteristic of the high Mphi:T cell ratios found in many tumors.

  17. The role of suppression in figurative language comprehension✩

    PubMed Central

    Gemsbacher, Morton Ann; Robertson, Rachel R.W.

    2014-01-01

    In this paper, we describe the crucial role that suppression plays in many aspects of language comprehension. We define suppression as a general, cognitive mechanism, the purpose of which is to attenuate the interference caused by the activation of extraneous, unnecessary, or inappropriate information. We illustrate the crucial role that suppression plays in general comprehension by reviewing numerous experiments. These experiments demonstrate that suppression attenuates interference during lexical access (how word meanings are ‘accessed’), anaphoric reference (how referents for anaphors, like pronouns, are computed), cataphoric reference (how concepts that are marked by devices, such as spoken stress, gain a privileged status), syntactic parsing (how grammatical forms of sentences are decoded), and individual differences in (adult) language comprehension skill. We also review research that suggests that suppression plays a crucial role in the understanding of figurative language, in particular, metaphors, idioms, and proverbs. PMID:25520540

  18. Surround suppression and sparse coding in visual and barrel cortices

    PubMed Central

    Sachdev, Robert N. S.; Krause, Matthew R.; Mazer, James A.

    2012-01-01

    During natural vision the entire retina is stimulated. Likewise, during natural tactile behaviors, spatially extensive regions of the somatosensory surface are co-activated. The large spatial extent of naturalistic stimulation means that surround suppression, a phenomenon whose neural mechanisms remain a matter of debate, must arise during natural behavior. To identify common neural motifs that might instantiate surround suppression across modalities, we review models of surround suppression and compare the evidence supporting the competing ideas that surround suppression has either cortical or sub-cortical origins in visual and barrel cortex. In the visual system there is general agreement lateral inhibitory mechanisms contribute to surround suppression, but little direct experimental evidence that intracortical inhibition plays a major role. Two intracellular recording studies of V1, one using naturalistic stimuli (Haider et al., 2010), the other sinusoidal gratings (Ozeki et al., 2009), sought to identify the causes of reduced activity in V1 with increasing stimulus size, a hallmark of surround suppression. The former attributed this effect to increased inhibition, the latter to largely balanced withdrawal of excitation and inhibition. In rodent primary somatosensory barrel cortex, multi-whisker responses are generally weaker than single whisker responses, suggesting multi-whisker stimulation engages similar surround suppressive mechanisms. The origins of suppression in S1 remain elusive: studies have implicated brainstem lateral/internuclear interactions and both thalamic and cortical inhibition. Although the anatomical organization and instantiation of surround suppression in the visual and somatosensory systems differ, we consider the idea that one common function of surround suppression, in both modalities, is to remove the statistical redundancies associated with natural stimuli by increasing the sparseness or selectivity of sensory responses. PMID:22783169

  19. Growth characteristics of a weed-suppressive indica x non-suppressive tropical japonica rice mapping population

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The indica rice cultivar, PI 312777, can be highly productive as well as suppressive to C4 grass species such as barnyardgrass (Echinochloa crus-galli). A recombinant inbred line (RIL) mapping population was developed using single seed descent from a cross between ‘Katy’ (non-weed-suppressive) and ...

  20. Using Correlated Photons to Suppress Background Noise

    NASA Technical Reports Server (NTRS)

    Jackson, Deborah; Hockney, George; Dowling, Jonathan

    2003-01-01

    A proposed method of suppressing the effect of background noise in an optical communication system would exploit the transmission and reception of correlated photons at the receiver. The method would not afford any advantage in a system in which performance is limited by shot noise. However, if the performance of the system is limited by background noise (e.g., sunlight in the case of a free-space optical communication system or incoherently scattered in-band photons in the case of a fiber-optic communication system), then the proposed method could offer an advantage: the proposed method would make it possible to achieve a signal-to-noise ratio (S/N) significantly greater than that of an otherwise equivalent background- noise-limited optical communication system based on the classical transmission and reception of uncorrelated photons. The figure schematically depicts a classical optical-communication system and a system according to the proposed method. In the classical system, a modulated laser beam is transmitted along an optical path to a receiver, the optics of which include a narrow-band-pass filter that suppresses some of the background noise. A photodetector in the receiver detects the laser-beam and background photons, most or all of which are uncorrelated. In the proposed system, correlated photons would be generated at the transmitter by making a modulated laser beam pass through a nonlinear parametric down-conversion crystal. The sum of frequencies of the correlated photons in each pair would equal the frequency of the incident photon from which they were generated. As in the classical system, the correlated photons would travel along an optical path to a receiver, where they would be band-pass filtered and detected. Unlike in the classical system, the photodetector in the receiver in this system would be one that intrinsically favors the detection of pairs of correlated photons over the detection of uncorrelated photons. Even though there would be no

  1. Suppression of fibroblast proliferation by oral spirochetes.

    PubMed Central

    Boehringer, H; Taichman, N S; Shenker, B J

    1984-01-01

    Soluble sonic extracts of several strains of Treponema denticola and Treponema vincentii were examined for their abilities to alter proliferation of both murine and human fibroblasts. We found that sonic extracts of all tested strains of T. denticola caused a dose-dependent inhibition of murine and human fibroblast proliferation when assessed by both DNA synthesis ([3H]thymidine incorporation) and direct cell counts. T. vincentii had only a minimal inhibitory effect at comparable doses. No inhibition was observed when sonic extracts were added simultaneously with [3H]thymidine, indicating that suppression was not due to the presence of excessive amounts of cold thymidine in the extract, nonspecific effects on thymidine utilization by the cells (transport and incorporation), or degradation of label. RNA ([3H]uridine incorporation) and protein ([3H]leucine incorporation) synthesis were similarly altered after exposure to the T. denticola sonic extracts. There was no effect on cell viability as measured by trypan blue exclusion. Inhibition could be reversed by extensive washing of the cells within the first few hours of exposure to sonic extracts. Preliminary characterization and purification indicated that the inhibitory factor(s) is not endotoxin since it is heat labile, and elutes in a single, well-defined peak on a Sephadex G-150 chromatography column corresponding to a molecular weight of approximately 50,000. Since oral spirochetes have been implicated in the pathogenesis of periodontal disorders, it is possible that they contribute to the disease process by inhibition of fibroblast growth and therefore may, at least in part, account for the loss of collagen seen in diseased tissue. PMID:6735466

  2. Online fluorescence suppression in modulated Raman spectroscopy.

    PubMed

    De Luca, Anna Chiara; Mazilu, Michael; Riches, Andrew; Herrington, C Simon; Dholakia, Kishan

    2010-01-15

    Label-free chemical characterization of single cells is an important aim for biomedical research. Standard Raman spectroscopy provides intrinsic biochemical markers for noninvasive analysis of biological samples but is often hindered by the presence of fluorescence background. In this paper, we present an innovative modulated Raman spectroscopy technique to filter out the Raman spectra from the fluorescence background. The method is based on the principle that the fluorescence background does not change whereas the Raman scattering is shifted by the periodical modulation of the laser wavelength. Exploiting this physical property and importantly the multichannel lock-in detection of the Raman signal, the modulation technique fulfills the requirements of an effective fluorescence subtraction method. Indeed, once the synchronization and calibration procedure is performed, minimal user intervention is required, making the method online and less time-consuming than the other fluorescent suppression methods. We analyze the modulated Raman signal and shifted excitation Raman difference spectroscopy (SERDS) signal of 2 mum-sized polystyrene beads suspended in a solution of fluorescent dye as a function of modulation rate. We show that the signal-to-noise ratio of the modulated Raman spectra at the highest modulation rate is 3 times higher than the SERDS one. To finally evaluate the real benefits of the modulated Raman spectroscopy, we apply our technique to Chinese hamster ovary cells (CHO). Specifically, by analyzing separate spectra from the membrane, cytoplasm, and nucleus of CHO cells, we demonstrate the ability of this method to obtain localized sensitive chemical information from cells, away from the interfering fluorescence background. In particular, statistical analysis of the Raman data and classification using PCA (principal component analysis) indicate that our method allows us to distinguish between different cell locations with higher sensitivity and

  3. Suppression of Insulin Production and Secretion by a Decretin Hormone

    PubMed Central

    Alfa, Ronald W.; Park, Sangbin; Skelly, Kathleen-Rose; Poffenberger, Gregory; Jain, Nimit; Gu, Xueying; Kockel, Lutz; Wang, Jing; Liu, Yinghua; Powers, Alvin C.; Kim, Seung K.

    2015-01-01

    SUMMARY Decretins, hormones induced by fasting that suppress insulin production and secretion, have been postulated from classical human metabolic studies. From genetic screens, we identified Drosophila Limostatin (Lst), a peptide hormone that suppresses insulin secretion. Lst is induced by nutrient restriction in gut-associated endocrine cells. limostatin deficiency led to hyperinsulinemia, hypoglycemia and excess adiposity. A conserved 15-residue polypeptide encoded by limostatin suppressed secretion by insulin-producing cells. Targeted knockdown of CG9918, a Drosophila orthologue of Neuromedin U receptors (NMUR), in insulin-producing cells phenocopied limostatin deficiency, and attenuated insulin suppression by purified Lst, suggesting CG9918 encodes an Lst receptor. NMUR1 is expressed in islet β-cells, and purified NMU suppresses insulin secretion from human islets. A human mutant NMU variant that co-segregates with familial early-onset obesity and hyperinsulinemia fails to suppress insulin secretion. We propose Lst as an index member of an ancient hormone class called decretins, which suppress insulin output. PMID:25651184

  4. fMRI repetition suppression: neuronal adaptation or stimulus expectation?

    PubMed

    Larsson, Jonas; Smith, Andrew T

    2012-03-01

    Measurements of repetition suppression with functional magnetic resonance imaging (fMRI adaptation) have been used widely to probe neuronal population response properties in human cerebral cortex. fMRI adaptation techniques assume that fMRI repetition suppression reflects neuronal adaptation, an assumption that has been challenged on the basis of evidence that repetition-related response changes may reflect unrelated factors, such as attention and stimulus expectation. Specifically, Summerfield et al. (Summerfield C, Trittschuh EH, Monti JM, Mesulam MM, Egner T. 2008. Neural repetition suppression reflects fulfilled perceptual expectations. Nat Neurosci. 11:1004-1006) reported that the relative frequency of stimulus repetitions and non-repetitions influenced the magnitude of repetition suppression in the fusiform face area, suggesting that stimulus expectation accounted for most of the effect of repetition. We confirm that stimulus expectation can significantly influence fMRI repetition suppression throughout visual cortex and show that it occurs with long as well as short adaptation durations. However, the effect was attention dependent: When attention was diverted away from the stimuli, the effects of stimulus expectation completely disappeared. Nonetheless, robust and significant repetition suppression was still evident. These results suggest that fMRI repetition suppression reflects a combination of neuronal adaptation and attention-dependent expectation effects that can be experimentally dissociated. This implies that with an appropriate experimental design, fMRI adaptation can provide valid measures of neuronal adaptation and hence response specificity.

  5. Suppression of insulin production and secretion by a decretin hormone.

    PubMed

    Alfa, Ronald W; Park, Sangbin; Skelly, Kathleen-Rose; Poffenberger, Gregory; Jain, Nimit; Gu, Xueying; Kockel, Lutz; Wang, Jing; Liu, Yinghua; Powers, Alvin C; Kim, Seung K

    2015-02-03

    Decretins, hormones induced by fasting that suppress insulin production and secretion, have been postulated from classical human metabolic studies. From genetic screens, we identified Drosophila Limostatin (Lst), a peptide hormone that suppresses insulin secretion. Lst is induced by nutrient restriction in gut-associated endocrine cells. limostatin deficiency led to hyperinsulinemia, hypoglycemia, and excess adiposity. A conserved 15-residue polypeptide encoded by limostatin suppressed secretion by insulin-producing cells. Targeted knockdown of CG9918, a Drosophila ortholog of Neuromedin U receptors (NMURs), in insulin-producing cells phenocopied limostatin deficiency and attenuated insulin suppression by purified Lst, suggesting CG9918 encodes an Lst receptor. NMUR1 is expressed in islet β cells, and purified NMU suppresses insulin secretion from human islets. A human mutant NMU variant that co-segregates with familial early-onset obesity and hyperinsulinemia fails to suppress insulin secretion. We propose Lst as an index member of an ancient hormone class called decretins, which suppress insulin output.

  6. Criteria for Neoclassical Tearing Modes Suppression in KSTAR

    NASA Astrophysics Data System (ADS)

    Park, Y. S.; Hwang, Y. S.

    2007-11-01

    In KSTAR, neoclassical tearing modes(NTMs) will be suppressed by using 170GHz electron cyclotron current drive(ECCD) system with steering mirrors that align the current deposition to NTM locations. As an initial stage of NTM suppression study, 1 MW ECCD power will be used to suppress m/n = 3/2 and 2/1 NTMs. To confirm the feasibility of successful suppression of the modes under the proposed KSTAR environment, modified Rutherford equation(MRE) which encapsulates stability of NTMs is constructed for the target equilibrium of KSTAR. The geometric coefficients in MRE are obtained by comparing saturated sizes of NTMs from ISLAND code [1] with the amounts of local bootstrap currents from ONETWO. Parameters related to the operation of ECCD are analyzed by TORAY-GA linear ray-tracing code. Due to the small ECCD power available at the initial stage of KSTAR, condition of the optimum ECCD modulation is considered in the analysis to maximize suppression performance. From the analyses, criteria such as the minimum ECCD power required for complete suppression of the modes and the optimum conditions of EC wave launch angle and modulation duty factor are derived for the successful NTM suppression in KSTAR. [1] C.N. Nguyen, G. Bateman and A.H. Kritz, Phys. Plasmas 11 3460 (2004)

  7. The proposed role of suppression in simultaneous interpretation

    PubMed Central

    Gernsbacher, Morton Ann; Shlesinger, Miriam

    2014-01-01

    In this paper we suggest that the cognitive mechanism of suppression attenuates interference in many language comprehension phenomena, and is particularly crucial when comprehension must share processing capacity with other cognitive tasks, as is manifestly the case in simultaneous interpreting. During lexical access, the mechanism of suppression attenuates the interference caused by the activation of other lexical information, such as the inappropriate meanings of homonyms. During anaphoric reference, the mechanism of suppression attenuates the interference caused by the activation of other potential referents. In this way, the referent to which the anaphor does refer becomes the most activated concept. During syntactic parsing, the mechanism of suppression attenuates the interference caused by a previous syntactic form. During metaphor comprehension, the mechanism of suppression attenuates the interference caused by a literal interpretation. During inferencing, the mechanism of suppression attenuates the interference caused by an initial but inappropriate inference. We propose therefore that suppression — a general, cognitive mechanism that attenuates interference — plays a crucial role in language comprehension and simultaneous interpretation. PMID:25520570

  8. Definition of experiments to investigate fire suppressants in microgravity

    NASA Technical Reports Server (NTRS)

    Reuther, James J.

    1990-01-01

    Defined and justified here are the conceptual design and operation of a critical set of experiments expected to yield information on suppressants and on suppressant delivery systems under realistic spacecraft-fire conditions (smoldering). Specific experiment parameters are provided on the solid fuel (carbon), oxidants (habitable spacecraft atmospheres), fuel/oxidant supply, mixing mode, and rate (quiescent and finite; ventilated and replenishable), ignition mode, event, and reignition tendency, fire-zone size, fire conditions, lifetime, and consequences (toxicity), suppressants (CO2, H2O, N2) and suppressant delivery systems, and diagnostics. Candidate suppressants were identified after an analysis of how reduced gravity alters combustion, and how these alterations may influence the modes, mechanisms, and capacities of terrestrial agents to suppress unwanted combustion, or fire. Preferred spacecraft suppression concepts included the local, near-quiescent application of a gas, vapor, or mist that has thermophysical fire-suppression activity and is chemically inert under terrestrial (normal gravity) combustion conditions. The scale, number, and duration (about 1 hour) of the proposed low-gravity experiments were estimated using data not only on the limitations imposed by spacecraft-carrier (Shuttle or Space Station Freedom) accommodations, but also data on the details and experience of standardized smolder-suppression experiments at normal gravity. Deliberately incorporated into the conceptual design was sufficient interchangeability for the prototype experimental package to fly either on Shuttle now or Freedom later. This flexibility is provided by the design concept of up to 25 modular fuel canisters within a containment vessel, which permits both integration into existing low-gravity in-space combustion experiments and simultaneous testing of separate experiments to conserve utilities and time.

  9. Effectors from Wheat Rust Fungi Suppress Multiple Plant Defense Responses.

    PubMed

    Ramachandran, Sowmya R; Yin, Chuntao; Kud, Joanna; Tanaka, Kiwamu; Mahoney, Aaron K; Xiao, Fangming; Hulbert, Scot H

    2017-01-01

    Fungi that cause cereal rust diseases (genus Puccinia) are important pathogens of wheat globally. Upon infection, the fungus secretes a number of effector proteins. Although a large repository of putative effectors has been predicted using bioinformatic pipelines, the lack of available high-throughput effector screening systems has limited functional studies on these proteins. In this study, we mined the available transcriptomes of Puccinia graminis and P. striiformis to look for potential effectors that suppress host hypersensitive response (HR). Twenty small (<300 amino acids), secreted proteins, with no predicted functions were selected for the HR suppression assay using Nicotiana benthamiana, in which each of the proteins were transiently expressed and evaluated for their ability to suppress HR caused by four cytotoxic effector-R gene combinations (Cp/Rx, ATR13/RPP13, Rpt2/RPS-2, and GPA/RBP-1) and one mutated R gene-Pto(Y207D). Nine out of twenty proteins, designated Shr1 to Shr9 (suppressors of hypersensitive response), were found to suppress HR in N. benthamiana. These effectors varied in the effector-R gene defenses they suppressed, indicating these pathogens can interfere with a variety of host defense pathways. In addition to HR suppression, effector Shr7 also suppressed PAMP-triggered immune response triggered by flg22. Finally, delivery of Shr7 through Pseudomonas fluorescens EtHAn suppressed nonspecific HR induced by Pseudomonas syringae DC3000 in wheat, confirming its activity in a homologous system. Overall, this study provides the first evidence for the presence of effectors in Puccinia species suppressing multiple plant defense responses.

  10. Suppression of NF-κB Activation By Gentian Violet Promotes Osteoblastogenesis and Suppresses Osteoclastogenesis

    PubMed Central

    Yamaguchi, M.; Vikulina, T.; Arbiser, J.L.; Weitzmann, M.N.

    2015-01-01

    Skeletal mass is regulated by the coordinated action of bone forming osteoblasts and bone resorbing osteoclasts. Accelerated rates of bone resorption relative to bone formation lead to net bone loss and the development of osteoporosis, a devastating disease that predisposes the skeleton to fractures. Bone fractures are associated with significant morbidity and in the case of hip fractures, high mortality. Gentian violet (GV), a cationic triphenylmethane dye, has long been used as an antifungal and antibacterial agent and is presently under investigation as a potential chemotherapeutic and antiangiogenic agent. However, effects on bone cells have not been previously reported and the mechanisms of action of GV, are poorly understood. In this study we show that GV suppresses receptor activator of NF-κB ligand (RANKL)-induced differentiation of RAW264.7 osteoclast precursors into mature osteoclasts, but paradoxically stimulates the differentiation of MC3T3 cells into mineralizing osteoblasts. These actions stem from the capacity of GV to suppress activation of the nuclear factor kappa B (NF-κB) signal transduction pathway that is required for osteoclastogenesis, but inhibitory to osteoblast differentiation and activity. Our data reveal that GV is an inhibitor of NF-κB activation and may hold promise for modulation of bone turnover to promote a balance between bone formation and bone resorption, favorable to gain of bone mass. PMID:25056540

  11. Burst suppression electroencephalogram with mushroom poisoning, Amanita pantherina

    PubMed Central

    Ogawa, Yuka; Sato, Hiromasa; Yamamoto, Motoyoshi; Tada, Hiroyuki; Hashimoto, Takao

    2015-01-01

    We report on a patient with Amanita pantherina poisoning who showed a burst suppression pattern on electroencephalography during a comatose state. The patient recovered without sequelae a week after ingestion. Burst suppression pattern is defined as alternating bursts and periods of electrical silence, and it is associated with comatose states of various causes. The major toxins contained in A. pantherina are ibotenic acid, an excitatory amino acid at the glutamate receptors, and muscimol, an agonist of the gamma-aminobutyric acid receptors. Alteration of the synaptic transmission in the central nervous system by these toxins may lead to a burst suppression pattern. PMID:26543811

  12. Local cortical dynamics of burst suppression in the anaesthetized brain.

    PubMed

    Lewis, Laura D; Ching, Shinung; Weiner, Veronica S; Peterfreund, Robert A; Eskandar, Emad N; Cash, Sydney S; Brown, Emery N; Purdon, Patrick L

    2013-09-01

    Burst suppression is an electroencephalogram pattern that consists of a quasi-periodic alternation between isoelectric 'suppressions' lasting seconds or minutes, and high-voltage 'bursts'. It is characteristic of a profoundly inactivated brain, occurring in conditions including hypothermia, deep general anaesthesia, infant encephalopathy and coma. It is also used in neurology as an electrophysiological endpoint in pharmacologically induced coma for brain protection after traumatic injury and during status epilepticus. Classically, burst suppression has been regarded as a 'global' state with synchronous activity throughout cortex. This assumption has influenced the clinical use of burst suppression as a way to broadly reduce neural activity. However, the extent of spatial homogeneity has not been fully explored due to the challenges in recording from multiple cortical sites simultaneously. The neurophysiological dynamics of large-scale cortical circuits during burst suppression are therefore not well understood. To address this question, we recorded intracranial electrocorticograms from patients who entered burst suppression while receiving propofol general anaesthesia. The electrodes were broadly distributed across cortex, enabling us to examine both the dynamics of burst suppression within local cortical regions and larger-scale network interactions. We found that in contrast to previous characterizations, bursts could be substantially asynchronous across the cortex. Furthermore, the state of burst suppression itself could occur in a limited cortical region while other areas exhibited ongoing continuous activity. In addition, we found a complex temporal structure within bursts, which recapitulated the spectral dynamics of the state preceding burst suppression, and evolved throughout the course of a single burst. Our observations imply that local cortical dynamics are not homogeneous, even during significant brain inactivation. Instead, cortical and, implicitly

  13. Enhancement of Antigen-Specific Suppression by Muramyl Dipeptide

    PubMed Central

    Ferguson, Thomas A.; Krieger, Nancy J.; Pesce, Amadeo; Michael, J. Gabriel

    1983-01-01

    The effect of the synthetic adjuvant MDP (N-acetyl-muramyl-L-alanyl-D-isoglu-tamine) on the generation of antigen-specific suppression was investigated. Suppression of the anti-bovine serum albumin response, which was achieved by intravenous administration of a peptic fragment of the antigen, was greatly enhanced by simultaneous administration of MDP. Induction of suppression by a combination of bovine serum albumin fragments and MDP was found to be antigen specific and appeared to occur via the generation of antigen-specific suppressor T cells. PMID:6187686

  14. Suppression of Odorant Responses by Odorants in Olfactory Receptor Cells

    NASA Astrophysics Data System (ADS)

    Kurahashi, Takashi; Lowe, Graeme; Gold, Geoffrey H.

    1994-07-01

    Odorants activate an inward current in vertebrate olfactory receptor cells. Here it is shown, in receptor cells from the newt, that odorants can also suppress this current, by a mechanism that is distinct from inhibition and adaptation. Suppression provides a simple explanation for two seemingly unrelated phenomena: the anomalously long latency of olfactory transduction and the existence of an "off response" at the end of a prolonged stimulus. Suppression may influence the perception of odorants by masking odorant responses and by sharpening the odorant specificities of single cells.

  15. Suppression of strike-slip fault systems

    NASA Astrophysics Data System (ADS)

    Curren, I. S.

    2012-12-01

    depth. Selected areas on Earth with anomalously undeveloped strike-slip faulting where plate models would predict otherwise were compared with results from the analog model experiments in this study. Physical similarities between this model and Brothers Fault Zone (BFZ), Walker Lane (WL) and the South Iceland Seismic Zone (SISZ) imply that strike-slip faulting may be suppressed at the surface in these regions due to the presence of pre-existing structures. Filled circles show offset required for breakthrough faulting, empty circles denote lower limit of breakthrough. Triangles show clay offset as a fraction of box offset. Note that clays with pre-existing structures showed larger offsets although breakthrough did not occur.

  16. Fire retardant foams developed to suppress fuel fires

    NASA Technical Reports Server (NTRS)

    Fish, R.; Gilwee, W. J.; Parker, J. A.; Riccitiello, S. R.

    1968-01-01

    Heat insulating polyurethane foam retards and suppresses fuel fires. Uniformly dispersed in the foam is a halogenated polymer capable of splitting off hydrogen halide upon heating and charring of the polyurethane.

  17. High-precision buffer circuit for suppression of regenerative oscillation

    NASA Technical Reports Server (NTRS)

    Tripp, John S.; Hare, David A.; Tcheng, Ping

    1995-01-01

    Precision analog signal conditioning electronics have been developed for wind tunnel model attitude inertial sensors. This application requires low-noise, stable, microvolt-level DC performance and a high-precision buffered output. Capacitive loading of the operational amplifier output stages due to the wind tunnel analog signal distribution facilities caused regenerative oscillation and consequent rectification bias errors. Oscillation suppression techniques commonly used in audio applications were inadequate to maintain the performance requirements for the measurement of attitude for wind tunnel models. Feedback control theory is applied to develop a suppression technique based on a known compensation (snubber) circuit, which provides superior oscillation suppression with high output isolation and preserves the low-noise low-offset performance of the signal conditioning electronics. A practical design technique is developed to select the parameters for the compensation circuit to suppress regenerative oscillation occurring when typical shielded cable loads are driven.

  18. Multifunction tests of a frequency domain based flutter suppression system

    NASA Technical Reports Server (NTRS)

    Christhilf, David M.; Adams, William M., Jr.

    1992-01-01

    The process is described of analysis, design, digital implementation, and subsonic testing of an active control flutter suppression system for a full span, free-to-roll wind tunnel model of an advanced fighter concept. The design technique uses a frequency domain representation of the plant and used optimization techniques to generate a robust multi input/multi output controller. During testing in a fixed-in-roll configuration, simultaneous suppression of both symmetric and antisymmetric flutter was successfully shown. For a free-to-roll configuration, symmetric flutter was suppressed to the limit of the tunnel test envelope. During aggressive rolling maneuvers above the open-loop flutter boundary, simultaneous flutter suppression and maneuver load control were demonstrated. Finally, the flutter damping controller was reoptimized overnight during the test using combined experimental and analytical frequency domain data, resulting in improved stability robustness.

  19. Acoustic Flame Suppression Mechanics in a Microgravity Environment

    NASA Astrophysics Data System (ADS)

    Beisner, Eryn; Wiggins, Nathanial David; Yue, Kwok-Bun; Rosales, Miguel; Penny, Jeremy; Lockridge, Jarrett; Page, Ryan; Smith, Alexander; Guerrero, Leslie

    2015-06-01

    The following paper deals with acoustic flame suppression mechanics in a microgravity environment with measurements taken from an Arduino-based sensor system and validation of the technique. A Zippo lighter is ignited in microgravity and then displaced from the base of the flame and suppressed using surface interactions with single tone acoustic waves to extinguished the flame. The analysis of data collected shows that the acoustic flame suppression measurementtechniques are effective to finding qualitative differences in extinguishing in microgravity and normal gravity. Further, the results suggest that the suppression may be more effective in a microgravity environment than in a normal (1g) environment and may be a viable method of extinguishing fires during space flight.

  20. Acetonitrile Ion Suppression in Atmospheric Pressure Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Colizza, Kevin; Mahoney, Keira E.; Yevdokimov, Alexander V.; Smith, James L.; Oxley, Jimmie C.

    2016-11-01

    Efforts to analyze trace levels of cyclic peroxides by liquid chromatography/mass spectrometry gave evidence that acetonitrile suppressed ion formation. Further investigations extended this discovery to ketones, linear peroxides, esters, and possibly many other types of compounds, including triazole and menadione. Direct ionization suppression caused by acetonitrile was observed for multiple adduct types in both electrospray ionization and atmospheric pressure chemical ionization. The addition of only 2% acetonitrile significantly decreased the sensitivity of analyte response. Efforts to identify the mechanism were made using various nitriles. The ion suppression was reduced by substitution of an acetonitrile hydrogen with an electron-withdrawing group, but was exacerbated by electron-donating or steric groups adjacent to the nitrile. Although current theory does not explain this phenomenon, we propose that polar interactions between the various functionalities and the nitrile may be forming neutral aggregates that manifest as ionization suppression.

  1. Acetonitrile Ion Suppression in Atmospheric Pressure Ionization Mass Spectrometry.

    PubMed

    Colizza, Kevin; Mahoney, Keira E; Yevdokimov, Alexander V; Smith, James L; Oxley, Jimmie C

    2016-11-01

    Efforts to analyze trace levels of cyclic peroxides by liquid chromatography/mass spectrometry gave evidence that acetonitrile suppressed ion formation. Further investigations extended this discovery to ketones, linear peroxides, esters, and possibly many other types of compounds, including triazole and menadione. Direct ionization suppression caused by acetonitrile was observed for multiple adduct types in both electrospray ionization and atmospheric pressure chemical ionization. The addition of only 2% acetonitrile significantly decreased the sensitivity of analyte response. Efforts to identify the mechanism were made using various nitriles. The ion suppression was reduced by substitution of an acetonitrile hydrogen with an electron-withdrawing group, but was exacerbated by electron-donating or steric groups adjacent to the nitrile. Although current theory does not explain this phenomenon, we propose that polar interactions between the various functionalities and the nitrile may be forming neutral aggregates that manifest as ionization suppression. Graphical Abstract ᅟ.

  2. Breeding a super nematode for enhanced insect pest suppression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Entomopathogenic nematodes in the genera Heterorhabditis and Steinernema are important regulators of natural insect populations, and are used commercially as biological control agents for pest suppression. Successful biocontrol applications depend on the introduced organism having an array of benef...

  3. Unnoticed intrusions: dissociations of meta-consciousness in thought suppression.

    PubMed

    Baird, Benjamin; Smallwood, Jonathan; Fishman, Daniel J F; Mrazek, Michael D; Schooler, Jonathan W

    2013-09-01

    The current research investigates the interaction between thought suppression and individuals' explicit awareness of their thoughts. Participants in three experiments attempted to suppress thoughts of a prior romantic relationship and their success at doing so was measured using a combination of self-catching and experience-sampling. In addition to thoughts that individuals spontaneously noticed, individuals were frequently caught engaging in thoughts of their previous partner at experience-sampling probes. Furthermore, probe-caught thoughts were: (i) associated with stronger decoupling of attention from the environment, (ii) more likely to occur under cognitive load, (iii) more frequent for individuals with a desire to reconcile, and (iv) associated with individual differences in the tendency to suppress thoughts. Together, these data suggest that individuals can lack meta-awareness that they have begun to think about a topic they are attempting to suppress, providing novel insight into the cognitive processes that are involved in attempting to control undesired mental states.

  4. Critical suppression of spin Seebeck effect by magnetic fields

    NASA Astrophysics Data System (ADS)

    Kikkawa, Takashi; Uchida, Ken-ichi; Daimon, Shunsuke; Qiu, Zhiyong; Shiomi, Yuki; Saitoh, Eiji

    2015-08-01

    The longitudinal spin Seebeck effect (LSSE) in Pt /Y3Fe5O12(YIG ) junction systems has been investigated at various magnetic fields and temperatures. We found that the LSSE voltage in a Pt/YIG-slab system is suppressed by applying high magnetic fields and this suppression is critically enhanced at low temperatures. The field-induced suppression of the LSSE in the Pt/YIG-slab system is too large at around room temperature to be explained simply by considering the effect of the Zeeman gap in magnon excitation. This result requires us to introduce a magnon-frequency-dependent mechanism into the scenario of LSSE; low-frequency magnons dominantly contribute to the LSSE. The magnetic field dependence of the LSSE voltage was observed to change by changing the thickness of YIG, suggesting that the thermospin conversion by the low-frequency magnons is suppressed in thin YIG films due to the long characteristic lengths of such magnons.

  5. Splash Suppression by Solvent Viscosity in Dense Suspension Impact

    NASA Astrophysics Data System (ADS)

    Zhang, Wendy; Dodge, Kevin; Peters, Ivo; Klein Schaarsberg, Martin; Jaeger, Heinrich

    2015-03-01

    When a dense suspension droplet impacts a hard surface, it will either break apart (``splash'') or remain in a compact configuration without ejecting any particles. We use experiments and discrete particle simulations in which relative particle motions are penalized by lubrication-flow drag to analyze the influence of solvent viscosity on splashing. We find that suspension splash is driven by particle inertia. It can be suppressed in 2 different ways. At low solvent viscosity, lubrication drag due to viscous flow has a negligible effect. Splash is suppressed by surface tension overcoming particle inertia. At high solvent viscosity, lubrication drag alone suppresses splashing. Because impact produces an expanding flow that stretches the suspension radially, suppression in the high-viscosity regime is largely accomplished by lubrication-flow drag preventing initially nearby particle pairs from separating fully. Energy dissipation by viscous flow during collisions plays a smaller role. Present Address: Physics of Fluids Group, University of Twente.

  6. Optical frequency tripling with improved suppression and sideband selection.

    PubMed

    Thakur, Manoj P; Medeiros, Maria C R; Laurêncio, Paula; Mitchell, John E

    2011-12-12

    A novel optical dispersion tolerant millimetre-wave radio-over-fibre system using optical frequency tripling technique with enhanced and selectable sideband suppression is demonstrated. The implementation utilises cascaded optical modulators to achieve either an optical single sideband (OSSB) or double sideband-suppressed carrier (DSB-SC) signal with high sideband suppression. Our analysis and simulation results indicate that the achievable suppression ratio of this configuration is only limited by other system factors such as optical noise and drifting of the operational conditions. The OSSB transmission system performance is assessed experimentally by the transport of 4 WiMax channels modulating a 10 GHz optical upconverted RF carrier as well as for optical frequency doubling and tripling. The 10 GHz and tripled carrier at 30 GHz are dispersion tolerant resulting both in an average relative constellation error (RCE) of -28.7 dB after 40 km of fibre.

  7. Probiotic Diversity Enhances Rhizosphere Microbiome Function and Plant Disease Suppression

    PubMed Central

    Hu, Jie; Friman, Ville-Petri; Gu, Shao-hua; Wang, Xiao-fang; Eisenhauer, Nico; Yang, Tian-jie; Ma, Jing; Shen, Qi-rong; Jousset, Alexandre

    2016-01-01

    ABSTRACT Bacterial communities associated with plant roots play an important role in the suppression of soil-borne pathogens, and multispecies probiotic consortia may enhance disease suppression efficacy. Here we introduced defined Pseudomonas species consortia into naturally complex microbial communities and measured the importance of Pseudomonas community diversity for their survival and the suppression of the bacterial plant pathogen Ralstonia solanacearum in the tomato rhizosphere microbiome. The survival of introduced Pseudomonas consortia increased with increasing diversity. Further, high Pseudomonas diversity reduced pathogen density in the rhizosphere and decreased the disease incidence due to both intensified resource competition and interference with the pathogen. These results provide novel mechanistic insights into elevated pathogen suppression by diverse probiotic consortia in naturally diverse plant rhizospheres. Ecologically based community assembly rules could thus play a key role in engineering functionally reliable microbiome applications. PMID:27965449

  8. Active Suppression Of Vibrations In Stirling-Cycle Coolers

    NASA Technical Reports Server (NTRS)

    Johnson, Bruce G.; Flynn, Frederick J.; Gaffney, Monique S.

    1995-01-01

    Report presents results of early research directed toward development of active control systems for suppression of vibrations in spacecraft Stirling-cycle cryocoolers. Researchers developed dynamical models of cryocooler compressor.

  9. 23. FIRE SUPPRESSION SYSTEM PIPE, 'GRINNELL VALVE', 'VICTROLIC COUPLING,' AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    23. FIRE SUPPRESSION SYSTEM PIPE, 'GRINNELL VALVE', 'VICTROLIC COUPLING,' AND ALARM AT THE REAR OF BAY NO. 5. - Barstow-Daggett Airport, Hangar Shed No. 4, 39500 National Trails Highway, Daggett, San Bernardino County, CA

  10. A model for tumor suppression using H-1 parvovirus.

    PubMed Central

    Telerman, A; Tuynder, M; Dupressoir, T; Robaye, B; Sigaux, F; Shaulian, E; Oren, M; Rommelaere, J; Amson, R

    1993-01-01

    A model system is proposed to investigate, at the molecular level, the pathways of tumor suppression. As a tool for the selection of cells with a suppressed phenotype, we used the H-1 parvovirus that preferentially kills various neoplastic cells. From the human K562 leukemia cells, we isolated a clone, KS, that is resistant to the cytopathic effect of the H-1 virus and displays a suppressed malignant phenotype. The suppressed malignancy and the cellular resistance to H-1 killing appear to depend on the activity of wild-type p53. Whereas the KS cells express wild-type p53, the protein is undetectable in the parental K562 cells. Experiments with p53 mutants suggest that wild-type p53, in its functionally intact state, contributes to the resistance against the cytopathic effect of H-1 parvovirus. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8378352

  11. Acute self-suppression of corticosteroidogenesis in isolated adrenocortical cells.

    PubMed

    Carsia, R V; Malamed, S

    1979-10-01

    The relation between steroidogenesis induced by ACTH and that induced by exogenous concentrations of glucocorticoids was studied in isolated adrenocortical cells. Exogenous corticosterone and cortisol, in concentrations within the production capacity of the adrenal gland, suppressed steroidogenesis induced by ACTH in rat and beef cells, respectively. The precursors pregnenolone and progesterone enhanced steroidogenesis in both rat and beef cells. Aldosterone in rat cells and 17 beta-estradiol in rat and beef cells had little if any effect on steroidogenesis. Either suppression or stimulation by exogenous steroids was acute, that is, after 2-h incubation for rat cells and 1-h incubation for beef cells. A direct suppressive action of end product glucocorticoids is indicated. This observed self-suppression of adrenocortical cells suggests the existence of a mechanism for the find adjustment of steroidogenesis that operates in addition to the classical control exerted by the anterior pituitary.

  12. DETAIL VIEW OF THE SOUND SUPPRESSION SPRAY NOZZLE POSITIONED BETWEEN ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL VIEW OF THE SOUND SUPPRESSION SPRAY NOZZLE POSITIONED BETWEEN THE TWO SRB EXHAUST OPENINGS - Cape Canaveral Air Force Station, Launch Complex 39, Mobile Launcher Platforms, Launcher Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  13. Suppression of translucent elongated structures: applications in chest radiography.

    PubMed

    Hogeweg, Laurens; Sanchez, Clara I; van Ginneken, Bram

    2013-11-01

    Projection images, such as those routinely acquired in radiological practice, are difficult to analyze because multiple 3-D structures superimpose at a single point in the 2-D image. Removal of particular superimposed structures may improve interpretation of these images, both by humans and by computers. This work therefore presents a general method to isolate and suppress structures in 2-D projection images. The focus is on elongated structures, which allows an intensity model of a structure of interest to be extracted using local information only. The model is created from profiles sampled perpendicular to the structure. Profiles containing other structures are detected and removed to reduce the influence on the model. Subspace filtering, using blind source separation techniques, is applied to separate the structure to be suppressed from other structures. By subtracting the modeled structure from the original image a structure suppressed image is created. The method is evaluated in four experiments. In the first experiment ribs are suppressed in 20 artificial radiographs simulated from 3-D lung computed tomography (CT) images. The proposed method with blind source separation and outlier detection shows superior suppression of ribs in simulated radiographs, compared to a simplified approach without these techniques. Additionally, the ability of three observers to discriminate between patches containing ribs and containing no ribs, as measured by the area under the receiver operating characteristic curve (AUC), reduced from 0.99-1.00 on original images to 0.75-0.84 on suppressed images. In the second experiment clavicles are suppressed in 253 chest radiographs. The effect of suppression on clavicle visibility is evaluated using the clavicle contrast and border response, showing a reduction of 78% and 34%, respectively. In the third experiment nodules extracted from CT were simulated close to the clavicles in 100 chest radiographs. It was found that after

  14. Robust control design techniques for active flutter suppression

    NASA Technical Reports Server (NTRS)

    Ozbay, Hitay; Bachmann, Glen R.

    1994-01-01

    In this paper, an active flutter suppression problem is studied for a thin airfoil in unsteady aerodynamics. The mathematical model of this system is infinite dimensional because of Theodorsen's function which is irrational. Several second order approximations of Theodorsen's function are compared. A finite dimensional model is obtained from such an approximation. We use H infinity control techniques to find a robustly stabilizing controller for active flutter suppression.

  15. Neuronal Networks during Burst Suppression as Revealed by Source Analysis

    PubMed Central

    Reinicke, Christine; Moeller, Friederike; Anwar, Abdul Rauf; Mideksa, Kidist Gebremariam; Pressler, Ronit; Deuschl, Günther; Stephani, Ulrich; Siniatchkin, Michael

    2015-01-01

    Introduction Burst-suppression (BS) is an electroencephalography (EEG) pattern consisting of alternant periods of slow waves of high amplitude (burst) and periods of so called flat EEG (suppression). It is generally associated with coma of various etiologies (hypoxia, drug-related intoxication, hypothermia, and childhood encephalopathies, but also anesthesia). Animal studies suggest that both the cortex and the thalamus are involved in the generation of BS. However, very little is known about mechanisms of BS in humans. The aim of this study was to identify the neuronal network underlying both burst and suppression phases using source reconstruction and analysis of functional and effective connectivity in EEG. Material/Methods Dynamic imaging of coherent sources (DICS) was applied to EEG segments of 13 neonates and infants with burst and suppression EEG pattern. The brain area with the strongest power in the analyzed frequency (1–4 Hz) range was defined as the reference region. DICS was used to compute the coherence between this reference region and the entire brain. The renormalized partial directed coherence (RPDC) was used to describe the informational flow between the identified sources. Results/Conclusion Delta activity during the burst phases was associated with coherent sources in the thalamus and brainstem as well as bilateral sources in cortical regions mainly frontal and parietal, whereas suppression phases were associated with coherent sources only in cortical regions. Results of the RPDC analyses showed an upwards informational flow from the brainstem towards the thalamus and from the thalamus to cortical regions, which was absent during the suppression phases. These findings may support the theory that a “cortical deafferentiation” between the cortex and sub-cortical structures exists especially in suppression phases compared to burst phases in burst suppression EEGs. Such a deafferentiation may play a role in the poor neurological outcome of

  16. Iridescence from photonic crystals and its suppression in butterfly scales

    PubMed Central

    Poladian, Leon; Wickham, Shelley; Lee, Kwan; Large, Maryanne C.J.

    2008-01-01

    Regular three-dimensional periodic structures have been observed in the scales of over half a dozen butterfly species. We compare several of these structures: we calculate their photonic bandgap properties; measure the angular variation of the reflection spectra; and relate the observed iridescence (or its suppression) to the structures. We compare the mechanisms for iridescence suppression in different species and conclude with some speculations about form, function, development and evolution. PMID:18980932

  17. Appetite suppressing pregnane glycosides from the roots of Cynanchum auriculatum.

    PubMed

    Liu, Shuangzhu; Chen, Zhenhua; Wu, Jian; Wang, Luoyi; Wang, Hongmin; Zhao, Weimin

    2013-09-01

    In the search for plant alternatives to Hoodia gordonii containing P57, a pregnane glycoside with potential appetite suppressant effect, the roots of Cynanchum auriculatum were investigated. As a result, 15 pregnane glycosides including nine never previously reported were isolated. Their structures were elucidated on the basis of extensive spectroscopic analyses and chemical methods. Appetite suppressant effect and body weight loss were observed when tested with the most abundant pregnane glycoside, wilfoside K1N, in an in vivo test with rats.

  18. Mode of ATM-dependent suppression of chromosome translocation

    SciTech Connect

    Yamauchi, Motohiro; Suzuki, Keiji; Oka, Yasuyoshi; Suzuki, Masatoshi; Kondo, Hisayoshi; Yamashita, Shunichi

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer We addressed how ATM suppresses frequency of chromosome translocation. Black-Right-Pointing-Pointer We found ATM/p53-dependent G1 checkpoint suppresses translocation frequency. Black-Right-Pointing-Pointer We found ATM and DNA-PKcs function in a common pathway to suppress translocation. -- Abstract: It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealed that ATM kinase functions in the same pathway that requires kinase activity of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to suppress dicentric frequency. From the results in the present study, we conclude that ATM minimizes translocation frequency through its commitment to G1 checkpoint and DNA double-strand break repair pathway that requires kinase activity of DNA-PKcs.

  19. Methods for suppressing isomerization of olefin metathesis products

    DOEpatents

    Firth, Bruce E.; Kirk, Sharon E.

    2015-10-27

    A method for suppressing isomerization of an olefin metathesis product produced in a metathesis reaction includes adding an isomerization suppression agent that includes nitric acid to a mixture that includes the olefin metathesis product and residual metathesis catalyst from the metathesis reaction under conditions that are sufficient to passivate at least a portion of the residual metathesis catalyst. Methods of refining a natural oil are described.

  20. Application of phase coherent transform to cloud clutter suppression

    SciTech Connect

    Ng, L.C.

    1994-11-15

    This paper describes a tracking algorithm using frame-to-frame correlation with frequency domain clutter suppression. Clutter suppression was mechanized via a `Phase Coherent Transform` (PCT) approach. This approach was applied to explore the feasibility of tracking a post-boost rocket from a low earth orbit satellite with real cloud background data. Simulation results show that the PCT/correlation tracking algorithm can perform satisfactorily at signal-to-clutter ratio (SCR) as low as 5 or 7 dB.

  1. [Suppression of epileptiform activity by micropolarizing brain structures].

    PubMed

    Tsukunov, S G; Gal'dinov, G V

    1980-05-01

    Penicillin administration elicited epileptiform responses whereas micropolarization (MCP) affected the epileptogenic foci in cats with indwelled electrodes and chemotrodes. Three types of experimental epilepsy models were obtained: focal petit mal seizures, adversive, and grand mal seizures. The MCP of amygdala and caudate nucleus completely suppressed all three types of seizures whereas MCP of hippocampus enhanced the pathology. Two mechanisms of seizure suppression seem to exist: the inhibitory and the activating ones.

  2. Expressive suppression and neural responsiveness to nonverbal affective cues

    PubMed Central

    Petrican, Raluca; Rosenbaum, R. Shayna; Grady, Cheryl

    2016-01-01

    Optimal social functioning occasionally requires concealment of one’s emotions in order to meet one’s immediate goals and environmental demands. However, because emotions serve an important communicative function, their habitual suppression disrupts the flow of social exchanges and, thus, incurs significant interpersonal costs. Evidence is accruing that the disruption in social interactions, linked to habitual expressive suppression use, stems not only from intrapersonal, but also from interpersonal causes, since the suppressors’ restricted affective displays reportedly inhibit their interlocutors’ emotionally expressive behaviors. However, expressive suppression use is not known to lead to clinically significant social impairments. One explanation may be that over the lifespan, individuals who habitually suppress their emotions come to compensate for their interlocutors’ restrained expressive behaviors by developing an increased sensitivity to nonverbal affective cues. To probe this issue, the present study used functional magnetic resonance imaging (fMRI) to scan healthy older women while they viewed silent videos of a male social target displaying nonverbal emotional behavior, together with a brief verbal description of the accompanying context, and then judged the target’s affect. As predicted, perceivers who reported greater habitual use of expressive suppression showed increased neural processing of nonverbal affective cues. This effect appeared to be coordinated in a top-down manner via cognitive control. Greater neural processing of nonverbal cues among perceivers who habitually suppress their emotions was linked to increased ventral striatum activity, suggestive of increased reward value/personal relevance ascribed to emotionally expressive nonverbal behaviors. These findings thus provide neural evidence broadly consistent with the hypothesized link between habitual use of expressive suppression and compensatory development of increased

  3. Social responses to expressive suppression: The role of personality judgments.

    PubMed

    Tackman, Allison M; Srivastava, Sanjay

    2016-04-01

    Why do people who suppress their emotion-expressive behavior have difficulty forming close, supportive relationships? Previous studies have found that suppression disrupts the dynamics of social interactions and existing relationships. We evaluated a complementary hypothesis: that suppression functions as a behavioral cue leading others to form negative personality impressions of suppressors, even at zero-acquaintance. In 2 studies, participants reported personality judgments and other impressions of targets who either suppressed or expressed their emotion-expressive behavior in response to amusing or sad film clips. In findings replicated across studies, targets who suppressed either amusement or sadness were judged as less extraverted, less agreeable, and more interpersonally avoidant and anxious than targets who expressed emotions, and participants were less interested in affiliating with suppressors compared with expressers. Effects were amplified when targets suppressed amusement (compared with sadness) and when participants knew the emotional context (compared with when they did not) and, thus, could form expectations about what emotions targets should be showing. Extraversion and agreeableness judgments mediated the effect of suppression on participants' disinterest in affiliating. In Study 2, which extended Study 1 in several ways, effects were pronounced for the enthusiasm aspect of extraversion and the compassion aspect of agreeableness. We also found evidence that judgments of suppressors do not simply fall between neutral and fully expressing targets; rather, judgments of suppressors are qualitatively different. We discuss implications for understanding the social consequences of emotion regulation-in particular, how beyond disrupting relationships, suppression may prevent some relationships from even forming in the first place.

  4. Failure of pyridoxine to suppress raised serum prolactin levels.

    PubMed

    de Waal, J M; Steyn, A F; Harms, J H; Slabber, C F; Pannall, P R

    1978-02-25

    Pyridoxine has been reported as having an antilactogenic effect, presumably by suppressing prolactin secretion. We have measured serum prolactin levels during pyridoxine administration in two groups of hyperprolactinaemic subjects. In normal postpartum women, the postdelivery fall in serum prolactin levels did not differ significantly in treated and control subjects. In patients with chlorpromazine-induced hyperprolactinaemia and galactorrhoea, pyridoxine did not reduce the elevated levels. In neither group was milk production suppressed.

  5. Suppression of antigen-specific lymphocyte activation in modeled microgravity

    NASA Technical Reports Server (NTRS)

    Cooper, D.; Pride, M. W.; Brown, E. L.; Risin, D.; Pellis, N. R.; McIntire, L. V. (Principal Investigator)

    2001-01-01

    Various parameters of immune suppression are observed in lymphocytes from astronauts during and after a space flight. It is difficult to ascribe this suppression to microgravity effects on immune cells in crew specimens, due to the complex physiological response to space flight and the resultant effect on in vitro immune performance. Use of isolated immune cells in true and modeled microgravity in immune performance tests, suggests a direct effect of microgravity on in vitro cellular function. Specifically, polyclonal activation of T-cells is severely suppressed in true and modeled microgravity. These recent findings suggest a potential suppression of oligoclonal antigen-specific lymphocyte activation in microgravity. We utilized rotating wall vessel (RWV) bioreactors as an analog of microgravity for cell cultures to analyze three models of antigen-specific activation. A mixed-lymphocyte reaction, as a model for a primary immune response, a tetanus toxoid response and a Borrelia burgdorferi response, as models of a secondary immune response, were all suppressed in the RWV bioreactor. Our findings confirm that the suppression of activation observed with polyclonal models also encompasses oligoclonal antigen-specific activation.

  6. Herbivore exploits orally secreted bacteria to suppress plant defenses

    PubMed Central

    Chung, Seung Ho; Rosa, Cristina; Scully, Erin D.; Peiffer, Michelle; Tooker, John F.; Hoover, Kelli; Luthe, Dawn S.; Felton, Gary W.

    2013-01-01

    Induced plant defenses in response to herbivore attack are modulated by cross-talk between jasmonic acid (JA)- and salicylic acid (SA)-signaling pathways. Oral secretions from some insect herbivores contain effectors that overcome these antiherbivore defenses. Herbivores possess diverse microbes in their digestive systems and these microbial symbionts can modify plant–insect interactions; however, the specific role of herbivore-associated microbes in manipulating plant defenses remains unclear. Here, we demonstrate that Colorado potato beetle (Leptinotarsa decemlineata) larvae exploit bacteria in their oral secretions to suppress antiherbivore defenses in tomato (Solanum lycopersicum). We found that antibiotic-untreated larvae decreased production of JA and JA-responsive antiherbivore defenses, but increased SA accumulation and SA-responsive gene expression. Beetles benefit from down-regulating plant defenses by exhibiting enhanced larval growth. In SA-deficient plants, suppression was not observed, indicating that suppression of JA-regulated defenses depends on the SA-signaling pathway. Applying bacteria isolated from larval oral secretions to wounded plants confirmed that three microbial symbionts belonging to the genera Stenotrophomonas, Pseudomonas, and Enterobacter are responsible for defense suppression. Additionally, reinoculation of these bacteria to antibiotic-treated larvae restored their ability to suppress defenses. Flagellin isolated from Pseudomonas sp. was associated with defense suppression. Our findings show that the herbivore exploits symbiotic bacteria as a decoy to deceive plants into incorrectly perceiving the threat as microbial. By interfering with the normal perception of herbivory, beetles can evade antiherbivore defenses of its host. PMID:24019469

  7. Suppression of antigen-specific lymphocyte activation in modeled microgravity.

    PubMed

    Cooper, D; Pride, M W; Brown, E L; Risin, D; Pellis, N R

    2001-02-01

    Various parameters of immune suppression are observed in lymphocytes from astronauts during and after a space flight. It is difficult to ascribe this suppression to microgravity effects on immune cells in crew specimens, due to the complex physiological response to space flight and the resultant effect on in vitro immune performance. Use of isolated immune cells in true and modeled microgravity in immune performance tests, suggests a direct effect of microgravity on in vitro cellular function. Specifically, polyclonal activation of T-cells is severely suppressed in true and modeled microgravity. These recent findings suggest a potential suppression of oligoclonal antigen-specific lymphocyte activation in microgravity. We utilized rotating wall vessel (RWV) bioreactors as an analog of microgravity for cell cultures to analyze three models of antigen-specific activation. A mixed-lymphocyte reaction, as a model for a primary immune response, a tetanus toxoid response and a Borrelia burgdorferi response, as models of a secondary immune response, were all suppressed in the RWV bioreactor. Our findings confirm that the suppression of activation observed with polyclonal models also encompasses oligoclonal antigen-specific activation.

  8. CMB quadrupole suppression. II. The early fast roll stage

    NASA Astrophysics Data System (ADS)

    Boyanovsky, D.; de Vega, H. J.; Sanchez, N. G.

    2006-12-01

    Within the effective field theory of inflation, an initialization of the classical dynamics of the inflaton with approximate equipartition between the kinetic and potential energy of the inflaton leads to a brief fast roll stage that precedes the slow roll regime. The fast roll stage leads to an attractive potential in the wave equations for the mode functions of curvature and tensor perturbations. The evolution of the inflationary perturbations is equivalent to the scattering by this potential and a useful dictionary between the scattering data and observables is established. Implementing methods from scattering theory we prove that this attractive potential leads to a suppression of the quadrupole moment for CMB and B-mode angular power spectra. The scale of the potential is determined by the Hubble parameter during slow roll. Within the effective field theory of inflation at the grand unification (GUT) energy scale we find that if inflation lasts a total number of e-folds Ntot˜59, there is a 10% 20% suppression of the CMB quadrupole and about 2% 4% suppression of the tensor quadrupole. The suppression of higher multipoles is smaller, falling off as 1/l2. The suppression is much smaller for Ntot>59, therefore if the observable suppression originates in the fast roll stage, there is the upper bound Ntot˜59.

  9. Knockdown of GALNT1 suppresses malignant phenotype of hepatocellular carcinoma by suppressing EGFR signaling

    PubMed Central

    Huang, Miao-Juei; Hu, Rey-Heng; Chou, Chih-Hsing; Hsu, Chia-Lang; Liu, Ya-Wen; Huang, John; Hung, Ji-Shiang; Lai, I-Rue; Juan, Hsueh-Fen; Yu, Sung-Liang; Wu, Yao-Ming; Huang, Min-Chuan

    2015-01-01

    O-glycosylation is a common protein modification. Aberrant O-glycosylation is associated with many cancers. GALNT1 is a GalNAc-transferase that initiates protein O-glycosylation. We found that GALNT1 is frequently up-regulated in hepatocellular carcinoma (HCC) and is associated with poor patient survival. Overexpression of GALNT1 increased and knockdown decreased HCC cell migration and invasion. Knockdown of GALNT1 inhibited EGF-induced migration and invasion. Knockdown of GALNT1 decreased EGFR activation and increased EGFR degradation, by decreasing EGFR O-glycosylation. This study demonstrates that down-regulation of GALNT1 is sufficient to suppress malignant phenotype of HCC cells by decreasing EGFR signaling. Thus, GALNT1 is a potential target in HCC. PMID:25730904

  10. Suppression of pool fires with HRC-125 in a simulated engine nacelle.

    SciTech Connect

    Keyser, David R.; Hewson, John C.

    2007-06-01

    CFD simulations are conducted to predict the distribution of fire suppressant in an engine nacelle and to predict the suppression of pool fires by the application of this suppressant. In the baseline configuration, which is based on an installed system, suppressant is injected through four nozzles at a rate fast enough to suppress all simulated pool fires. Variations that reduce the mass of the suppression system (reducing the impact of the suppression system on meeting mission needs) are considered, including a reduction in the rate of suppressant injection, a reduction in the mass of suppressant and a reduction in the number of nozzles. In general, these variations should work to reduce the effectiveness of the suppression system, but the CFD results point out certain changes that have negligible impact, at least for the range of phenomena considered here. The results are compared with measurements where available. Comparisons with suppressant measurements are reasonable. A series of twenty-three fire suppression tests were conducted to check the predictions. The pre-test predictions were generally successful in identifying the range of successful suppression tests. In two separate cases, each where one nozzle of the suppression system was capped, the simulation results did indicate a failure to suppress for a condition where the tests indicated successful suppression. When the test-suppressant discharge rate was reduced by roughly 25%, the tests were in agreement with the predictions. That is, the simulations predict a failure to suppress slightly before observed in these cases.

  11. Dendritic Cell-Based Genetic Immunotherapy for Ovarian Cancer

    DTIC Science & Technology

    2007-12-01

    a gamma-counter. Maximum and spontaneous release of 51 Cr was obtained from the supernatants of the target cells in 1% Nonidet P-40 and in...16: 1045-9. 7. Piazzolla, G., C. Tortorella, G. Fiore, M. Fanelli, A. Pisconti, and S. Antonaci, Interleukin-12 p40 /p70 ratio and in vivo

  12. Two Components of Nocturnal Locomotor Suppression by Light

    PubMed Central

    Morin, Lawrence P.; Lituma, Pablo J.; Studholme, Keith M.

    2010-01-01

    In nocturnal rodents, millisecond light (“flash”) stimuli can induce both a large circadian rhythm phase shift and an associated state change from highly active to quiescence followed by behavioral sleep. Suppression of locomotion (“negative masking”) is an easily measured correlate of the state change. The present mouse studies used both flashes and longer light stimuli (“pulses”) to distinguish initiation from maintenance effects of light on locomotor suppression and to determine whether the locomotor suppression exhibits temporal integration as is thought to be characteristic of phase shift responses to pulse, but not flash, stimuli. In Expt. 1, locomotor suppression increased with irradiance (0.01–100 μW/cm2), in accordance with previous reports. It also increased with stimulus duration (3–3000 sec), but interpretation of this result is complicated by the ability of light to both initiate and maintain locomotor suppression. In Expt. 2, an irradiance response curve was determined using a stimulus series of 10 flashes, 2 msec each, with total flash energy varying from 0.0025 – 110.0 J/m2. This included a test for temporal integration in which the effects of two equal energy series of flashes were compared, but which differed in the number of flashes per series (10 vs 100). The 10 flash series more effectively elicited locomotor suppression than the 100 flash series, a result consistent with prior observations involving flash-induced phase shifts. In Expt. 3, exposure of mice to an 11 hr light stimulus yielded irradiance-dependent locomotor suppression that can be maintained for the entire stimulus duration by a 100 μW/cm2 stimulus. Light has the ability to initiate a time-limited (30–40 min) interval of locomotor suppression (initiation effect) that can be extended by additional light (maintenance effect). Temporal integration resembling that seen in phase shifting responses to light does not exist for either phase shift or locomotor

  13. Persistence and Suppressiveness of Pasteuria penetrans to Meloidogyne arenaria Race

    PubMed Central

    Cetintas, R.; Dickson, D. W.

    2004-01-01

    The long-term persistence and suppressiveness of Pasteuria penetrans against Meloidogyne arenaria race 1 were investigated in a formerly root-knot nematode suppressive site following 9 years of continuous cultivation of three treatments and 4 years of continuous peanut. The three treatments were two M. arenaria race 1 nonhost crops, bahiagrass (Paspalum notatum cv. Pensacola var. Tifton 9), rhizomal peanut (Arachis glabrata cv. Florigraze), and weed fallow. Two root-knot nematode susceptible weeds commonly observed in weed fallow plots were hairy indigo (Indigofera hirsuta) and alyce clover (Alysicarpus vaginalis). The percentage of J2 with endospores attached reached the highest level of 87% in 2000 in weed fallow, and 63% and 53% in 2002 in bahiagrass and rhizomal peanut, respectively. The percentage of endospore-filled females extracted from peanut roots grown in weed fallow plots increased from nondetectable in 1999 to 56% in 2002, whereas the percentages in bahiagrass and rhizomal peanut plots were 41% and 16%, respectively. Over 4 years, however, there was no strong evidence that endospores densities reached suppressive levels because peanut roots, pods, and pegs were heavily galled, and yields were suppressed. This might be attributed to the discovery of M. javanica infecting peanut in this field in early autumn 2001. A laboratory test confirmed that although the P. penetrans isolate specific to M. arenaria attached to M. javanica J2, no development occurred. In summary, P. penetrans increased on M. arenaria over a 4-year period, but apparently because of infection of M. javanica on peanut at the field site root-knot disease was not suppressed. This was confirmed by a suppressive soil test that showed a higher level of soil suppressiveness than occurred in the field (P ≤ 0.01). PMID:19262836

  14. Persistence and Suppressiveness of Pasteuria penetrans to Meloidogyne arenaria Race.

    PubMed

    Cetintas, R; Dickson, D W

    2004-12-01

    The long-term persistence and suppressiveness of Pasteuria penetrans against Meloidogyne arenaria race 1 were investigated in a formerly root-knot nematode suppressive site following 9 years of continuous cultivation of three treatments and 4 years of continuous peanut. The three treatments were two M. arenaria race 1 nonhost crops, bahiagrass (Paspalum notatum cv. Pensacola var. Tifton 9), rhizomal peanut (Arachis glabrata cv. Florigraze), and weed fallow. Two root-knot nematode susceptible weeds commonly observed in weed fallow plots were hairy indigo (Indigofera hirsuta) and alyce clover (Alysicarpus vaginalis). The percentage of J2 with endospores attached reached the highest level of 87% in 2000 in weed fallow, and 63% and 53% in 2002 in bahiagrass and rhizomal peanut, respectively. The percentage of endospore-filled females extracted from peanut roots grown in weed fallow plots increased from nondetectable in 1999 to 56% in 2002, whereas the percentages in bahiagrass and rhizomal peanut plots were 41% and 16%, respectively. Over 4 years, however, there was no strong evidence that endospores densities reached suppressive levels because peanut roots, pods, and pegs were heavily galled, and yields were suppressed. This might be attributed to the discovery of M. javanica infecting peanut in this field in early autumn 2001. A laboratory test confirmed that although the P. penetrans isolate specific to M. arenaria attached to M. javanica J2, no development occurred. In summary, P. penetrans increased on M. arenaria over a 4-year period, but apparently because of infection of M. javanica on peanut at the field site root-knot disease was not suppressed. This was confirmed by a suppressive soil test that showed a higher level of soil suppressiveness than occurred in the field (P

  15. Suppression of proinflammatory cytokines in monocytes by a tetravalent guanylhydrazone

    PubMed Central

    1996-01-01

    An overproduction of proinflammatory cytokines by activated macrophages/monocytes mediates the injurious sequelae of inflammation, septic shock, tissue injury, and cachexia. We recently synthesized a tetravalent guanylhydrazone compound (CNI-1493) that inhibits cytokine- inducible arginine transport and nitric oxide (NO) production in macrophages, and protects mice against lethal endotoxemia and carrageenan-induced inflammation. During these investigations we noticed that CNI-1493 effectively prevented lipopolysaccharide (LPS)- induced NO production, even when added in concentrations 10-fold less than required to competitively inhibit L-arginine uptake, suggesting that the suppressive effects of this guanylhydrazone compound might extend to other LPS-induced responses. Here, we report that CNI-1493 suppressed the LPS-stimulated production of proinflammatory cytokines (tumor necrosis factor [TNF], interleukins 1beta and 6, macrophage inflammatory proteins 1alpha and 1beta) from human peripheral blood mononuclear cells. Cytokine suppression was specific, in that CNI-1493 did not inhibit either the constitutive synthesis of transforming growth factor beta or the upregulation of major histocompatibility complex class II by interferon gamma (IFN-gamma). In contrast to the macrophage suppressive actions of dexamethasone, which are overridden in the presence of IFN-gamma, CNI-1493 retained its suppressive effects even in the presence of IFN-gamma. The mechanism of cytokine- suppressive action by CNI-1493 was independent of extracellular L- arginine content and NO production and is not restricted to induction by LPS. As a selective inhibitor of macrophage activation that prevents TNF production, this tetravalent guanylhydrazone could be useful in the development of cytokine-suppressive agents for the treatment of diseases mediated by overproduction of cytokines. PMID:8642296

  16. Retinal Pigment Epithelial Cell Line Suppression of Phagolysosome Activation.

    PubMed

    Taylor, A W; Dixit, S; Yu, J

    2015-01-29

    The eye is an immune privileged tissue with multiple mechanisms of immunosuppression to protect the light gathering tissues from the damage of inflammation. One of theses mechanisms involves retinal pigment epithelial cell suppression of phagosome activation in macrophages. The objective of this work is to determine if the human RPE cell line ARPE-19 is capable of suppressing the activation of the phagolysosome in macrophages in a manner similar to primary RPE. The conditioned media of RPE eyecups, sub-confluent, just confluent cultures, or established confluent cultures of human ARPE-19 cells were generated. These condition media were used to treat macrophages phagocytizing pHrodo bioparticles. After 24 hours incubation the macrophages were imaged by fluorescent microscopy, and fluorescence was measured. The fluorescent intensity is proportional to the amount of bioparticles phagocytized and are in an activated phagolysosome. The conditioned media of in situ mouse RPE eyecups significantly suppressed the activation of phagolysosome. The conditioned media from cultures of human ARPE-19 cells, grown to sub-confluence (50%) or grown to confluence had no effect on phagolysosome activation. In contrast, the conditioned media from established confluent cultures significantly suppressed phagolysosome activation. The neuropeptides alpha-MSH and NPY were depleted from the conditioned media of established confluent ARPE-19 cell cultures. This depleted conditioned media had diminished suppression of phagolysosome activation while promoting macrophage cell death. In addition, the condition media from cultures of ARPE-19 monolayers wounded with a bisecting scrape was diminished in suppressing phagolysosome activation. This technical report suggests that like primary RPE monolayers, established confluent cultures of ARPE-19 cells produce soluble factors that suppress the activation of macrophages, and can be used to study the molecular mechanisms of retinal immunobiology. In

  17. Diversity and Activity of Lysobacter Species from Disease Suppressive Soils

    PubMed Central

    Gómez Expósito, Ruth; Postma, Joeke; Raaijmakers, Jos M.; De Bruijn, Irene

    2015-01-01

    The genus Lysobacter includes several species that produce a range of extracellular enzymes and other metabolites with activity against bacteria, fungi, oomycetes, and nematodes. Lysobacter species were found to be more abundant in soil suppressive against the fungal root pathogen Rhizoctonia solani, but their actual role in disease suppression is still unclear. Here, the antifungal and plant growth-promoting activities of 18 Lysobacter strains, including 11 strains from Rhizoctonia-suppressive soils, were studied both in vitro and in vivo. Based on 16S rRNA sequencing, the Lysobacter strains from the Rhizoctonia-suppressive soil belonged to the four species Lysobacter antibioticus, Lysobacter capsici, Lysobacter enzymogenes, and Lysobacter gummosus. Most strains showed strong in vitro activity against R. solani and several other pathogens, including Pythium ultimum, Aspergillus niger, Fusarium oxysporum, and Xanthomonas campestris. When the Lysobacter strains were introduced into soil, however, no significant and consistent suppression of R. solani damping-off disease of sugar beet and cauliflower was observed. Subsequent bioassays further revealed that none of the Lysobacter strains was able to promote growth of sugar beet, cauliflower, onion, and Arabidopsis thaliana, either directly or via volatile compounds. The lack of in vivo activity is most likely attributed to poor colonization of the rhizosphere by the introduced Lysobacter strains. In conclusion, our results demonstrated that Lysobacter species have strong antagonistic activities against a range of pathogens, making them an important source for putative new enzymes and antimicrobial compounds. However, their potential role in R. solan