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Sample records for montanide adjuvanted staphylococcus

  1. Montanide ISA 71 VG is Advantageous to Freund's Adjuvant in Immunization Against S. aureus Infection of Mice.

    Science.gov (United States)

    Klimka, A; Michels, L; Glowalla, E; Tosetti, B; Krönke, M; Krut, O

    2015-05-01

    The enormous capacity of Staphylococcus aureus to acquire antibiotic resistance makes it a permanent task to search for and to develop new anti-infectives. One of the possible approaches is the early active immunization of risk patients and animal stocks to prevent S. aureus infections. Based on a S. aureus proteome screen with S. aureus-specific human antiserum, we have previously identified several anchorless cell wall proteins to be used as novel vaccine candidates. To develop an efficient anti-S. aureus vaccine, the supplemented adjuvants Montanide(™) ISA 71 VG and ISA 206 were compared to Freund's adjuvant in terms of handling, induction of cytokine profile, triggering antigen-specific immunoglobulin production of different IgG subclasses and provision of increased survival rates in our S. aureus sepsis mouse model. Immunization with ISA 71 VG in comparison with Freund's adjuvant induced slightly delayed but comparably strong increase of antigen-specific antibody titres and conferred protective effect against S. aureus challenge. In contrast using ISA 206 as adjuvant, significantly lower IgG titres and consequently, no protective effect against S. aureus infection were observed. Handling and tolerability of the Montanide is superior to Freund's adjuvant. Montanide(™) ISA 71 VG can serve as an effective adjuvant replacement for Freund's adjuvant in research with a prospective usage in animal and human vaccines against bacterial pathogens. © 2015 John Wiley & Sons Ltd.

  2. 新佐剂--Montanide ISA 50 V2在马免疫中的应用研究%Application of a new adjuvant-Montanide ISA 50 V2 in horse immunization program

    Institute of Scientific and Technical Information of China (English)

    刘卫涛; 柳洲; 李育合; 谢小荣; 孟祥玉; 张廷芬; 高建军

    2013-01-01

    Objective To improve the titers of antitoxin serum prepared in horses immunization program .Methods Mon-tanide ISA 50V2 was used as a new adjuvant in immunization program for rabbits and horses .Montanide SA 50V2 and Clostridium botulinum type A and F toxoids antigens were emulsified to O /W emulsion, and then using this emulsion to im-munize the horses , and compared with the conventional adjuvant ( FIA) with the same antigen of clostridium botulinum type A and F toxoids .Results The immune effect was the best when two emulsions were alternately used ,the titer of antitoxin serum was the highest .Conclusion Montanide ISA 50V2 could be used as a adjuvant in horses immunization program for production of higher titers of antitoxin serum .%目的研究新佐剂-Montanide ISA 50V2在马免疫中的应用,制定合理的免疫程序,提高马免疫血清效价。方法用Montanide ISA 50V2乳化A型和F型肉毒类毒素制备成油乳抗原,免疫家兔和马,并与福氏不完全佐剂进行对比。结果在马免疫程序中,Montanide ISA 50V2与福氏不完全佐剂交替使用效果更好,免疫效价较高。结论在进一步试验确证后,将Montanide ISA 50V2作为佐剂应用于马免疫中,以获得更高的免疫血清的效价。

  3. Evaluation of Montanide ISA 71 VG adjuvant during profilin vaccination against experimental coccidiosis

    Science.gov (United States)

    Chickens were immunized subcutaneously with an Eimeria recombinant profilin protein plus ISA 70 VG (ISA 70) or ISA 71 VG (ISA 71) water-in-oil adjuvants, or with profilin alone, and comparative RNA microarray hybridizations were performed to ascertain global transcriptome changes induced by profilin...

  4. In ovo vaccination using Eimeria profilin and Clostridium perfringens NetB proteins in Montanide IMS adjuvant increases protective immunity against experimentally-induced necrotic enteritis.

    Science.gov (United States)

    Lillehoj, Hyun Soon; Jang, Seung Ik; Panebra, Alfredo; Lillehoj, Erik Peter; Dupuis, Laurent; Ben Arous, Juliette; Lee, Seung Kyoo; Oh, Sung Taek

    2017-10-01

    The effects of vaccinating 18-day-old chicken embryos with the combination of recombinant Eimeria profilin plus Clostridium perfringens (C. perfringens) NetB proteins mixed in the Montanide IMS adjuvant on the chicken immune response to necrotic enteritis (NE) were investigated using an Eimeria maxima (E. maxima)/C. perfringens co-infection NE disease model that we previously developed. Eighteen-day-old broiler embryos were injected with 100 μL of phosphate-buffered saline, profilin, profilin plus necrotic enteritis B-like (NetB), profilin plus NetB/Montanide adjuvant (IMS 106), and profilin plus Net-B/Montanide adjuvant (IMS 101). After post-hatch birds were challenged with our NE experimental disease model, body weights, intestinal lesions, serum antibody levels to NetB, and proinflammatory cytokine and chemokine mRNA levels in intestinal intraepithelial lymphocytes were measured. Chickens in ovo vaccinated with recombinant profilin plus NetB proteins/IMS106 and recombinant profilin plus NetB proteins/IMS101 showed significantly increased body weight gains and reduced gut damages compared with the profilin-only group, respectively. Greater antibody response to NetB toxin were observed in the profilin plus NetB/IMS 106, and profilin plus NetB/IMS 101 groups compared with the other three vaccine/adjuvant groups. Finally, diminished levels of transcripts encoding for proinflammatory cytokines such as lipopolysaccharide-induced tumor necrosis factor-α factor, tumor necrosis factor superfamily 15, and interleukin-8 were observed in the intestinal lymphocytes of chickens in ovo injected with profilin plus NetB toxin in combination with IMS 106, and profilin plus NetB toxin in combination with IMS 101 compared with profilin protein alone bird. These results suggest that the Montanide IMS adjuvants potentiate host immunity to experimentally-induced avian NE when administered in ovo in conjunction with the profilin and NetB proteins, and may reduce disease pathology by

  5. vaccination using profilin and NetB proteins in Montanide IMS adjuvant increases protective immunity against experimentally-induced necrotic enteritis

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    Hyun Soon Lillehoj

    2017-10-01

    Full Text Available Objective The effects of vaccinating 18-day-old chicken embryos with the combination of recombinant Eimeria profilin plus Clostridium perfringens (C. perfringens NetB proteins mixed in the Montanide IMS adjuvant on the chicken immune response to necrotic enteritis (NE were investigated using an Eimeria maxima (E. maxima/C. perfringens co-infection NE disease model that we previously developed. Methods Eighteen-day-old broiler embryos were injected with 100 μL of phosphate-buffered saline, profilin, profilin plus necrotic enteritis B-like (NetB, profilin plus NetB/Montanide adjuvant (IMS 106, and profilin plus Net-B/Montanide adjuvant (IMS 101. After post-hatch birds were challenged with our NE experimental disease model, body weights, intestinal lesions, serum antibody levels to NetB, and proinflammatory cytokine and chemokine mRNA levels in intestinal intraepithelial lymphocytes were measured. Results Chickens in ovo vaccinated with recombinant profilin plus NetB proteins/IMS106 and recombinant profilin plus NetB proteins/IMS101 showed significantly increased body weight gains and reduced gut damages compared with the profilin-only group, respectively. Greater antibody response to NetB toxin were observed in the profilin plus NetB/IMS 106, and profilin plus NetB/IMS 101 groups compared with the other three vaccine/adjuvant groups. Finally, diminished levels of transcripts encoding for proinflammatory cytokines such as lipopolysaccharide-induced tumor necrosis factor-α factor, tumor necrosis factor superfamily 15, and interleukin-8 were observed in the intestinal lymphocytes of chickens in ovo injected with profilin plus NetB toxin in combination with IMS 106, and profilin plus NetB toxin in combination with IMS 101 compared with profilin protein alone bird. Conclusion These results suggest that the Montanide IMS adjuvants potentiate host immunity to experimentally-induced avian NE when administered in ovo in conjunction with the profilin and

  6. Vaccine Adjuvants in Fish Vaccines Make a Difference: Comparing Three Adjuvants (Montanide ISA763A Oil, CpG/Poly I:C Combo and VHSV Glycoprotein) Alone or in Combination Formulated with an Inactivated Whole Salmonid Alphavirus Antigen.

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    Thim, Hanna L; Villoing, Stéphane; McLoughlin, Marian; Christie, Karen Elina; Grove, Søren; Frost, Petter; Jørgensen, Jorunn B

    2014-03-25

    Most commercial vaccines offered to the aquaculture industry include inactivated antigens (Ag) formulated in oil adjuvants. Safety concerns are related to the use of oil adjuvants in multivalent vaccines for fish, since adverse side effects (e.g., adhesions) can appear. Therefore, there is a request for vaccine formulations for which protection will be maintained or improved, while the risk of side effects is reduced. Here, by using an inactivated salmonid alphavirus (SAV) as the test Ag, the combined use of two Toll-like receptor (TLR) ligand adjuvants, CpG oligonucleotides (ODNs) and poly I:C, as well as a genetic adjuvant consisting of a DNA plasmid vector expressing the viral haemorrhagic septicaemia virus (VHSV) glycoprotein (G) was explored. VHSV-G DNA vaccine was intramuscularly injected in combination with intraperitoneal injection of either SAV Ag alone or combined with the oil adjuvant, Montanide ISA763, or the CpG/polyI:C combo. Adjuvant formulations were evaluated for their ability to boost immune responses and induce protection against SAV in Atlantic salmon, following cohabitation challenge. It was observed that CpG/polyI:C-based formulations generated the highest neutralizing antibody titres (nAbs) before challenge, which endured post challenge. nAb responses for VHSV G-DNA- and oil-adjuvanted formulations were marginal compared to the CpG/poly I:C treatment. Interestingly, heat-inactivated sera showed reduced nAb titres compared to their non-heated counterparts, which suggests a role of complement-mediated neutralization against SAV. Consistently elevated levels of innate antiviral immune genes in the CpG/polyI:C injected groups suggested a role of IFN-mediated responses. Co-delivery of the VHSV-G DNA construct with either CpG/polyI:C or oil-adjuvanted SAV vaccine generated higher CD4 responses in head kidney at 48 h compared to injection of this vector or SAV Ag alone. The results demonstrate that a combination of pattern recognizing receptor (PRR

  7. Vaccine Adjuvants in Fish Vaccines Make a Difference: Comparing Three Adjuvants (Montanide ISA763A Oil, CpG/Poly I:C Combo and VHSV Glycoprotein Alone or in Combination Formulated with an Inactivated Whole Salmonid Alphavirus Antigen

    Directory of Open Access Journals (Sweden)

    Hanna L. Thim

    2014-03-01

    Full Text Available Most commercial vaccines offered to the aquaculture industry include inactivated antigens (Ag formulated in oil adjuvants. Safety concerns are related to the use of oil adjuvants in multivalent vaccines for fish, since adverse side effects (e.g., adhesions can appear. Therefore, there is a request for vaccine formulations for which protection will be maintained or improved, while the risk of side effects is reduced. Here, by using an inactivated salmonid alphavirus (SAV as the test Ag, the combined use of two Toll-like receptor (TLR ligand adjuvants, CpG oligonucleotides (ODNs and poly I:C, as well as a genetic adjuvant consisting of a DNA plasmid vector expressing the viral haemorrhagic septicaemia virus (VHSV glycoprotein (G was explored. VHSV-G DNA vaccine was intramuscularly injected in combination with intraperitoneal injection of either SAV Ag alone or combined with the oil adjuvant, Montanide ISA763, or the CpG/polyI:C combo. Adjuvant formulations were evaluated for their ability to boost immune responses and induce protection against SAV in Atlantic salmon, following cohabitation challenge. It was observed that CpG/polyI:C-based formulations generated the highest neutralizing antibody titres (nAbs before challenge, which endured post challenge. nAb responses for VHSV G-DNA- and oil-adjuvanted formulations were marginal compared to the CpG/poly I:C treatment. Interestingly, heat-inactivated sera showed reduced nAb titres compared to their non-heated counterparts, which suggests a role of complement-mediated neutralization against SAV. Consistently elevated levels of innate antiviral immune genes in the CpG/polyI:C injected groups suggested a role of IFN-mediated responses. Co-delivery of the VHSV-G DNA construct with either CpG/polyI:C or oil-adjuvanted SAV vaccine generated higher CD4 responses in head kidney at 48 h compared to injection of this vector or SAV Ag alone. The results demonstrate that a combination of pattern recognizing

  8. Montanide ISA 71 VG adjuvant enhances antibody and cell-ediated immune responses to profilin subunit antigen vaccination and promotes protection against Eimeria acervulina and Eimeria tenella

    Science.gov (United States)

    The present study was conducted to investigate the immunoenhancing effects of ISA 71 VG adjuvant on profilin subunit antigen vaccination. Broiler chickens were immunized subcutaneously with a purified Eimeria acervulina recombinant profilin protein, either alone or mixed with ISA 71 VG, and host imm...

  9. Safety and enhanced immunogenicity of a hepatitis B core particle Plasmodium falciparum malaria vaccine formulated in adjuvant Montanide ISA 720 in a phase I trial.

    NARCIS (Netherlands)

    Oliveira, G.A.; Wetzel, K.; Calvo-Calle, J.M.; Nussenzweig, R.; Schmidt, A.; Birkett, A.; Dubovsky, F.; Tierney, E.; Gleiter, C.H.; Boehmer, G.; Luty, A.J.F.; Ramharter, M.; Thornton, G.B.; Kremsner, P.G.; Nardin, E.H.

    2005-01-01

    Highly purified subunit vaccines require potent adjuvants in order to elicit optimal immune responses. In a previous phase I trial, an alum formulation of ICC-1132, a malaria vaccine candidate comprising hepatitis B core (HBc) virus-like particle containing Plasmodium falciparum circumsporozoite

  10. 抑制素主动免疫对大鼠生殖激素及卵巢发育的影响:Montanide和Freund's佐剂效应比较%Effects of Active Immunization against Inhibin on Hormonal Level and Ovarian Development in Rats:Comparison of Montanide and Freund's Adjuvant

    Institute of Scientific and Technical Information of China (English)

    曹晓涵; 王振华; 韩兴发; 朱时雅; 张福刚; 曾宪垠

    2012-01-01

    The aim of this study was to investigate the effect of active immunization using inhibin o subunit mature peptide(roINH) with Montanide(MON) and Freund's (FA) adjuvants on ovarian development in Xinjiang Fine-wool sheep. 72 Sprague Dawley female rats of (9-10)-week-old were divided into 3 groups and actively immunized against the recombination fusion protein of Xinjiang Fine-wool sheep roINH with roINH+MON adjuvant (MON group) or roINH+FA adjuvant (FA group), or injected with physiological saline (control group), respectively. Each rat received a primary immunization and 2 booster immunization at 20-day interval. The results showed that, the antibody titer of MON group was significantly higher than that of FA group (P 0. 05); mean concentration and peak of LH between the two immune groups had no significant difference(P>0. 05).There was no significant increase between MON and FA groups in the number of mature follicle (P>0. 05), which were both significant higher than that in control group (P<0. 05). Compared to FA group, the inflammatorial size was smaller and the inflammatory reaction was weaker in MON group. These results clearly demonstrate that active immunization against inhibin a subunit mature peptide in MON or FA adjuvants both can enhance immune effect, furthermore, the inflammatory reaction of MON adjuvant is less than that of FA adjuvant.%本研究采用新疆细毛羊抑制素成熟区序列重组融合蛋白(roINH)作为免疫原,以Montanide (MON)和Freund's (FA)作为佐剂,主动免疫SD大鼠,测定生殖激素及卵巢发育情况,评价佐剂效应.选用72只9~10周龄性成熟雌性SD大鼠,随机分为3组,分别皮下注射生理盐水(对照组)、roINH+ MON(MON组)和roINH+FA (FA组).各组大鼠每20 d免疫1次,连续免疫3次.结果,MON组产生的抗体滴度显著高于FA组(P<0.05);与对照组相比,注射roINH+MON和roINH+FA均可极显著提高大鼠血清FSH平均含量(P<0.01),显著提高P峰值(P<0.05),

  11. EVALUATION OF OIL BASED AVIAN INFLUENZA VACCINE (H5NI PREPARED WITH DIFFERENT CONCENTRATIONS OF ADJUVANT

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    M. IQBAL, M. NISAR, ANWARUL-HAQ, S. NOOR AND Z. J. GILL

    2008-12-01

    Full Text Available Bird flu vaccine from H5N1 strain of avian influenza virus was prepared with two concentrations of adjuvant (Montanide ISA 70MVG. Two vaccines (I and II were prepared containing 50 and 60% Montanide, respectively. Immune response of both the vaccines as single, as well as booster, dose was evaluated in layer birds through haemagglutination inhibition test. Single dose of both vaccines showed poor immune response, while booster dose gave better response with both the vaccines. However, the vaccine prepared with 60% Montanide provided better immune response compared with the vaccine containing 50% montanide.

  12. Induction of systemic and mucosal immunity against methicillin-resistant Staphylococcus aureus infection by a novel nanoemulsion adjuvant vaccine

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    Sun HW

    2015-12-01

    Full Text Available HongWu Sun,1,* Chao Wei,1,* BaoShuai Liu,1 HaiMing Jing,1 Qiang Feng,2 YaNan Tong,1 Yun Yang,1 LiuYang Yang,1 QianFei Zuo,1 Yi Zhang,1 QuanMing Zou,1 Hao Zeng1 1National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University of Chinese PLA, 2Department of Biological and Chemical Engineering, Chongqing University of Education, Chongqing, People’s Republic of China *These authors contributed equally to this work Abstract: The Gram-positive bacterial pathogen methicillin-resistant Staphylococcus aureus (MRSA can cause infections in the bloodstream, endocardial tissue, respiratory tract, culture-confirmed skin, or soft tissue. There are currently no effective vaccines, and none are expected to become available in the near future. An effective vaccine capable of eliciting both systemic and mucosal immune responses is also urgently needed. Here, we reported a novel oil-in-water nanoemulsion adjuvant vaccine containing an MRSA recombination protein antigen, Cremophor EL-35® as a surfactant, and propylene glycol as a co-surfactant. This nanoemulsion vaccine, whose average diameter was 31.34±0.49 nm, demonstrated good protein structure integrity, protein specificity, and good stability at room temperature for 1 year. The intramuscular systemic and nasal mucosal immune responses demonstrated that this nanoemulsion vaccine could improve the specific immune responses of immunoglobulin (IgG and related subclasses, such as IgG1, IgG2a, and IgG2b, as well as IgA, in the serum after Balb/c mice intramuscular immunization and C57 mice nasal immunization. Furthermore, this nanoemulsion vaccine also markedly enhanced the interferon-γ and interleukin-17A cytokine cell immune response, improved the survival ratio, and reduced bacterial colonization. Taken together, our results show that this novel nanoemulsion vaccine has great potential and is a

  13. Induction of systemic and mucosal immunity against methicillin-resistant Staphylococcus aureus infection by a novel nanoemulsion adjuvant vaccine.

    Science.gov (United States)

    Sun, HongWu; Wei, Chao; Liu, BaoShuai; Jing, HaiMing; Feng, Qiang; Tong, YaNan; Yang, Yun; Yang, LiuYang; Zuo, QianFei; Zhang, Yi; Zou, QuanMing; Zeng, Hao

    2015-01-01

    The Gram-positive bacterial pathogen methicillin-resistant Staphylococcus aureus (MRSA) can cause infections in the bloodstream, endocardial tissue, respiratory tract, culture-confirmed skin, or soft tissue. There are currently no effective vaccines, and none are expected to become available in the near future. An effective vaccine capable of eliciting both systemic and mucosal immune responses is also urgently needed. Here, we reported a novel oil-in-water nanoemulsion adjuvant vaccine containing an MRSA recombination protein antigen, Cremophor EL-35(®) as a surfactant, and propylene glycol as a co-surfactant. This nanoemulsion vaccine, whose average diameter was 31.34±0.49 nm, demonstrated good protein structure integrity, protein specificity, and good stability at room temperature for 1 year. The intramuscular systemic and nasal mucosal immune responses demonstrated that this nanoemulsion vaccine could improve the specific immune responses of immunoglobulin (Ig)G and related subclasses, such as IgG1, IgG2a, and IgG2b, as well as IgA, in the serum after Balb/c mice intramuscular immunization and C57 mice nasal immunization. Furthermore, this nanoemulsion vaccine also markedly enhanced the interferon-γ and interleukin-17A cytokine cell immune response, improved the survival ratio, and reduced bacterial colonization. Taken together, our results show that this novel nanoemulsion vaccine has great potential and is a robust generator of an effective intramuscular systemic and nasal mucosal immune response without the need for an additional adjuvant. Thus, the present study serves as a sound scientific foundation for future strategies in the development of this novel nanoemulsion adjuvant vaccine to enhance both the intramuscular systemic and nasal mucosal immune responses.

  14. Montanide, Poly I:C and nanoparticle based vaccines promote differential suppressor and effector cell expansion: a study of induction of CD8 T cells to a minimal Plasmodium berghei epitope

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    Kirsty Lee Wilson

    2015-02-01

    Full Text Available The development of practical and flexible vaccines to target liver stage malaria parasites would benefit from an ability to induce high levels of CD8 T cells to minimal peptide epitopes. Herein we compare different adjuvant and carrier systems in a murine model for induction of interferon gamma (IFN-γ producing CD8 T cells to the minimal immuno-dominant peptide epitope from the circumsporozoite protein (CSP of Plasmodium berghei, pb9 (SYIPSAEKI, referred to as KI. Two pro-inflammatory adjuvants, Montanide and Poly I:C, and a non-classical, non-inflammatory nanoparticle based carrier (polystyrene nanoparticles, PSNPs, were compared side-by-side for their ability to induce potentially protective CD8 T cell responses after two immunisations. KI in Montanide (Montanide + KI or covalently conjugated to PSNPs (PSNPs-KI induced such high responses, whereas adjuvanting with Poly I:C or PSNPs without conjugation was ineffective. This result was consistent with an observed induction of an immunosuppressed environment by Poly I:C in the draining lymph node (dLN 48 hours post injection, which was reflected by increased frequencies of myeloid derived suppressor cells (MDSC and a proportion of inflammation reactive regulatory T cells (Treg expressing the tumour necrosis factor receptor 2 (TNFR2, as well as decreased dendritic cell (DC maturation. The other inflammatory adjuvant, Montanide, also promoted proportional increases in the TNFR2+ Treg subpopulation, but not MDSCs, in the dLN. By contrast, injection with non-inflammatory PSNPs did not cause these changes. Induction of high CD8 T cell responses, using minimal peptide epitopes, can be achieved by non-inflammatory carrier nanoparticles, which in contrast to some conventional inflammatory adjuvants, do not expand either MDSCs or inflammation reactive Tregs at the site of priming.

  15. The effect of adjuvants on the immune response induced by a DBL4e-ID4 VAR2CSA based Plasmodium falciparum vaccine against placental malaria

    DEFF Research Database (Denmark)

    Pinto, V V; Salanti, A; Joergensen, L M;

    2012-01-01

    ¿-ID4 to induce binding-inhibitory antibodies when formulated with adjuvants approved for human use. We have characterized the immune response of DBL4¿-ID4 in combination with Freund's complete and incomplete adjuvant and with three adjuvants currently being used in clinical trials: Montanide(®) ISA...

  16. Safety and immunogenicity of multi-antigen AMA1-based vaccines formulated with CoVaccine HT™ and Montanide ISA 51 in rhesus macaques

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    Walraven Vanessa

    2011-07-01

    Full Text Available Abstract Background Increasing the breadth of the functional antibody response through immunization with Plasmodium falciparum apical membrane antigen 1 (PfAMA1 multi-allele vaccine formulations has been demonstrated in several rodent and rabbit studies. This study assesses the safety and immunogenicity of three PfAMA1 Diversity-Covering (DiCo vaccine candidates formulated as an equimolar mixture (DiCo mix in CoVaccine HT™ or Montanide ISA 51, as well as that of a PfAMA1-MSP119 fusion protein formulated in Montanide ISA 51. Methods Vaccine safety in rhesus macaques was monitored by animal behaviour observation and assessment of organ and systemic functions through clinical chemistry and haematology measurements. The immunogenicity of vaccine formulations was assessed by enzyme-linked immunosorbent assays and in vitro parasite growth inhibition assays with three culture-adapted P. falciparum strains. Results These data show that both adjuvants were well tolerated with only transient changes in a few of the chemical and haematological parameters measured. DiCo mix formulated in CoVaccine HT™ proved immunologically and functionally superior to the same candidate formulated in Montanide ISA 51. Immunological data from the fusion protein candidate was however difficult to interpret as four out of six immunized animals were non-responsive for unknown reasons. Conclusions The study highlights the safety and immunological benefits of DiCo mix as a potential human vaccine against blood stage malaria, especially when formulated in CoVaccine HT™, and adds to the accumulating data on the specificity broadening effects of DiCo mix.

  17. Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs25 formulated with montanide ISA 51.

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    Yimin Wu

    Full Text Available BACKGROUND: Pfs25 and Pvs25, surface proteins of mosquito stage of the malaria parasites P. falciparum and P. vivax, respectively, are leading candidates for vaccines preventing malaria transmission by mosquitoes. This single blinded, dose escalating, controlled Phase 1 study assessed the safety and immunogenicity of recombinant Pfs25 and Pvs25 formulated with Montanide ISA 51, a water-in-oil emulsion. METHODOLOGY/PRINCIPAL FINDINGS: The trial was conducted at The Johns Hopkins Center for Immunization Research, Washington DC, USA, between May 16, 2005-April 30, 2007. The trial was designed to enroll 72 healthy male and non-pregnant female volunteers into 1 group to receive adjuvant control and 6 groups to receive escalating doses of the vaccines. Due to unexpected reactogenicity, the vaccination was halted and only 36 volunteers were enrolled into 4 groups: 3 groups of 10 volunteers each were immunized with 5 microg of Pfs25/ISA 51, 5 microg of Pvs25/ISA 51, or 20 microg of Pvs25/ISA 51, respectively. A fourth group of 6 volunteers received adjuvant control (PBS/ISA 51. Frequent local reactogenicity was observed. Systemic adverse events included two cases of erythema nodosum considered to be probably related to the combination of the antigen and the adjuvant. Significant antibody responses were detected in volunteers who completed the lowest scheduled doses of Pfs25/ISA 51. Serum anti-Pfs25 levels correlated with transmission blocking activity. CONCLUSION/SIGNIFICANCE: It is feasible to induce transmission blocking immunity in humans using the Pfs25/ISA 51 vaccine, but these vaccines are unexpectedly reactogenic for further development. This is the first report that the formulation is associated with systemic adverse events including erythema nodosum. TRIAL REGISTRATION: ClinicalTrials.gov NCT00295581.

  18. Montanide ISA 720 vaccines: quality control of emulsions, stability of formulated antigens, and comparative immunogenicity of vaccine formulations.

    Science.gov (United States)

    Miles, Aaron P; McClellan, Holly A; Rausch, Kelly M; Zhu, Daming; Whitmore, Michael D; Singh, Sanjay; Martin, Laura B; Wu, Yimin; Giersing, Birgitte K; Stowers, Anthony W; Long, Carole A; Saul, Allan

    2005-03-31

    Montanide ISA 720 is an experimental adjuvant, formulated as water-in-oil emulsions, that induces high antibody titers in several animal species. It has been used in human vaccine trials with malaria and HIV vaccines. The heightened response is likely due, in part, to the formation of a depot at the injection site. However, post-formulation modifications were seen with seven proteins tested during storage of ISA 720 formulations at 37 degrees C for 1 week and two proteins stored longer at 4 degrees C. Potency studies in mice, in which the stored vaccines were diluted into placebo emulsions for appropriate dosing, indicated that this instability could lead to loss of immunogenicity in the post-injection depot, limiting the allowable storage time of preformed vaccines. We describe point-of-injection formulation for ISA 720 vaccines that meets the requirement for in vitro stability. For preformed vaccines, addition of glycine or glycylglycine prevented antigen modification on storage at 37 degrees C, providing a potential way of stabilizing antigen/ISA 720 formulations for in vitro storage and the post-injection depot.

  19. Tumor-reactive CD8+ T-cell responses after vaccination with NY-ESO-1 peptide, CpG 7909 and Montanide ISA-51: association with survival.

    Science.gov (United States)

    Karbach, Julia; Gnjatic, Sacha; Bender, Armin; Neumann, Antje; Weidmann, Eckhart; Yuan, Jianda; Ferrara, Cathy A; Hoffmann, Eric; Old, Lloyd J; Altorki, Nasser K; Jäger, Elke

    2010-02-15

    Peptide-based vaccines have led to the induction of antigen-specific CD8(+) T-cell responses in patients with NY-ESO-1 positive cancers. However, vaccine-induced T-cell responses did not generally correlate with improved survival. Therefore, we tested whether a synthetic CpG 7909 ODN (deoxycytidyl-deoxyguanosin oligodeoxy-nucleotides) mixed with NY-ESO-1 peptide p157-165 and incomplete Freund's adjuvants (Montanide(R) ISA-51) led to enhanced NY-ESO-1 antigen-specific CD8(+) immune responses in patients with NY-ESO-1 or LAGE-1 expressing tumors. Of 14 HLA-A2+ patients enrolled in the study, 5 patients withdrew prematurely because of progressive disease and 9 patients completed 1 cycle of immunization. Nine of 14 patients developed measurable and sustained antigen-specific CD8(+) T-cell responses: Four had detectable CD8+ T-cells against NY-ESO-1 after only 2 vaccinations, whereas 5 patients showed a late-onset but durable induction of NY-ESO-1 p157-165 specific T-cell response during continued vaccination after 4 months. In 6 patients, vaccine-induced antigen-specific T-cells became detectable ex vivo and reached frequencies of up to 0.16 % of all circulating CD8(+) T-cells. Postvaccine T-cell clones were shown to recognize and lyse NY-ESO-1 expressing tumor cell lines in vitro. In 6 of 9 patients developing NY-ESO-1-specific immune responses, a favorable clinical outcome with overall survival times of 43+, 42+, 42+, 39+, 36+ and 27+ months, respectively, was observed.

  20. Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy

    Science.gov (United States)

    2015-09-01

    Mesothelioma after Completion of Multimodality Therapy PRINCIPAL INVESTIGATOR: Dr. Marjorie Zauderer CONTRACTING ORGANIZATION: Sloan-Kettering Cancer ...peptides that are given together with Montanide and GM-CSF as immunologic adjuvants. This WT1 vaccine was previously tested in a small pilot trial, and...GM- CSF as immunologic adjuvants. This WT1 vaccine was previously tested in a small pilot trial, and shown to be safe and immunogenic. We have

  1. Montanide™ ISA 71 VG adjuvant enhances antibody and cell-mediated immune responses to profilin subunit antigen vaccination and promotes protection against Eimeria acervulina and Eimeria tenella. Experimental Parasitology

    Science.gov (United States)

    The present study was conducted to investigate the immunoenhancing effects of MontanideTM ISA 71 VG adjuvant on profilin subunit antigen vaccination. Broiler chickens were immunized subcutaneously with a purified Eimeria acervulina recombinant profilin protein, either alone or mixed with ISA 71 VG, ...

  2. A phase 1 trial of MSP2-C1, a blood-stage malaria vaccine containing 2 isoforms of MSP2 formulated with Montanide® ISA 720.

    Directory of Open Access Journals (Sweden)

    James S McCarthy

    Full Text Available BACKGROUND: In a previous Phase 1/2b malaria vaccine trial testing the 3D7 isoform of the malaria vaccine candidate Merozoite surface protein 2 (MSP2, parasite densities in children were reduced by 62%. However, breakthrough parasitemias were disproportionately of the alternate dimorphic form of MSP2, the FC27 genotype. We therefore undertook a dose-escalating, double-blinded, placebo-controlled Phase 1 trial in healthy, malaria-naïve adults of MSP2-C1, a vaccine containing recombinant forms of the two families of msp2 alleles, 3D7 and FC27 (EcMSP2-3D7 and EcMSP2-FC27, formulated in equal amounts with Montanide® ISA 720 as a water-in-oil emulsion. METHODOLOGY/PRINCIPAL FINDINGS: The trial was designed to include three dose cohorts (10, 40, and 80 µg, each with twelve subjects receiving the vaccine and three control subjects receiving Montanide® ISA 720 adjuvant emulsion alone, in a schedule of three doses at 12-week intervals. Due to unexpected local reactogenicity and concern regarding vaccine stability, the trial was terminated after the second immunisation of the cohort receiving the 40 µg dose; no subjects received the 80 µg dose. Immunization induced significant IgG responses to both isoforms of MSP2 in the 10 µg and 40 µg dose cohorts, with antibody levels by ELISA higher in the 40 µg cohort. Vaccine-induced antibodies recognised native protein by Western blots of parasite protein extracts and by immunofluorescence microscopy. Although the induced anti-MSP2 antibodies did not directly inhibit parasite growth in vitro, IgG from the majority of individuals tested caused significant antibody-dependent cellular inhibition (ADCI of parasite growth. CONCLUSIONS/SIGNIFICANCE: As the majority of subjects vaccinated with MSP2-C1 developed an antibody responses to both forms of MSP2, and that these antibodies mediated ADCI provide further support for MSP2 as a malaria vaccine candidate. However, in view of the reactogenicity of this

  3. MF59- and Al(OH3-adjuvanted Staphylococcus aureus (4C-Staph vaccines induce sustained protective humoral and cellular immune responses, with a critical role for effector CD4 T cells at low antibody titers.

    Directory of Open Access Journals (Sweden)

    Elisabetta eMonaci

    2015-09-01

    Full Text Available Staphylococcus aureus (S. aureus is an important opportunistic pathogen that may cause invasive life-threatening infections like sepsis and pneumonia. Due to increasing antibiotic-resistance, the development of an effective vaccine against S. aureus is needed. Although a correlate of protection against staphylococcal diseases is not yet established, several findings suggest that both antibodies and CD4 T cells might contribute to optimal immunity. In this study, we show that adjuvanting a multivalent vaccine (4C-Staph with MF59, an oil-in-water emulsion licensed in human vaccines, further potentiated antigen-specific IgG titers and CD4 T cell responses compared to alum and conferred protection in the peritonitis model of S. aureus infection. Moreover, we showed that MF59- and alum-adjuvanted 4C-Staph vaccines induced persistent antigen-specific humoral and T cell responses, and protected mice from infection up to 4 months after immunization. Furthermore, 4C-Staph formulated with MF59 was used to investigate which immune compartment is involved in vaccine-induced protection. Using CD4 T cell-depleted mice or B cell deficient mice, we demonstrated that both T and B cell responses contributed to 4C-Staph vaccine-mediated protective immunity. However, the role of CD4 T cells seemed more evident in the presence of low antibody responses. This study provides preclinical data further supporting the use of the adjuvanted 4C-Staph vaccines against S. aureus diseases, and provides critical insights on the correlates of protective immunity necessary to combat this pathogen.

  4. Resiquimod as an Immunologic Adjuvant for NY-ESO-1 Protein Vaccination in Patients with High Risk Melanoma

    Science.gov (United States)

    Gnjatic, Sacha; Cruz, Crystal M.; Vengco, Isabelita; Hasan, Farah; Spadaccia, Meredith; Darvishian, Farbod; Chiriboga, Luis; Holman, Rose Marie; Escalon, Juliet; Muren, Caroline; Escano, Crystal; Yepes, Ethel; Sharpe, Dunbar; Vasilakos, John P.; Rolnitzsky, Linda; Goldberg, Judith; Mandeli, John; Adams, Sylvia; Jungbluth, Achim; Pan, Linda; Venhaus, Ralph; Ott, Patrick A.; Bhardwaj, Nina

    2015-01-01

    The TLR7/8 agonist, Resiquimod has been used as an immune adjuvant in cancer vaccines. We evaluated the safety and immunogenicity of the cancer testis antigen NY-ESO-1 given in combination with Montanide with or without Resiquimod in high-risk melanoma patients. In Part I of the study, patients received 100ug full length NY-ESO-1 protein emulsified in 1.25mL Montanide (day 1) followed by topical application of 1000mg of 0.2% Resiquimod gel on days 1 and 3 (Cohort 1) versus days 1, 3, and 5 (Cohort 2) of a 21 day cycle. In Part II, patients were randomized to receive 100ug NY-ESO-1 protein plus Montanide (day 1) followed by topical application of placebo gel (Arm-A; N=8) or 1000mg of 0.2% Resiquimod gel (Arm-B; N=12) using the dosing regimen established in Part I. The vaccine regimens were generally well-tolerated. NY-ESO-1-specific humoral responses were induced or boosted in all patients, many of whom had high titer antibodies. In Part II, 16 of 20 patients in both arms had NY-ESO-1-specific CD4+ T-cell responses. CD8+ T-cell responses were only seen in 3 of 12 patients in Arm B. Patients with TLR7 SNP rs179008 had a greater likelihood of developing NY-ESO-1-specific CD8+ responses. In conclusion, NY-ESO-1 protein in combination with Montanide with or without topical Resiquimod is safe and induces both antibody and CD4+ T-cell responses in the majority of patients; the small proportion of CD8+ T-cell responses suggests that the addition of topical Resiquimod to Montanide is not sufficient to induce consistent NY-ESO-1-specific CD8+ T-cell responses. PMID:25633712

  5. CpG Oligodeoxynucleotide and Montanide ISA 51 Adjuvant Combination Enhanced the Protective Efficacy of a Subunit Malaria Vaccine

    Science.gov (United States)

    2004-02-01

    resistance by the parasite and mosquito resistance to commonly used insecticides. A vaccine that would reduce malaria-related mortality and morbidity of- fers...2002. A recombinant vaccine expressed in the milk of transgenic mice pro- tects Aotus monkeys from a lethal challenge with Plasmodium falciparum. Proc

  6. Novel adjuvants & delivery vehicles for vaccines development: a road ahead.

    Science.gov (United States)

    Mohan, Teena; Verma, Priyanka; Rao, D Nageswara

    2013-11-01

    The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines.

  7. Comparison of adjuvant formulations for cytotoxic T cell induction using synthetic peptides.

    Science.gov (United States)

    Hioe, C E; Qiu, H; Chend, P D; Bian, Z; Li, M L; Li, J; Singh, M; Kuebler, P; McGee, P; O'Hagan, D; Zamb, T; Koff, W; Allsopp, C; Wang, C Y; Nixon, D F

    1996-04-01

    We have investigated the capacity of synthetic peptides delivered in different adjuvant formulations to induce cytotoxic T lymphocyte (CTL) responses to a class I H-2Kd-restricted Plasmodium berghei circumsporozoite epitope, CS 252-260. Using three immunogen formulations: soybean emulsion; Montanide ISA720; and lipopeptide (P3-CS), we first evaluated the effects of immunization routes on CTL induction. No CTL response was induced in mice immunized s.c. or i.p. with CS peptide formulated in soybean emulsion. In contrast, immunization with lipopeptide P3-CS either s.c. or i.p. effectively primed for CTL. Interestingly, CS peptide emulsified in Montanide ISA720 induced a CTL response only when delivered s.c. and not i.p., indicating the critical influence of immunization routes on CTL induction. We then compared the effectiveness of eight adjuvant formulations to induce CTL response following a single s.c. immunization. Notably, lipopeptide P3-CS and CS peptide admixed with P3 or POE lipid molecules stimulated a vigorous CTL response. However, only mice immunized with P3-CS and CS peptide admixed with P3 molecule generated long-lived CTL which persisted in vivo for 5 months. Thus, based on a simultaneous comparison of the different adjuvant formulations, we demonstrated that the conjugated and unconjugated P3 lipopeptides were the most effective immunogens for eliciting primary and memory CTL in mice.

  8. Comparative assessment of humoral immune responses of aluminum hydroxide and oil-emulsion adjuvants in Influenza (H9N2) and Newcastle inactive vaccines to chickens.

    Science.gov (United States)

    Jafari, Mahdie; Moghaddam Pour, Masoud; Taghizadeh, Morteza; Masoudi, Shahin; Bayat, Zahra

    2017-02-01

    Context Adjuvants are compounds used in the preparation of inactive vaccines to enhance the immune response. Aluminum hydroxide (alum) is one of the first compounds approved by the Food and Drug Administration, which is used as adjuvants in vaccine products for humans. Montanide ISA 70 is an oil-emulsion adjuvant and is used in poultry inactive vaccines. Objective In this study, the effects of alum adjuvant on the efficiency and induction of immune response in inactive vaccines of Influenza and Newcastle are compared with those of ISA 70. Materials and methods Six groups of 7-d-old specific-pathogen-free chickens were inoculated with 0.3 ml of the prepared vaccines via the subcutaneous route in the neck. Immune response in each group after 7, 14, 21, 31, 41, and 45 d was evaluated using the technique of hemagglutination inhibition. Results The results were compared using SPSS software. Results showed that vaccines containing adjuvant ISA 70 depicted a higher increase in the immune response and adjuvant of 20% alum is similar to adjuvant of ISA 70 in boosting the immune system. There was no statistically significant difference between 10% and 20% alum, but these adjuvants are visibly different from ISA 70. Conclusion In conclusion, alum can be used as an easily accessible, harmless, and effective adjuvant; however, to increase the immune period using the inactive vaccines for poultry, more research would be necessary.

  9. Resiquimod as an immunologic adjuvant for NY-ESO-1 protein vaccination in patients with high-risk melanoma.

    Science.gov (United States)

    Sabado, Rachel Lubong; Pavlick, Anna; Gnjatic, Sacha; Cruz, Crystal M; Vengco, Isabelita; Hasan, Farah; Spadaccia, Meredith; Darvishian, Farbod; Chiriboga, Luis; Holman, Rose Marie; Escalon, Juliet; Muren, Caroline; Escano, Crystal; Yepes, Ethel; Sharpe, Dunbar; Vasilakos, John P; Rolnitzsky, Linda; Goldberg, Judith D; Mandeli, John; Adams, Sylvia; Jungbluth, Achim; Pan, Linda; Venhaus, Ralph; Ott, Patrick A; Bhardwaj, Nina

    2015-03-01

    The Toll-like receptor (TLR) 7/8 agonist resiquimod has been used as an immune adjuvant in cancer vaccines. We evaluated the safety and immunogenicity of the cancer testis antigen NY-ESO-1 given in combination with Montanide (Seppic) with or without resiquimod in patients with high-risk melanoma. In part I of the study, patients received 100 μg of full-length NY-ESO-1 protein emulsified in 1.25 mL of Montanide (day 1) followed by topical application of 1,000 mg of 0.2% resiquimod gel on days 1 and 3 (cohort 1) versus days 1, 3, and 5 (cohort 2) of a 21-day cycle. In part II, patients were randomized to receive 100-μg NY-ESO-1 protein plus Montanide (day 1) followed by topical application of placebo gel [(arm A; n = 8) or 1,000 mg of 0.2% resiquimod gel (arm B; n = 12)] using the dosing regimen established in part I. The vaccine regimens were generally well tolerated. NY-ESO-1-specific humoral responses were induced or boosted in all patients, many of whom had high titer antibodies. In part II, 16 of 20 patients in both arms had NY-ESO-1-specific CD4⁺ T-cell responses. CD8⁺ T-cell responses were only seen in 3 of 12 patients in arm B. Patients with TLR7 SNP rs179008 had a greater likelihood of developing NY-ESO-1-specific CD8⁺ responses. In conclusion, NY-ESO-1 protein in combination with Montanide with or without topical resiquimod is safe and induces both antibody and CD4⁺ T-cell responses in the majority of patients; the small proportion of CD8⁺ T-cell responses suggests that the addition of topical resiquimod to Montanide is not sufficient to induce consistent NY-ESO-1-specific CD8⁺ T-cell responses.

  10. Immunization with analog peptide in combination with CpG and montanide expands tumor antigen-specific CD8+ T cells in melanoma patients.

    Science.gov (United States)

    Fourcade, Julien; Kudela, Pavol; Andrade Filho, Pedro A; Janjic, Bratislav; Land, Stephanie R; Sander, Cindy; Krieg, Arthur; Donnenberg, Albert; Shen, Hongmei; Kirkwood, John M; Zarour, Hassane M

    2008-10-01

    Analog peptides represent a promising tool to further optimize peptide-based vaccines in promoting the expansion of tumor antigen-specific cytotoxic T lymphocytes. Here, we report the results of a pilot trial designed to study the immunogenicity of the analog peptide NY-ESO-1 157-165V in combination with CpG 7909/PF3512676 and Montanide ISA 720 in patients with stage III/IV NY-ESO-1-expressing melanoma. Eight patients were immunized either with Montanide and CpG (arm 1, 3 patients); Montanide and peptide NY-ESO-1 157-165V (arm 2, 2 patients); or with Montanide, CpG, and peptide NY-ESO-1 157-165V (arm 3, 3 patients). Only the 3 patients immunized with Montanide, CpG, and peptide NY-ESO-1 157-165V in arm 3 developed a rapid increase of effector-memory NY-ESO-1-specific CD8+ T cells, detectable ex vivo. The majority of these cells exhibited an intermediate/late-stage differentiated phenotype (CD28-). Our study further demonstrated that our vaccine approach stimulated spontaneous tumor-reactive NY-ESO-1-specific CD8+ T cells in 2 patients with advanced disease, but failed to prime tumor-reactive NY-ESO-1-specific T cells in 1 patient with no spontaneously tumor-induced CD8+ T-cell responses to NY-ESO-1. Collectively, our data support the capability of the analog peptide NY-ESO-1 157-165V in combination with CpG and Montanide to promote the expansion of NY-ESO-1-specific CD8+ T cells in patients with advanced cancer. They also suggest that the presence of tumor-induced NY-ESO-1-specific T cells of well-defined clonotypes is critical for the expansion of tumor-reactive NY-ESO-1-specific CD8+ T cells after peptide-based vaccine strategies.

  11. Adjuvants for Animal Vaccines.

    Science.gov (United States)

    Burakova, Yulia; Madera, Rachel; McVey, Scott; Schlup, John R; Shi, Jishu

    2017-06-15

    Vaccines are essential tools for the prevention and control of infectious diseases in animals. One of the most important steps in vaccine development is the selection of a suitable adjuvant. The focus of this review is the adjuvants used in vaccines for animals. We will discuss current commercial adjuvants and experimental formulations with attention to mineral salts, emulsions, bacterial-derived components, saponins, and several other immunoactive compounds. In addition, we will also examine the mechanisms of action for different adjuvants, examples of adjuvant combinations in one vaccine formulation, and challenges in the research and development of veterinary vaccine adjuvants.

  12. Adjuvants for malaria vaccines.

    Science.gov (United States)

    Coler, R N; Carter, D; Friede, M; Reed, S G

    2009-09-01

    There is a renewed enthusiasm about subunit vaccines for malaria coincident with the formation of new alliances and partnerships raising international public awareness, attracting increased resources and the re-focusing of research programs on adjuvant development for infectious disease vaccines. It is generally accepted that subunit vaccines for malaria will require adjuvants to induce protective immune responses, and availability of suitable adjuvants has in the past been a barrier to the development of malaria vaccines. Several novel adjuvants are now in licensed products or in late stage clinical development, while several others are in the earlier development pipeline. Successful vaccine development requires knowing which adjuvants to use and knowing how to formulate adjuvants and antigens to achieve stable, safe, and immunogenic vaccines. For the majority of vaccine researchers this information is not readily available, nor is access to well-characterized adjuvants. In this minireview, we outline the current state of adjuvant research and development as it pertains to effective malaria vaccines.

  13. Trends in vaccine adjuvants

    NARCIS (Netherlands)

    Schijns, V.E.J.C.; Lavelle, E.C.

    2011-01-01

    Adjuvants are essential components of most clinically used vaccines. This is because the majority of nonliving vaccines are relatively poor inducers of adaptive immunity unless effective adjuvants are co-administered. Aluminum salts (alum) have been used as adjuvants with great success for almost a

  14. Genomics of Staphylococcus

    Science.gov (United States)

    Lindsay, Jodi A.

    The staphylococci are Gram-positive cocci that divide to form clusters that look like grapes. By 16S ribosomal sequencing, they are most closely related to the Gram-positive, low G+C content Bacillus-Lactobacillus-Staphylococcus genera (Woese, 1987). There are over 30 species of staphylococci identified, and they are typically found on the skin and mucous membranes of mammals. About a dozen species are frequently carried on humans, including Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus capitis, Staphylococcus hominis, Staphylococcus cohnii, Staphylococcus lugdunensis, Staphylococcus schleiferi, Staphylococcus saprophyticus, Staphylococcus simulans, Staphylococcus warneri and Staphylococcus xylosus.

  15. [Influenza vaccine and adjuvant].

    Science.gov (United States)

    Nakayama, Tetsuo

    2011-01-01

    Adjuvant is originated from the Latin word "adjuvare" which means "help" in English to enhance the immunological responses when given together with antigens. The beginning of adjuvant was mineral oil which enhanced the immune response when it was given with inactivated Salmonella typhimurium. Aluminium salt was used to precipitate diphtheria toxoid and increased level of antibody response was demonstrated when administered with alum-precipitated antigens. Since 1930, aluminium salt has been used as DTaP (diphtheria-tetanus-acellular pertussis vaccine) adjuvant. Many candidates were tested for adjuvant activity but only aluminum salt is allowed to use for human vaccines. New adjuvant MF59, oil-in-water emulsion type, was developed for influenza vaccine for elderly (Fluad) and series of AS adjuvant are used for hepatitis B, pandemic flue, and human papiloma virus vaccines. Oil-adjuvanted influenza pandemic vaccines induced higher antibody response than alum-adjuvanted vaccine with higher incidence of adverse events, especially for local reactions. Alum-adjuvanted whole virion inactivated H5N1 vaccine was developed in Japan, and it induced relatively well immune responses in adults. When it applied for children, febrile reaction was noted in approximately 60% of the subjects, with higher antibodies. Recent investigation on innate immunity demonstrates that adjuvant activity is initiated from the stimulation on innate immunity and/or inflammasome, resulting in cytokine induction and antigen uptake by monocytes and macrophages. The probable reason for high incidence of febrile reaction should be investigated to develop a safe and effective influenza vaccine.

  16. Adjuvants for allergy vaccines

    National Research Council Canada - National Science Library

    Moingeon, Philippe

    2012-01-01

    .... Aluminum hydroxide or calcium phosphate are broadly used as adjuvants for subcutaneous allergy vaccines, whereas commercial sublingual vaccines rely upon high doses of aqueous allergen extracts...

  17. A single, low dose oral antigen exposure in newborn piglets primes mucosal immunity if administered with CpG oligodeoxynucleotides and polyphosphazene adjuvants.

    Science.gov (United States)

    Pasternak, J Alex; Ng, Siew Hon; Wilson, Heather L

    2014-10-15

    By definition, soluble antigens ingested orally trigger mucosal tolerance such that any subsequent re-exposure by a systemic route results in suppression of immunity. We propose that antigens introduced in extreme early life can readily traverse the gut wall and therefore circumvent induction of mucosal tolerance and instead induce immunity. Piglets were drenched with low-doses of ovalbumin (OVA; 5mg or 0.05 mg) alone, OVA plus adjuvants (CpG oligodeoxynucleotides and PCEP polyphosphazene) or saline within 6h of birth. At 28 days of age, they were administered 10mg OVA plus 1:1 Montanide adjuvant (or saline) via the intraperitoneal (i.p.) route or via the oral route. Serum was obtained on day 28 and day 49 to measure OVA-specific antibodies titres. All piglets boosted orally with OVA plus Montanide, regardless of prior OVA exposure, failed to induce immunity. As expected, piglets drenched with saline but boosted via the i.p. route with OVA plus Montanide showed significant induction of anti-OVA IgA, IgG, IgG1 and IgG2 relative to saline control piglets. Newborn animals drenched with 5mg or 0.05 mg OVA failed to induce oral immunity. A second intramuscular injection in adulthood triggered immunity in the piglets that were drenched with 0.05 mg OVA and boosted initially by the i.p. route suggesting that some systemic lymphocytes were primed despite initial lack of induction of humoral immunity. In contrast, piglets orally immunized with 5mg or 0.05 mg OVA plus adjuvants resulted in significant induction of anti-OVA IgA (5mg only), IgM, IgG, IgG1 and IgG2 in serum relative to saline control piglets as well as significant induction of anti-OVA IgA, IgM (5mg only) IgG, IgG1 (5mg only) or IgG2 relative to piglets drenched with OVA alone. These data clearly show that the response was sensitive to the oral vaccine components and was not simply a response to the i.p. immunization at day 28. This work demonstrates that newborn piglets respond to oral antigens with immunity

  18. Assessment of efficacy and safety of various adjuvant formulations with a total soluble extract of Trichinella spiralis

    Directory of Open Access Journals (Sweden)

    Aucouturier J.

    2001-06-01

    Full Text Available Trichinellosis, a re-emerging zoonosis in several countries and pig, is the main species responsible for its transmission to human. Vaccination of swine could be an alternative to prevent the risk of human contamination. In order to develop an efficient and safe inactivate vaccine, the choice of the adjuvant is an important issue. The aim of this study was to develop and select potent and safe adjuvants by screening them in an experimental model with a crude soluble antigen from L1 muscular larvae (ML of Trichinella spiralis (Ts. The efficacy was checked by the quantification of specific antibody levels. Specific and non-specific IgE antibody levels were also assessed. Safety was checked by the assessment of the local reaction at the injection site.Various Montanide® ISA adjuvant formulations including water in oil, oil in water and multiphasic emulsions, but also nanoparticles or microbeads were tested. The results clearly showed differences between the antibody responses induced by the adjuvants and demonstrated the necessity to use an adjuvant to obtain a specific IgG (IgG1or lgG2a response directed against the total soluble extract of Ts. All the formulations enhanced the humoral immune response. The origin of the oil contained in the emulsions played an important role on the efficacy. Indeed emulsions based on mineral oils were more efficient than those based on metabolisable oils. However it was linked with stronger local reactions. Multiphasic and oil in water emulsions but also nanoparticles failed to induce 1gG2a antibody levels. Microbeads and water in oil formulations based on mineral oils were more efficient. This experimentation allowed then the selection of several adjuvants which efficacy will be further Investigated by a challenge test and an analysis of the cellular populations involved in the mechanism of the immune response.

  19. Vaccination with NY-ESO-1 overlapping peptides mixed with Picibanil OK-432 and montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen.

    Science.gov (United States)

    Wada, Hisashi; Isobe, Midori; Kakimi, Kazuhiro; Mizote, Yu; Eikawa, Shingo; Sato, Eiichi; Takigawa, Nagio; Kiura, Katsuyuki; Tsuji, Kazuhide; Iwatsuki, Keiji; Yamasaki, Makoto; Miyata, Hiroshi; Matsushita, Hirokazu; Udono, Heiichiro; Seto, Yasuyuki; Yamada, Kazuhiro; Nishikawa, Hiroyoshi; Pan, Linda; Venhaus, Ralph; Oka, Mikio; Doki, Yuichiro; Nakayama, Eiichi

    2014-01-01

    We conducted a clinical trial of an NY-ESO-1 cancer vaccine using 4 synthetic overlapping long peptides (OLP; peptides #1, 79-108; #2, 100-129; #3, 121-150; and #4, 142-173) that include a highly immunogenic region of the NY-ESO-1 molecule. Nine patients were immunized with 0.25 mg each of three 30-mer and a 32-mer long NY-ESO-1 OLP mixed with 0.2 KE Picibanil OK-432 and 1.25 mL Montanide ISA-51. The primary endpoints of this study were safety and NY-ESO-1 immune responses. Five to 18 injections of the NY-ESO-1 OLP vaccine were well tolerated. Vaccine-related adverse events observed were fever and injection site reaction (grade 1 and 2). Two patients showed stable disease after vaccination. An NY-ESO-1-specific humoral immune response was observed in all patients and an antibody against peptide #3 (121-150) was detected firstly and strongly after vaccination. NY-ESO-1 CD4 and CD8 T-cell responses were elicited in these patients and their epitopes were identified. Using a multifunctional cytokine assay, the number of single or double cytokine-producing cells was increased in NY-ESO-1-specific CD4 and CD8 T cells after vaccination. Multiple cytokine-producing cells were observed in PD-1 (-) and PD-1 (+) CD4 T cells. In conclusion, our study indicated that the NY-ESO-1 OLP vaccine mixed with Picibanil OK-432 and Montanide ISA-51 was well tolerated and elicited NY-ESO-1-specific humoral and CD4 and CD8 T-cell responses in immunized patients.

  20. Randomized Phase II Trial of Adjuvant WT -1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy

    Science.gov (United States)

    2016-09-01

    randomized trial comparing treatment with the WT-1 peptide vaccine + Montanide/GM-CSF to treatment with Montanide/ GM-CSF alone in patients with MPM who...WT-1 peptide vaccine + Montanide/GM-CSF to treatment with Montanide/GM-CSF alone in patients with MPM who have completed multimodality therapy. The...GMP conditions by University of Iowa Pharmaceuticals. The investigational agent completed sterility and stability testing to ensure safety for human

  1. Adjuvant-enhanced antibody and cellular responses to inclusion bodies expressing FhSAP2 correlates with protection of mice to Fasciola hepatica.

    Science.gov (United States)

    Rivera, Francheska; Espino, Ana M

    2016-01-01

    Fasciola hepatica saposin-like protein-2 (FhSAP2) is a protein differentially expressed in various developmental stages of F. hepatica. Recombinant FhSAP2 has demonstrated the induction of partial protection in mice and rabbits when it is administered subcutaneously (SC) in Freund's adjuvant. Because FhSAP2 is overexpressed in bacteria in the form of inclusion bodies (IBs), we isolated IBs expressing FhSAP2 and tested their immunogenicity when administered SC in mice emulsified in two different adjuvants: QS-21 and Montanide TM ISA720. Animals received three injections containing 20 μg of protein two weeks apart and 4 weeks after the third injection, mice were infected with 10 F. hepatica metacercariae by oral route. The percentages of protection induced by FhSAP2-IBs were estimated to be between 60.0 and 62.5% when compared with adjuvant-vaccinated, infected controls. By determining the levels of IgG1 and IgG2a antibodies and IL-4 and IFNγ cytokines in the serum of experimental animals, it was found that both Th1 and Th2 immune responses were significantly increased in the FhSAP2-IBs vaccinated groups compared with the adjuvant-vaccinated, infected control groups. The adjuvant-vaccinated groups had significantly lower IgG1 to IgG2a ratios and lower IL-4 to IFNγ ratios than the FhSAP2-IBs vaccinated animals, which is indicative of higher levels of Th2 immune responses. Irrespective to the adjuvant used, animals vaccinated with FhSAP2-IBs exhibited significantly higher survival percentage and less liver damage than the adjuvant-control groups. This study suggests that FhSAP2 has potential as vaccine against F. hepatica and that the protection elicited by this molecule could be linked to a mechanism driven by the CD4-Th1 cells.

  2. Vaccines, adjuvants and autoimmunity.

    Science.gov (United States)

    Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

    2015-10-01

    Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Adjuvants for allergy vaccines.

    Science.gov (United States)

    Moingeon, Philippe

    2012-10-01

    Allergen-specific immunotherapy is currently performed via either the subcutaneous or sublingual routes as a treatment for type I (IgE dependent) allergies. Aluminum hydroxide or calcium phosphate are broadly used as adjuvants for subcutaneous allergy vaccines, whereas commercial sublingual vaccines rely upon high doses of aqueous allergen extracts in the absence of any immunopotentiator. Adjuvants to be included in the future in products for allergen specific immunotherapy should ideally enhance Th1 and CD4+ regulatory T cell responses. Imunomodulators impacting dendritic or T cell functions to induce IL10, IL12 and IFNγ production are being investigated in preclinical allergy models. Such candidate adjuvants encompass synthetic or biological immunopotentiators such as glucocorticoids, 1,25-dihydroxy vitamin D3, selected probiotic strains (e.g., Lactobacillus and Bifidobacterium species) as well as TLR2 (Pam3CSK4), TLR4 (monophosphoryl lipid A, synthetic lipid A analogs) or TLR9 (CpGs) ligands. Furthermore, the use of vector systems such as mucoadhesive particules, virus-like particles or liposomes are being considered to enhance allergen uptake by tolerogenic antigen presenting cells present in mucosal tissues.

  4. Staphylococcus aureus and Pregnancy

    Science.gov (United States)

    Staphylococcus aureus and Pregnancy In every pregnancy, a woman starts out with a 3-5% chance of having a ... This sheet talks about whether exposure to staphylococcus aureus may increase the risk for birth defects over ...

  5. Staphylococcus aureus and Pregnancy

    Science.gov (United States)

    Staphylococcus aureus (Staph Infection) In every pregnancy, a woman starts out with a 3-5% chance of having ... risk. This sheet talks about whether exposure to staphylococcus aureus may increase the risk for birth defects over ...

  6. Carbohydrate-based immune adjuvants

    Science.gov (United States)

    Petrovsky, Nikolai; Cooper, Peter D

    2011-01-01

    The role for adjuvants in human vaccines has been a matter of vigorous scientific debate, with the field hindered by the fact that for over 80 years, aluminum salts were the only adjuvants approved for human use. To this day, alum-based adjuvants, alone or combined with additional immune activators, remain the only adjuvants approved for use in the USA. This situation has not been helped by the fact that the mechanism of action of most adjuvants has been poorly understood. A relative lack of resources and funding for adjuvant development has only helped to maintain alum’s relative monopoly. To seriously challenge alum’s supremacy a new adjuvant has many major hurdles to overcome, not least being alum’s simplicity, tolerability, safety record and minimal cost. Carbohydrate structures play critical roles in immune system function and carbohydrates also have the virtue of a strong safety and tolerability record. A number of carbohydrate compounds from plant, bacterial, yeast and synthetic sources have emerged as promising vaccine adjuvant candidates. Carbohydrates are readily biodegradable and therefore unlikely to cause problems of long-term tissue deposits seen with alum adjuvants. Above all, the Holy Grail of human adjuvant development is to identify a compound that combines potent vaccine enhancement with maximum tolerability and safety. This has proved to be a tough challenge for many adjuvant contenders. Nevertheless, carbohydrate-based compounds have many favorable properties that could place them in a unique position to challenge alum’s monopoly over human vaccine usage. PMID:21506649

  7. Adjuvant Therapy: Melanoma

    Directory of Open Access Journals (Sweden)

    Diwakar Davar

    2011-01-01

    Full Text Available With an incidence that is increasing at 2–5% per year, cutaneous melanoma is an international scourge that disproportionately targets young individuals. Despite much research, the treatment of advanced disease is still quite challenging. Immunotherapy with high-dose interferon-α2b or interleukin-2 benefits a select group of patients in the adjuvant and metastatic settings, respectively, with significant attendant toxicity. Advances in the biology of malignant melanoma and the role of immunomodulatory therapy have produced advances that have stunned the field. In this paper, we review the data for the use of interferon-α2b in various dosing ranges, vaccine therapy, and the role of radiotherapy in the adjuvant setting for malignant melanoma. Recent trials in the metastatic setting using anticytoxic T-lymphocyte antigen-4 (anti-CTLA-4 monoclonal antibody therapy and BRAF inhibitor therapy have demonstrated clear benefit with prolongation of survival. Trials investigating combinations of these novel agents with existing immunomodulators are at present underway.

  8. Alzheimer’s disease AdvaxCpG- adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules

    Science.gov (United States)

    Davtyan, Hayk; Zagorski, Karen; Rajapaksha, Harinda; Hovakimyan, Armine; Davtyan, Arpine; Petrushina, Irina; Kazarian, Konstantin; Cribbs, David H.; Petrovsky, Nikolai; Agadjanyan, Michael G.; Ghochikyan, Anahit

    2016-01-01

    Although β-amyloid (Aβ) may be the primary driver of Alzheimer’s disease (AD) pathology, accumulation of pathological tau correlates with dementia in AD patients. Thus, the prevention/inhibition of AD may require vaccine/s targeting Aβ and tau simultaneously or sequentially. Since high antibody titers are required for AD vaccine efficacy, we have decided to generate vaccines, targeting Aβ (AV-1959R), Tau (AV-1980R) or Aβ/tau (AV-1953R) B cell epitopes, based on immunogenic MultiTEP platform and evaluate the immunogenicity of these vaccines formulated with AdvaxCpG, delta inulin, Alhydrogel®, Montanide-ISA51, Montanide-ISA720, MPLA-SM pharmaceutical grade adjuvants. Formulation of AV-1959R in AdvaxCpG induced the highest cellular and humoral immune responses in mice. The dual-epitope vaccine, AV-1953R, or the combination of AV-1959R and AV-1980R vaccines formulated with AdvaxCpG induced robust antibody responses against various forms of both, Aβ and tau pathological molecules. While anti-Aβ antibody titers after AV-1953R immunization were similar to that in mice vaccinated with AV-1959R or AV-1959R/AV-1980R combination, anti-tau titers were significantly lower after AV-1953R injection when compared to the AV-1980R or AV-1959R/AV-1980R. In silico 3D-modeling provided insight into the differences in immunogenicity of these vaccine constructs. In sum, AV-1959R and AV-1980R formulated with AdvaxCpG adjuvant were identified as promising immunogenic vaccines for ongoing pre-clinical assessment and future human clinical trials. PMID:27363809

  9. Alzheimer's disease Advax(CpG)- adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules.

    Science.gov (United States)

    Davtyan, Hayk; Zagorski, Karen; Rajapaksha, Harinda; Hovakimyan, Armine; Davtyan, Arpine; Petrushina, Irina; Kazarian, Konstantin; Cribbs, David H; Petrovsky, Nikolai; Agadjanyan, Michael G; Ghochikyan, Anahit

    2016-07-01

    Although β-amyloid (Aβ) may be the primary driver of Alzheimer's disease (AD) pathology, accumulation of pathological tau correlates with dementia in AD patients. Thus, the prevention/inhibition of AD may require vaccine/s targeting Aβ and tau simultaneously or sequentially. Since high antibody titers are required for AD vaccine efficacy, we have decided to generate vaccines, targeting Aβ (AV-1959R), Tau (AV-1980R) or Aβ/tau (AV-1953R) B cell epitopes, based on immunogenic MultiTEP platform and evaluate the immunogenicity of these vaccines formulated with Advax(CpG), delta inulin, Alhydrogel(®), Montanide-ISA51, Montanide-ISA720, MPLA-SM pharmaceutical grade adjuvants. Formulation of AV-1959R in Advax(CpG) induced the highest cellular and humoral immune responses in mice. The dual-epitope vaccine, AV-1953R, or the combination of AV-1959R and AV-1980R vaccines formulated with Advax(CpG) induced robust antibody responses against various forms of both, Aβ and tau pathological molecules. While anti-Aβ antibody titers after AV-1953R immunization were similar to that in mice vaccinated with AV-1959R or AV-1959R/AV-1980R combination, anti-tau titers were significantly lower after AV-1953R injection when compared to the AV-1980R or AV-1959R/AV-1980R. In silico 3D-modeling provided insight into the differences in immunogenicity of these vaccine constructs. In sum, AV-1959R and AV-1980R formulated with Advax(CpG) adjuvant were identified as promising immunogenic vaccines for ongoing pre-clinical assessment and future human clinical trials.

  10. Adjuvant therapies for colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The management of colon and rectal cancer has changed dramatically over the last 25 years. The use of adjuvant therapies has become standard practice in locally advanced (stage Ⅲ and selected stage Ⅱ) colorectal cancer. Improved surgical techniques, chemotherapeutics and radiotherapy are resulting in higher cure rates and the development of agents targeting proliferative and angiogenic pathways offer further promise. Here we explore risk factors for local and distant recurrence after resection of colon and rectal cancer, and the role of adjuvant treatments. Discussion will focus on the evidence base for adjuvant therapies utilised in colorectal cancer, and the treatment of sub-groups such as the elderly and stage Ⅱ disease. The role of adjuvant radiotherapy in rectal cancer in reduction of recurrence will be explored and the role and optimal methods for surveillance post-curative resection with or without adjuvant therapy will also be addressed.

  11. Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections.

    Science.gov (United States)

    Draughn, G Logan; Allen, C Leigh; Routh, Patricia A; Stone, Maria R; Kirker, Kelly R; Boegli, Laura; Schuchman, Ryan M; Linder, Keith E; Baynes, Ronald E; James, Garth; Melander, Christian; Pollard, Angela; Cavanagh, John

    2017-01-01

    2-Aminoimidazole (2-AI)-based compounds have been shown to efficiently disrupt biofilm formation, disperse existing biofilms, and resensitize numerous multidrug-resistant bacteria to antibiotics. Using Pseudomonas aeruginosa and Staphylococcus aureus, we provide initial pharmacological studies regarding the application of a 2-AI as a topical adjuvant for persistent dermal infections. In vitro assays indicated that the 2-AI H10 is nonbactericidal, resensitizes bacteria to antibiotics, does not harm the integument, and promotes wound healing. Furthermore, in vivo application of H10 on swine skin caused no gross abnormalities or immune reactions. Taken together, these results indicate that H10 represents a promising lead dermal adjuvant compound.

  12. Immunogenicity of a virosomally-formulated Plasmodium falciparum GLURP-MSP3 chimeric protein-based malaria vaccine candidate in comparison to adjuvanted formulations

    Directory of Open Access Journals (Sweden)

    Tamborrini Marco

    2011-12-01

    Full Text Available Abstract Background In clinical trials, immunopotentiating reconstituted influenza virosomes (IRIVs have shown great potential as a versatile antigen delivery platform for synthetic peptides derived from Plasmodium falciparum antigens. This study describes the immunogenicity of a virosomally-formulated recombinant fusion protein comprising domains of the two malaria vaccine candidate antigens MSP3 and GLURP. Methods The highly purified recombinant protein GMZ2 was coupled to phosphatidylethanolamine and the conjugates incorporated into the membrane of IRIVs. The immunogenicity of this adjuvant-free virosomal formulation was compared to GMZ2 formulated with the adjuvants Montanide ISA 720 and Alum in three mouse strains with different genetic backgrounds. Results Intramuscular injections of all three candidate vaccine formulations induced GMZ2-specific antibody responses in all mice tested. In general, the humoral immune response in outbred NMRI mice was stronger than that in inbred BALB/c and C57BL/6 mice. ELISA with the recombinant antigens demonstrated immunodominance of the GLURP component over the MSP3 component. However, compared to the Al(OH3-adjuvanted formulation the two other formulations elicited in NMRI mice a larger proportion of anti-MSP3 antibodies. Analyses of the induced GMZ2-specific IgG subclass profiles showed for all three formulations a predominance of the IgG1 isotype. Immune sera against all three formulations exhibited cross-reactivity with in vitro cultivated blood-stage parasites. Immunofluorescence and immunoblot competition experiments showed that both components of the hybrid protein induced IgG cross-reactive with the corresponding native proteins. Conclusion A virosomal formulation of the chimeric protein GMZ2 induced P. falciparum blood stage parasite cross-reactive IgG responses specific for both MSP3 and GLURP. GMZ2 thus represents a candidate component suitable for inclusion into a multi-valent virosomal

  13. ERM immersion vaccination and adjuvants

    DEFF Research Database (Denmark)

    Skov, J.; Chettri, J. K.; Jaafar, R. M.

    2015-01-01

    Two candidate adjuvants were tested with a commercial ERM dip vaccine (AquaVac™ Relera, MSD Animal Health) for rainbow trout in an experimental design compatible with common vaccination practices at farm level, i.e. immersion of fish in vaccine (±adjuvant) for 30 s. The adjuvants were...... the commercial product Montanide™ IMS 1312 VG PR (SEPPIC), and a soluble and ≥98% pure β-glucan from yeast (Saccharomyces cerevisiae) (Sigma-Aldrich). Hence, five experimental groups in duplicate were established and exposed to vaccine and adjuvants in the following combinations: AquaVac™ Relera (alone); Aqua......Vac™ Relera + Montanide™; AquaVac™ Relera + β-glucan; Montanide™ (alone); and β-glucan (alone). Approximately 450 degree days post-vaccination, the fish were bath-challenged with live Yersinia ruckeri to produce survival curves. Blood, skin and gills were sampled at selected time points during the course...

  14. How to define green adjuvants.

    Science.gov (United States)

    Beck, Bert; Steurbaut, Walter; Spanoghe, Pieter

    2012-08-01

    The concept 'green adjuvants' is difficult to define. This paper formulates an answer based on two approaches. Starting from the Organisation for Economic Cooperation and Development (OECD) definition for green chemistry, production-based and environmental-impact-based definitions for green adjuvants are proposed. According to the production-based approach, adjuvants are defined as green if they are manufactured using renewable raw materials as much as possible while making efficient use of energy, preferably renewable energy. According to the environmental impact approach, adjuvants are defined as green (1) if they have a low human and environmental impact, (2) if they do not increase active ingredient environmental mobility and/or toxicity to humans and non-target organisms, (3) if they do not increase the exposure to these active substances and (4) if they lower the impact of formulated pesticides by enhancing the performance of active ingredients, thus potentially lowering the required dosage of active ingredients. Based on both approaches, a tentative definition for 'green adjuvants' is given, and future research and legislation directions are set out.

  15. Chemokines as Cancer Vaccine Adjuvants

    Directory of Open Access Journals (Sweden)

    Agne Petrosiute

    2013-10-01

    Full Text Available We are witnessing a new era of immune-mediated cancer therapies and vaccine development. As the field of cancer vaccines advances into clinical trials, overcoming low immunogenicity is a limiting step in achieving full success of this therapeutic approach. Recent discoveries in the many biological roles of chemokines in tumor immunology allow their exploitation in enhancing recruitment of antigen presenting cells (APCs and effector cells to appropriate anatomical sites. This knowledge, combined with advances in gene therapy and virology, allows researchers to employ chemokines as potential vaccine adjuvants. This review will focus on recent murine and human studies that use chemokines as therapeutic anti-cancer vaccine adjuvants.

  16. New horizons in adjuvants for vaccine development.

    Science.gov (United States)

    Reed, Steven G; Bertholet, Sylvie; Coler, Rhea N; Friede, Martin

    2009-01-01

    Over the last decade, there has been a flurry of research on adjuvants for vaccines, and several novel adjuvants are now in licensed products or in late stage clinical development. The success of adjuvants in enhancing the immune response to recombinant antigens has led many researchers to re-focus their vaccine development programs. Successful vaccine development requires knowing which adjuvants to use and knowing how to formulate adjuvants and antigens to achieve stable, safe and immunogenic vaccines. For the majority of vaccine researchers this information is not readily available, nor is access to well-characterized adjuvants. In this review, we outline the current state of adjuvant research and development and how formulation parameters can influence the effectiveness of adjuvants.

  17. A Review and Prospect on Herbicide Adjuvants

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The history, present status and future prospects of adjuvants application in herbicides were briefly reviewed. Adjuvants can be separated into two groups, activator adjuvants and utility adjuvants. The former directly enhances the efficacy of a herbicide through increasement of herbicide absorption, spreading, cuticular penetration, rainfastness and retention enhancement, and photodegradation of the herbicide can also be decreased. And the latter is utilized for improving application characteristics, behaviors and physical properties of herbicides and reducing or minimizing unwanted side effects on application.

  18. Adjuvant therapy in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Paula Ghaneh; John Slavin; Robert Sutton; Mark Hartley; John P Neoptolemos

    2001-01-01

    The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic csncer, leading to a drsmatic reduction in post-operative mortality from the development of high volume specialized centres. This stimulated the study of adjuvant and neoadjuvant treatments in pancreatic cancer including chemoradiotherapy and chemotherapy. Initial protocols have been based on the original but rather small GITSG study first reported in 1985. There have been two large European trials totalling over 600 patients (EORTC and ESPAC-1) that do not support the use of chemoradiation as adjuvant therapy. A second major finding from the ESPAC-1 trial (541 patients randomized) was some but not conclusive evidence for a survival benefit associated with chemotherapy. A third major finding from the ESPAC-1 trial was that the quality of life was not affected by the use of adjuvant treatments compared to surgery alone.The ESPAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a randomized controlled trial of 990 patients.

  19. Combined synthetic and recombinant techniques for the development of lipoprotein-based, self-adjuvanting vaccines targeting human papillomavirus type-16 associated tumors.

    Science.gov (United States)

    Moyle, Peter M; Dai, Wei; Liu, Tzu-Yu; Hussein, Waleed M; Maruthayanar, Pirashanthini; Wells, James W; McMillan, Nigel A J; Skwarczynski, Mariusz; Toth, Istvan

    2015-12-01

    Human papillomaviruses (HPVs) are associated with various cancers, with HPV16 linked to more than half of cervical cancer cases. Vaccines to prevent HPV infection and cancer development have proven effective, but are not useful in individuals with prior HPV exposure. Treatment vaccines to eradicate or control HPV-associated lesions are therefore desirable for these patients. Herein we describe the development of a process to enable the production of semisynthetic vaccines based on the site-specific attachment of synthetic bacterial lipid analogs (e.g., Pam2Cys) to a non-oncogenic mutant HPV16 E7 protein to generate molecularly defined vaccines. Many cytotoxic lymphocyte (CTL) epitopes from E7 are delivered by this approach; potentially ensuring that large numbers of immunized individuals can generate CTLs to clear HPV infected cells. Delivery of this construct reduced the growth of HPV16-associated tumors in a TC1 mouse model, the effects of which were better than the potent CTL epitope HPV16 E7(44-57) administered with Montanide ISA51 adjuvant.

  20. Immunization with cocktail of HIV-derived peptides in montanide ISA-51 is immunogenic, but causes sterile abscesses and unacceptable reactogenicity.

    Directory of Open Access Journals (Sweden)

    Barney S Graham

    Full Text Available BACKGROUND: A peptide vaccine was produced containing B and T cell epitopes from the V3 and C4 Envelope domains of 4 subtype B HIV-1 isolates (MN, RF, CanO, & Ev91. The peptide mixture was formulated as an emulsion in incomplete Freund's adjuvant (IFA. METHODS: Low-risk, healthy adult subjects were enrolled in a randomized, placebo-controlled dose-escalation study, and selected using criteria specifying that 50% in each study group would be HLA-B7+. Immunizations were scheduled at 0, 1, and 6 months using a total peptide dose of 1 or 4 mg. Adaptive immune responses in16 vaccine recipients and two placebo recipients after the 2nd immunization were evaluated using neutralization assays of sera, as well as ELISpot and ICS assays of cryopreserved PBMCs to assess CD4 and CD8 T-cell responses. In addition, (51Cr release assays were performed on fresh PBMCs following 14-day stimulation with individual vaccine peptide antigens. RESULTS: 24 subjects were enrolled; 18 completed 2 injections. The study was prematurely terminated because 4 vaccinees developed prolonged pain and sterile abscess formation at the injection site-2 after dose 1, and 2 after dose 2. Two other subjects experienced severe systemic reactions consisting of headache, chills, nausea, and myalgia. Both reactions occurred after the second 4 mg dose. The immunogenicity assessments showed that 6/8 vaccinees at each dose level had detectable MN-specific neutralizing (NT activity, and 2/7 HLA-B7+ vaccinees had classical CD8 CTL activity detected. However, using both ELISpot and ICS, 8/16 vaccinees (5/7 HLA-B7+ and 0/2 controls had detectable vaccine-specific CD8 T-cell responses. Subjects with moderate or severe systemic or local reactions tended to have more frequent T cell responses and higher antibody responses than those with mild or no reactions. CONCLUSIONS: The severity of local responses related to the formulation of these four peptides in IFA is clinically unacceptable for continued

  1. Staphylococcus epidermidis infections.

    Science.gov (United States)

    Vuong, Cuong; Otto, Michael

    2002-04-01

    The opportunistic human pathogen Staphylococcus epidermidis has become the most important cause of nosocomial infections in recent years. Its pathogenicity is mainly due to the ability to form biofilms on indwelling medical devices. In a biofilm, S. epidermidis is protected against attacks from the immune system and against antibiotic treatment, making S. epidermidis infections difficult to eradicate.

  2. Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-priming.

    Science.gov (United States)

    Valmori, Danila; Souleimanian, Naira E; Tosello, Valeria; Bhardwaj, Nina; Adams, Sylvia; O'Neill, David; Pavlick, Anna; Escalon, Juliet B; Cruz, Crystal M; Angiulli, Angelica; Angiulli, Francesca; Mears, Gregory; Vogel, Susan M; Pan, Linda; Jungbluth, Achim A; Hoffmann, Eric W; Venhaus, Ralph; Ritter, Gerd; Old, Lloyd J; Ayyoub, Maha

    2007-05-22

    The use of recombinant tumor antigen proteins is a realistic approach for the development of generic cancer vaccines, but the potential of this type of vaccines to induce specific CD8(+) T cell responses, through in vivo cross-priming, has remained unclear. In this article, we report that repeated vaccination of cancer patients with recombinant NY-ESO-1 protein, Montanide ISA-51, and CpG ODN 7909, a potent stimulator of B cells and T helper type 1 (Th1)-type immunity, resulted in the early induction of specific integrated CD4(+) Th cells and antibody responses in most vaccinated patients, followed by the development of later CD8(+) T cell responses in a fraction of them. The correlation between antibody and T cell responses, together with the ability of vaccine-induced antibodies to promote in vitro cross-presentation of NY-ESO-1 by dendritic cells to vaccine-induced CD8(+) T cells, indicated that elicitation of NY-ESO-1-specific CD8(+) T cell responses by cross-priming in vivo was associated with the induction of adequate levels of specific antibodies. Together, our data provide clear evidence of in vivo cross-priming of specific cytotoxic T lymphocytes by a recombinant tumor antigen vaccine, underline the importance of specific antibody induction for the cross-priming to occur, and support the use of this type of formulation for the further development of efficient cancer vaccines.

  3. Nod2-mediated recognition of the microbiota is critical for mucosal adjuvant activity of cholera toxin

    Science.gov (United States)

    Kim, Donghyun; Kim, Yun-Gi; Seo, Sang-Uk; Kim, Dong-Jae; Kamada, Nobuhiko; Prescott, Dave; Philpott, Dana J.; Rosenstiel, Philip; Inohara, Naohiro; Núñez, Gabriel

    2016-01-01

    Cholera toxin (CT) is a potent adjuvant for inducing mucosal immune responses. However, the mechanism by which CT induces adjuvant activity remains unclear. Here we show that the microbiota is critical for inducing antigen-specific IgG production after intranasal immunization. After mucosal vaccination with CT, both antibiotic-treated mice and germ-free (GF) had reduced antigen-specific IgG, recall-stimulated cytokine responses, an impaired follicular helper T (TFH) response and reduced plasma cells. Recognition of symbiotic bacteria via Nod2 in CD11c+ cells was required for the adjuvanticity of CT. Reconstitution of GF mice with a Nod2 agonist or Staphylococcus sciuri having high Nod2-stimulatory activity was sufficient to promote robust CT adjuvant activity whereas bacteria with low Nod2-stimulatory activity did not. Mechanistically, CT enhanced Nod2-mediated cytokine production in DCs via intracellular cAMP. These results show an important role for the microbiota and the intracellular receptor Nod2 in promoting the mucosal adjuvant activity of CT. PMID:27064448

  4. Adjuvant

    Directory of Open Access Journals (Sweden)

    Ramadan M. Nafae

    2013-07-01

    Conclusion: Adjunctive 7 day course of low dose hydrocortisone IV in patients with CAP hastens clinical recovery and prevents the development of sepsis-related complications with a significant reduction in the duration of mechanical ventilation, duration of IV antibiotics and length of hospital stay with the improvement in hospital outcome and weaning success from mechanical ventilation.

  5. Novel Adjuvants and Immunomodulators for Veterinary Vaccines

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Fang, Yongxiang; Jungersen, Gregers

    2016-01-01

    Adjuvants are crucial for efficacy of vaccines, especially subunit and recombinant vaccines. Rational vaccine design, including knowledge-based and molecularly defined adjuvants tailored for directing and potentiating specific types of host immune responses towards the antigens included in the va...

  6. House dust extracts contain potent immunological adjuvants

    NARCIS (Netherlands)

    Beukelman, C.J.; Dijk, H. van; Aerts, P.C.; Rademaker, P.M.; Berrens, L.; Willers, J.M.N.

    1987-01-01

    A crude aqueous extract of house dust and two house dust subfractions were tested for adjuvant activity in a sensitivity assay performed in mice. Evidence is presented that house dust contains at least two potent immunological adjuvants. One of these, present in both subfractions, was probably endot

  7. The Position of His-Tag in Recombinant OspC and Application of Various Adjuvants Affects the Intensity and Quality of Specific Antibody Response after Immunization of Experimental Mice.

    Directory of Open Access Journals (Sweden)

    Michal Krupka

    Full Text Available Lyme disease, Borrelia burgdorferi-caused infection, if not recognized and appropriately treated by antibiotics, may lead to chronic complications, thus stressing the need for protective vaccine development. The immune protection is mediated by phagocytic cells and by Borrelia-specific complement-activating antibodies, associated with the Th1 immune response. Surface antigen OspC is involved in Borrelia spreading through the host body. Previously we reported that recombinant histidine tagged (His-tag OspC (rOspC could be attached onto liposome surfaces by metallochelation. Here we report that levels of OspC-specific antibodies vary substantially depending upon whether rOspC possesses an N' or C' terminal His-tag. This is the case in mice immunized: (a with rOspC proteoliposomes containing adjuvants MPLA or non-pyrogenic MDP analogue MT06; (b with free rOspC and Montanide PET GEL A; (c with free rOspC and alum; or (d with adjuvant-free rOspC. Stronger responses are noted with all N'-terminal His-tag rOspC formulations. OspC-specific Th1-type antibodies predominate post-immunization with rOspC proteoliposomes formulated with MPLA or MT06 adjuvants. Further analyses confirmed that the structural features of soluble N' and C' terminal His-tag rOspC and respective rOspC proteoliposomes are similar including their thermal stabilities at physiological temperatures. On the other hand, a change in the position of the rOspC His-tag from N' to C' terminal appears to affect substantially the immunogenicity of rOspC arguably due to steric hindrance of OspC epitopes by the C' terminal His-tag itself and not due to differences in overall conformations induced by changes in the His-tag position in rOspC variants.

  8. Adjuvants: Classification, Modus Operandi, and Licensing

    Science.gov (United States)

    Apostólico, Juliana de Souza

    2016-01-01

    Vaccination is one of the most efficient strategies for the prevention of infectious diseases. Although safer, subunit vaccines are poorly immunogenic and for this reason the use of adjuvants is strongly recommended. Since their discovery in the beginning of the 20th century, adjuvants have been used to improve immune responses that ultimately lead to protection against disease. The choice of the adjuvant is of utmost importance as it can stimulate protective immunity. Their mechanisms of action have now been revealed. Our increasing understanding of the immune system, and of correlates of protection, is helping in the development of new vaccine formulations for global infections. Nevertheless, few adjuvants are licensed for human vaccines and several formulations are now being evaluated in clinical trials. In this review, we briefly describe the most well known adjuvants used in experimental and clinical settings based on their main mechanisms of action and also highlight the requirements for licensing new vaccine formulations. PMID:27274998

  9. Vaccine Adjuvants: Putting Innate Immunity to Work

    Science.gov (United States)

    Coffman, Robert L.; Sher, Alan; Seder, Robert A.

    2012-01-01

    Adjuvants enhance immunity to vaccines and experimental antigens by a variety of mechanisms. In the past decade, many receptors and signaling pathways in the innate immune system have been defined and these innate responses strongly influence the adaptive immune response. The focus of this review is to delineate the innate mechanisms by which adjuvants mediate their effects. We highlight how adjuvants can be used to influence the magnitude and alter the quality of the adaptive response in order to provide maximum protection against specific pathogens. Despite the impressive success of currently approved adjuvants for generating immunity to viral and bacterial infections, there remains a need for improved adjuvants that enhance protective antibody responses, especially in populations that respond poorly to current vaccines. However, the larger challenge is to develop vaccines that generate strong T cell immunity with purified or recombinant vaccine antigens. PMID:21029960

  10. Staphylococcus aureus in cheese

    Directory of Open Access Journals (Sweden)

    Dubravka Samaržija

    2007-04-01

    Full Text Available Growth of Staphylococcus aureus in cheese during production and storage can lead to production of enterotoxins responsible for human diseases. Due to specificity of those bacteria and complexity of cheese as a grown media, sometimes in the field it is very difficult to estimate an initial risk assessment of the S. aureus surveying in different cheese varieties. Moreover, the literature data on frequency and proportion of enterotoxigenic strains that cause cheese contamination are significantly different. The purpose of the present review is to objectively assess the risk of the potential occurrences of S. aureus in cheese and significance with respect to safety. The basic characteristics of Staphylococcus aureus, their presence in cheese and its potential risk for health are briefly reviewed. The own results of study relating to the presence of S. aureus in traditional (autochthonous hard sheep cheese made from raw milk are also discussed in this review.

  11. Linezolid resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Pavani Gandham

    2014-08-01

    Full Text Available Linezolid is the only antibiotic available as an oral formulation for resistant staphylococcal infections. It is effective in skin and soft tissue infections, nosocomial pneumonias including VAP, infective endocarditis and MRSA meningitis. It is also effective in the eradication of both nasal and throat colonization of MRSA. Its high bioavailability and post antibiotic effect, ease of switching to oral therapy during its use and the fact that it can be used in patients of all ages, also in patients with liver disease and poor kidney function and its increased effectiveness over glycopeptides makes this drug a precious drug in the treatment of resistant staphylococcal infections. Linezolid resistance in staphylococcus is defined as a linezolid MIC of and #8805;8 mg/L. Reported Linezolid resistance in India and elsewhere is 2-20%. There is clonal dissemination of Linezolid Resistant Staphylococcus aureus (LRSA within or across health care settings which demands continuous surveillance to determine the emergent risk of resistance strains and to establish guidelines for appropriate use. Clinical laboratories should confirm any LRSA preferably by a second method, prior to using linezolid for serious infections. Effective surveillance, more judicious use of this antibiotic, avoiding linezolid usage for empiric therapy in hospital acquired staphylococcus infections, optimization of the pharmacological parameters of the antibiotics in specific clinical situation, decreasing bacterial load by timely surgical debridement or drainage of collections, use of combination therapies would prevent the emergence of resistance to linezolid in staphylococcus aureus. [Int J Res Med Sci 2014; 2(4.000: 1253-1256

  12. Adjuvants are Key Factors for the Development of Future Vaccines: Lessons from the Finlay Adjuvant Platform

    Science.gov (United States)

    Pérez, Oliver; Romeu, Belkis; Cabrera, Osmir; González, Elizabeth; Batista-Duharte, Alexander; Labrada, Alexis; Pérez, Rocmira; Reyes, Laura M.; Ramírez, Wendy; Sifontes, Sergio; Fernández, Nelson; Lastre, Miriam

    2013-01-01

    The development of effective vaccines against neglected diseases, especially those associated with poverty and social deprivation, is urgently needed. Modern vaccine technologies and a better understanding of the immune response have provided scientists with the tools for rational and safer design of subunit vaccines. Often, however, subunit vaccines do not elicit strong immune responses, highlighting the need to incorporate better adjuvants; this step therefore becomes a key factor for vaccine development. In this review we outline some key features of modern vaccinology that are linked with the development of better adjuvants. In line with the increased desire to obtain novel adjuvants for future vaccines, the Finlay Adjuvant Platform offers a novel approach for the development of new and effective adjuvants. The Finlay Adjuvants (AFs), AFPL (proteoliposome), and AFCo (cochleate), were initially designed for parenteral and mucosal applications, and constitute potent adjuvants for the induction of Th1 responses against several antigens. This review summarizes the status of the Finlay technology in producing promising adjuvants for unsolved-vaccine diseases including mucosal approaches and therapeutic vaccines. Ideas related to adjuvant classification, adjuvant selection, and their possible influence on innate recognition via multiple toll-like receptors are also discussed. PMID:24348475

  13. Safety of vaccine adjuvants: focus on autoimmunity.

    Science.gov (United States)

    van der Laan, Jan Willem; Gould, Sarah; Tanir, Jennifer Y

    2015-03-24

    Questions have been recently raised regarding the safety of vaccine adjuvants, particularly in relation to autoimmunity or autoimmune disease(s)/disorder(s) (AID). The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) formed a scientific committee and convened a 2-day workshop, consisting of technical experts from around the world representing academia, government regulatory agencies, and industry, to investigate and openly discuss the issues around adjuvant safety in vaccines. The types of adjuvants considered included oil-in-water emulsions and toll-like receptor (TLR) agonists. The state of science around the use of animal models and biomarkers for the evaluation and prediction of AID were also discussed. Following extensive literature reviews by the HESI committee, and presentations by experts at the workshop, several key points were identified, including the value of animal models used to study autoimmunity and AID toward studying novel vaccine adjuvants; whether there is scientific evidence indicating an intrinsic risk of autoimmunity and AID with adjuvants, or a higher risk resulting from the mechanism of action; and if there is compelling clinical data linking adjuvants and AID. The tripartite group of experts concluded that there is no compelling evidence supporting the association of vaccine adjuvants with autoimmunity signals. Additionally, it is recommended that future research on the potential effects of vaccine adjuvants on AID should consider carefully the experimental design in animal models particularly if they are to be used in any risk assessment, as an improper design and model could result in misleading information. Finally, studies on the mechanistic aspects and potential biomarkers related to adjuvants and autoimmunity phenomena could be developed.

  14. A phase I study of vaccination with NY-ESO-1f peptide mixed with Picibanil OK-432 and Montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen.

    Science.gov (United States)

    Kakimi, Kazuhiro; Isobe, Midori; Uenaka, Akiko; Wada, Hisashi; Sato, Eiichi; Doki, Yuichiro; Nakajima, Jun; Seto, Yasuyuki; Yamatsuji, Tomoki; Naomoto, Yoshio; Shiraishi, Kenshiro; Takigawa, Nagio; Kiura, Katsuyuki; Tsuji, Kazuhide; Iwatsuki, Keiji; Oka, Mikio; Pan, Linda; Hoffman, Eric W; Old, Lloyd J; Nakayama, Eiichi

    2011-12-15

    We conducted a phase I clinical trial of a cancer vaccine using a 20-mer NY-ESO-1f peptide (NY-ESO-1 91-110) that includes multiple epitopes recognized by antibodies, and CD4 and CD8 T cells. Ten patients were immunized with 600 μg of NY-ESO-1f peptide mixed with 0.2 KE Picibanil OK-432 and 1.25 ml Montanide ISA-51. Primary end points of the study were safety and immune response. Subcutaneous injection of the NY-ESO-1f peptide vaccine was well tolerated. Vaccine-related adverse events observed were fever (Grade 1), injection-site reaction (Grade 1 or 2) and induration (Grade 2). Vaccination with the NY-ESO-1f peptide resulted in an increase or induction of NY-ESO-1 antibody responses in nine of ten patients. The sera reacted with recombinant NY-ESO-1 whole protein as well as the NY-ESO-1f peptide. An increase in CD4 and CD8 T cell responses was observed in nine of ten patients. Vaccine-induced CD4 and CD8 T cells responded to NY-ESO-1 91-108 in all patients with various HLA types with a less frequent response to neighboring peptides. The findings indicate that the 20-mer NY-ESO-1f peptide includes multiple epitopes recognized by CD4 and CD8 T cells with distinct specificity. Of ten patients, two with lung cancer and one with esophageal cancer showed stable disease. Our study shows that the NY-ESO-1f peptide vaccine was well tolerated and elicited humoral, CD4 and CD8 T cell responses in immunized patients. Copyright © 2011 UICC.

  15. Glucocorticosteroids: as Adjuvant Therapy for Bacterial Infections

    Directory of Open Access Journals (Sweden)

    WONDIM MELKAM

    2015-01-01

    Full Text Available Glucocorticoids (GCs, synthetic analogues of the natural steroid hormones, are well known for their antiinflammatory and immunosuppressive properties in the periphery. They are widely and successfully used in the treatment of autoimmune diseases, chronic inflammation, and transplant rejection. Nowadays, GCs are claimed to have a beneficial role being as adjunct therapy in various infections. Different studies have been conducted to investigate their use as adjuvant therapy for different bacterial infection. This review, therefore, summarizes various bacterial infections for which glucocorticoids are reported to be used as adjuvant therapy, strategies for administration of glucocorticoids, and challenges of using glucocorticoids as adjuvant therapy.

  16. [Adjuvant dermato-cosmetic acne therapy].

    Science.gov (United States)

    Bayerl, Christiane; Degitz, Klaus; Meigel, Eva; Kerscher, Martina

    2010-03-01

    Adjuvant dermato-cosmetic therapy in acne is an essential part of the concept of treating acne after initiation and during maintenance therapy. Those are mechanical peeling, chemical peeling and its combination. It needs supervision by an experienced dermatologist.

  17. Adjuvants for spraying of fungicides in wheat

    OpenAIRE

    2014-01-01

    The foliar diseases and spike can markedly reduce the yield of wheat. Despite prevailing chemical control in the management of disease, studies with adjuvants to improve the performance of fungicides are still incipient. The aim of this study was to evaluate the effect of adding adjuvants to chemical fungicides to control leaf diseases and spike, as well as on the yield of wheat crop. The experimental design was a randomized block design with 05 treatments: control (no fungicide application i...

  18. Applications of nanomaterials as vaccine adjuvants.

    Science.gov (United States)

    Zhu, Motao; Wang, Rongfu; Nie, Guangjun

    2014-01-01

    Vaccine adjuvants are applied to amplify the recipient's specific immune responses against pathogen infection or malignancy. A new generation of adjuvants is being developed to meet the demands for more potent antigen-specific responses, specific types of immune responses, and a high margin of safety. Nanotechnology provides a multifunctional stage for the integration of desired adjuvant activities performed by the building blocks of tailor-designed nanoparticles. Using nanomaterials for antigen delivery can provide high bioavailability, sustained and controlled release profiles, and targeting and imaging properties resulting from manipulation of the nanomaterials' physicochemical properties. Moreover, the inherent immune-regulating activity of particular nanomaterials can further promote and shape the cellular and humoral immune responses toward desired types. The combination of both the delivery function and immunomodulatory effect of nanomaterials as adjuvants is thought to largely benefit the immune outcomes of vaccination. In this review, we will address the current achievements of nanotechnology in the development of novel adjuvants. The potential mechanisms by which nanomaterials impact the immune responses to a vaccine and how physicochemical properties, including size, surface charge and surface modification, impact their resulting immunological outcomes will be discussed. This review aims to provide concentrated information to promote new insights for the development of novel vaccine adjuvants.

  19. Review: Adjuvant effects of saponins on animal immune responses

    Institute of Scientific and Technical Information of China (English)

    RAJPUT Zahid Iqbal; HU Song-hua; XIAO Chen-wen; ARIJO Abdullah G.

    2007-01-01

    Vaccines require optimal adjuvants including immunopotentiator and delivery systems to offer long term protection from infectious diseases in animals and man. Initially it was believed that adjuvants are responsible for promoting strong and sustainable antibody responses. Now it has been shown that adjuvants influence the isotype and avidity of antibody and also affect the properties of cell-mediated immunity. Mostly oil emulsions, lipopolysaccharides, polymers, saponins, liposomes, cytokines,ISCOMs (immunostimulating complexes), Freund's complete adjuvant, Freund's incomplete adjuvant, alums, bacterial toxins etc.,are common adjuvants under investigation. Saponin based adjuvants have the ability to stimulate the cell mediated immune system as well as to enhance antibody production and have the advantage that only a low dose is needed for adjuvant activity. In the present study the importance of adjuvants, their role and the effect of saponin in immune system is reviewed.

  20. Staphylococcus aureus toxins.

    Science.gov (United States)

    Otto, Michael

    2014-02-01

    Staphylococcus aureus is a dangerous pathogen that causes a variety of severe diseases. The virulence of S. aureus is defined by a large repertoire of virulence factors, among which secreted toxins play a preeminent role. Many S. aureus toxins damage biological membranes, leading to cell death. In particular, S. aureus produces potent hemolysins and leukotoxins. Among the latter, some were recently identified to lyse neutrophils after ingestion, representing an especially powerful weapon against bacterial elimination by innate host defense. Furthermore, S. aureus secretes many factors that inhibit the complement cascade or prevent recognition by host defenses. Several further toxins add to this multi-faceted program of S. aureus to evade elimination in the host. This review will give an overview over S. aureus toxins focusing on recent advances in our understanding of how leukotoxins work in receptor-mediated or receptor-independent fashions.

  1. [Protein toxins of Staphylococcus aureus].

    Science.gov (United States)

    Shamsutdinov, A F; Tiurin, Iu A

    2014-01-01

    Main scientific-research studies regarding protein bacterial toxins of the most widespread bacteria that belong to Staphylococcus spp. genus and in particular the most pathogenic species for humans--Staphylococcus aureus, are analyzed. Structural and biological properties of protein toxins that have received the name of staphylococcus pyrogenic toxins (PTSAg) are presented. Data regarding genetic regulation of secretion and synthesis of these toxins and 3 main regulatory genetic systems (agr--accessory gene regulator, xpr--extracellular protein regulator, sar--staphylococcal accessory regulator) that coordinate synthesis of the most important protein toxins and enzymes for virulence of S. aureus, are presented.

  2. Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

    Science.gov (United States)

    Payne, Richard; McDonald, David; Byrne, Scott

    2015-10-01

    Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

  3. (Neo)adjuvant systemic therapy for melanoma.

    Science.gov (United States)

    van Zeijl, M C T; van den Eertwegh, A J; Haanen, J B; Wouters, M W J M

    2017-03-01

    Surgery still is the cornerstone of treatment for patients with stage II and III melanoma, but despite great efforts to gain or preserve locoregional control with excision of the primary tumour, satellites, intransits, sentinel node biopsy and lymphadenectomy, surgery alone does not seem to improve survival any further. Prognosis for patients with high risk melanoma remains poor with 5-year survival rates of 40 to 80%. Only interferon-2b has been approved as adjuvant therapy since 1995, but clinical integration is low considering the high risk-benefit ratio. In recent years systemic targeted- and immunotherapy have proven to be beneficial in advanced melanoma and could be a promising strategy for (neo)adjuvant treatment of patients with resectable high risk melanomas as well. Randomised, placebo- controlled phase III trials on adjuvant systemic targeted- and immunotherapy are currently being performed using new agents like ipilimumab, pembrolizumab, nivolumab, vemurafenib and dabrafenib plus trametinib. In this article we review the literature on currently known adjuvant therapies and currently ongoing trials of (neo)adjuvant therapies in high risk melanomas.

  4. Mycophenolate mofetil as adjuvant in pemphigus vulgaris

    Directory of Open Access Journals (Sweden)

    Sarma Nilendu

    2007-01-01

    Full Text Available Pemphigus vulgaris (PV is a life threatening autoimmune blistering disease of skin and mucous membranes. Advent of systemic steroids has greatly reduced the mortality rate. However, steroids and adjuvant immunosuppressive therapy are nowadays frequent contributory agents of morbidity and mortality of PV. Mycophenolate mofetil (MMF has been reported to be an effective adjuvant to systemic steroids. It helps in increasing the immunosuppressive effect and minimizing the toxicities by steroid sparing effect. However, its efficacy in refractory cases of PV is not well documented. The lowest possible dose with satisfactory therapeutic efficacy and least side effects is known. We used MMF 1 g/day and systemic steroids in 3 Indian patients with pemphigus vulgaris who were resistant to systemic steroid monotherapy or combination treatment with azathioprine. In our experience, MMF offers an effective adjuvant with minimal side-effects in the treatment of resistant PV.

  5. Adjuvant chemotherapy in early breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent

    2016-01-01

    % of patients aged 40 or younger in 77B had regular menses throughout chemotherapy, the corresponding percentage was 37 in 82B and 47 in 89B. The DBCG in collaboration with a Swedish and a Dutch centre participating in the DBCG trial 89B compared CMF with ovarian ablation in premenopausal high-risk breast...... are not clinically useful by themselves as other chemotherapy regimens have been more efficacious, and knowledge is still lacking regarding the benefits from adding ovarian suppression to chemotherapy plus tamoxifen. The results from the DBCG 77B and 82C are in accordance with other large adjuvant trials...... adjuvant trials demonstrated that patients with either TOP2A or centromere 17 aberrations, but not with HER2 amplification, benefit from anthracycline-containing adjuvant chemotherapy. Anthracyclins have additional distinct biological mechanisms; and results from the DBCG 89D suggested that tumours...

  6. Mixed adjuvant formulations reveal a new combination that elicit antibody response comparable to Freund's adjuvants.

    Directory of Open Access Journals (Sweden)

    Rachel P J Lai

    Full Text Available Adjuvant formulations capable of inducing high titer and high affinity antibody responses would provide a major advance in the development of vaccines to viral infections such as HIV-1. Although oil-in-water emulsions, such as Freund's adjuvant (FCA/FIA, are known to be potent, their toxicity and reactogenicity make them unacceptable for human use. Here, we explored different adjuvants and compared their ability to elicit antibody responses to FCA/FIA. Recombinant soluble trimeric HIV-1 gp140 antigen was formulated in different adjuvants, including FCA/FIA, Carbopol-971P, Carbopol-974P and the licensed adjuvant MF59, or combinations of MF59 and Carbopol. The antigen-adjuvant formulation was administered in a prime-boost regimen into rabbits, and elicitation of antigen binding and neutralizing antibodies (nAbs was evaluated. When used individually, only FCA/FIA elicited significantly higher titer of nAbs than the control group (gp140 in PBS (p<0.05. Sequential prime-boost immunizations with different adjuvants did not offer improvements over the use of FCA/FIA or MF59. Remarkably however, the concurrent use of the combination of Carbopol-971P and MF59 induced potent adjuvant activity with significantly higher titer nAbs than FCA/FIA (p<0.05. This combination was not associated with any obvious local or systemic adverse effects. Antibody competition indicated that the majority of the neutralizing activities were directed to the CD4 binding site (CD4bs. Increased antibody titers to the gp41 membrane proximal external region (MPER and gp120 V3 were detected when the more potent adjuvants were used. These data reveal that the combination of Carbopol-971P and MF59 is unusually potent for eliciting nAbs to a variety of HIV-1 nAb epitopes.

  7. Microbiota Influences Vaccine and Mucosal Adjuvant Efficacy

    Science.gov (United States)

    2017-01-01

    A symbiotic relationship between humans and the microbiota is critical for the maintenance of our health, including development of the immune system, enhancement of the epithelial barrier, and acquisition of nutrients. Recent research has shown that the microbiota impacts immune cell development and differentiation. These findings suggest that the microbiota may also influence adjuvant and vaccine efficacy. Indeed, several factors such as malnutrition and poor sanitation, which affect gut microbiota composition, impair the efficacy of vaccines. Although there is little evidence that microbiota alters vaccine efficacy, further understanding of human immune system-microbiota interactions may lead to the effective development of adjuvants and vaccines for the treatment of diseases. PMID:28261017

  8. [Adjuvant chemotherapy for patients with rectal cancer].

    Science.gov (United States)

    Qvortrup, Camilla; Mortensen, John Pløen; Pfeiffer, Per

    2013-09-09

    A new Cochrane meta-analysis evaluated adjuvant chemotherapy (5-fluorouracil (5FU)-based, not modern combination chemotherapy) in almost 10,000 patients with rectal cancer and showed a 17% reduction in mortality corresponding well to the efficacy observed in recent studies, which reported a reduction in mortality just about 20%. The authors recommend adjuvant chemotherapy which is in accordance with the Danish national guidelines where 5-FU-based chemotherapy is recommended for stage III and high-risk stage II rectal cancer.

  9. Adjuvants and vector systems for allergy vaccines.

    Science.gov (United States)

    Moingeon, Philippe; Lombardi, Vincent; Saint-Lu, Nathalie; Tourdot, Sophie; Bodo, Véronique; Mascarell, Laurent

    2011-05-01

    Allergen-specific immunotherapy represents a curative treatment of type I allergies. Subcutaneous immunotherapy is conducted with allergens adsorbed on aluminum hydroxide or calcium phosphate particles, whereas sublingual immunotherapy relies on high doses of soluble allergen without any immunopotentiator. There is a potential benefit of adjuvants enhancing regulatory and Th1 CD4+T cell responses during specific immunotherapy. Molecules affecting dendritic cells favor the induction of T regulatory cell and Th1 responses and represent valid candidate adjuvants for allergy vaccines. Furthermore, the interest in viruslike particles and mucoadhesive particulate vector systems, which may better address the allergen(s) to tolerogenic antigen-presenting cells, is documented.

  10. Modulation of Drug Resistance in Staphylococcus aureus with Coumarin Derivatives

    Directory of Open Access Journals (Sweden)

    Rodrigo Santos Aquino de Araújo

    2016-01-01

    Full Text Available Semisynthetic and commercial coumarins were investigated for their antibacterial and adjuvant properties with antibiotic agents against norfloxacin, erythromycin, and tetracycline resistant Staphylococcus aureus as based on efflux mechanisms. The coumarins and certain commercial antibiotics had their Minimum Inhibitory Concentrations determined by broth microdilution assay against resistant S. aureus strains which overexpress efflux pump proteins. For evaluation of the modulatory activity, the antibiotics MICs were determined in the presence of the coumarin derivatives at subinhibitory concentration. Although the coumarins did not display relevant antibacterial activity (MIC ≥ 128 µg/mL, they did modulate the antibiotics activities. Various coumarins, especially the alkylated derivatives in combination with antibiotics at subinhibitory concentrations, modulated antibiotic activity, reducing the MIC for tetracycline and norfloxacin by 2 to 8 times. Polar Surface Area (PSA studies were performed and the fact that the presence of apolar groups is an important factor for the modulatory activity of coumarins was corroborated. Docking on the Penicillin-Binding Protein from MRSA identified that 18 is a potential ligand presenting low Ebinding. The results indicate that coumarin derivatives modulated antibiotic resistance and may be used as potential antibiotic adjuvants, acting by bacterial efflux pump inhibition in S. aureus.

  11. Staphylococcus aureus Bacteraemia

    Directory of Open Access Journals (Sweden)

    James Price

    2010-01-01

    Full Text Available Staphylococcus aureus bacteraemia (SAB is commonly complicated by metastatic infection or relapse after treatment. Objectives. The study aim was to determine the role of bacterial, host, and management factors in development of complicated SAB. Methods. A prospectively-conducted observational study gathered data on predisposition, management and outcome of 100 consecutive SAB cases. Antibiotic susceptibilities and genetic lineage of bacterial isolates were determined. Further clinical and microbiological data were gathered on two retrospective series from 1999–2000 (n=57 and 2004 (n=116. Results. In the prospective cases, 27% met our definition of complicated disease. Expressed as RR and 95% CI, complicated disease was associated with diabetes (1.58, 1.00–2.48, injecting-drug use (5.48, 0.88–33.49, community-onset of symptoms (1.4, 1.02–1.92, and symptom duration ≥48 hours prior to starting effective antibiotic therapy (2.10, 1.22–3.61. Uncomplicated disease was associated with the presence of a central line (0.69, 0.55–0.88 and prompt removal of a primary focus (0.71, 0.57–0.90. Neither methicillin resistance nor genetic lineage was associated with complicated disease, but methicillin resistance was associated with higher mortality. Conclusions. This study demonstrates that clinical rather than microbial factors are the major determinants of SAB outcome and underscores the importance of early treatment.

  12. Gaps in knowledge and prospects for research of adjuvanted vaccines.

    Science.gov (United States)

    Seder, Robert; Reed, Steven G; O'Hagan, Derek; Malyala, Padma; D'Oro, Ugo; Laera, Donatello; Abrignani, Sergio; Cerundolo, Vincenzo; Steinman, Lawrence; Bertholet, Sylvie

    2015-06-08

    A panel of researchers working in different areas of adjuvanted vaccines deliberated over the topic, "Gaps in knowledge and prospects for research of adjuvanted vaccines" at, "Enhancing Vaccine Immunity and Value" conference held in July 2014. Several vaccine challenges and applications for new adjuvant technologies were discussed.

  13. Vitamins as influenza vaccine adjuvant components.

    Science.gov (United States)

    Quintilio, Wagner; de Freitas, Fábio Alessandro; Rodriguez, Dunia; Kubrusly, Flavia Saldanha; Yourtov, Dimitri; Miyaki, Cosue; de Cerqueira Leite, Luciana Cezar; Raw, Isaias

    2016-10-01

    A number of adjuvant formulations were assayed in mice immunized with 3.75 µg of A/California/7/2009 (H1N1) pdm09 influenza vaccine with vitamins A, D and/or E in emulsions or B2 and/or B9 combined with Bordetella pertussis MPLA and/or alum as adjuvants. Squalene was used as positive control, as well as MPLA with alum. The immune response was evaluated by a panel of tests, including a hemagglutination inhibition (HAI) test, ELISA for IgG, IgG1, and IgG2a and IFN-γ, IL-2, IL-6 and IL-10 quantification in splenocyte culture supernatant after stimulus with influenza antigen. Immunological memory was evaluated using a 1/10 dose booster 60 days after the first immunization followed by assessment of the response by HAI, IgG ELISA, and determination of the antibody affinity index. The highest increases in HAI, IgG1 and IgG2a titers were obtained with the adjuvant combinations containing vitamin E, or the hydrophilic combinations containing MPLA and alum or B2 and alum. The IgG1/IgG2a ratio indicates that the response to the combination of B2 with alum would have more Th2 character than the combination of MPLA with alum. In an assay to investigate the memory response, a significant increase in HAI titer was observed with a booster vaccine dose at 60 days after immunization with vaccines containing MPLA with alum or B2 with alum. Overall, of the 27 adjuvant combinations, MPLA with alum and B2 with alum were the most promising adjuvants to be evaluated in humans.

  14. Review article: surgical, neo-adjuvant and adjuvant management strategies in biliary tract cancer.

    Science.gov (United States)

    Skipworth, J R A; Olde Damink, S W M; Imber, C; Bridgewater, J; Pereira, S P; Malagó, M

    2011-11-01

    The majority of patients with cholangiocarcinoma present with advanced, irresectable tumours associated with poor prognosis. The incidence and mortality rates associated with cholangiocarcinoma continue to rise, mandating the development of novel strategies for early detection, improved resection and treatment of residual lesions. To review the current evidence base for surgical, adjuvant and neo-adjuvant techniques in the management of cholangiocarcinoma. A search strategy incorporating PubMed/Medline search engines and utilising the key words biliary tract carcinoma; cholangiocarcinoma; management; surgery; chemotherapy; radiotherapy; photodynamic therapy; and radiofrequency ablation, in various combinations, was employed. Data on neo-adjuvant and adjuvant techniques remain limited, and much of the literature concerns palliation of inoperable disease. The only opportunity for long-term survival remains surgical resection with negative pathological margins or liver transplantation, both of which remain possible in only a minority of selected patients. Neo-adjuvant and adjuvant techniques currently provide only limited success in improving survival. The development of novel strategies and treatment techniques is crucial. However, the shortage of randomised controlled trials is compounded by the low feasibility of conducting adequately powered trials in liver surgery, due to the large sample sizes that are required. © 2011 Blackwell Publishing Ltd.

  15. Methicillin-resistant Staphylococcus aureus (MRSA)

    Science.gov (United States)

    Methicillin-resistant Staphylococcus aureus; Hospital-acquired MRSA (HA-MRSA); Staph - MRSA; Staphylococcal - MRSA ... Que YA, Moreillon P. Staphylococcus aureus (including ... MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice ...

  16. Staphylococcus aureus Isolates from Kenyan Milk

    African Journals Online (AJOL)

    Milk; Staphylococcus aureus; Antimicrobial Resistance; Multiple resistance. Introduction ... of antibiotic resistant bacterial strains in food in Africa. ..... spread of methicillin resistant staphylococcus aureus. Clin. Infect. Disease. 24S-.74-S79.

  17. New generation adjuvants--from empiricism to rational design.

    Science.gov (United States)

    O'Hagan, Derek T; Fox, Christopher B

    2015-06-08

    Adjuvants are an essential component of modern vaccine development. Despite many decades of development, only a few types of adjuvants are currently included in vaccines approved for human use. In order to better understand the reasons that development of some adjuvants succeeded while many others failed, we discuss some of the common attributes of successful first generation adjuvants. Next, we evaluate current trends in the development of second generation adjuvants, including the potential advantages of rationally designed synthetic immune potentiators appropriately formulated. Finally, we discuss desirable attributes of next generation adjuvants. Throughout, we emphasize that the importance of formulation and analytical characterization in all aspects of vaccine adjuvant development is often underappreciated. We highlight the formulation factors that must be evaluated in order to optimize interactions between vaccine antigens, immune potentiators, and particulate formulations, and the resulting effects on safety, biological activity, manufacturability, and stability. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. [Gastrointestinal surgeons should master the adjuvant therapy of colorectal cancer].

    Science.gov (United States)

    Gu, Jin; Chen, Pengju

    2015-10-01

    The diagnosis and treatment of colorectal cancer is one of the main diseases of gastrointestinal surgeons. It is very important to master the adjuvant chemotherapy of colorectal cancer for gastrointestinal surgeons. In recent years, with the development of a number of clinical trials and the appearance of new drugs, fluorouracil combined with oxaliplatin had been established as the standard regimen of adjuvant chemotherapy for colorectal cancer. In the current guidelines, stage III( colon cancer is the indication for adjuvant chemotherapy, while stage II( colon cancer should receive adjuvant chemotherapy is uncertain. Unlike colon cancer, adjuvant therapy of rectal cancer is not evidence-based. Especially, the indication and duration of adjuvant chemotherapy for rectal cancer after neoadjuvant chemoradiotherapy remain controversial. Adjuvant therapy of colorectal cancer still needs further investigation.

  19. Neonatal Staphylococcus lugdunensis urinary tract infection.

    Science.gov (United States)

    Hayakawa, Itaru; Hataya, Hiroshi; Yamanouchi, Hanako; Sakakibara, Hiroshi; Terakawa, Toshiro

    2015-08-01

    Staphylococcus lugdunensis is a known pathogen of infective endocarditis, but not of urinary tract infection. We report a previously healthy neonate without congenital anomalies of the kidney and urinary tract who developed urinary tract infection due to Staphylococcus lugdunensis, illustrating that Staphylococcus lugdunensis can cause urinary tract infection even in those with no urinary tract complications.

  20. The adjuvant mechanism of cationic dimethyldioctadecylammonium liposomes

    DEFF Research Database (Denmark)

    Korsholm, Karen Smith; Agger, Else Marie; Foged, Camilla

    2007-01-01

    Cationic liposomes are being used increasingly as efficient adjuvants for subunit vaccines but their precise mechanism of action is still unknown. Here, we investigated the adjuvant mechanism of cationic liposomes based on the synthetic amphiphile dimethyldioctadecylammonium (DDA). The liposomes...... concentrations. This efficient adsorption onto the liposomes led to an enhanced uptake of OVA by BM-DCs as assessed by flow cytometry and confocal fluorescence laser-scanning microscopy. This was an active process, which was arrested at 4 degrees and by an inhibitor of actin-dependent endocytosis, cytochalasin D....... In vivo studies confirmed the observed effect because adsorption of OVA onto DDA liposomes enhanced the uptake of the antigen by peritoneal exudate cells after intraperitoneal injection. The liposomes targeted antigen preferentially to antigen-presenting cells because we only observed a minimal uptake...

  1. Stress Responses in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Frees, Dorte; Ingmer, Hanne

    2016-01-01

    Staphylococcus aures are prominent members of the normal flora of humans and animals, but are also a major cause of mild and severe infections. To persist and disseminate in the human host, and to survive in environmental settings, such as hospitals, S. aureus have developed a plethora of cellula...

  2. Binary typing of staphylococcus aureus

    NARCIS (Netherlands)

    W.B. van Leeuwen (Willem)

    2002-01-01

    textabstractThis thesis describes the development. application and validation of straindifferentiating DNA probes for the characterization of Staphylococcus aureus strains in a system. that yields a binary output. By comparing the differential hybridization of these DNA probes to staphylococcal geno

  3. Slime production by Staphylococcus saprophyticus.

    OpenAIRE

    Hjelm, E.; Lundell-Etherden, I

    1991-01-01

    Only 9 of 30 Staphylococcus saprophyticus strains produced slime in trypticase soy broth, while all did so in urine. It was found that urea was essential for the production of slime. The pH, the iron concentration, or the presence of sex hormones did not affect slime production.

  4. Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections

    Directory of Open Access Journals (Sweden)

    Draughn GL

    2017-01-01

    Full Text Available G Logan Draughn,1 C Leigh Allen,1 Patricia A Routh,2 Maria R Stone,2 Kelly R Kirker,3 Laura Boegli,3 Ryan M Schuchman,1 Keith E Linder,2 Ronald E Baynes,2 Garth James,3 Christian Melander,4 Angela Pollard,5 John Cavanagh1 1Department of Molecular and Structural Biochemistry, 2Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; 3Center for Biofilm Engineering, Montana State University, Bozeman, MT, USA; 4Department of Chemistry, North Carolina State University, Raleigh, NC, USA; 5Agile Sciences Inc., Raleigh, NC, USA Abstract: 2-Aminoimidazole (2-AI-based compounds have been shown to efficiently disrupt biofilm formation, disperse existing biofilms, and resensitize numerous multidrug-resistant bacteria to antibiotics. Using Pseudomonas aeruginosa and Staphylococcus aureus, we provide initial pharmacological studies regarding the application of a 2-AI as a topical adjuvant for persistent dermal infections. In vitro assays indicated that the 2-AI H10 is nonbactericidal, resensitizes bacteria to antibiotics, does not harm the integument, and promotes wound healing. Furthermore, in vivo application of H10 on swine skin caused no gross abnormalities or immune reactions. Taken together, these results indicate that H10 represents a promising lead dermal adjuvant compound. Keywords: transdermal absorption, antimicrobial activity, skin irritation, synergism, oroidin derivative, drip-flow reactor, ESKAPE pathogens

  5. Glucocorticosteroids: as Adjuvant Therapy for Bacterial Infections

    OpenAIRE

    2015-01-01

    Glucocorticoids (GCs), synthetic analogues of the natural steroid hormones, are well known for their antiinflammatory and immunosuppressive properties in the periphery. They are widely and successfully used in the treatment of autoimmune diseases, chronic inflammation, and transplant rejection. Nowadays, GCs are claimed to have a beneficial role being as adjunct therapy in various infections. Different studies have been conducted to investigate their use as adjuvant therapy for different bact...

  6. Inflammatory responses following intramuscular and subcutaneous immunization with aluminum-adjuvanted or non-adjuvanted vaccines.

    Science.gov (United States)

    Kashiwagi, Yasuyo; Maeda, Mika; Kawashima, Hisashi; Nakayama, Tetsuo

    2014-06-05

    Aluminum-adjuvanted vaccines are administered through an intramuscular injection (IM) in the US and EU, however, a subcutaneous injection (SC) has been recommended in Japan because of serious muscle contracture previously reported following multiple IMs of antibiotics. Newly introduced adjuvanted vaccines, such as the human papillomavirus (HPV) vaccines, have been recommended through IM. In the present study, currently available vaccines were evaluated through IM in mice. Aluminum-adjuvanted vaccines induced inflammatory nodules at the injection site, which expanded into the intra-muscular space without any muscle degeneration or necrosis, whereas non-adjuvanted vaccines did not. These nodules consisted of polymorph nuclear neutrophils with some eosinophils within the initial 48h, then monocytes/macrophages 1 month later. Inflammatory nodules were observed 6 months after IM, had decreased in size, and were absorbed 12 months after IM, which was earlier than that after SC. Cytokine production was examined in the injected muscular tissues and AS04 adjuvanted HPV induced higher IL-1β, IL-6, KC, MIP-1, and G-CSF levels in muscle tissues than any other vaccine, but similar serum cytokine profiles were observed to those induced by the other vaccines. Currently available vaccines did not induce muscular degeneration or fibrotic scar as observed with muscle contracture caused by multiple IMs of antibiotics in the past.

  7. Staphylococcus aureus bacteremia.

    Science.gov (United States)

    Jensen, Allan Garlik

    2003-11-01

    Staphylococcus aureus bacteremia (SAB) is still associated with a high mortality, and knowledge on risk factors and the clinical and the therapeutic aspects of SAB is still limited. This thesis focuses on the clinical aspects of SAB and its metastatic infections. In a study of all patients with bacteremia in Copenhagen County October 1992 through April 1993 (study I) we emphasized previous findings, that S. aureus is one of the most frequent pathogens in bacteremia, and in a case control study also in Copenhagen County 1994-95 (study II) we demonstrated, that not only an inserted central venous catheter and nasal S. aureus carriage but also hyponatremia and anemia are important risk factors for hospital-acquired SAB (study II). Studies on the treatment of SAB have pointed out, that the eradication of a primary is important, but there are only limited clinical studies dealing with antibiotic treatment. By logistic regression analysis, we were able to demonstrate that focus eradication is essential, but also that treatment with dicloxacillin 1 g x 4 or 2 g x 3 are superior to 1 g x 3 (studie III), indicating that the time for serum concentration above the Minimal Inhibitory Concentration (MIC) for the bacteria plays a role in the outcome of SAB treatment. S. aureus osteomyelitis secondary to SAB is frequently observed. No other countries, however, have a centralized registration, which make it possible to evaluate a large number of these patients. Since 1960, The Staphylococcal Laboratory, Statens Serum Institut in Copenhagen, has registrated selected clinical informations from nearly all patients with positive blood cultures of S. aureus. Based on this registration, we were able to show an increased number of S. aureus osteomyelitis among older patients and a decreased number of S. aureus osteomyelitis of femur and tibia among younger infants in the period 1980-90 (study IV). By reviewing the records of a large number of patients with vertebral S. aureus

  8. Adjuvant and neoadjuvant treatment in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Marta Herreros-Villanueva; Elizabeth Hijona; Angel Cosme; Luis Bujanda

    2012-01-01

    Pancreatic adenocarcinoma is one of the most aggressive human malignancies,ranking 4th among causes for cancer-related death in the Western world including the United States.Surgical resection offers the only chance of cure,but only 15 to 20 percent of cases are potentially resectable at presentation.Different studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and radiotherapy.Currently there is no consensus around the world on what constitutes "standard"adjuvant therapy for pancreatic cancer.This controversy derives from several studies,each fraught with its own limitations.Standards of care also vary somewhat with regard to geography and economy,for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in Europe.Regardless of the efforts in adjuvant and neoadjuvant improved therapy,the major goal to combat pancreatic cancer is to find diagnostic markers,identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more patients.In this review,authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients.

  9. Adjuvant chemotherapy for advanced endometrial cancer.

    Science.gov (United States)

    Galaal, Khadra; Al Moundhri, Mansour; Bryant, Andrew; Lopes, Alberto D; Lawrie, Theresa A

    2014-05-15

    Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective. To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV). We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials. Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer. Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software. We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data

  10. Adjuvant chemotherapy for early-stage cervical cancer.

    Science.gov (United States)

    Asano, Hiroshi; Todo, Yukiharu; Watari, Hidemichi

    2016-04-01

    The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable

  11. Staphylococcus lugdunensis, a serious pathogen in periprosthetic joint infections: comparison to Staphylococcus aureus and Staphylococcus epidermidis.

    Science.gov (United States)

    Lourtet-Hascoët, J; Bicart-See, A; Félicé, M P; Giordano, G; Bonnet, E

    2016-10-01

    The aim of this study was to assess the characteristics of periprosthetic joint infection (PJI) due to Staphylococcus lugdunensis and to compare these to the characteristics of PJI due to Staphylococcus aureus and Staphylococcus epidermidis. A retrospective multicentre study including all consecutive cases of S. lugdunensis PJI (2000-2014) was performed. Eighty-eight cases of staphylococcal PJI were recorded: 28 due to S. lugdunensis, 30 to S. aureus, and 30 to S. epidermidis, as identified by Vitek 2 or API Staph (bioMérieux). Clinical symptoms were more often reported in the S. lugdunensis group, and the median delay between surgery and infection was shorter for the S. lugdunensis group than for the S. aureus and S. epidermidis groups. Regarding antibiotic susceptibility, the S. lugdunensis strains were susceptible to antibiotics and 61% of the patients could be treated with levofloxacin + rifampicin. The outcome of the PJI was favourable for 89% of patients with S. lugdunensis, 83% with S. aureus, and 97% with S. epidermidis. S. lugdunensis is an emerging pathogen with a pathogenicity quite similar to that of S. aureus. This coagulase-negative Staphylococcus must be identified precisely in PJI, in order to select the appropriate surgical treatment and antibiotics . Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. From discovery to licensure, the Adjuvant System story

    Science.gov (United States)

    Garçon, Nathalie; Di Pasquale, Alberta

    2017-01-01

    ABSTRACT Adjuvants are substances added to vaccines to improve their immunogenicity. Used for more than 80 years, aluminum, the first adjuvant in human vaccines, proved insufficient to develop vaccines that could protect against new challenging pathogens such as HIV and malaria. New adjuvants and new combinations of adjuvants (Adjuvant Systems) have opened the door to the delivery of improved and new vaccines against re-emerging and difficult pathogens. Adjuvant Systems concept started through serendipity. The access to new developments in technology, microbiology and immunology have been instrumental for the dicephering of what they do and how they do it. This knowledge opens the door to more rational vaccine design with implications for developing new and better vaccines. PMID:27636098

  13. Towards an understanding of the adjuvant action of aluminium

    Science.gov (United States)

    Marrack, Philippa; McKee, Amy S.; Munks, Michael W.

    2011-01-01

    The efficacy of vaccines depends on the presence of an adjuvant in conjunction with the antigen. Of these adjuvants, the ones that contain aluminium, which were first discovered empirically in 1926, are currently the most widely used. However, a detailed understanding of their mechanism of action has only started to be revealed. In this Timeline article, we briefly describe the initial discovery of aluminium adjuvants and discuss historically important advances. We also summarize recent progress in the field and discuss their implications and the remaining questions on how these adjuvants work. PMID:19247370

  14. Immunogenicity and immunization costs of adjuvanted versus non-adjuvanted hepatitis B vaccine in chronic kidney disease patients.

    Science.gov (United States)

    Vilajeliu, Alba; Sequera, Víctor-Guillermo; García-Basteiro, Alberto L; Sicuri, Elisa; Aldea, Marta; Velasco, César; Bayas, José M

    2016-09-01

    Hepatitis B virus (HBV) vaccination is recommended for all susceptible chronic pre-hemodialysis and hemodialysis patients. This study assessed the immunogenicity of HBV vaccines (adjuvanted and non-adjuvanted) in chronic kidney disease patients vaccinated at the Hospital Clinic of Barcelona (Spain) between January 2007 and July 2012. In addition, the costs for the health system were evaluated accor-ding to the proportion of vaccine responders after receiving either vaccine. Patients receiving 3 doses of hepatitis B adjuvanted vaccine were 3 times more likely to seroconvert than patients immunized with non-adjuvanted vaccines, OR 3.56 (95% CI 1.84-6.85). This resulted in fewer patients requiring a second course of HBV vaccination and fewer outpatient visits, saving more than €9,500 per 100 patients. The higher immunogenicity of the adjuvanted HBV vaccine would counterbalance the lower costs associated with the non-adjuvanted vaccine.

  15. Stress Responses in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Frees, Dorte; Ingmer, Hanne

    2016-01-01

    Staphylococcus aures are prominent members of the normal flora of humans and animals, but are also a major cause of mild and severe infections. To persist and disseminate in the human host, and to survive in environmental settings, such as hospitals, S. aureus have developed a plethora of cellular...... of the specific and general S. aureusstress responses, with a special emphasis on how stress responses contribute to virulence and antibiotic resistance in this important human pathogen....

  16. Antimicrobial resistance of Staphylococcus pseudintermedius.

    Science.gov (United States)

    Kadlec, Kristina; Schwarz, Stefan

    2012-08-01

    Staphylococcus pseudintermedius, Staphylococcus intermedius and Staphylococcus delphini together comprise the S. intermedius group (SIG). Within the SIG, S. pseudintermedius represents the major pathogenic species and is involved in a wide variety of infections, mainly in dogs, but to a lesser degree also in other animal species and humans. Antimicrobial agents are commonly applied to control S. pseudintermedius infections; however, during recent years S. pseudintermedius isolates have been identified that are meticillin-resistant and have also proved to be resistant to most of the antimicrobial agents approved for veterinary applications. This review deals with the genetic basis of antimicrobial resistance properties in S. pseudintermedius and other SIG members. A summary of the known resistance genes and their association with mobile genetic elements is given, as well as an update of the known resistance-mediating mutations. These data show that, in contrast to other staphylococcal species, S. pseudintermedius seems to prefer transposon-borne resistance genes, which are then incorporated into the chromosomal DNA, over plasmid-located resistance genes.

  17. Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant.

    Science.gov (United States)

    Coler, Rhea N; Bertholet, Sylvie; Moutaftsi, Magdalini; Guderian, Jeff A; Windish, Hillarie Plessner; Baldwin, Susan L; Laughlin, Elsa M; Duthie, Malcolm S; Fox, Christopher B; Carter, Darrick; Friede, Martin; Vedvick, Thomas S; Reed, Steven G

    2011-01-26

    Innate immune responses to vaccine adjuvants based on lipopolysaccharide (LPS), a component of gram-negative bacterial cell walls, are driven by Toll-like receptor (TLR) 4 and adaptor proteins including MyD88 and TRIF, leading to the production of inflammatory cytokines, type I interferons, and chemokines. We report here on the characterization of a synthetic hexaacylated lipid A derivative, denoted as glucopyranosyl lipid adjuvant (GLA). We assessed the effects of GLA on murine and human dendritic cells (DC) by combining microarray, mRNA and protein multiplex assays and flow cytometry analyses. We demonstrate that GLA has multifunctional immunomodulatory activity similar to naturally-derived monophosphory lipid A (MPL) on murine DC, including the production of inflammatory cytokines, chemokines, DC maturation and antigen-presenting functions. In contrast, hexaacylated GLA was overall more potent on a molar basis than heterogeneous MPL when tested on human DC and peripheral blood mononuclear cells (PBMC). When administered in vivo, GLA enhanced the immunogenicity of co-administered recombinant antigens, producing strong cell-mediated immunity and a qualitative T(H)1 response. We conclude that the GLA adjuvant stimulates and directs innate and adaptive immune responses by inducing DC maturation and the concomitant release of pro-inflammatory cytokines and chemokines associated with immune cell trafficking, activities which have important implications for the development of future vaccine adjuvants.

  18. Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant.

    Directory of Open Access Journals (Sweden)

    Rhea N Coler

    Full Text Available Innate immune responses to vaccine adjuvants based on lipopolysaccharide (LPS, a component of gram-negative bacterial cell walls, are driven by Toll-like receptor (TLR 4 and adaptor proteins including MyD88 and TRIF, leading to the production of inflammatory cytokines, type I interferons, and chemokines. We report here on the characterization of a synthetic hexaacylated lipid A derivative, denoted as glucopyranosyl lipid adjuvant (GLA. We assessed the effects of GLA on murine and human dendritic cells (DC by combining microarray, mRNA and protein multiplex assays and flow cytometry analyses. We demonstrate that GLA has multifunctional immunomodulatory activity similar to naturally-derived monophosphory lipid A (MPL on murine DC, including the production of inflammatory cytokines, chemokines, DC maturation and antigen-presenting functions. In contrast, hexaacylated GLA was overall more potent on a molar basis than heterogeneous MPL when tested on human DC and peripheral blood mononuclear cells (PBMC. When administered in vivo, GLA enhanced the immunogenicity of co-administered recombinant antigens, producing strong cell-mediated immunity and a qualitative T(H1 response. We conclude that the GLA adjuvant stimulates and directs innate and adaptive immune responses by inducing DC maturation and the concomitant release of pro-inflammatory cytokines and chemokines associated with immune cell trafficking, activities which have important implications for the development of future vaccine adjuvants.

  19. Postoperative adjuvant chemoradiotherapy in rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Sei Kyung; Kim, Jong Woo; Oh, Do Yeun; Chong, So Young; Shin, Hyun Soo [Bundang CHA General Hospital, Pochon CHA University, Seongnam (Korea, Republic of)

    2006-09-15

    To evaluate the role of postoperative adjuvant chemoradiotherapy in rectal cancer, we retrospectively analyzed the treatment outcome of patients with rectal cancer taken curative surgical resection and postoperative adjuvant chemoradiotherapy. A total 46 patients with AJCC stage II and III carcinoma of rectum were treated with curative surgical resection and postoperative adjuvant chemoradiotherapy. T3 and T4 stage were 38 and 8 patients, respectively. N0, N1, and N2 stage were 12, 16, 18 patients, respectively. Forty patients received bolus infusions of 5-fluorouracil (500 mg/m{sup 2}/day) with leucovorin (20 mg/m{sup 2}/day), every 4 weeks interval for 6 cycles. Oral Uracil/Tegafur on a daily basis for 6 {approx} 12 months was given in 6 patients. Radiotherapy with 45 Gy was delivered to the surgical bed and regional pelvic lymph node area, followed by 5.4 {approx} 9 Gy boost to the surgical bed. The follow up period ranged from 8 to 75 months with a median 35 months. Treatment failure occurred in 17 patients (37%). Locoregional failure occurred in 4 patients (8.7%) and distant failure in 16 patients (34.8%). There was no local failure only. Five year actuarial overall survival (OS) was 51.5% and relapse free survival (RFS) was 58.7%. The OS and RFS were 100%, 100% in stage N0 patients, 53.7%, 47.6% in N1 patients, and 0%, 41.2% in N2 patients ({rho} = 0.012, {rho} = 0.009). The RFS was 55%, 78.5%, and 31.2% in upper, middle, and lower rectal cancer patients, respectively ({rho} = 0.006). Multivariate analysis showed that N stage ({rho} = 0.012) was significant prognostic factor for OS and that N stage ({rho} = 0.001) and location of tumor ({rho} = 0.006) were for RFS. Bowel complications requiring surgery occurred in 3 patients. Postoperative adjuvant chemoradiotherapy was an effective modality for locoregional control of rectal cancer. But further investigations for reducing the distant failure rate are necessary because distant failure rate is still high.

  20. 21 CFR 178.3010 - Adjuvant substances used in the manufacture of foamed plastics.

    Science.gov (United States)

    2010-04-01

    ...: ADJUVANTS, PRODUCTION AIDS, AND SANITIZERS Certain Adjuvants and Production Aids § 178.3010 Adjuvant... weight of finished foamed polyethylene. 1,1-Difluoroethane (CAS Reg. No. 75-37-6) For use as a blowing...

  1. CHROMOSOMAL MAPPING IN STRAINS OF STAPHYLOCOCCUS AUREUS,

    Science.gov (United States)

    STAPHYLOCOCCUS AUREUS , CHROMOSOMES), (*CHROMOSOMES, MAPPING), NITROSO COMPOUNDS, GUANIDINES, GENETICS, MUTATIONS, DRUGS, TOLERANCES(PHYSIOLOGY), TEST METHODS, DEOXYRIBONUCLEIC ACIDS, INHIBITION, RESISTANCE(BIOLOGY).

  2. The mode of action of immunological adjuvants.

    Science.gov (United States)

    Allison, A C

    1998-01-01

    Adjuvants augment immune responses to antigens and influence the balance between cell-mediated and humoral responses, as well as the isotypes of antibodies formed. New adjuvant formulations include antigen-carrying vehicles and small molecules with immunomodulating activity. Widely used two-phase vehicles comprise liposomes and microfluidized squalene or squalane emulsions. These are believed to target antigens to antigen-presenting cells, including dendritic cells (DC), follicular dendritic cells (FDC) and B-lymphocytes. Activation of complement generates C3d, which binds CR2 (CD21) on FDC and B-lymphocytes, thereby stimulating the proliferation of the latter and the generation of B-memory. Targeting of antigens to DC may favour cell-mediated immunity. Immunomodulating agents induce the production of cytokine cascades. In a primary cascade at injection sites TNF-alpha, GM-CSF and IL-1 are produced. TNF-alpha promotes migration of DC to lymphoid tissues, while GM-CSF and IL-1 accelerate the maturation of DC into efficient antigen-presenting cells for T-lymphocytes. In a secondary cytokine cascade in draining lymph nodes, DC produce IL-12, which induces Th1 responses with the production of IFN-gamma. The cytokines elicit cell-mediated immune responses and the formation of antibodies of protective isotypes, such as IgG2a in the mouse and IgG1 in humans. Antibodies of these isotypes activate complement and collaborate with antibody-dependent effector cells in protective immune responses.

  3. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    Science.gov (United States)

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

  4. Protein antigen adsorption to the DDA/TDB liposomal adjuvant

    DEFF Research Database (Denmark)

    Hamborg, Mette; Jorgensen, Lene; Bojsen, Anders Riber;

    2013-01-01

    Understanding the nature of adjuvant-antigen interactions is important for the future design of efficient and safe subunit vaccines, but remains an analytical challenge. We studied the interactions between three model protein antigens and the clinically tested cationic liposomal adjuvant composed...

  5. Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

    OpenAIRE

    Samantha Sayers; Guerlain Ulysse; Zuoshuang Xiang; Yongqun He

    2012-01-01

    Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bi...

  6. Immune adjuvant activity of the olive, soybean and corn oils

    Directory of Open Access Journals (Sweden)

    Ana Claudia Marinho da Silva

    2016-08-01

    Full Text Available In the last half of the century, a large amount of substances has been used as immune adjuvant. The immune adjuvant effect of olive, soybean and corn oils in Swiss mice immunized with ovalbumin (OVA plus aluminum hydroxide or emulsified in Marcol, soybean, olive or corn oils was evaluated through the OVA-specific antibodies determined by ELISA and Passive Cutaneous Anaphylaxis. In this work the comparison of the intensity of the immune response was established by the Bayesian analysis. The adjuvant effect of the vegetable oils was shown to be more effective than aluminium hydroxide. Regarding to OVA-specific IgE synthesis, olive oil had the slowest adjuvant effect of the three vegetable oils. Accordingly, olive oil was the most convenient among the vegetable oils to be used as immune adjuvant, since it stimulated a higher production of OVA-specific Ig and lower levels of anti-OVA IgE.

  7. Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

    Directory of Open Access Journals (Sweden)

    Samantha Sayers

    2012-01-01

    Full Text Available Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO in the Web Ontology Language (OWL format.

  8. Advax-adjuvanted recombinant protective antigen provides protection against inhalational anthrax that is further enhanced by addition of murabutide adjuvant.

    Science.gov (United States)

    Feinen, Brandon; Petrovsky, Nikolai; Verma, Anita; Merkel, Tod J

    2014-04-01

    Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ∼4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy.

  9. Advax-Adjuvanted Recombinant Protective Antigen Provides Protection against Inhalational Anthrax That Is Further Enhanced by Addition of Murabutide Adjuvant

    Science.gov (United States)

    Feinen, Brandon; Petrovsky, Nikolai; Verma, Anita

    2014-01-01

    Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ∼4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy. PMID:24554695

  10. Decolonization of Staphylococcus aureus carriage.

    Science.gov (United States)

    Botelho-Nevers, E; Gagnaire, J; Verhoeven, P O; Cazorla, C; Grattard, F; Pozzetto, B; Berthelot, P; Lucht, F

    2017-09-01

    Staphylococcus aureus nasal colonization is a well-known independent risk factor for infection caused by this bacterium. Screening and decolonization of carriers have been proven effective in reducing S. aureus infections in some populations. However, a gap remains between what has been proven effective and what is currently done. We aimed to summarize recommendations and current knowledge of S. aureus decolonization to answer the following questions: Why? For whom? How? When? And what are the perspectives? Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. Modern Vaccines/Adjuvants Formulation Session 6: Vaccine &Adjuvant Formulation & Production 15-17 May 2013, Lausanne, Switzerland.

    Science.gov (United States)

    Fox, Christopher B

    2013-09-01

    The Modern Vaccines/Adjuvants Formulation meeting aims to fill a critical gap in current vaccine development efforts by bringing together formulation scientists and immunologists to emphasize the importance of rational formulation design in order to optimize vaccine and adjuvant bioactivity, safety, and manufacturability. Session 6 on Vaccine and Adjuvant Formulation and Production provided three examples of this theme, with speakers emphasizing the need for extensive physicochemical characterization of adjuvant-antigen interactions, the rational formulation design of a CD8+ T cell-inducing adjuvant based on immunological principles, and the development and production of a rabies vaccine by a developing country manufacturer. Throughout the session, the practical importance of sound formulation and manufacturing design accompanied by analytical characterization was highlighted.

  12. Designing CAF-adjuvanted dry powder vaccines: Spray drying preserves the adjuvant activity of CAF01

    DEFF Research Database (Denmark)

    Ingvarsson, Pall Thor; Schmidt, Signe Tandrup; Christensen, Dennis

    2013-01-01

    spray drying. The optimal excipient to stabilize CAF01 during spray drying and for the design of nanocomposite microparticles was identified among mannitol, lactose and trehalose. Trehalose and lactose were promising stabilizers with respect to preserving liposome size, as compared to mannitol......Dry powder vaccine formulations are highly attractive due to improved storage stability and the possibility for particle engineering, as compared to liquid formulations. However, a prerequisite for formulating vaccines into dry formulations is that their physicochemical and adjuvant properties...... remain unchanged upon rehydration. Thus, we have identified and optimized the parameters of importance for the design of a spray dried powder formulation of the cationic liposomal adjuvant formulation 01 (CAF01) composed of dimethyldioctadecylammonium (DDA) bromide and trehalose 6,6′-dibehenate (TDB) via...

  13. Inducible clindamycin resistance in Staphylococcus species.

    Science.gov (United States)

    Afridi, Faisal Iqbal; Zeb, Mubarak; Hussain, Arif; Farooqi, Badar Jahan; Murtuza, Ghulam

    2014-07-01

    To determine the frequency of inducible clindamycin resistance in clinical isolates of Staphylococcus species by phenotypic D-test. Observational study. Ziauddin University Hospital, Karachi, from July to December 2011. Consecutive clinical isolates of Staphylococcus species were collected and identified by conventional microbiological techniques. Antimicrobial susceptibility testing and inducible clindamycin resistance was carried out by performing D-test using CLSI criteria. Methicillin resistance was detected by using Cefoxitin disk as a surrogate marker. Statistical analysis was performed by SPSS version-17. A total of 667 clinical isolates of Staphylococcus species were obtained during the study period. In these isolates, 177 (26.5%) were Staphylococcus aureus, and 490 (73.5%) were coagulase negative Staphylococci. The total frequency of inducible clindamycin resistance among isolates of Staphylococcus species was 120/667 (18%). Frequency of inducible clindamycin resistance among coagulase negative Staphylococci group and Staphylococcus aureus group were 18.57% and 16.38% respectively. Median age of patients in D-test positive group was 19.5 (1 - 54) years. The frequency of inducible clindamycin resistance among Staphylococcus species may differ in different hospital setup. Clinical microbiology laboratories should implement testing simple and effective D-test on all Staphylococcus species. D-test positive isolates should be reported clindamycin resistant to decrease treatment failure.

  14. Staphylococcus saprophyticus causing native valve endocarditis.

    Science.gov (United States)

    Garduño, Eugenio; Márquez, Irene; Beteta, Alicia; Said, Ibrahim; Blanco, Javier; Pineda, Tomás

    2005-01-01

    Coagulase negative staphylococci are a rare cause of native valve endocarditis. Staphylococcus saprophyticus is a coagulase-negative Staphylococcus infrequently reported as a human pathogen, and most of the cases reported are urinary tract infections. We describe a case of native valve endocarditis attributed to this organism. The patient needed valve replacement due to heart failure.

  15. Ranitidine as adjuvant treatment in colorectal cancer

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Christensen, Ib Jarle; Moesgaard, F;

    2002-01-01

    by oral ranitidine 150 mg or placebo twice daily for 5 years. Adjuvant cytotoxic or radiation therapy was not given. An observer-blinded interim analysis performed after 40 months showed that there was no effect of ranitidine on overall survival, and the study was discontinued in accordance......BACKGROUND: Results from short-term studies of histamine type 2 (H2) receptor antagonists on survival of patients with solid tumours are debatable. In this study the efficacy of the H2-receptor antagonist ranitidine on long-term survival of patients with colorectal cancer was evaluated. METHODS...... curative resection of colorectal cancer and who do not receive perioperative blood transfusion and do not develop postoperative infectious complications....

  16. Phage typing of Staphylococcus saprophyticus.

    Science.gov (United States)

    Torres Pereira, A.; Melo Cristino, J. A.

    1991-01-01

    This study included 502 staphylococcus strains; Staphylococcus saprophyticus (297 strains) S. cohnii (47), S. xylosus (10), S. epidermidis (67) and S. aureus (81). Mitomycin C induction was performed on 100 isolates of S. saprophyticus and all induced strains were reacted with each other. Twenty-six strains proved to be lysogenic. Phages were propagated and titrated. With 12 of the phages there were three frequent associations, named lytic groups A, B and C, which included 75% of all typable strains. Typability of the system was 45% and reproducibility was between 94.2% and 100%. Phages did not lyse S. aureus and S. epidermidis strains, but they lysed S. saprophyticus and only rare strains of other novobiocin resistant species. Effective S. saprophyticus typing serves ecological purposes and tracing the origin of urinary strains from the skin or mucous membranes. Phage typing in association with plasmid profiling previously described, are anticipated as complementary methods with strong discriminatory power for differentiating among S. saprophyticus strains. PMID:1752305

  17. Development and controversies of adjuvant therapy for pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Wan-Yee Lau; Eric C. H. Lai

    2008-01-01

    BACKGROUND:Pancreatic cancer is an aggressive malignancy with a dismal prognosis. Radical surgery provides the only chance for a cure with a 5-year survival rate of 7%-25%. An effective adjuvant therapy is urgently needed to improve the surgical outcome. This review describes the current status of adjuvant therapy for pancreatic cancer, and highlights its controversies. DATA SOURCES:A Medline database search was performed to identify relevant articles using the keywords"pancreatic neoplasm", and"adjuvant therapy". Additional papers were identiifed by a manual search of the references from the key articles. RESULTS:Eight prospective randomized controlled trials (RCTs) on the use of adjuvant chemotherapy and chemoradiation for pancreatic cancer could be identiifed. The results for adjuvant regimens based on systemic 5-lfuorouracil with or without external radiotherapy were conlficting. The recent two RCTs on gemcitabine based regimen gave promising results. CONCLUSIONS:Based on the available data, no standard adjuvant therapy for pancreatic cancer can be established yet. The best adjuvant regimen remains to be determined in large-scale RCTs. Future trials should use a gemcitabine based regimen.

  18. The role of adjuvant in mediating antigen structure and stability.

    Science.gov (United States)

    Braun, Latoya Jones; Eldridge, Aimee M; Cummiskey, Jessica; Arthur, Kelly K; Wuttke, Deborah S

    2012-04-01

    The purpose of this study was to probe the fate of a model antigen, a cysteine-free mutant of bacteriophage T4 lysozyme, to the level of fine structural detail, as a consequence of its interaction with an aluminum (Al)-containing adjuvant. Fluorescence spectroscopy and differential scanning calorimetry were used to compare the thermal stability of the protein in solution versus adsorbed onto an Al-containing adjuvant. Differences in accessible hydrophobic surface areas were investigated using an extrinsic fluorescence probe, 8-Anilino-1-naphthalenesulfonic acid (ANS). As has been observed with other model antigens, the apparent thermal stability of the protein decreased following adsorption onto the adjuvant. ANS spectra suggested that adsorption onto the adjuvant caused an increase in exposure of hydrophobic regions of the protein. Electrostatic interactions drove the adsorption, and disruption of these interactions with high ionic strength buffers facilitated the collection of two-dimensional (15) N heteronuclear single quantum coherence nuclear magnetic resonance data of protein released from the adjuvant. Although the altered stability of the adsorbed protein suggested changes to the protein's structure, the fine structure of the desorbed protein was nearly identical to the protein's structure in the adjuvant-free formulation. Thus, the adjuvant-induced changes to the protein that were responsible for the reduced thermal stability were not observed upon desorption.

  19. Progress in adjuvant chemotherapy for breast cancer: an overview.

    Science.gov (United States)

    Anampa, Jesus; Makower, Della; Sparano, Joseph A

    2015-01-01

    Breast cancer is the most common cause of cancer and cancer death worldwide. Although most patients present with localized breast cancer and may be rendered disease-free with local therapy, distant recurrence is common and is the primary cause of death from the disease. Adjuvant systemic therapies are effective in reducing the risk of distant and local recurrence, including endocrine therapy, anti-HER2 therapy, and chemotherapy, even in patients at low risk of recurrence. The widespread use of adjuvant systemic therapy has contributed to reduced breast cancer mortality rates. Adjuvant cytotoxic chemotherapy regimens have evolved from single alkylating agents to polychemotherapy regimens incorporating anthracyclines and/or taxanes. This review summarizes key milestones in the evolution of adjuvant systemic therapy in general, and adjuvant chemotherapy in particular. Although adjuvant treatments are routinely guided by predictive factors for endocrine therapy (hormone receptor expression) and anti-HER2 therapy (HER2 overexpression), predicting benefit from chemotherapy has been more challenging. Randomized studies are now in progress utilizing multiparameter gene expression assays that may more accurately select patients most likely to benefit from adjuvant chemotherapy.

  20. Adjuvants for veterinary vaccines--types and modes of action.

    Science.gov (United States)

    Gerdts, Volker

    2015-01-01

    Adjuvants are used to improve the immune response to vaccines. Formulation with adjuvants can result in an earlier onset of immunity, an overall stronger immune response, a specific type of immunity, or a longer duration of immunity to the vaccine. Adjuvants were discovered empirically, and for decades, have been used in both humans and animals without understanding the mechanisms of action. With an improved understanding of the immune system, and in particular the interplay between innate and adaptive immunity, we are now getting better insight into the function of adjuvants. As a result, new adjuvants are being developed that are safe and highly effective for common use in humans and animals, as well as for use in high risk populations such as immunocompromised animals, neonates or very old animals. Furthermore, adjuvants can help to reduce the amount of antigen needed in the vaccine, increase the stability of the vaccine and enable alternatiye administration routes such as needle-free delivery of the vaccine. Here, I will provide an over view of the existing adjuvant technologies for veterinary vaccines and provide an outlook into some of the new technologies in preclinical and clinical development.

  1. Characterization of the in situ immunological responses to vaccine adjuvants.

    Science.gov (United States)

    Horohov, D W; Dunham, J; Liu, C; Betancourt, A; Stewart, J C; Page, A E; Chambers, T M

    2015-03-15

    Adjuvants are included with many inactivated and some modified live vaccines to enhance immune responses to specific antigens. While early vaccines relied exclusively upon aluminum salts, still the major adjuvant used in human vaccines, other adjuvant products are used in veterinary medicine. In addition to enhancing antigen presentation, adjuvants can also enhance the development of specific immune responses. Thus, alum adjuvants often preferentially stimulate humoral immune responses. By contrast, lipid-based adjuvants are often more effective at stimulating cell-mediated immune responses. Metastim(®) is a lipid-based adjuvant reported to elicit both humoral and cellular immune responses, though the mechanism responsible for this activity remains unclear. In this study, we compared the ability of equine influenza virus vaccines containing either saline or Metastim(®) or an aluminum phosphate adjuvant to stimulate antigen presenting cell function in vivo. Six ponies were intradermally inoculated with inactivated equine influenza (KY97) mixed with either adjuvant or saline. Multiple sites were injected so that biopsies could be collected at different times post injection. The 4mm punch biopsies were formalin-fixed, paraffin-embedded, and stained with hematoxylin and eosin (H&E). Total RNA was isolated from 2mm punch biopsies for the determination of gene expression by real-time PCR. H&E staining revealed a variety of cells recruited to the injection sites, including lymphocytes, neutrophils, eosinophils and macrophages. Real-time PCR analysis of the injection site confirmed this cellular infiltration and identified increased expression of activation markers. Both vaccines also stimulated gene expressions of pro-inflammatory cytokines. The vaccine containing Metastim(®) elicited significantly higher gene expression of interferon-γ, IL-12, CD4 and CD83 compared to alum (psalt, there was also evidence of Th2 cytokine induction. Copyright © 2015 Elsevier B.V. All

  2. Adjuvants for vaccines to drugs of abuse and addiction.

    Science.gov (United States)

    Alving, Carl R; Matyas, Gary R; Torres, Oscar; Jalah, Rashmi; Beck, Zoltan

    2014-09-22

    Immunotherapeutic vaccines to drugs of abuse, including nicotine, cocaine, heroin, oxycodone, methamphetamine, and others are being developed. The theoretical basis of such vaccines is to induce antibodies that sequester the drug in the blood in the form of antibody-bound drug that cannot cross the blood brain barrier, thereby preventing psychoactive effects. Because the drugs are haptens a successful vaccine relies on development of appropriate hapten-protein carrier conjugates. However, because induction of high and prolonged levels of antibodies is required for an effective vaccine, and because injection of T-independent haptenic drugs of abuse does not induce memory recall responses, the role of adjuvants during immunization plays a critical role. As reviewed herein, preclinical studies often use strong adjuvants such as complete and incomplete Freund's adjuvant and others that cannot be, or in the case of many newer adjuvants, have never been, employed in humans. Balanced against this, the only adjuvant that has been included in candidate vaccines in human clinical trials to nicotine and cocaine has been aluminum hydroxide gel. While aluminum salts have been widely utilized worldwide in numerous licensed vaccines, the experience with human responses to aluminum salt-adjuvanted vaccines to haptenic drugs of abuse has suggested that the immune responses are too weak to allow development of a successful vaccine. What is needed is an adjuvant or combination of adjuvants that are safe, potent, widely available, easily manufactured, and cost-effective. Based on our review of the field we recommend the following adjuvant combinations either for research or for product development for human use: aluminum salt with adsorbed monophosphoryl lipid A (MPLA); liposomes containing MPLA [L(MPLA)]; L(MPLA) adsorbed to aluminum salt; oil-in-water emulsion; or oil-in-water emulsion containing MPLA.

  3. Adjuvant Strategies for Resectable Pancreatic Cancer: Have We Made Progress?

    Directory of Open Access Journals (Sweden)

    Suzanne Russo

    2012-03-01

    Full Text Available Substantial controversy remains regarding the optimal adjuvant treatment for patients with resectable pancreatic adenocarcinoma. Despite improvements in radiation techniques, systemic therapies, and incorporation of targeted agents, the 5-year survival rates for early stage patients remains less than 25% and the optimal adjuvant treatment approach remains unclear. Here we summarize the data presented at the 2012 American Society of Clinical Oncology (ASCO Gastrointestinal Cancers Symposium regarding controversial issues surrounding the role, timing, and selection of patients for adjuvant chemoradiation strategies following curative resection for pancreatic adenocarcinoma. (Abstracts #301, #333, and #206.

  4. Prevalence of Staphylococcus aureus and Staphylococcus saprophyticus in Imam Khomayni Hospital, Ilam, 2011-2012

    Directory of Open Access Journals (Sweden)

    Reza Azizian

    2014-01-01

    Full Text Available Abstract Background and objective: Staphylococcus aureus is one of the main causes of hospital infections. Staphylococcus saprophyticus is a common agent of urinary tract infections. Hospital acquired infection as an old challenge has high importance in hospital infection control and Staphylococcus spp. play main role among routine pathogens. this study designed to investigate the of Staphylococcus aureus and Staphylococcus saprophyticus among ICU, Men and Children wards. Materials and methods: Samples collected randomly from ICU, Men and Children wards. Through 203 sampling of wall, floor, bed, pillow and blanket, 75 Staphylococcus spp. isolated. Species recognizes base on culture on Mannitol salt agar and Novobiocin susceptibility determination. Result: Among 75 positive samples, 62 (82.7%, and 13 isolates were Staphylococcus saprophyticus, Staphylococcus aureus, respectively. 51% of bacteria isolated from ICU, 29% from children ward and 20% from men surgery ward. Staphylococcus saprophyticus comprised 87%, 82% and 73% of isolates pertaining to ICU, pediatric and men surgery wards, in a row. Conclusion: Our funding indicate there is an inappropriate instrument to deal with infection in hospital specially ICU. Regards to this issue that Staphylococcus spp. as a main pathogen which has potency to form biofilm and show high resistance to extended broad antibiotics therefore it is suggested to prepare proper guideline to cope with bacteria dissemination and resistance emergence in hospital.

  5. 9 CFR 113.115 - Staphylococcus Aureus Bacterin-Toxoid.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Staphylococcus Aureus Bacterin-Toxoid... REQUIREMENTS Inactivated Bacterial Products § 113.115 Staphylococcus Aureus Bacterin-Toxoid. Staphylococcus... Staphylococcus aureus which has been inactivated and is nontoxic. Each serial of biological product...

  6. Exfoliative Toxins of Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Michal Bukowski

    2010-05-01

    Full Text Available Staphylococcus aureus is an important pathogen of humans and livestock. It causes a diverse array of diseases, ranging from relatively harmless localized skin infections to life-threatening systemic conditions. Among multiple virulence factors, staphylococci secrete several exotoxins directly associated with particular disease symptoms. These include toxic shock syndrome toxin 1 (TSST-1, enterotoxins, and exfoliative toxins (ETs. The latter are particularly interesting as the sole agents responsible for staphylococcal scalded skin syndrome (SSSS, a disease predominantly affecting infants and characterized by the loss of superficial skin layers, dehydration, and secondary infections. The molecular basis of the clinical symptoms of SSSS is well understood. ETs are serine proteases with high substrate specificity, which selectively recognize and hydrolyze desmosomal proteins in the skin. The fascinating road leading to the discovery of ETs as the agents responsible for SSSS and the characterization of the molecular mechanism of their action, including recent advances in the field, are reviewed in this article.

  7. The Vaccine Formulation Laboratory: a platform for access to adjuvants.

    Science.gov (United States)

    Collin, Nicolas; Dubois, Patrice M

    2011-07-01

    Adjuvants are increasingly used by the vaccine research and development community, particularly for their ability to enhance immune responses and for their dose-sparing properties. However, they are not readily available to the majority of public sector vaccine research groups, and even those with access to suitable adjuvants may still fail in the development of their vaccines because of lack of knowledge on how to correctly formulate the adjuvants. This shortcoming led the World Health Organization to advocate for the establishment of the Vaccine Formulation Laboratory at the University of Lausanne, Switzerland. The primary mission of the laboratory is to transfer adjuvants and formulation technology free of intellectual property rights to academic institutions, small biotechnology companies and developing countries vaccine manufacturers. In this context, the transfer of an oil-in-water emulsion to Bio Farma, an Indonesian vaccine manufacturer, was initiated to increase domestic pandemic influenza vaccine production capacity as part of the national pandemic influenza preparedness plan.

  8. Activity of glycated chitosan and other adjuvants to PDT vaccines

    Science.gov (United States)

    Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

    2015-03-01

    Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

  9. A randomised controlled trial comparing the effect of adjuvant ...

    African Journals Online (AJOL)

    between adjuvant intrathecal 2 mg midazolam as compared to intrathecal 20 micrograms fentanyl for patients undergoing ... in mental processes, respiratory depression, and other .... nificance level and power of 90%, the required sample.

  10. Editorial: Short-course adjuvant trastuzumab will increase cure rates ...

    African Journals Online (AJOL)

    Editorial: Short-course adjuvant trastuzumab will increase cure rates in patients with human epidermal growth factor receptor 2-positive breast cancer. ... Journal Home > Vol 107, No 8 (2017) >. Log in or Register to get ... from 32 Countries:.

  11. Endometrial adenocarcinoma, adjuvant radiotherapy tailored to prognostic factors.

    Science.gov (United States)

    Meerwaldt, J H; Hoekstra, C J; van Putten, W L; Tjokrowardojo, A J; Koper, P C

    1990-02-01

    The optimal adjuvant radiotherapy for surgically treated endometrial cancer has not yet been defined. We report on 389 patients treated between 1970 and 1985 with adjuvant radiotherapy. The treatment was tailored to the known prognostic factors: myometrial invasion and grade of differentiation of the tumor. Ten-year overall survival was 67%, 10-year relapse-free survival 77%; 23% relapse, of which 21% distant and 6% locoregional relapse. In a multivariate analysis, stage (pT), grade, and myometrial invasion were prognostic factors. The number of locoregional failures was very small (n = 23). This small number, the fact that radiation treatment was tailored to prognostic factors, and the absence of a nontreated control group precluded an analysis of the effect of the adjuvant irradiation. Large randomized studies with a control (no treatment) arm should be performed to determine the value of adjuvant radiotherapy.

  12. Triple negative breast cancer: adjuvant chemotherapy effect on survival

    National Research Council Canada - National Science Library

    Steponaviciene, L; Lachej-Mikeroviene, N; Smailyte, G; Aleknavicius, E; Meskauskas, R; Didziapetriene, J

    2011-01-01

    Purpose: The purpose of this study was to evaluate the overall survival of patients with triple negative breast cancer and the impact of different adjuvant chemotherapy regimens on survival.Material/Methods...

  13. Mx bio adjuvant for enhancing immune responses against influenza virus

    Directory of Open Access Journals (Sweden)

    Sina Soleimani

    2015-06-01

    Conclusion: These data revealed that Mx1 as biological adjuvant was able to increase antibody titer and induction memory immune responses against influenza immunization without causing any side effects.

  14. Engineering of an Inhalable DDA/TDB Liposomal Adjuvant

    DEFF Research Database (Denmark)

    Ingvarsson, Pall Thor; Yang, Mingshi; Mulvad, Helle

    2013-01-01

    The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB).......The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB)....

  15. Learning impairment in honey bees caused by agricultural spray adjuvants.

    Directory of Open Access Journals (Sweden)

    Timothy J Ciarlo

    Full Text Available BACKGROUND: Spray adjuvants are often applied to crops in conjunction with agricultural pesticides in order to boost the efficacy of the active ingredient(s. The adjuvants themselves are largely assumed to be biologically inert and are therefore subject to minimal scrutiny and toxicological testing by regulatory agencies. Honey bees are exposed to a wide array of pesticides as they conduct normal foraging operations, meaning that they are likely exposed to spray adjuvants as well. It was previously unknown whether these agrochemicals have any deleterious effects on honey bee behavior. METHODOLOGY/PRINCIPAL FINDINGS: An improved, automated version of the proboscis extension reflex (PER assay with a high degree of trial-to-trial reproducibility was used to measure the olfactory learning ability of honey bees treated orally with sublethal doses of the most widely used spray adjuvants on almonds in the Central Valley of California. Three different adjuvant classes (nonionic surfactants, crop oil concentrates, and organosilicone surfactants were investigated in this study. Learning was impaired after ingestion of 20 µg organosilicone surfactant, indicating harmful effects on honey bees caused by agrochemicals previously believed to be innocuous. Organosilicones were more active than the nonionic adjuvants, while the crop oil concentrates were inactive. Ingestion was required for the tested adjuvant to have an effect on learning, as exposure via antennal contact only induced no level of impairment. CONCLUSIONS/SIGNIFICANCE: A decrease in percent conditioned response after ingestion of organosilicone surfactants has been demonstrated here for the first time. Olfactory learning is important for foraging honey bees because it allows them to exploit the most productive floral resources in an area at any given time. Impairment of this learning ability may have serious implications for foraging efficiency at the colony level, as well as potentially many

  16. Effect of Freund's adjuvant on standard dark and pastel mink.

    Science.gov (United States)

    Tabel, H; Ingram, D G

    1971-04-01

    Following a long series of injections of homologous immunoglobulin in complete and incomplete Freund's adjuvant into mink, a moderate elevation in the level of gammaglobulin in the serum was observed in a few animals. Relatively mild pathological changes also were seen in liver, spleen, lymph nodes, lungs and kidney. It is concluded that the injection of Freund's adjuvant, under the experimental conditions described, produced lesions which were readily distinguishable from the lesions characteristic of aleutian disease of mink.

  17. Comparative genomic analysis of the genus Staphylococcus including Staphylococcus aureus and its newly described sister species Staphylococcus simiae

    Science.gov (United States)

    2012-01-01

    Background Staphylococcus belongs to the Gram-positive low G + C content group of the Firmicutes division of bacteria. Staphylococcus aureus is an important human and veterinary pathogen that causes a broad spectrum of diseases, and has developed important multidrug resistant forms such as methicillin-resistant S. aureus (MRSA). Staphylococcus simiae was isolated from South American squirrel monkeys in 2000, and is a coagulase-negative bacterium, closely related, and possibly the sister group, to S. aureus. Comparative genomic analyses of closely related bacteria with different phenotypes can provide information relevant to understanding adaptation to host environment and mechanisms of pathogenicity. Results We determined a Roche/454 draft genome sequence for S. simiae and included it in comparative genomic analyses with 11 other Staphylococcus species including S. aureus. A genome based phylogeny of the genus confirms that S. simiae is the sister group to S. aureus and indicates that the most basal Staphylococcus lineage is Staphylococcus pseudintermedius, followed by Staphylococcus carnosus. Given the primary niche of these two latter taxa, compared to the other species in the genus, this phylogeny suggests that human adaptation evolved after the split of S. carnosus. The two coagulase-positive species (S. aureus and S. pseudintermedius) are not phylogenetically closest but share many virulence factors exclusively, suggesting that these genes were acquired by horizontal transfer. Enrichment in genes related to mobile elements such as prophage in S. aureus relative to S. simiae suggests that pathogenesis in the S. aureus group has developed by gene gain through horizontal transfer, after the split of S. aureus and S. simiae from their common ancestor. Conclusions Comparative genomic analyses across 12 Staphylococcus species provide hypotheses about lineages in which human adaptation has taken place and contributions of horizontal transfer in pathogenesis. PMID

  18. Comparative genomic analysis of the genus Staphylococcus including Staphylococcus aureus and its newly described sister species Staphylococcus simiae

    Directory of Open Access Journals (Sweden)

    Suzuki Haruo

    2012-01-01

    Full Text Available Abstract Background Staphylococcus belongs to the Gram-positive low G + C content group of the Firmicutes division of bacteria. Staphylococcus aureus is an important human and veterinary pathogen that causes a broad spectrum of diseases, and has developed important multidrug resistant forms such as methicillin-resistant S. aureus (MRSA. Staphylococcus simiae was isolated from South American squirrel monkeys in 2000, and is a coagulase-negative bacterium, closely related, and possibly the sister group, to S. aureus. Comparative genomic analyses of closely related bacteria with different phenotypes can provide information relevant to understanding adaptation to host environment and mechanisms of pathogenicity. Results We determined a Roche/454 draft genome sequence for S. simiae and included it in comparative genomic analyses with 11 other Staphylococcus species including S. aureus. A genome based phylogeny of the genus confirms that S. simiae is the sister group to S. aureus and indicates that the most basal Staphylococcus lineage is Staphylococcus pseudintermedius, followed by Staphylococcus carnosus. Given the primary niche of these two latter taxa, compared to the other species in the genus, this phylogeny suggests that human adaptation evolved after the split of S. carnosus. The two coagulase-positive species (S. aureus and S. pseudintermedius are not phylogenetically closest but share many virulence factors exclusively, suggesting that these genes were acquired by horizontal transfer. Enrichment in genes related to mobile elements such as prophage in S. aureus relative to S. simiae suggests that pathogenesis in the S. aureus group has developed by gene gain through horizontal transfer, after the split of S. aureus and S. simiae from their common ancestor. Conclusions Comparative genomic analyses across 12 Staphylococcus species provide hypotheses about lineages in which human adaptation has taken place and contributions of horizontal

  19. Designing CAF-adjuvanted dry powder vaccines: spray drying preserves the adjuvant activity of CAF01.

    Science.gov (United States)

    Ingvarsson, Pall Thor; Schmidt, Signe Tandrup; Christensen, Dennis; Larsen, Niels Bent; Hinrichs, Wouter Leonardus Joseph; Andersen, Peter; Rantanen, Jukka; Nielsen, Hanne Mørck; Yang, Mingshi; Foged, Camilla

    2013-05-10

    Dry powder vaccine formulations are highly attractive due to improved storage stability and the possibility for particle engineering, as compared to liquid formulations. However, a prerequisite for formulating vaccines into dry formulations is that their physicochemical and adjuvant properties remain unchanged upon rehydration. Thus, we have identified and optimized the parameters of importance for the design of a spray dried powder formulation of the cationic liposomal adjuvant formulation 01 (CAF01) composed of dimethyldioctadecylammonium (DDA) bromide and trehalose 6,6'-dibehenate (TDB) via spray drying. The optimal excipient to stabilize CAF01 during spray drying and for the design of nanocomposite microparticles was identified among mannitol, lactose and trehalose. Trehalose and lactose were promising stabilizers with respect to preserving liposome size, as compared to mannitol. Trehalose and lactose were in the glassy state upon co-spray drying with the liposomes, whereas mannitol appeared crystalline, suggesting that the ability of the stabilizer to form a glassy matrix around the liposomes is one of the prerequisites for stabilization. Systematic studies on the effect of process parameters suggested that a fast drying rate is essential to avoid phase separation and lipid accumulation at the surface of the microparticles during spray drying. Finally, immunization studies in mice with CAF01 in combination with the tuberculosis antigen Ag85B-ESAT6-Rv2660c (H56) demonstrated that spray drying of CAF01 with trehalose under optimal processing conditions resulted in the preservation of the adjuvant activity in vivo. These data demonstrate the importance of liposome stabilization via optimization of formulation and processing conditions in the engineering of dry powder liposome formulations.

  20. Autoimmune/Inflammatory Syndrome Induced by Adjuvants and Thyroid Autoimmunity

    Science.gov (United States)

    Watad, Abdulla; David, Paula; Brown, Stav; Shoenfeld, Yehuda

    2017-01-01

    The autoimmune/inflammatory syndrome induced by adjuvants (ASIA), presented by Shoenfeld and Agmon-Levin in 2011, is an entity that incorporates diverse autoimmune conditions induced by the exposure to various adjuvants. Adjuvants are agents that entail the capability to induce immune reactions. Adjuvants are found in many vaccines and used mainly to increase the response to vaccination in the general population. Silicone has also been reported to be able to induce diverse immune reactions. Clinical cases and series of heterogeneous autoimmune conditions including systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis have been reported to be induced by several adjuvants. However, only a small number of cases of autoimmune thyroid disorder have been included under the umbrella of ASIA syndrome. Indeed, clinical cases of Hashimoto’s thyroiditis and/or subacute thyroiditis were observed after the exposure to vaccines as well as silicone implantation. In our review, we aimed to summarize the current knowledge on ASIA syndrome presented as endocrinopathies, focusing on autoimmune thyroid disorders associated with the various adjuvants. PMID:28167927

  1. Spa adjuvant therapy improves diabetic lower extremity arterial disease.

    Science.gov (United States)

    Qiu, Yongbin; Zhu, Yi; Jia, Wei; Chen, Songhua; Meng, Qingzhou

    2014-08-01

    To investigate the effect of spa adjuvant therapy on diabetic lower extremity arterial disease (LEAD). 128 patients with type II diabetes were separated into three groups according to the degree of lower extremity vascular stenosis. Patients within each group were then randomly divided to receive no treatment (control) or spa adjuvant therapy (treatment). Clinical symptoms, blood pressure and hemodynamic analyses were compared between control and treatment groups by Chi square or t-test. After adjuvant therapy with spa, patients' pain, numbness, and cold sensation were significantly improved compared with control groups (PSpa adjuvant therapy also significantly increased the dorsalis pedis pulse and systolic peak velocity ratio of patients with mild lower extremity vascular stenosis compared with control groups (P0.05). Both in the spa and control groups, there were no significant differences before and after medication for fasting, 2-h postprandial blood glucose and glycosylated hemoglobin (HbA1C) analyses (P>0.05). Spa adjuvant therapy can significantly alleviate lower extremity pain, numbness, and cold sensory symptoms in diabetic LEAD patients with stenosis. Moreover, in LEAD patients with mild stenosis, spa adjuvant therapy also improves the dorsalis pedis pulse and systolic peak velocity ratio, suggesting a potential role for spa therapy as an early intervention strategy to treat the initial stages of disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Communicating the role and value of vaccine adjuvants.

    Science.gov (United States)

    Gellin, Bruce G; Salisbury, David M

    2015-06-08

    Despite the inclusion of adjuvants in many routinely used vaccines to improve the immune response, their presence and role are neither clear in product details such as the packaging or in the Summaries of Product Characteristics, nor understood by health professionals or the public. For many vaccines the adjuvant may simply be described as 'Adsorbed' without clarification that the adsorbing onto a material such as aluminium hydroxide adjuvants the antigens. As many future vaccines are likely to be adjuvanted, the presence of adjuvants, either those used in existing vaccines or novel formulations, may raise public and professional concerns unless communication materials are prepared in advance to allay anxieties such as those that have arisen over some present vaccine ingredients such as thiomersal. This raises a dilemma about how active such communications should be: over-promotion of the presence of a new adjuvant may cause unneeded anxieties; under-promotion may raise concerns over concealment of information. Research is needed and appropriate communication materials should be prepared. Copyright © 2015. Published by Elsevier Ltd.

  3. Mast cells contribute to the mucosal adjuvant effect of CTA1-DD after IgG-complex formation.

    Science.gov (United States)

    Fang, Yu; Larsson, Lisa; Mattsson, Johan; Lycke, Nils; Xiang, Zou

    2010-09-01

    Mast cell activation is one of the most dramatic immune-mediated responses the body can encounter. In the worst scenario (i.e., anaphylaxis), this response is fatal. However, the importance of mast cells as initiators and effectors of both innate and adaptive immunity in healthy individuals has recently been appreciated. It was reported that mast cell activation can be used as an adjuvant to promote Ag-specific humoral immune responses upon vaccination. In this study, we have used a clinically relevant mucosal adjuvant, cholera toxin A1 subunit (CTA1)-DD, which is a fusion protein composed of CTA1, the ADP-ribosylating part of cholera toxin, and DD, two Ig-binding domains derived from Staphylococcus aureus protein A. CTA1-DD in combination with polyclonal IgG induced degranulation and production of TNF-alpha from mouse mast cells. Furthermore, CTA1-DD and polyclonal IgG complex induced mast cell degranulation in mouse skin tissue and nasal mucosa. We also found that intranasal immunization with hapten (4-hydroxy-3-nitrophenyl) acetyl (NP) coupled to chicken gammaglobulin admixed with CTA1-DD complexed with polyclonal IgG greatly enhanced serum IgG anti-NP Ab responses and stimulated higher numbers of NP-specific plasma cells in the bone marrow as compared with that observed in mice immunized with NP-chicken gammaglobulin with CTA1-DD alone. This CTA1-DD/IgG complex-mediated enhancement was mast cell dependent because it was absent in mast cell-deficient Kit(W-sh/W-sh) mice. In conclusion, our data suggest that a clinically relevant adjuvant, CTA1-DD, exerts additional augmenting effects through activation of mucosal mast cells, clearly demonstrating that mast cells could be further exploited for improving the efficacy of mucosal vaccines.

  4. Squalene and squalane emulsions as adjuvants.

    Science.gov (United States)

    Allison, A C

    1999-09-01

    Microfluidized squalene or squalane emulsions are efficient adjuvants, eliciting both humoral and cellular immune responses. Microfluidization stabilizes the emulsions and allows sterilization by terminal filtration. The emulsions are stable for years at ambient temperature and can be frozen. Antigens are added after emulsification so that conformational epitopes are not lost by denaturation and to facilitate manufacture. A Pluronic block copolymer can be added to the squalane or squalene emulsion. Soluble antigens administered in such emulsions generate cytotoxic T lymphocytes able to lyse target cells expressing the antigen in a genetically restricted fashion. Optionally a relatively nontoxic analog of muramyl dipeptide (MDP) or another immunomodulator can be added; however, the dose of MDP must be restricted to avoid systemic side effects in humans. Squalene or squalane emulsions without copolymers or MDP have very little toxicity and elicit potent antibody responses to several antigens in nonhuman primates. They could be used to improve a wide range of vaccines. Squalene or squalane emulsions have been administered in human cancer vaccines, with mild side effects and evidence of efficacy, in terms of both immune responses and antitumor activity.

  5. Epidemiology of Methicillin-Resistant Staphylococcus aureus

    National Research Council Canada - National Science Library

    Helen W. Boucher; G. Ralph Corey

    2008-01-01

    The frequency of methicillin-resistant Staphylococcus aureus (MRSA) infections continues to grow in hospital-associated settings and, more recently, in community settings in the United States and globally...

  6. Acute Pyelonephritis Caused by Staphylococcus xylosus

    Science.gov (United States)

    Tselenis-Kotsowilis, Angelina D.; Koliomichalis, Maria P.; Papavassiliou, John T.

    1982-01-01

    Staphylococcus xylosus was recovered from the urine of a patient with pyelonephritis. Antibodies against the teichoic acid of the microorganism were demonstrated in the patient's serum by the agar gel diffusion technique. PMID:7130375

  7. Sensitization of Staphylococcus aureus to methicillin and other antibiotics in vitro and in vivo in the presence of HAMLET.

    Science.gov (United States)

    Marks, Laura R; Clementi, Emily A; Hakansson, Anders P

    2013-01-01

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex from human milk with both tumoricidal and bactericidal activities. HAMLET exerts a rather specific bactericidal activity against some respiratory pathogens, with highest activity against Streptococcus pneumoniae, but lacks activity against most other bacterial pathogens, including Staphylococci. Still, ion transport associated with death in S. pneumoniae is also detected to a lower degree in insensitive organisms. In this study we demonstrate that HAMLET acts as an antimicrobial adjuvant that can increase the activity of a broad spectrum of antibiotics (methicillin, vancomycin, gentamicin and erythromycin) against multi-drug resistant Staphylococcus aureus, to a degree where they become sensitive to those same antibiotics, both in antimicrobial assays against planktonic and biofilm bacteria and in an in vivo model of nasopharyngeal colonization. We show that HAMLET exerts these effects specifically by dissipating the proton gradient and inducing a sodium-dependent calcium influx that partially depolarizes the plasma membrane, the same mechanism induced during pneumococcal death. These effects results in an increased cell associated binding and/or uptake of penicillin, gentamicin and vancomycin, especially in resistant stains. Finally, HAMLET inhibits the increased resistance of methicillin seen under antibiotic pressure and the bacteria do not become resistant to the adjuvant, which is a major advantageous feature of the molecule. These results highlight HAMLET as a novel antimicrobial adjuvant with the potential to increase the clinical usefulness of antibiotics against drug resistant strains of S. aureus.

  8. Sensitization of Staphylococcus aureus to methicillin and other antibiotics in vitro and in vivo in the presence of HAMLET.

    Directory of Open Access Journals (Sweden)

    Laura R Marks

    Full Text Available HAMLET (human alpha-lactalbumin made lethal to tumor cells is a protein-lipid complex from human milk with both tumoricidal and bactericidal activities. HAMLET exerts a rather specific bactericidal activity against some respiratory pathogens, with highest activity against Streptococcus pneumoniae, but lacks activity against most other bacterial pathogens, including Staphylococci. Still, ion transport associated with death in S. pneumoniae is also detected to a lower degree in insensitive organisms. In this study we demonstrate that HAMLET acts as an antimicrobial adjuvant that can increase the activity of a broad spectrum of antibiotics (methicillin, vancomycin, gentamicin and erythromycin against multi-drug resistant Staphylococcus aureus, to a degree where they become sensitive to those same antibiotics, both in antimicrobial assays against planktonic and biofilm bacteria and in an in vivo model of nasopharyngeal colonization. We show that HAMLET exerts these effects specifically by dissipating the proton gradient and inducing a sodium-dependent calcium influx that partially depolarizes the plasma membrane, the same mechanism induced during pneumococcal death. These effects results in an increased cell associated binding and/or uptake of penicillin, gentamicin and vancomycin, especially in resistant stains. Finally, HAMLET inhibits the increased resistance of methicillin seen under antibiotic pressure and the bacteria do not become resistant to the adjuvant, which is a major advantageous feature of the molecule. These results highlight HAMLET as a novel antimicrobial adjuvant with the potential to increase the clinical usefulness of antibiotics against drug resistant strains of S. aureus.

  9. Staphylococcus aureus resistente a vancomicina.

    Directory of Open Access Journals (Sweden)

    Carlos Andrés Rodríguez

    2005-12-01

    Full Text Available Objetivo. Revisar la evolución y mecanismos moleculares de la resistencia de Staphylococcus aureus a vancomicina. Fuente de los datos. Se consultó la base de datos MEDLINE y se seleccionaron artículos tipo reportes de caso, estudios bioquímicos, de microscopía electrónica y biología molecular pertinentes. Síntesis. Después de casi 40 años de eficacia ininterrumpida de la vancomicina, en 1997 se reportaron los primeros casos de fracaso terapéutico debido a cepas de Staphylococcus aureus con resistencia intermedia, denominadas VISA (concentración inhibitoria mínima, CIM, 8 a 16 ?g/ml, así como a cepas con resistencia heterogénea hVISA (CIM global = 4 ?g/ml, pero con subpoblaciones VISA, en las cuales la resistencia está mediada por engrosamiento de la pared celular y disminución de su entrecruzamiento, lo que afecta la llegada del antibiótico al blanco principal, los monómeros del peptidoglicano en la membrana plasmática. En 2002 se aisló la primera de las 3 cepas reportadas hasta la fecha con resistencia total al antibiótico, denominadas VRSA (CIM>32 ?g/ml, en las que se encontró el transposón Tn1546 proveniente de Enterococcus spp, responsable del reemplazo de la terminación D-Ala-D-Ala por D-Ala-Dlactato en los precursores de la pared celular con pérdida de la afinidad por el glicopéptido. Conclusiones. La resistencia a vancomicina es una realidad en S. aureus, mediada en el caso de VISA por alteraciones en la pared celular que atrapan el antibiótico antes de llegar al sitio de acción, y en el caso de VRSA, por transferencia desde Enterococcus spp. de genes que llevan a la modificación del blanco molecular.

  10. Gastric carcinoma: curative resection and adjuvant chemotherapy.

    Science.gov (United States)

    Carrillo Hernández, J F; Ernesto de Obaldía Castillo, G; Ramírez Ortega, C; Frías Mendivil, M; Pardo, M

    1994-01-01

    A retrospective study of gastric adenocarcinoma treated with surgery as curative attempt was performed at the Oncology Service, in the Hospital Regional 20 de Noviembre, ISSSTE. Morbidity and mortality of the surgical procedures were evaluated, the significance of several risk factors and the survival impact of adjuvant chemotherapy with 5-fluorouracil (5-FU) and mitomycin C (MMC). In the period from 1975 to 1991 a total of 483 new cases were seen. In only 54 patients (11.2%) was it possible to undertake a curative resection. The patients were assigned to three groups of treatment: surgery alone (14 cases), surgery + 5-FU (19 cases), and surgery + 5-FU+MMC (21 cases). Three different types of surgical techniques are regularly performed in our service for gastric cancer treatment: Billroth II distal gastrectomy, total gastrectomy with Roux-En-Y reconstruction, and esophagogastrectomy with esophagogastrostomy. Surgical morbidity and mortality was low, with 9% of duodenal stump fistulas and 27% with partial stenosis of esophagojejunostomy; the operative mortality was zero. Chemotherapy toxicity was transient and low, no related deaths were recorded. The prognostic factors associated significantly with survival were lymph node status and tumor penetration. The histologic differentiation as well as the tumor location and type of surgery had no significance. The estimated 5-year survival of the patients treated with surgery alone was 62%, while that of the patients treated with surgery plus chemotherapy was 38%. These groups were not comparable, however, because of important differences in their prognostic factors. The groups treated with 5-FU alone or in combination with MMC had no survival difference between them.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Adjuvant radiotherapy for stage I endometrial cancer.

    Science.gov (United States)

    Kong, Anthony; Johnson, Nick; Kitchener, Henry C; Lawrie, Theresa A

    2012-04-18

    This is an updated version of the original Cochrane review published in Issue 2, 2007. The role of radiotherapy (both pelvic external beam radiotherapy (EBRT) and vaginal intracavity brachytherapy (VBT)) in stage I endometrial cancer following hysterectomy remains controversial. To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Specialised Register to end-2005 for the original review, and extended the search to January 2012 for the update. We included randomised controlled trials (RCTs) that compared post-operative adjuvant radiotherapy (either EBRTor VBT, or both) versus no radiotherapy or VBT in women with stage I endometrial cancer. Two review authors independently assessed trials and extracted data to a specifically designed data collection form. The primary outcome was overall survival. Secondary outcomes were endometrial cancer-related deaths, locoregional recurrence and distant recurrence. Meta-analyses were performed using Cochrane Review Manager Software 5.1. We included eight trials. Seven trials (3628 women) compared EBRT with no EBRT (or VBT), and one trial (645 women) compared VBTwith no additional treatment. We considered six of the eight trials to be of a high quality. Time-to-event data were not available for all trials and all outcomes.EBRT (with or without VBT) compared with no EBRT (or VBT alone) for stage I endometrial carcinoma significantly reduced locoregional recurrence (time-to-event data: five trials, 2965 women; Hazard Ratio (HR) 0.36, 95% Confidence Interval (CI) 0.25 to 0.52; and dichotomous data: seven trials, 3628 women; Risk Ratio (RR) 0.33, 95% CI 0.23 to 0.47). This reduced risk of locoregional recurrence did not translate into improved overall survival (time-to-event data: five trials, 2,965 women; HR 0.99, 95% CI 0.82 to1.20; and dichotomous data: seven trials, 3628 women; RR 0.98, 95

  12. Volatiles produced by Staphylococcus xylosus and Staphylococcus carnosus during growth in sausage minces

    DEFF Research Database (Denmark)

    Stahnke, Marie Louise Heller

    1999-01-01

    of air. Volatiles produced by the cultures were collected during growth, identified and quantified. The data were analysed by partial least squares regression. The results showed that oxygen in general had more influence on the aroma producing capacity of Staphylococcus xylosus than of Staphylococcus...

  13. Staphylococcus chromogenes, a Coagulase-Negative Staphylococcus Species That Can Clot Plasma.

    Science.gov (United States)

    Dos Santos, Danielle Cabral; Lange, Carla Christine; Avellar-Costa, Pedro; Dos Santos, Katia Regina Netto; Brito, Maria Aparecida Vasconcelos Paiva; Giambiagi-deMarval, Marcia

    2016-05-01

    Staphylococcus chromogenes is one of the main coagulase-negative staphylococci isolated from mastitis of dairy cows. We describe S. chromogenes isolates that can clot plasma. Since the main pathogen causing mastitis is coagulase-positive Staphylococcus aureus, the coagulase-positive phenotype of S. chromogenes described here can easily lead to misidentification. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. Carotenoid Formation by Staphylococcus aureus

    Science.gov (United States)

    Hammond, Ray K.; White, David C.

    1970-01-01

    The carotenoid pigments of Staphylococcus aureus U-71 were identified as phytoene; ζ-carotene; δ-carotene; phytofluenol; a phytofluenol-like carotenoid, rubixanthin; and three rubixanthin-like carotenoids after extraction, saponification, chromatographic separation, and determination of their absorption spectra. There was no evidence of carotenoid esters or glycoside ethers in the extract before saponification. During the aerobic growth cycle the total carotenoids increased from 45 to 1,000 nmoles per g (dry weight), with the greatest increases in the polar, hydroxylated carotenoids. During the anaerobic growth cycle, the total carotenoids increased from 20 nmoles per g (dry weight) to 80 nmoles per g (dry weight), and only traces of the polar carotenoids were formed. Light had no effect on carotenoid synthesis. About 0.14% of the mevalonate-2-14C added to the culture was incorporated into the carotenoids during each bacterial doubling. The total carotenoids did not lose radioactivity when grown in the absence of 14C for 2.5 bacterial doublings. The total carotenoids did not lose radioactivity when grown in the absence of 14C for 2.5 bacterial doublings. The incorporation and turnover of 14C indicated the carotenes were sequentially desaturated and hydroxylated to form the polar carotenoids. PMID:5423369

  15. Desiccation tolerance in Staphylococcus aureus.

    Science.gov (United States)

    Chaibenjawong, Plykaeow; Foster, Simon J

    2011-02-01

    Staphylococcus aureus is a multidrug-resistant pathogen that not only causes a diverse array of human diseases, but also is able to survive in potentially dry and stressful environments, such as the human nose, on skin and on inanimate surfaces such as clothing and surfaces. This study investigated parameters governing desiccation tolerance of S. aureus and identified several components involved in the process. Initially, the role of environmental parameters such as temperature, growth phase, cell density, desiccation time and protectants in desiccation tolerance were determined. This established a robust model of desiccation tolerance in which S. aureus has the ability to survive on dry plastic surfaces for more than 1,097 days. Using a combination of a random screen and defined mutants, clpX, sigB and yjbH were identified as being required for desiccation tolerance. ClpX is a part of the ATP-dependent ClpXP protease, important for protein turnover, and YjbH has a proposed linked function. SigB is an accessory sigma factor with a role in generalized stress resistance. Understanding the molecular mechanisms that govern desiccation tolerance may determine the break points to be exploited to prevent the spread of this dangerous pathogen in hospitals and communities.

  16. Pathogenesis of Staphylococcus aureus abscesses.

    Science.gov (United States)

    Kobayashi, Scott D; Malachowa, Natalia; DeLeo, Frank R

    2015-06-01

    Staphylococcus aureus causes many types of human infections and syndromes-most notably skin and soft tissue infections. Abscesses are a frequent manifestation of S. aureus skin and soft tissue infections and are formed, in part, to contain the nidus of infection. Polymorphonuclear leukocytes (neutrophils) are the primary cellular host defense against S. aureus infections and a major component of S. aureus abscesses. These host cells contain and produce many antimicrobial agents that are effective at killing bacteria, but can also cause non-specific damage to host tissues and contribute to the formation of abscesses. By comparison, S. aureus produces several molecules that also contribute to the formation of abscesses. Such molecules include those that recruit neutrophils, cause host cell lysis, and are involved in the formation of the fibrin capsule surrounding the abscess. Herein, we review our current knowledge of the mechanisms and processes underlying the formation of S. aureus abscesses, including the involvement of polymorphonuclear leukocytes, and provide a brief overview of therapeutic approaches.

  17. Preparation and identification of transfer factor specific to Staphylococcus aureus in vitro.

    Science.gov (United States)

    Zhou, Jianwei; Kong, Cui; Wang, Xiukui; Shao, Jun; Feng, Lin; Zhang, Zhaocai

    2015-01-01

    The objective of the study was to explore the methods for preparing transfer factor specific to Staphylococcus aureus (SA-STF) in vitro. Under the optimum conditions, the spleen cells of rabbits were immunized with SA in vitro to prepare SA-STF, and the immune activities were identified with the phagocytosis and sterilization, skin delayed-type hypersensitivity, and immune protection tests. The concentration of polypeptide was 2.26 ± 0.27 mg/mL, and ribose was 0.684 ± 0.094 mg/mL. The phagocytosis and sterilization rates of the STF group were 70.9 ± 12.4% and 62.1 ± 12.2%, respectively, and compared with the non-specific transfer factor (NTF) group, there were no significant differences (P = 0.074 and 0.069, respectively). The skin was inflamed and marked nodules formed at the injection site in the mice of the STF group rather than the NTF and control groups. The survival rate of the STF-1 group was significantly higher than the survival rates of the STF-2 (P = 0.024) and NTF groups (P = 0.016). SA-STF was prepared and characterized successfully in vitro, and it probably is a biological candidate for therapy or adjuvant therapy for diseases caused by Staphylococcus aureus. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

  18. Environmental adjuvants, apoptosis and the censorship over autoimmunity.

    Science.gov (United States)

    Rovere-Querini, Patrizia; Manfredi, Angelo A; Sabbadini, Maria Grazia

    2005-11-01

    Alterations during apoptosis lead to the activation of autoreactive T cells and the production of autoantibodies. This article discusses the pathogenic potential of cells dying in vivo, dissecting the role of signals that favor immune responses (adjuvants) and the influence of genetic backgrounds. Diverse factors determine whether apoptosis leads or not to a self-sustaining, clinically apparent autoimmune disease. The in vivo accumulation of uncleared dying cells per se is not sufficient to cause disease. However, dying cells are antigenic and their complementation with immune adjuvants causes lethal diseases in predisposed lupus-prone animals. At least some adjuvant signals directly target the function and the activation state of antigen presenting cells. Several laboratories are aggressively pursuing the molecular identification of endogenous adjuvants. Sodium monourate and the high mobility group B1 protein (HMGB1) are, among those identified so far, well known to rheumatologists. However, even the complementation of apoptotic cells with potent adjuvant signals fail to cause clinical autoimmunity in most strains: autoantibodies generated are transient, do not undergo to epitope/spreading and do not cause disease. Novel tools for drug development will derive from the molecular identification of the constraints that prevent autoimmunity in normal subjects.

  19. Nanoparticulate Adjuvants and Delivery Systems for Allergen Immunotherapy

    Directory of Open Access Journals (Sweden)

    Juliana De Souza Rebouças

    2012-01-01

    Full Text Available In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of allergic diseases. However, current allergen immunotherapy shows limitations concerning the long-term efficacy and safety due to local side effects and risk of anaphylaxis. Thus, effective and safe vaccines with reduced dose of allergen have been developed using adjuvants. Nevertheless, the use of adjuvants still has several disadvantages, which limits its use in human vaccines. In this context, several novel adjuvants for allergen immunotherapy are currently being investigated and developed. Currently, nanoparticles-based allergen-delivery systems have received much interest as potential adjuvants for allergen immunotherapy. It has been demonstrated that the incorporation of allergens into a delivery system plays an important role in the efficacy of allergy vaccines. Several nanoparticles-based delivery systems have been described, including biodegradable and nondegradable polymeric carriers. Therefore, this paper provides an overview of the current adjuvants used for allergen immunotherapy. Furthermore, nanoparticles-based allergen-delivery systems are focused as a novel and promising strategy for allergy vaccines.

  20. Optimizing Adherence to Adjuvant Imatinib in Gastrointestinal Stromal Tumor

    Science.gov (United States)

    Tetzlaff, Eric D.; Davey, Monica P.

    2013-01-01

    The increasing use of patient-administered oral anticancer drugs is paralleled by new challenges in maintaining treatment adherence. These challenges are particularly significant with adjuvant therapies for prevention of disease recurrence, where the benefits of ongoing treatment are not readily apparent to patients. Nurse practitioners and physician assistants (collectively referred to as advanced practitioners) play integral roles in providing education on disease and treatment to patients that can increase adherence to oral therapies and ideally improve outcomes. For patients with gastrointestinal stromal tumor (GIST), the oral targeted therapy imatinib has become the mainstay of treatment for advanced and recurrent disease and as adjuvant therapy following surgical resection. Recent data indicate significantly improved overall survival with 3 years vs. 1 year of adjuvant imatinib therapy. Continuous dosing with imatinib is needed for optimal efficacy and to limit additional health-care costs associated with management of disease progression in GIST. However, longer duration of therapy increases the risk of nonadherence. Imatinib adherence rates, as well as factors contributing to nonadherence to adjuvant therapy in routine clinical practice, are discussed in this review. Also explored are practical approaches for improving adherence to adjuvant imatinib therapy through greater patient education, in light of the increased duration of therapy in select patients. PMID:25032004

  1. Regulatory considerations on new adjuvants and delivery systems.

    Science.gov (United States)

    Sesardic, D

    2006-04-12

    New and improved vaccines and delivery systems are increasingly being developed for prevention, treatment and diagnosis of human diseases. Prior to their use in humans, all new biological products must undergo pre-clinical evaluation. These pre-clinical studies are important not only to establish the biological properties of the material and to evaluate its possible risk to the public, but also to plan protocols for subsequent clinical trials from which safety and efficacy can be evaluated. For vaccines, evaluation in pre-clinical studies is particularly important as information gained may also contribute to identifying the optimum composition and formulation process and provide an opportunity to develop suitable indicator tests for quality control. Data from pre-clinical and laboratory evaluation studies, which continue during clinical studies, is used to support an application for marketing authorisation. Addition of a new adjuvant and exploration of new delivery systems for vaccines presents challenges to both manufacturers and regulatory authorities. Because no adjuvant is licensed as a medicinal product in its own right, but only as a component of a particular vaccine, pre-clinical and appropriate toxicology studies need to be designed on a case-by-case basis to evaluate the safety profile of the adjuvant and adjuvant/vaccine combination. Current regulatory requirements for the pharmaceutical and pre-clinical safety assessment of vaccines are insufficient and initiatives are in place to develop more specific guidelines for evaluation of adjuvants in vaccines.

  2. Nanoparticulate adjuvants and delivery systems for allergen immunotherapy.

    Science.gov (United States)

    De Souza Rebouças, Juliana; Esparza, Irene; Ferrer, Marta; Sanz, María Luisa; Irache, Juan Manuel; Gamazo, Carlos

    2012-01-01

    In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of allergic diseases. However, current allergen immunotherapy shows limitations concerning the long-term efficacy and safety due to local side effects and risk of anaphylaxis. Thus, effective and safe vaccines with reduced dose of allergen have been developed using adjuvants. Nevertheless, the use of adjuvants still has several disadvantages, which limits its use in human vaccines. In this context, several novel adjuvants for allergen immunotherapy are currently being investigated and developed. Currently, nanoparticles-based allergen-delivery systems have received much interest as potential adjuvants for allergen immunotherapy. It has been demonstrated that the incorporation of allergens into a delivery system plays an important role in the efficacy of allergy vaccines. Several nanoparticles-based delivery systems have been described, including biodegradable and nondegradable polymeric carriers. Therefore, this paper provides an overview of the current adjuvants used for allergen immunotherapy. Furthermore, nanoparticles-based allergen-delivery systems are focused as a novel and promising strategy for allergy vaccines.

  3. Adjuvants for Clostridium tetani and Clostridium diphtheriae vaccines updating.

    Science.gov (United States)

    Alshanqiti, Fatimah M; Al-Masaudi, Saad B; Al-Hejin, Ahmed M; Redwan, Elrashdy M

    2017-01-01

    It's known that diphtheria and tetanus are a contagious lethal diseases over the years, they caused by pathogenic microbes corynebacterium diphtheria and Clostridium tetani, respectively. The diseases result from the production of bacterial toxin. Vaccination with bacterial toxoid vaccines adsorbed on particulates adjuvants still are the best way to prevent this epidemic diseases from spread. The particulate vaccines have been shown to be more efficient than soluble one for the induction of the immune responses. Nanoparticles can be engineered to enhance the immune responses. As well known the immune response to inactivate killed and subunit vaccine enhances by alum adjuvants. The adjuvants examined and tested after reducing its size to particle size, thus mimic size of viruses which is considered smallest units can derive the immune system. The major issue is minimizing the adjuvant particles, to gain insight of resulting immunity types and impact on immune response. The adjuvant effect of micro/nanoparticles appears to largely be a consequence of their uptake into antigen presenting cells.

  4. Differentiation of Staphylococcus spp. by high-resolution melting analysis.

    Science.gov (United States)

    Slany, Michal; Vanerkova, Martina; Nemcova, Eva; Zaloudikova, Barbora; Ruzicka, Filip; Freiberger, Tomas

    2010-12-01

    High-resolution melting analysis (HRMA) is a fast (post-PCR) high-throughput method to scan for sequence variations in a target gene. The aim of this study was to test the potential of HRMA to distinguish particular bacterial species of the Staphylococcus genus even when using a broad-range PCR within the 16S rRNA gene where sequence differences are minimal. Genomic DNA samples isolated from 12 reference staphylococcal strains (Staphylococcus aureus, Staphylococcus capitis, Staphylococcus caprae, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus intermedius, Staphylococcus saprophyticus, Staphylococcus sciuri, Staphylococcus simulans, Staphylococcus warneri, and Staphylococcus xylosus) were subjected to a real-time PCR amplification of the 16S rRNA gene in the presence of fluorescent dye EvaGreen™, followed by HRMA. Melting profiles were used as molecular fingerprints for bacterial species differentiation. HRMA of S. saprophyticus and S. xylosus resulted in undistinguishable profiles because of their identical sequences in the analyzed 16S rRNA region. The remaining reference strains were fully differentiated either directly or via high-resolution plots obtained by heteroduplex formation between coamplified PCR products of the tested staphylococcal strain and phylogenetically unrelated strain.

  5. Suppression of complete Freund's adjuvant-induced adjuvant arthritis by cobratoxin

    Institute of Scientific and Technical Information of China (English)

    Yan-li LIU; Hai-ming LIN; Rong ZOU; Jun-chao WU; Rong HAN; Laurence N RAYMOND; Paul F REID; Zheng-hong QIN

    2009-01-01

    Aim:Cobratoxin (CTX),the long-chain α-neurotoxin from Thailand cobra venom,has been demonstrated to have analgesic action in rodent pain models.The present study evaluated the anti-inflammatory and anti-nociceptive effects of CTX on adju-vant arthritis (AA) in rats.Methods: Arthritis was induced by injection of complete Freund's adjuvant (CFA) in rats.Paw swelling and hyperalgesia of AA rats were measured at various times after CFA administration.Tumor necrosis factor-a (TNF-α),interleukin-1 (IL-1),interleukin-2 (IL-2) and interleukin-10 (IL-10) levels in serum were determined with ELISA.Histopathological changes in synoviocytes were examined under a microscope.Involvement of the cholinergic system in the effects of CTX was examinedby pretreatment of animals with the α7 nicotinic receptor (α7-nAChR) antagonist methyllycaconitine (MLA).Results: CFA induced marked paw swelling and reduced thresholds of mechanical and cold-induced paw withdrawal.The lev-els of TNF-α,IL-1 and IL-2 in the serum of AA rats were increased,whereas the level of IL-10 was decreased.Histopathologi-cal examination of synoviocytes showed pronounced inflammation and accumulation of collagen.The administration of CTX (17.0 μg/kg,ip) significantly reduced paw swelling and mechanical and thermal hyperalgesia.CTX also reduced the produc-tion ofTNF-α,IL-1,and IL-2 but increased the production of IL-10 and altered pathohistological changes.The analgesic and anti-inflammatory efficacy of CTX was significantly reduced by MLA (3 mg/kg,sc).Conclusion: These results indicate that CTX has a beneficial effect on CFA-induced arthritis by modulating the production of inflammatory cytokines,α7-nAChR appears to mediate the anti-nociceptive and anti-inflammatory actions of CTX.

  6. Vancomycin Resistance in Staphylococcus aureus


    Science.gov (United States)

    McGuinness, Will A.; Malachowa, Natalia; DeLeo, Frank R.

    2017-01-01

    The evolution of Staphylococcus aureus during the modern antibiotic era has been delineated by distinct strain emergence events, many of which include acquisition of antibiotic resistance. The relative high burden of methicillin-resistant S. aureus (MRSA) in healthcare and community settings is a major concern worldwide. Vancomycin, a glycopeptide antibiotic that inhibits cell wall biosynthesis, remains a drug of choice for treatment of severe MRSA infections. S. aureus strains exhibiting increased resistance to vancomycin, known as vancomycin intermediate-resistant S. aureus (VISA) (MIC = 4-8 µg/mL), were discovered in the 1990s. The molecular basis of resistance in VISA is polygenic and involves stepwise mutations in genes encoding molecules predominantly involved in cell envelope biosynthesis. S. aureus isolates with complete resistance to vancomycin (MIC ≥ 16 µg/mL) are termed vancomycin-resistant S. aureus (VRSA)—they were first reported in the U.S. in 2002. Resistance in VRSA is conferred by the vanA gene and operon, which is present on a plasmid. Although treatment of VRSA infections is challenging, the total number of human VRSA infections to date is limited (14 in the U.S.). By comparison, the burden of VISA is relatively high and the molecular mechanisms of resistance are less well-defined. VISA are associated with persistent infections, vancomycin treatment failure, and poor clinical outcomes. Here, we review in brief progress made toward understanding the acquisition of antibiotic resistance in S. aureus, with an emphasis on the molecular mechanisms underlying vancomycin resistance. PMID:28656013

  7. The immunobiology of aluminium adjuvants: how do they really work?

    Science.gov (United States)

    Exley, Christopher; Siesjö, Peter; Eriksson, Håkan

    2010-03-01

    Aluminium adjuvants potentiate the immune response, thereby ensuring the potency and efficacy of typically sparingly available antigen. Their concomitant critical importance in mass vaccination programmes may have prompted recent intense interest in understanding how they work and their safety. Progress in these areas is stymied, however, by a lack of accessible knowledge pertaining to the bioinorganic chemistry of aluminium adjuvants, and, consequently, the inappropriate application and interpretation of experimental models of their mode of action. The objective herein is, therefore, to identify the many ways that aluminium chemistry contributes to the wide and versatile armoury of its adjuvants, such that future research might be guided towards a fuller understanding of their role in human vaccinations.

  8. Management of Pediatric Myxopapillary Ependymoma: The Role of Adjuvant Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Agbahiwe, Harold C.; Wharam, Moody [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Batra, Sachin [Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Cohen, Kenneth [Division of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Terezakis, Stephanie A., E-mail: sterezak@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2013-02-01

    Introduction: Myxopapillary ependymoma (MPE) is a rare tumor in children. The primary treatment is gross total resection (GTR), with no clearly defined role for adjuvant radiation therapy (RT). Published reports, however, suggest that children with MPE present with a more aggressive disease course. The goal of this study was to assess the role of adjuvant RT in pediatric patients with MPE. Methods: Sixteen patients with MPE seen at Johns Hopkins Hospital (JHH) between November 1984 and December 2010 were retrospectively reviewed. Fifteen of the patients were evaluable with a mean age of 16.8 years (range, 12-21 years). Kaplan-Meier curves and descriptive statistics were used for analysis. Results: All patients received surgery as the initial treatment modality. Surgery consisted of either a GTR or a subtotal resection (STR). The median dose of adjuvant RT was 50.4 Gy (range, 45-54 Gy). All patients receiving RT were treated at the involved site. After a median follow-up of 7.2 years (range, 0.75-26.4 years), all patients were alive with stable disease. Local control at 5 and 10 years was 62.5% and 30%, respectively, for surgery alone versus 100% at both time points for surgery and adjuvant RT. Fifty percent of the patients receiving surgery alone had local failure. All patients receiving STR alone had local failure compared to 33% of patients receiving GTR alone. One patient in the surgery and adjuvant RT group developed a distant site of recurrence 1 year from diagnosis. No late toxicity was reported at last follow-up, and neurologic symptoms either improved or remained stable following surgery with or without RT. Conclusions: Adjuvant RT improved local control compared to surgery alone and should be considered after surgical resection in pediatric patients with MPE.

  9. Toxicity test and bacteriophage typing of Staphylococcus aureus ...

    African Journals Online (AJOL)

    African Journal of Biotechnology ... Strains of Staphylococcus aureus isolated from foods prepared in five families in Zaria Local ... Keywords: Staphylococcus aureus, enterotoxin production, phage typing, haemolysis and food poisoning ...

  10. Neisseria lactamica antigens complexed with a novel cationic adjuvant

    OpenAIRE

    Gaspar, Emanuelle B.; Rosetti, Andreza S.; Lincopan, Nilton; De Gaspari, Elizabeth

    2013-01-01

    Colonization of the nasopharynx by non-pathogenic Neisseria species, including N. lactamica, has been suggested to lead to the acquisition of natural immunity against Neisseria meningitidis in young children. The aim of this study was to identify a model complex of antigens and adjuvant for immunological preparation against N. meningitidis B, based on cross reactivity with N. lactamica outer membrane vesicles (OMV) antigens and the (DDA-BF) adjuvant. Complexes of 25 µg of OMV in 0.1 mM of DDA...

  11. Aluminium: a natural adjuvant in Leishmania transmission via sand flies?

    Science.gov (United States)

    Maingon, Rhayza; Khela, Amandeep; Sampson, Christopher; Ward, Richard; Walker, Karen; Exley, Christopher

    2008-11-01

    Genetically identical Leishmania chagasi/infantum parasites cause both atypical cutaneous leishmaniasis and visceral leishmaniasis. In this report we have tested the first part of a hypothesis that states that the form of this disease that is manifested depends upon the adjuvant-like activity of aluminium of dietary origin accumulated in the salivary gland of the sand fly vector. In sand flies fed aluminium-supplemented sucrose we have used histochemistry to qualitatively identify aluminium in their salivary glands and graphite furnace atomic absorption spectrometry to quantify the aluminium content of dissected salivary glands. Aluminium may be acting as a natural adjuvant in some forms of leishmaniasis.

  12. Staphylococcus aureus and hand eczema severity

    DEFF Research Database (Denmark)

    Haslund, P; Bangsgaard, N; Jarløv, J O

    2009-01-01

    BACKGROUND: The role of bacterial infections in hand eczema (HE) remains to be assessed. OBJECTIVES: To determine the prevalence of Staphylococcus aureus in patients with HE compared with controls, and to relate presence of S. aureus, subtypes and toxin production to severity of HE. METHODS......: Bacterial swabs were taken at three different visits from the hand and nose in 50 patients with HE and 50 controls. Staphylococcus aureus was subtyped by spa typing and assigned to clonal complexes (CCs), and isolates were tested for exotoxin-producing S. aureus strains. The Hand Eczema Severity Index...... was used for severity assessment. RESULTS: Staphylococcus aureus was found on the hands in 24 patients with HE and four controls (P hands...

  13. Investigate Nasal Colonize Staphylococcus Species Biofilm Produced

    Directory of Open Access Journals (Sweden)

    Cemil Demir

    2014-03-01

    Full Text Available Aim: 127 S.aureus and 65 CoNS strains were isolated from patients noses%u2019. To produce a biofilm ability was investigated using three different methods. Slime-positive and negative staphylococcies%u2019 resistance were evaluated against different antibiotics. Material and Method: Swap samples puted 7% blood agar. Staphylococcus aureus and coagulase-negative staphylococci (CoNS isolates biofilm produced ability were investigated using Congo Red Agar (CRA, microplates (MP and Standard Tube (ST methods. In addition to that, presence of antibiotic resistance of the staphylococcal isolates are determined agar disc diffusion method. Results: The rate of biofilm producing Staphylococcus spp strains was found to be 72.4%, 67.7%, and 62.9%, respectively with CRA, MP, and ST tests. There was no significant relationship among the tests (p>0.05. In addition, antibiotic resistance of Staphylococcus spp. against various antibiotics was also determined by the agar disk diffusion method. Resistance rates of biofilm positive (BP Staphylococcus spp for penicilin G, ampicilin, amocycilin/clavulanic acid, tetracyclin, eritromycin, gentamycin, and enrofloxacin 71.7%, 69.7%, 6.2%, 20.7%, 21.4%, 1.4%, and 0.7%, respectively. Resistance rates of biofilm negative (BN spp for 42.6%, 23.4%, 4.3%, 14.9%, 19.1%, 0.0%, 0.0% respectively. All Staphylococcus isolates were found to be susceptible to vancomycin and teicaplonin. Although BP strains antibiotic resistance rates were observed higher than BN strains. But resistance rates were not found statistically significant (p>0.05. Discussion: CRA is the reliablity and specifity method to determine Staphylococcus spp. biofilm produce ability.

  14. Staphylococcus pseudintermedius for CAMP-test.

    Science.gov (United States)

    Savini, Vincenzo; Paparella, Antonello; Serio, Annalisa; Marrollo, Roberta; Carretto, Edoardo; Fazii, Paolo

    2014-01-01

    CAMP test reliably detects Listeria monocytogenes (Lm) and Streptococcus agalactiae (group B streptococcus, GBS); it is traditionally performed streaking the tested isolate perpendicularly to Staphylococcus aureus (Sa), provided that reference Sa strains (that produce β-hemolysin) are used. In a zone of β-hemolysin activity, in fact, GBS and Lm form typical arrow-shaped hemolytic areas. While Sa production of the toxin is strain-dependent, however, that of Staphylococcus pseudintermedius (Sp), a pet-owner colonizer and an emerging human pathogen, is constitutive, then observed in all clinical isolates. Therefore, Sp may indeed represent a valid alternative to perform the assay.

  15. Treatment of Staphylococcus aureus Infections.

    Science.gov (United States)

    David, Michael Z; Daum, Robert S

    2017-09-13

    Staphylococcus aureus, although generally identified as a commensal, is also a common cause of human bacterial infections, including of the skin and other soft tissues, bones, bloodstream, and respiratory tract. The history of S. aureus treatment is marked by the development of resistance to each new class of antistaphylococcal antimicrobial drugs, including the penicillins, sulfonamides, tetracyclines, glycopeptides, and others, complicating therapy. S. aureus isolates identified in the 1960s were sometimes resistant to methicillin, a ß-lactam antimicrobial active initially against a majority S. aureus strains. These MRSA isolates, resistant to nearly all ß-lactam antimicrobials, were first largely confined to the health care environment and the patients who attended it. However, in the mid-1990s, new strains, known as community-associated (CA-) MRSA strains, emerged. CA-MRSA organisms, compared with health care-associated (HA-) MRSA strain types, are more often susceptible to multiple classes of non ß-lactam antimicrobials. While infections caused by methicillin-susceptible S. aureus (MSSA) strains are usually treated with drugs in the ß-lactam class, such as cephalosporins, oxacillin or nafcillin, MRSA infections are treated with drugs in other antimicrobial classes. The glycopeptide drug vancomycin, and in some countries teicoplanin, is the most common drug used to treat severe MRSA infections. There are now other classes of antimicrobials available to treat staphylococcal infections, including several that have been approved after 2009. The antimicrobial management of invasive and noninvasive S. aureus infections in the ambulatory and in-patient settings is the topic of this review. Also discussed are common adverse effects of antistaphylococcal antimicrobial agents, advantages of one agent over another for specific clinical syndromes, and the use of adjunctive therapies such as surgery and intravenous immunoglobulin. We have detailed considerations in the

  16. Pacemaker Related Infective Endocarditis from Staphylococcus Lugdunensis: A Case Report

    Directory of Open Access Journals (Sweden)

    Michael Ward

    2013-01-01

    Full Text Available Staphylococcus lugdunensis is a common skin flora not typically associated with infection. There are, however, several cases reported in the literature of Staphylococcus lugdunensis as a causative bacterium of various infections. This paper reports an additional case of pacemaker associated endocarditis with Staphylococcus lugdunensis as the causative bacterium.

  17. Contamination of DNase Preparations Confounds Analysis of the Role of DNA in Alum-Adjuvanted Vaccines

    OpenAIRE

    Noges, Laura E.; White, Janice; Cambier, John C.; Kappler, John W.; Marrack, Philippa

    2016-01-01

    Aluminum salt (alum) adjuvants have been used for many years as adjuvants for human vaccines because they are safe and effective. Despite its widespread use, the means by which alum acts as an adjuvant remains poorly understood. Recently, it was shown that injected alum is rapidly coated with host chromatin within mice. Experiments suggested that the host DNA in the coating chromatin contributed to alum’s adjuvant activity. Some of the experiments used commercially purchased DNase and showed ...

  18. 75 FR 66766 - NIAID Blue Ribbon Panel Meeting on Adjuvant Discovery and Development

    Science.gov (United States)

    2010-10-29

    ... discovery, development and clinical evaluation of adjuvants for use with preventive vaccines. NIAID has developed a draft Strategic Plan and Research Agenda for Adjuvant Discovery and Development, which... HUMAN SERVICES NIAID Blue Ribbon Panel Meeting on Adjuvant Discovery and Development Notice is...

  19. Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines.

    Science.gov (United States)

    Hayashi, Masayuki; Aoshi, Taiki; Haseda, Yasunari; Kobiyama, Kouji; Wijaya, Edward; Nakatsu, Noriyuki; Igarashi, Yoshinobu; Standley, Daron M; Yamada, Hiroshi; Honda-Okubo, Yoshikazu; Hara, Hiromitsu; Saito, Takashi; Takai, Toshiyuki; Coban, Cevayir; Petrovsky, Nikolai; Ishii, Ken J

    2017-02-01

    Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th)2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV), a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR) 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF)-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs) and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.

  20. Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines

    Directory of Open Access Journals (Sweden)

    Masayuki Hayashi

    2017-02-01

    Full Text Available Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV, a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.

  1. Lipopolysaccharide contamination in intradermal DNA vaccination : toxic impurity or adjuvant?

    NARCIS (Netherlands)

    Berg, J.H. van den; Quaak, S.G.L.; Beijnen, J.H.; Hennink, W.E.; Storm, G.; Schumacher, T.N.; Haanen, J.B.A.G.; Nuijen, B.

    2010-01-01

    Purpose: Lipopolysaccharides (LPS) are known both as potential adjuvants for vaccines and as toxic impurity in pharmaceutical preparations. The aim of this study was to assess the role of LPS in intradermal DNA vaccination administered by DNA tattooing. Method: Micewere vaccinated with a model DNA v

  2. Postoperative adjuvant chemotherapy in rectal cancer operated for cure

    DEFF Research Database (Denmark)

    Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky

    2012-01-01

    in Dukes´ C (TNM stage III) colon tumours i.e. tumours with metastases in the regional lymph nodes but no distant metastases. In contrast, the evidence for recommendations of adjuvant therapy in rectal cancer is sparse. In Europe it is generally acknowledged that locally advanced rectal tumours receive...

  3. Evaluation of adjuvant effects of fucoidan for improving vaccine efficacy.

    Science.gov (United States)

    Kim, Su-Yeon; Joo, Hong-Gu

    2015-01-01

    Fucoidan is a sulfated polysaccharide derived from brown seaweed, including Fucus vesiculosus. This compound is known to have immunostimulatory effects on various types of immune cells including macrophages and dendritic cells. A recent study described the application of fucoidan as a vaccine adjuvant. Vaccination is regarded as the most efficient prophylactic method for preventing harmful or epidemic diseases. To increase vaccine efficacy, effective adjuvants are needed. In the present study, we determined whether fucoidan can function as an adjuvant using vaccine antigens. Flow cytometric analysis revealed that fucoidan increases the expression of the activation markers major histocompatibility complex class II, cluster of differentiation (CD)25, and CD69 in spleen cells. In combination with Bordetella bronchiseptica antigen, fucoidan increased the viability and tumor necrosis factor-α production of spleen cells. Furthermore, fucoidan increased the in vivo production of antigen-specific antibodies in mice inoculated with Mycoplasma hyopneumoniae antigen. Overall, this study has provided valuable information about the use of fucoidan as a vaccine adjuvant.

  4. Teaching adjuvant endocrine breast cancer treatment to medical students

    NARCIS (Netherlands)

    Visser, M. de; Fluit, C.R.M.G.; Timmer-Bonte, J.N.H.; Ottevanger, P.B.; Verhagen, C.A.H.H.V.M.; Klaassen, T.; Laarhoven, H.W.M. van

    2013-01-01

    Background: In undergraduate medical education, students are supposed to acquire knowledge and understanding about the basic principles of adjuvant breast cancer treatment. The best education method in this context is unknown. In this randomised study we assessed the effect of designing a patient ed

  5. Local anesthetis and adjuvants in pediatric regional anesthesia.

    Science.gov (United States)

    Mossetti, Valeria; Vicchio, Noemi; Ivani, Giorgio

    2012-06-01

    The pediatric loco-regional techniques are considered very safe and effective, first of all because they target the therapy directly to the site of surgery, decreasing the risks of intravenous analgesia. The quality of local anesthesia is influenced by structural and biophysical characteristics of local anesthetics drug, dose, site of injection, mixture of local anesthetics and possible addition of a vasoconstrictor or an adjuvant to prolong the analgesic effect. In children, unlike adults, small nerve diameters and short distance between Ranvier nodes permit to use large volumes and low concentrations of local anesthetics. The clinical practice has shown that in pediatric population, effective analgesia is obtained by 1% mepivacaine, 1% lidocaine and 0.25% bupivacaine or better 0.2% ropivacaine, 0.2-0.25% levobupivacaine. In addition, levobupivacaine and ropivacaine have a better profile in terms of safety in comparison to bupivacaine and are the local anesthetics of choice for the daily clinical practice also in children as in adults. Among the adjuvant, clonidine and ketamine showed the best pharmacokinetic and pharmacodynamic profiles of effective and safety, improving and prolonging the action of associated local anesthetics. Therefore, the use of enantiomers, in association with adjuvants as clonidine or ketamine, using the multimodal approach of integrated anesthesia, makes the clinical practice effective and safe in the pediatric operating rooms. This review focuses on the overview of local anesthetics and adjuvants used today in locoregional pediatric anesthesia, with an emphasis on the advantages and disadvantages of each drug.

  6. Lipopolysaccharide contamination in intradermal DNA vaccination : toxic impurity or adjuvant?

    NARCIS (Netherlands)

    Berg, J.H. van den; Quaak, S.G.L.; Beijnen, J.H.; Hennink, W.E.; Storm, G.; Schumacher, T.N.; Haanen, J.B.A.G.; Nuijen, B.

    Purpose: Lipopolysaccharides (LPS) are known both as potential adjuvants for vaccines and as toxic impurity in pharmaceutical preparations. The aim of this study was to assess the role of LPS in intradermal DNA vaccination administered by DNA tattooing. Method: Micewere vaccinated with a model DNA

  7. Effects of 5-fluorouracil adjuvant treatment of colon cancer

    NARCIS (Netherlands)

    Kelder, Wendy; Hospers, Geke A. P.; Plukker, John T. M.

    2006-01-01

    Since the late 1980s and early 1990s, 5-fluorouracil-based chemotherapy has been the standard adjuvant treatment for Stage III colon cancer. After the initial introduction of 5-fluorouracil in standard treatment protocols, several changes have been made based on results of randomized studies on vari

  8. Postoperative adjuvant chemotherapy in rectal cancer operated for cure.

    Science.gov (United States)

    Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky; Wille-Jørgensen, Peer; Mocellin, Simone

    2012-03-14

    Colorectal cancer is one of the most common types of cancer in the Western world. Apart from surgery - which remains the mainstay of treatment for resectable primary tumours - postoperative (i.e., adjuvant) chemotherapy with 5-fluorouracil (5-FU) based regimens is now the standard treatment in Dukes' C (TNM stage III) colon tumours i.e. tumours with metastases in the regional lymph nodes but no distant metastases. In contrast, the evidence for recommendations of adjuvant therapy in rectal cancer is sparse. In Europe it is generally acknowledged that locally advanced rectal tumours receive preoperative (i.e., neoadjuvant) downstaging by radiotherapy (or chemoradiotion), whereas in the US postoperative chemoradiotion is considered the treatment of choice in all Dukes' C rectal cancers. Overall, no universal consensus exists on the adjuvant treatment of surgically resectable rectal carcinoma; moreover, no formal systematic review and meta-analysis has been so far performed on this subject. We undertook a systematic review of the scientific literature from 1975 until March 2011 in order to quantitatively summarize the available evidence regarding the impact of postoperative adjuvant chemotherapy on the survival of patients with surgically resectable rectal cancer. The outcomes of interest were overall survival (OS) and disease-free survival (DFS). CCCG standard search strategy in defined databases with the following supplementary search. 1. Rect* or colorect* - 2. Cancer or carcinom* or adenocarc* or neoplasm* or tumour - 3. Adjuv* - 4. Chemother* - 5. Postoper* Randomised controlled trials (RCT) comparing patients undergoing surgery for rectal cancer who received no adjuvant chemotherapy with those receiving any postoperative chemotherapy regimen. Two authors extracted data and a third author performed an independent search for verification. The main outcome measure was the hazard ratio (HR) between the risk of event between the treatment arm (adjuvant chemotherapy

  9. Persistent neurocognitive problems after adjuvant chemotherapy for breast cancer

    NARCIS (Netherlands)

    Kreukels, B.P.C.; van Dam, F.S.A.M.; Ridderinkhof, K.R.; Boogerd, W.; Schagen, S.B.

    2008-01-01

    Background: Neurocognitive problems have been observed in a number of women previously treated with adjuvant chemotherapy for breast cancer. The present study aims to combine the results of neuropsychological and electrophysiological techniques collected in patients with breast cancer treated with c

  10. Adjuvant chemotherapy compliance is not superior after thoracoscopic lobectomy

    DEFF Research Database (Denmark)

    Licht, Peter B; Schytte, Tine; Jakobsen, Erik

    2014-01-01

    BACKGROUND: It is generally assumed that patient compliance with adjuvant chemotherapy is superior after video-assisted thoracoscopic surgery compared with open lobectomy for non-small cell lung cancer (NSCLC). The level of evidence for this assumption, however, is limited to single-institution, ......BACKGROUND: It is generally assumed that patient compliance with adjuvant chemotherapy is superior after video-assisted thoracoscopic surgery compared with open lobectomy for non-small cell lung cancer (NSCLC). The level of evidence for this assumption, however, is limited to single...... histopathology. A clinical oncologist, who was blinded to the surgical approach, reviewed all medical oncology charts for types of adjuvant chemotherapy, reasons for not initiating or stopping treatment, number of cycles delivered, and time interval from surgery to initial chemotherapy. RESULTS: During a 6-year...... adjuvant chemotherapy and 121 (38.7%) completed all four cycles. Ordinal logistic regression revealed that chemotherapy compliance (none, partial, and full chemotherapy) was significantly reduced by the patient's age (p

  11. Adjuvant chemotherapy for the perineural invasion of colorectal cancer.

    Science.gov (United States)

    Suzuki, Toshiaki; Suwa, Katsuhito; Ogawa, Masaichi; Eto, Ken; Kawahara, Hidejiro; Fujita, Tetsuji; Ikegami, Masahiro; Yanaga, Katsuhiko

    2015-11-01

    To evaluate the association of perineural invasion (PNI) with outcomes in patients after colorectal resection of colorectal cancer (CRC) and to assess the effect of PNI on the response to adjuvant chemotherapy. Data were retrospectively reviewed for 178 patients with consecutive stages I-III CRC who underwent curative surgery between January 1999 and December 2004. PNI data were examined, and the overall survival (OS) and disease-free survival rates were analyzed. PNI was detected in 36 of 178 patients (20%) and positively correlated with lymphatic invasion (P = 0.020), venous invasion (P = 0.037), and the incidence of metastasis or recurrence (P = 0.029). Five-year disease-free survival was 46% and 68% (P negative prognostic factor of OS; among PNI-positive patients, median OS with adjuvant chemotherapy was almost twofold higher than that without adjuvant chemotherapy (6 versus 2.8 y; P = 0.017). PNI was a poor predictor of survival among patients with stage III CRC, and adjuvant chemotherapy may attenuate the adverse effects of PNI on survival. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Ecological Overlap and Horizontal Gene Transfer in Staphylococcus aureus and Staphylococcus epidermidis

    OpenAIRE

    Méric, Guillaume; Miragaia, Maria; de Been, Mark; Yahara, Koji; Pascoe, Ben; Mageiros, Leonardos; Mikhail, Jane; Harris, Llinos G; Wilkinson, Thomas S.; Rolo, Joana; Lamble, Sarah; Bray, James E.; Jolley, Keith A.; Hanage, William P.; Bowden, Rory

    2015-01-01

    The opportunistic pathogens Staphylococcus aureus and Staphylococcus epidermidis represent major causes of severe nosocomial infection, and are associated with high levels of mortality and morbidity worldwide. These species are both common commensals on the human skin and in the nasal pharynx, but are genetically distinct, differing at 24% average nucleotide divergence in 1,478 core genes. To better understand the genome dynamics of these ecologically similar staphylococcal species, we carrie...

  13. Prevalence of mupirocin resistance in Staphylococcus pseudintermedius.

    Science.gov (United States)

    Godbeer, Stacey M; Gold, Randi M; Lawhon, Sara D

    2014-04-01

    In the United States, veterinary use of mupirocin is primarily limited to the treatment of canine pyoderma caused by methicillin-resistant Staphylococcus pseudintermedius (MRSP). In this study, only 1 of 581 S. pseudintermedius isolates tested was resistant to mupirocin and carried the high-level mupirocin resistance gene, ileS2, on a plasmid.

  14. Prevalence of Mupirocin Resistance in Staphylococcus pseudintermedius

    OpenAIRE

    Godbeer, Stacey M.; Gold, Randi M.; Lawhon, Sara D.

    2014-01-01

    In the United States, veterinary use of mupirocin is primarily limited to the treatment of canine pyoderma caused by methicillin-resistant Staphylococcus pseudintermedius (MRSP). In this study, only 1 of 581 S. pseudintermedius isolates tested was resistant to mupirocin and carried the high-level mupirocin resistance gene, ileS2, on a plasmid.

  15. Staphylococcus aureus spa type t437

    DEFF Research Database (Denmark)

    Glasner, C; Pluister, G; Westh, H;

    2015-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) belonging to the multilocus sequence type clonal complex 59 (MLST CC59) is the predominant community-associated MRSA clone in Asia. This clone, which is primarily linked with the spa type t437, has so far only been reported in low numbers among...

  16. Meticillin-resistant Staphylococcus aureus (MRSA)

    DEFF Research Database (Denmark)

    Stefani, Stefania; Chung, Doo Ryeon; Lindsay, Jodi A;

    2012-01-01

    This article reviews recent findings on the global epidemiology of healthcare-acquired/associated (HA), community-acquired/associated (CA) and livestock-associated (LA) meticillin-resistant Staphylococcus aureus (MRSA) and aims to reach a consensus regarding the harmonisation of typing methods...

  17. Immunogenicity of toxins during Staphylococcus aureus infection

    NARCIS (Netherlands)

    N.J. Verkaik (Nelianne); O. Dauwalder (Olivier); K. Antri (Kenza); I. Boubekri (Ilhem); C.P. de Vogel (Corné); C. Badiou (Cédric); M. Bes (Michèle); F. Vandenesch (François); M. Tazir (Mohammed); H. Hooijkaas (Herbert); H.A. Verbrugh (Henri); A.F. van Belkum (Alex); J. Etienne (Jerome); G. Lina (Gérard); N. Ramdani-Bouguessa (Nadjia); W.J.B. van Wamel (Willem)

    2010-01-01

    textabstractAB - BACKGROUND: Toxins are important Staphylococcus aureus virulence factors, but little is known about their immunogenicity during infection. Here, additional insight is generated. METHODS: Serum samples from 206 S. aureus-infected patients and 201 hospital-admitted control subjects we

  18. Profiling the surfacome of Staphylococcus aureus

    NARCIS (Netherlands)

    Dreisbach, Annette; Hempel, Kristina; Buist, Girbe; Hecker, Michael; Becher, Doerte; van Dijl, Jan Maarten

    2010-01-01

    Staphylococcus aureus is a widespread opportunistic pathogen that can cause a wide variety of life-threatening diseases. Especially for the colonization of human tissues and the development of invasiveness, surface-exposed proteins are of major importance. In the present studies, we optimized a prot

  19. Staphylococcus simulans osteitis in a diabetic patient.

    Science.gov (United States)

    Désidéri-Vaillant, C; Nédelec, Y; Guichon, J-M; Le Louarn, S; Noyer, V; Sapin-Lory, J; Le Guen, P; Nicolas, X

    2011-12-01

    Staphylococcus simulans was identified as the aetiological agent of osteitis in a diabetic woman. Its identifying characteristics and antibiogram were confirmed. Diabetic foot frequently becomes infected and the spread of infection to bone is a major causal factor behind lower-limb amputation. Early diagnosis and appropriate treatment are essential in such cases.

  20. Intrinsic Novobiocin Resistance in Staphylococcus saprophyticus▿

    Science.gov (United States)

    Vickers, Anna A.; Chopra, Ian; O'Neill, Alex J.

    2007-01-01

    Intrinsic novobiocin resistance in Staphylococcus saprophyticus was associated with expression of a novobiocin-resistant form of the drug target protein (GyrB). Site-directed mutagenesis established that resistance depends upon the presence of two specific amino acid residues in GyrB: a glycine at position 85 and a lysine at position 140. PMID:17876001

  1. Identification and characterization of methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus pettenkoferi from a small animal clinic.

    Science.gov (United States)

    Weiss, Sonja; Kadlec, Kristina; Fessler, Andrea T; Schwarz, Stefan

    2013-12-27

    The aim of this study was to isolate and characterize methicillin-resistant staphylococci (MRS) in a small animal clinic and to investigate their distribution and possible transmission. Swabs (n=72) were taken from hospitalized pets, the environment and employees of a small animal clinic and screened for the presence of MRS. The staphylococcal species was confirmed biochemically or by 16S rDNA sequencing. Susceptibility to antimicrobial agents was tested by broth dilution. The presence of mecA and other resistance genes was confirmed by PCR. Molecular typing of the isolates followed standard procedures. In total, 34 MRS belonging to the four species Staphylococcus aureus (n=5), Staphylococcus epidermidis (n=21), Staphylococcus haemolyticus (n=6) or Staphylococcus pettenkoferi (n=2) were isolated. All isolates were multidrug-resistant with resistance to at least three classes of antimicrobial agents. Among the five methicillin-resistant S. aureus (MRSA) isolates, four belonged to the clonal complex CC398; two of them were isolated from cats, the remaining two from pet cages. Overall, the MRS isolates differed in their characteristics, except for one S. epidermidis clone (n=9) isolated from hospitalized cats without clinical staphylococcal infections, pet cages, the clinic environment as well as from a healthy employee. This MRSE clone was resistant to 10 classes of antimicrobial agents, including aminocyclitols, β-lactams, fluoroquinolones, lincosamides, macrolides, phenicols, pleuromutilins, sulfonamides, tetracyclines and trimethoprim. These findings suggest a possible transmission of specific MRS isolates between animal patients, employees and the clinic environment.

  2. Meningitis causada por staphylococcus aureus catalasa negativa

    OpenAIRE

    Álvarez Moreno, Carlos Arturo; Arroyo A., Claudia Patricia; Rodríguez, Elizabeth; Martínez R., Luz Marina; Quevedo S., Ruth

    2011-01-01

    En un paciente con cáncer se aisló del liquido cefaloraquideo y ascitico un coco gram positivo coagulasa positivo. El germen aislado mostró las características típicas de un Staphylococcus aureus, a excepción de la actividad de la catalasa, la cual no pudo ser encontrada.

  3. Pork fat hydrolysed by Staphylococcus xylosus

    DEFF Research Database (Denmark)

    Sørensen, B. B.; Stahnke, Louise Heller; Zeuthen, Peter

    1993-01-01

    Staphylococcus xylosus is used as a starter culture in the production of fermented sausages. Its ability to hydrolyse pork fat was investigated. Within 15 days of incubation an interaction of bacterial growth, lipase production and lipase activity in a pork fat containing medium caused liberation...

  4. Pork fat hydrolysed by Staphylococcus xylosus

    DEFF Research Database (Denmark)

    Sørensen, B. B.; Stahnke, Louise Heller; Zeuthen, Peter

    1993-01-01

    Staphylococcus xylosus is used as a starter culture in the production of fermented sausages. Its ability to hydrolyse pork fat was investigated. Within 15 days of incubation an interaction of bacterial growth, lipase production and lipase activity in a pork fat containing medium caused liberation...

  5. Methicillin-resistant Staphylococcus aureus and athletes.

    Science.gov (United States)

    Kirkland, Eugene Brent; Adams, Brian B

    2008-09-01

    Methicillin-resistant Staphylococcus aureus infections have become an increasingly common condition among athletes. Physical contact, shared facilities and equipment, and hygienic practices of athletes all contribute to methicillin-resistant S. aureus transmission among sports participants. This review elucidates the risk factors predisposing to methicillin-resistant S. aureus infection in athletes and provides guidance for treatment and prevention.

  6. Intrinsic novobiocin resistance in Staphylococcus saprophyticus.

    Science.gov (United States)

    Vickers, Anna A; Chopra, Ian; O'Neill, Alex J

    2007-12-01

    Intrinsic novobiocin resistance in Staphylococcus saprophyticus was associated with expression of a novobiocin-resistant form of the drug target protein (GyrB). Site-directed mutagenesis established that resistance depends upon the presence of two specific amino acid residues in GyrB: a glycine at position 85 and a lysine at position 140.

  7. Who are you--Staphylococcus saprophyticus?

    Science.gov (United States)

    Raz, Raul; Colodner, Raul; Kunin, Calvin M

    2005-03-15

    Staphylococcus saprophyticus is a leading cause of cystitis in young women. S. saprophyticus shares many clinical features of urinary tract infection caused by Escherichia coli, but differs in pathogenesis, seasonal variation, and geographic distribution. This review summarizes what is known and what still needs to be learned about this microorganism.

  8. Staphylococcus aureus resistente a la meticilina (SARM)

    Centers for Disease Control (CDC) Podcasts

    2007-10-22

    Datos importantes sobre las infecciones por SARM en Estados Unidos, en las escuelas y los entornos médicos. (Title: Methicillin-resistant Staphylococcus aureus (MRSA)Created: 10/2007).  Created: 10/22/2007 by National Center for Preparedness, Detection, and Control of Infectious Diseases.   Date Released: 11/9/2007.

  9. Methicillin-resistant Staphylococcus aureus transmission

    DEFF Research Database (Denmark)

    Andersen, Leif Percival; Nielsen, Xiaohui

    2015-01-01

    INTRODUCTION: Even though methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of nosocomial infections, it may often be difficult to evaluate the exact route of transmission. METHODS: In this study, we describe four cases of nosocomial transmission of MRSA in a hospital with a low...

  10. Modulation of primary immune response by different vaccine adjuvants

    Directory of Open Access Journals (Sweden)

    Annalisa Ciabattini

    2016-10-01

    Full Text Available Adjuvants contribute to enhancing and shaping the vaccine immune response through different modes of action. Since the primary immune response can influence the overall quality of the response generated, here we investigate early biomarkers of adjuvanticity after primary immunization with four different adjuvants combined with the chimeric tuberculosis vaccine antigen H56. C57BL/6 mice were immunized by the subcutaneous route with different vaccine formulations, and the modulation of primary CD4+ T cell and B cell responses was assessed within draining lymph nodes, blood and spleen, 7 and 12 days after priming. Vaccine formulations containing the liposome system CAF01 or a squalene-based oil-in-water emulsion (o/w Squalene, but not aluminum hydroxide (Alum or CpG ODN 1826, elicited a significant primary antigen-specific CD4+ T cell response compared to antigen alone, 7 days after immunization. The effector function of activated CD4+ T cells was skewed towards a Th1/Th17 response by CAF01, while a Th1/Th2 response was elicited by o/w Squalene. Differentiation of B cells in short-lived plasma cells, and subsequent early H56-specific IgG secretion, was observed in mice immunized with o/w Squalene or CpG adjuvants. Tested adjuvants promoted the germinal centre reaction with different magnitude. These results show that the immunological activity of different adjuvants can be characterized by profiling early immunization biomarkers after primary immunization. These data and this approach could give an important contribution to the rational development of heterologous prime-boost vaccine immunization protocols.

  11. Triple negative breast cancer: adjuvant chemotherapy effect on survival.

    Science.gov (United States)

    Steponaviciene, L; Lachej-Mikeroviene, N; Smailyte, G; Aleknavicius, E; Meskauskas, R; Didziapetriene, J

    2011-01-01

    The purpose of this study was to evaluate the overall survival of patients with triple negative breast cancer and the impact of different adjuvant chemotherapy regimens on survival. The study group consisted of 99 breast cancer patients with immunohistochemically confirmed triple negative breast cancer. The impact of various factors as well as the impact of different chemotherapy regimens on survival was evaluated. The overall survival of breast cancer patients was 97.0% (95% CI 90.9-99.0), 84.9% (95% CI 76.1-90.6) and 66.5% (95% CI 55.5-75.3) 10, 30 and 60 months after diagnosis, respectively. Univariate analysis demonstrated that the following were significant risk factors for breast cancer patients survival: patient's age, stage of disease, tumour size, lymph node status, type of surgery and chemotherapy. Better survival was related to younger patients' age, smaller tumour size, lower stage of disease, no lymph nodes involvement. Survival rates were higher among patients who received adjuvant chemotherapy and underwent quadrantectomy. In the multivariate statistical analysis the significant independent prognostic variables influencing survival were lymph node status and adjuvant chemotherapy. Survival rates of the patients, who received adjuvant anthracycline containing chemotherapy were higher, than those in non-anthracycline containing treatment group, but the difference was not statistically significant. Patients who had lymph node status N2-3 and those who did not receive adjuvant chemotherapy showed worse prognosis and survival than other patients. The impact of chemotherapy type (anthracycline containing or non-anthracycline containing) on patients survival was not statistically significant.

  12. Inhibition of Quorum Sensing in Staphylococcus spp.

    Science.gov (United States)

    Brackman, Gilles; Coenye, Tom

    2015-01-01

    The Gram-positive, facultative anaerobic coccus-shaped bacteria of the genus Staphylococcus are among the most important causative agents of acute and chronic bacterial infections in humans as well as in animals. Treatment of Staphylococcus infections has become increasingly challenging due to the growing problem of antibiotic resistance. For this reason innovative antimicrobials with novel targets and modes of action are needed. Since the discovery that QS is used by Staphylococcus spp. to coordinate the expression of several genes involved in virulence, biofilm formation and pathogenicity, QS inhibition has gained increasing attention as an alternative anti-pathogenic strategy. A major advantage compared with antibiotic therapy is that QSIs are used in concentrations that do not affect bacterial growth. For this reason, it is expected that these compounds would exert less pressure towards the development of resistance. However, some important points still need to be addressed. Although several inhibitors have proven to be active antipathogenic agents in vitro and in several in vivo models, it is still unknown whether these compounds will also be useful in humans. Furthermore, several fundamental mechanisms by which the different QS systems in Staphylococcus spp. exert their regulatory functions and how they are inhibited by QSIs are still poorly understood. In order to achieve real-life applications with QSIs, these challenges should be addressed and more research will be needed. In this article, we will discuss the different QS systems present in Staphylococcus spp., how they are used to control virulence and biofilm formation and how they can be blocked.

  13. Evaluation of mucoadhesive carrier adjuvant: toward an oral anthrax vaccine.

    Science.gov (United States)

    Mangal, Sharad; Pawar, Dilip; Agrawal, Udita; Jain, Arvind K; Vyas, Suresh P

    2014-02-01

    The aim of present study was to evaluate the potential of mucoadhesive alginate-coated chitosan microparticles (A-CHMp) for oral vaccine against anthrax. The zeta potential of A-CHMp was -29.7 mV, and alginate coating could prevent the burst release of antigen in simulated gastric fluid. The results indicated that A-CHMp was mucoadhesive in nature and transported it to the peyer's patch upon oral delivery. The immunization studies indicated that A-CHMp resulted in the induction of potent systemic and mucosal immune responses, whereas alum-adjuvanted rPA could induce only systemic immune response. Thus, A-CHMp represents a promising acid carrier adjuvant for oral immunization against anthrax.

  14. Plant Viruses as Nanoparticle-Based Vaccines and Adjuvants

    Directory of Open Access Journals (Sweden)

    Marie-Ève Lebel

    2015-08-01

    Full Text Available Vaccines are considered one of the greatest medical achievements in the battle against infectious diseases. However, the intractability of various diseases such as hepatitis C, HIV/AIDS, malaria, tuberculosis, and cancer poses persistent hurdles given that traditional vaccine-development methods have proven to be ineffective; as such, these challenges have driven the emergence of novel vaccine design approaches. In this regard, much effort has been put into the development of new safe adjuvants and vaccine platforms. Of particular interest, the utilization of plant virus-like nanoparticles and recombinant plant viruses has gained increasing significance as an effective tool in the development of novel vaccines against infectious diseases and cancer. The present review summarizes recent advances in the use of plant viruses as nanoparticle-based vaccines and adjuvants and their mechanism of action. Harnessing plant-virus immunogenic properties will enable the design of novel, safe, and efficacious prophylactic and therapeutic vaccines against disease.

  15. Antifungal adjuvants: Preserving and extending the antifungal arsenal.

    Science.gov (United States)

    Butts, Arielle; Palmer, Glen E; Rogers, P David

    2017-02-17

    As the rates of systemic fungal infections continue to rise and antifungal drug resistance becomes more prevalent, there is an urgent need for new therapeutic options. This issue is exacerbated by the limited number of systemic antifungal drug classes. However, the discovery, development, and approval of novel antifungals is an extensive process that often takes decades. For this reason, there is growing interest and research into the possibility of combining existing therapies with various adjuvants that either enhance activity or overcome existing mechanisms of resistance. Reports of antifungal adjuvants range from plant extracts to repurposed compounds, to synthetic peptides. This approach would potentially prolong the utility of currently approved antifungals and mitigate the ongoing development of resistance.

  16. Adjuvant postoperative radiotherapy for gastric carcinoma with poor prognostic signs.

    Science.gov (United States)

    Slot, A; Meerwaldt, J H; van Putten, W L; Treurniet-Donker, A D

    1989-12-01

    Fifty-seven patients with poor prognostic factors following resection with curative intent for gastric adenocarcinoma (T3 or T4, positive lymph nodes, positive resection line) received adjuvant radiotherapy. A dose of 30.0-50.0 Gy was given in 10-25 fractions in one course or with a split of 2 weeks after 15 fractions. This was combined with 5-fluorouracil (5-FU) (375 mg/m2) given i.v. as a bolus during the first 4 days of radiation (n = 49). The 5-year survival was 26%; this rate is higher than the figures mentioned in the literature after surgery alone. The only way to prove the role of adjuvant radiotherapy for gastric carcinoma is a prospective randomized trial.

  17. [Stomach carcinoma. Optimizing therapy by neoadjuvant or adjuvant therapy?].

    Science.gov (United States)

    Rosen, H

    1999-01-01

    Despite the decreasing frequency of gastric cancer in most Western countries prognosis could not be improved by surgery alone in the past. Advanced tumor stage due to late diagnosis is one of the reasons for this observation. Contrary to breast and colorectal cancer, postoperative chemotherapy failed to improve prognosis in gastric cancer. Small number of patients in Western studies, insufficient surgical procedures and the high frequency of locoregional relapse may be attributed for this observation. Intraperitoneal, adjuvant chemotherapy showed a positive impact on survival in Asian studies only, but was also used successfully as a part of a multimodality approach in Western phase II trials. Since neoadjuvant therapy proved to create downstaging of tumor size in some patients with advanced gastric cancer some working groups tried to influence prognosis of potentially resectable tumors by preoperative chemotherapy, surgical resection and postoperative, adjuvant therapy in the recent past. However, the efficacy of this therapeutic approach has to be reconfirmed in a controlled, phase III fashion.

  18. Adjuvant postoperative radiotherapy for gastric carcinoma with poor prognostic signs

    Energy Technology Data Exchange (ETDEWEB)

    Slot, A.; Meerwaldt, J.H.; Treurniet-Donker, A.D. (Dr. Daniel Den Hoed Cancer Center, Rotteram (Netherlands). Department of Radiotherapy); Putten, W.L.J. van (Dr. Daniel Den Hoed Cancer Center, Rotterdam (Netherlands). Department of Statistics)

    1989-12-01

    Fifty-seven patients with poor prognostic factors following resection with curative intent for gastric adenocarcinoma T{sub 3} or T{sub 4}, positive lymph nodes, positive resection line received adjuvant radiotherapy. A dose of 30.0-50.0 Gy was given in 10-25 fraction in one course or with a split of 2 weeks after 15 fractions. This was combined with 5-fluorouracil (5-FU) (375 mg/m{sup 2}) given i.v. as a bolus during the first 4 days of radiation (n = 49). The 5-year survival was 26%; this rate is higher than the figures mentioned in the literature after surgery alone. The only way to prove the role of adjuvant radiotherapy for gastric carcinoma is a prospective randomized trial. (author). 11 refs., 2 figs., 6 tabs.

  19. [How I treat colorectal cancer. I. Prevention and adjuvant treatment].

    Science.gov (United States)

    Bours, V; Jerusalem, G; Fillet, G

    1998-04-01

    Colorectal adenocarcinoma is a major cause of cancer-related morbidity and mortality in Belgium and in other western countries. Prevention implies a modification of alimentation and maybe a chronic uptake of acetylsalicylic acid. Treatment of colorectal cancers is based on surgery and the prognosis is determined by the locoregional or metastatic tumor spread. Complete resection of any Astler Coller stage C colorectal malignant tumor has to be followed by a 5-fluorouracil-based adjuvant chemotherapy. In these protocols, 5-fluorouracil is administered together with folinic acid or levamisole. The administration of an adjuvant chemotherapy could also be considered for stage BII diseases. As rectal cancers are characterized by high local relapse rates, their treatment should associate radiotherapy, given either post-surgery or preferentially pre-surgery, with resection and chemotherapy. Appropriate treatment of colorectal cancers thus requires a concerted multidisciplinary approach.

  20. Antibiotic adjuvants - A strategy to unlock bacterial resistance to antibiotics.

    Science.gov (United States)

    González-Bello, Concepción

    2017-09-15

    Resistance to available antibiotics in pathogenic bacteria is currently a global challenge since the number of strains that are resistant to multiple types of antibiotics has increased dramatically each year and has spread worldwide. To unlock this problem, the use of an 'antibiotic adjuvant' in combination with an antibiotic is now being exploited. This approach enables us to prolong the lifespan of these life-saving drugs. This digests review provides an overview of the main types of antibiotic adjuvants, the basis of their operation and the remaining issues to be tackled in this field. Particular emphasis is placed on those compounds that are already in clinical development, namely β-lactamase inhibitors. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  1. Transfer of Antibiotic Resistance in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Haaber, Jakob; Penadés, José R; Ingmer, Hanne

    2017-01-01

    Staphylococcus aureus is a serious human pathogen with remarkable adaptive powers. Antibiotic-resistant clones rapidly emerge mainly by acquisition of antibiotic-resistance genes from other S. aureus strains or even from other genera. Transfer is mediated by a diverse complement of mobile genetic...... of plasmids that can be transferred by conjugation and the efficiency with which transduction occurs. Here, we review the main routes of antibiotic resistance gene transfer in S. aureus in the context of its biology as a human commensal and a life-threatening pathogen. Staphylococcus aureus cells...... are effective in exchanging mobile genetic elements, including antibiotic-resistance genes.During colonization or infection of host organisms, the exchange appears to be particularly effective.Bacteriophage-mediated transfer involves both transduction and autotransduction, which may enable lysogenic S. aureus...

  2. Infectious olecranon and patellar bursitis: short-course adjuvant antibiotic therapy is not a risk factor for recurrence in adult hospitalized patients.

    Science.gov (United States)

    Perez, Cédric; Huttner, Angela; Assal, Mathieu; Bernard, Louis; Lew, Daniel; Hoffmeyer, Pierre; Uçkay, Ilker

    2010-05-01

    No evidence-based recommendations exist for the management of infectious bursitis. We examined epidemiology and risk factors for recurrence of septic bursitis. Specifically, we compared outcome in patients receiving bursectomy plus short-course adjuvant antibiotic therapy (7 days). Retrospective study of adult patients with infectious olecranon and patellar bursitis requiring hospitalization at Geneva University Hospital from January 1996 to March 2009. We identified 343 episodes of infectious bursitis (237 olecranon and 106 patellar). Staphylococcus aureus predominated among the 256 cases with an identifiable pathogen (85%). Three hundred and twelve cases (91%) were treated surgically; 142 (41%) with one-stage bursectomy and closure and 146 with two-stage bursectomy. All received antibiotics for a median duration of 13 days with a median intravenous component of 3 days. Cure was achieved in 293 (85%) episodes. Total duration of antibiotic therapy [odds ratio (OR) 0.9; 95% confidence interval (95% CI) 0.8-1.1] showed no association with cure. In multivariate analysis, only immunosuppression was linked to recurrence (OR 5.6; 95% CI 1.9-18.4). Compared with 14 days of antibiotic treatment (OR 0.9; 95% CI 0.1-10.7) was equivalent, as was the intravenous component (OR 1.1; 95% CI 1.0-1.3). In severe infectious bursitis requiring hospitalization, adjuvant antibiotic therapy might be limited to 7 days in non-immunosuppressed patients.

  3. Preparation and evaluation of functional foods in adjuvant arthritis

    OpenAIRE

    2012-01-01

    Adjuvant arthritis is an animal model that closely resembles rheumatoid arthritis in humans. It is a successful working model used to study new anti-inflammatory agents. In previous studies (animal and clinical) we have shown that evening primrose oil, fish oil and the methanol extract of date fruits and fenugreek seeds have anti-inflammatory activity and that the methanol extract of dates has an antioxidant effect. Based on these studies, the aim of the present study was to prepare 7 functio...

  4. Adjuvant properties of a simplified C32 monomycolyl glycerol analogue.

    Science.gov (United States)

    Bhowruth, Veemal; Minnikin, David E; Agger, Else Marie; Andersen, Peter; Bramwell, Vincent W; Perrie, Yvonne; Besra, Gurdyal S

    2009-04-01

    A simplified C(32) monomycolyl glycerol (MMG) analogue demonstrated enhanced immunostimulatory activity in a dioctadecyl ammonium bromide (DDA)/Ag85B-ESAT-6 formulation. Elevated levels of IFN-gamma and IL-6 were produced in spleen cells from mice immunised with a C(32) MMG analogue comparable activity to the potent Th1 adjuvant, trehalose 6,6'-di-behenate (TDB).

  5. Adjuvants to local anesthetics: Current understanding and future trends

    Science.gov (United States)

    Swain, Amlan; Nag, Deb Sanjay; Sahu, Seelora; Samaddar, Devi Prasad

    2017-01-01

    Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by its duration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids (dexamethasone), anti-inflammatory agents (parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action (tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability (liposomal

  6. Hypothesis: Silver Nanoparticles as an Adjuvant for Cancertherapy

    Directory of Open Access Journals (Sweden)

    Ramin Mohammadzadeh

    2012-06-01

    Full Text Available Cytotoxic agents are a main part of therapeutic process against the observed tumors, which lead to some unwished damages, due to drug uptake by normal body cells causing various tissue/organ failures associated with formal administration manners. But nowadays the risk is reduced by new target therapy techniques, of which the observed physical nature of micelles and nanosilver particles, governing their special behavior, could help using micelle-coated silver nanoparticles as a novel adjuvant for cancer target therapy.

  7. Tocotrienols are good adjuvants for developing cancer vaccines

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Ammu

    2010-01-01

    Full Text Available Abstract Background Dendritic cells (DCs have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours. Methods In this study we have used tocotrienol-rich fraction (TRF, a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF and DC pulsed with tumour lysate from 4T1 cells (DC+TL. Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF while two groups of animal which were supplemented daily with carrier oil (control and with TRF (TRF. After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour. Results Our study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-γ and IL-12 in experimental mice (DC+TL+TRF compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8 and natural killer cells (NK were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice. Conclusion Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy.

  8. Penetration of erythromycin through Staphylococcus epidermidis biofilm

    Institute of Scientific and Technical Information of China (English)

    LIN Mao-hu; HE Lei; GAO Jie; LIU Yun-xi; SUO Ji-jiang; XING Yu-bin; JIA Ning

    2013-01-01

    Background The catheter related infection caused by Staphylococcus epiderrnidis biofilm is increasing and difficult to treat by antimicrobial chemotherapy.The properties of biofilms that give rise to antibiotic resistance are only partially understood.This study aimed to elucidate the penetration of erythromycin through Staphylococcus epidermidis biofilm.Methods The penetration ratio of erythromycin through Staphylococcus epidermidis biofilms of 1457,1457-msrA,and wild isolate S68 was detected by biofilm penetration model at different time points according to the standard regression curve.The RNNDNA ratio and the cell density within the biofilms were observed by confocal laser microscope and transmission electromicroscope,respectively.Results The penetration ratios of erythromycin through the biofilms of 1457,1457-msrA,and S68 after cultivation for 36 hours were 0.93,0.55 and 0.4,respectively.The erythromycin penetration ratio through 1457 biofilm (0.58 after 8 hours)was higher than that through the other two (0.499 and 0.31 after 24 hours).Lower growth rate of the cells in biofilm was shown,with reduction of RNA/DNA proportion observed by confocal laser microscope through acridine orange stain.Compared with the control group observed by transmission electrmicroscope,the cell density of biofilm air face was lower than that of agar face,with more cell debris.Conclusions Erythromycin could penetrate to the Staphylococcus epidermidis biofilm,but could not kill the cells thoroughly.The lower growth rate of the cells within biofilm could help decreasing the erythromycin susceptibility.

  9. Etudes structurales du ribosome de Staphylococcus aureus

    OpenAIRE

    Khusainov, Iskander

    2015-01-01

    The ribosome is a large cellular machinery that performs the protein synthesis in every living cell. Therefore, the ribosome is one of the major targets of naturally produced antibiotics, which can kill bacterial cells by blocking protein synthesis. However, some bacteria are resistant to these antibiotics due to small modifications of their ribosomes. Among them, Staphylococcus aureus (S. aureus) is a severe pathogen that causes numerous infections in humans. The crystal structures of comple...

  10. Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

    Directory of Open Access Journals (Sweden)

    Ivana Škrnjug

    Full Text Available The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

  11. [Adjuvant chemotherapy in colon cancer. About 119 cases].

    Science.gov (United States)

    Yaich, Asma; Khanfir, Afef; Bayrouti, Mohamed Issam; Frikha, Mounir

    2015-04-01

    colon cancer is a public health problem worldwide and in Tunisia. The prognosis of patients with unresectable colorectal cancer varies according to the stage. The indication for adjuvant chemotherapy is well established in the colon cancer stage III, while it remains a matter of controversy for stage II. The aim of this work is to identify the epidemiological and anatomoclinical assess therapeutic outcomes in terms of overall survival of patients with high-risk stage II and stage III colon cancer treated with surgery and adjuvant chemotherapy. DS: It's a retrospective study based on 119 patients with colon adenocarcinoma from 1996 to 2010. This patients suffering from colon cancer classified stage II and III having them all radical surgery and adjuvant chemotherapy. The average age of our patients was 53 years. The surgery was performed in an emergency situation in 53 patients (44%). Stages II and III, respectively, were observed in 47% and 53% of cases. Three regimens of chemotherapy were used: protocol FUFOL (50%), followed by FOLFOX (34%) and the protocol LV5FU2 (16%). Overall survival of patients all stages combined was 73.4% at 5 years. Stage III of the TNM classification (p = 0.03) and the number of cycles of chemotherapy colon cancer is improving thanks to recent advances that have enabled the integration of new cytogenetic factors in the therapeutic decision.

  12. [Development of Nucleic Acid-Based Adjuvant for Cancer Immunotherapy].

    Science.gov (United States)

    Kobiyama, Kouji; Ishii, Ken J

    2015-09-01

    Since the discovery of the human T cell-defined tumor antigen, the cancer immunotherapy field has rapidly progressed, with the research and development of cancer immunotherapy, including cancer vaccines, being conducted actively. However, the disadvantages of most cancer vaccines include relatively weak immunogenicity and immune escape or exhaustion. Adjuvants with innate immunostimulatory activities have been used to overcome these issues, and these agents have been shown to enhance the immunogenicity of cancer vaccines and to act as mono-therapeutic anti-tumor agents. CpG ODN, an agonist for TLR9, is one of the promising nucleic acid-based adjuvants, and it is a potent inducer of innate immune effector functions. CpG ODN suppresses tumor growth in the absence of tumor antigens and peptide administration. Therefore, CpG ODN is expected to be useful as a cancer vaccine adjuvant as well as a cancer immunotherapy agent. In this review, we discuss the potential therapeutic applications and mechanisms of CpG ODN for cancer immunotherapy.

  13. A Purified Recombinant Lipopeptide as Adjuvant for Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Ying-Chyi Song

    2014-01-01

    Full Text Available Synthetic lipopeptides have been widely used as vaccine adjuvants to enhance immune responses. The present study demonstrated that the tryptic N-terminal fragment of the lipoprotein rlipo-D1E3 (lipo-Nter induces superior antitumor effects compared to a synthetic lipopeptide. The lipo-Nter was purified and formulated with protein or peptide vaccines to determine if lipo-Nter could be used as a novel adjuvant and could induce antitumor immunity in a cervical cancer model. Purified lipo-Nter activated the maturation of bone marrow-derived dendritic cells (BM-DCs, leading to the secretion of TNF-α through TLR2/6 but not TLR1/2. A recombinant mutant HPV16 E7 (rE7m protein was mixed with lipo-Nter to immunize the mice; the anti-E7 antibody titers were increased, and the T helper cells were skewed toward the Th1 fate (increased IL-2 and decreased IL-5 secretion. Single-dose injection of rE7m and lipo-Nter inhibited tumor growth, but the injection of rE7m alone did not. Accordingly, lipo-Nter also enhanced the antitumor immunity of the E7-derived peptide but not the synthetic lipopeptide (Pam3CSK4. We demonstrated that the lipo-Nter of a bacterial-derived recombinant lipoprotein is a novel adjuvant that could be used for the development of a new generation of vaccines.

  14. Adherence to adjuvant endocrine therapy in women with breast cancer.

    Science.gov (United States)

    Danilak, Melanie; Chambers, Carole R

    2013-06-01

    To determine how many breast cancer patients who initiated adjuvant endocrine therapy discontinued early and to evaluate adherence in patients who persisted with therapy. Secondary objectives were to explore possible trends to see if certain factors may correlate to early discontinuation of therapy. A retrospective review of charts and pharmacy dispensing records was conducted, including patients who initiated adjuvant endocrine therapy for breast cancer at the Cross Cancer Institute from 1 January to 31 December, 2006. Out of 346 patients, 81 (22%) discontinued therapy within 2 years. Adherence rates calculated for the 265 patients who remained on therapy beyond 2 years showed that 247 (93%) of these patients had 80% or better adherence. Patients who did not undergo chemotherapy and patients with Cross Cancer Institute follow-up times of less than 1 year were significantly more likely to discontinue therapy early. The majority of patients who were prescribed adjuvant endocrine therapy for breast cancer at the Cross Cancer Institute remained on therapy for at least 2 years and were adherent. Longer follow-up by Cross Cancer Institute practitioners may help decrease discontinuation rates.

  15. Freund's vaccine adjuvant promotes Her2/Neu breast cancer

    Directory of Open Access Journals (Sweden)

    Woditschka Stephan

    2009-01-01

    Full Text Available Abstract Background Inflammation has been linked to the etiology of many organ-specific cancers. Indirect evidence suggests a possible role for inflammation in breast cancer. We investigated whether the systemic inflammation induced by Freund's adjuvant (FA promotes mammary carcinogenesis in a rat model in which cancer is induced by the neu oncogene. Methods The effects of FA on hyperplastic mammary lesions and mammary carcinomas were determined in a neu-induced rat model. The inflammatory response to FA treatment was gauged by measuring acute phase serum haptoglobin. In addition, changes in cell proliferation and apoptosis following FA treatment were assessed. Results Rats receiving FA developed twice the number of mammary carcinomas as controls. Systemic inflammation following FA treatment is chronic, as shown by a doubling of the levels of the serum biomarker, haptoglobin, 15 days following initial treatment. We also show that this systemic inflammation is associated with the increased growth of hyperplastic mammary lesions. This increased growth results from a higher rate of cellular proliferation in the absence of changes in apoptosis. Conclusion Our data suggests that systemic inflammation induced by Freund's adjuvant (FA promotes mammary carcinogenesis. It will be important to determine whether adjuvants currently used in human vaccines also promote breast cancer.

  16. Neisseria lactamica antigens complexed with a novel cationic adjuvant.

    Science.gov (United States)

    Gaspar, Emanuelle B; Rosetti, Andreza S; Lincopan, Nilton; De Gaspari, Elizabeth

    2013-03-01

    Colonization of the nasopharynx by non-pathogenic Neisseria species, including N. lactamica, has been suggested to lead to the acquisition of natural immunity against Neisseria meningitidis in young children. The aim of this study was to identify a model complex of antigens and adjuvant for immunological preparation against N. meningitidis B, based on cross reactivity with N. lactamica outer membrane vesicles (OMV) antigens and the (DDA-BF) adjuvant. Complexes of 25 µg of OMV in 0.1 mM of DDA-BF were colloidally stable, exhibiting a mean diameter and charge optimal for antigen presentation. Immunogenicity tests for these complexes were performed in mice. A single dose of OMV/DDA-BF was sufficient to induce a (DTH) response, while the same result was achieved only after two doses of OMV/alum. In addition, to achieve total IgG levels that are similar to a single immunization with OMV/DDA-BF, it was necessary to give the mice a second dose of OMV/alum. Moreover, the antibodies induced from a single immunization with OMV/DDA-BF had an intermediate avidity, but antibodies with a similar avidity were only induced by OMV/alum after two immunizations. The use of this novel cationic adjuvant for the first time with a N. lactamica OMV preparation revealed good potential for future vaccine design.

  17. [Change in drug resistance of Staphylococcus aureus].

    Science.gov (United States)

    Lin, Yan; Liu, Yan; Luo, Yan-Ping; Liu, Chang-Ting

    2013-11-01

    To analyze the change in drug resistance of Staphylococcus aureus (SAU) in the PLA general hospital from January 2008 to December 2012, and to provide solid evidence to support the rational use of antibiotics for clinical applications. The SAU strains isolated from clinical samples in the hospital were collected and subjected to the Kirby-Bauer disk diffusion test. The results were assessed based on the 2002 American National Committee for Clinical Laboratory Standards (NCCLS) guidelines. SAU strains were mainly isolated from sputum, urine, blood and wound excreta and distributed in penology, neurology wards, orthopedics and surgery ICU wards. Except for glycopeptide drugs, methicillin-resistant Staphylococcus aureus (MRSA) had a higher drug resistance rate than those of the other drugs and had significantly more resistance than methicillin-sensitive Staphylococcus aureus (MSSA) (P resistance, we discovered a gradual increase in drug resistance to fourteen test drugs during the last five years. Drug resistance rate of SAU stayed at a higher level over the last five years; moreover, the detection ratio of MRSA keeps rising year by year. It is crucial for physicians to use antibiotics rationally and monitor the change in drug resistance in a dynamic way.

  18. External validation of Adjuvant! Online breast cancer prognosis tool. Prioritising recommendations for improvement.

    Directory of Open Access Journals (Sweden)

    David Hajage

    Full Text Available BACKGROUND: Adjuvant! Online is a web-based application designed to provide 10 years survival probability of patients with breast cancer. Several predictors have not been assessed in the original Adjuvant! Online study. We provide the validation of Adjuvant! Online algorithm on two breast cancer datasets, and we determined whether the accuracy of Adjuvant! Online is improved with other well-known prognostic factors. PATIENTS AND METHODS: The French data set is composed of 456 women with early breast cancer. The Dutch data set is composed of 295 women less than 52 years of age. Agreement between observation and Adjuvant! Online prediction was checked, and logistic models were performed to estimate the prognostic information added by risk factors to Adjuvant! Online prediction. RESULTS: Adjuvant! Online prediction was overall well-calibrated in the French data set but failed in some subgroups of such high grade and HER2 positive patients. HER2 status, Mitotic Index and Ki67 added significant information to Adjuvant! Online prediction. In the Dutch data set, the overall 10-year survival was overestimated by Adjuvant! Online, particularly in patients less than 40 years old. CONCLUSION: Adjuvant! Online needs to be updated to adjust overoptimistic results in young and high grade patients, and should consider new predictors such as Ki67, HER2 and Mitotic Index.

  19. The Quest for an HIV-1 Vaccine Adjuvant: Bacterial Toxins as New Potential Platforms.

    Science.gov (United States)

    Nashar, Toufic O

    2014-06-01

    While tremendous efforts are undergoing towards finding an effective HIV-1 vaccine, the search for an HIV-1 vaccine adjuvant lags behind and is understudied. More recently, however, efforts have focused on testing adjuvant formulations that can boost the immune response and generate broadly neutralizing antibodies to HIV-1 ENV (gp160). Despite this, there remain a number of challenges towards achieving this goal. These include safety of adjuvant formulations; stability of the incorporated antigens; maintenance of ENV immunogenicity; optimal inoculation sites; the effective combination of adjuvants; stability of ENV neutralizing epitopes in some adjuvant formulations; mucosal immunity; and long-term maintenance of the immune response. A new class of adjuvants for HIV-1 proteins is suggested to overcome many of the limitations of some other adjuvants. Type 1 (LT-I) and type 2 (LT-II) human E. coli enterotoxins (HLTs) and their non-toxic B-subunits derivatives are strong systemic and mucosal adjuvants and effective carriers for other proteins and epitopes. Their stable molecular structure in the presence of fused proteins and epitopes, and their ability to target surface receptors on antigen presenting cells make them ideal for the delivery of HIV-1 ENV or HIV other proteins. Importantly, unlike some other adjuvants, HLTs and derivatives have well-defined modes of immune system activation. The challenges in finding optimal HIV-1 vaccine adjuvant formulation and the important properties of HLTs are discussed.

  20. Comparable quality attributes of hepatitis E vaccine antigen with and without adjuvant adsorption-dissolution treatment.

    Science.gov (United States)

    Zhang, Yue; Li, Min; Yang, Fan; Li, Yufang; Zheng, Zizheng; Zhang, Xiao; Lin, Qingshan; Wang, Ying; Li, Shaowei; Xia, Ningshao; Zhang, Jun; Zhao, Qinjian

    2015-01-01

    Most vaccines require adjuvants for antigen stabilization and immune potentiation. Aluminum-based adjuvants are the most widely used adjuvants for human vaccines. Previous reports demonstrated the preservation of antigen conformation and other antigen characteristics after recovery from adjuvanted Hepatitis B and human papillomavirus vaccines. In this study, we used a combination of various physiochemical and immunochemical methods to analyze hepatitis E vaccine antigen quality attributes after recovery from adjuvants. All biochemical and biophysical methods showed similar characteristics of the p239 protein after recovery from adjuvanted vaccine formulation compared to the antigen in solution which never experienced adsorption/desorption process. Most importantly, we demonstrated full preservation of key antigen epitopes post-recovery from adjuvanted vaccine using a panel of murine monoclonal antibodies as exquisite probes. Antigenicity of p239 was probed with a panel of 9 mAbs using competition/blocking ELISA, surface plasmon resonance and sandwich ELISA methods. These multifaceted analyses demonstrated the preservation of antigen key epitopes and comparable protein thermal stability when adsorbed on adjuvants or of the recovered antigen post-dissolution treatment. A better understanding of the antigen conformation in adjuvanted vaccine will enhanced our knowledge of antigen-adjuvant interactions and facilitate an improved process control and development of stable vaccine formulation.

  1. The Effect of Neoadjuvant Chemotherapy Compared to Adjuvant Chemotherapy in Healing after Nipple-Sparing Mastectomy.

    Science.gov (United States)

    Frey, Jordan D; Choi, Mihye; Karp, Nolan S

    2017-01-01

    Nipple-sparing mastectomy is the latest advancement in the treatment of breast cancer. The authors aimed to investigate the effects of neoadjuvant and adjuvant chemotherapy in nipple-sparing mastectomy. Patients undergoing nipple-sparing mastectomy from 2006 to June of 2015 were identified. Results were stratified by presence of neoadjuvant or adjuvant chemotherapy. A total of 840 nipple-sparing mastectomies were performed. Twenty-eight were in those who received neoadjuvant chemotherapy and 93 were in patients receiving adjuvant chemotherapy. Patients receiving both neoadjuvant and adjuvant chemotherapy were included in the neoadjuvant group. Nipple-sparing mastectomies that received neoadjuvant (with or without adjuvant) chemotherapy were compared to those in patients who received adjuvant chemotherapy. Those with neoadjuvant (with or without adjuvant) chemotherapy were more likely to have explantation (p = 0.0239) and complete nipple-areola complex necrosis (p = 0.0021). Those with neoadjuvant (with or without adjuvant) chemotherapy were more likely to have implant explantation (p = 0.0015) and complete nipple-areola complex necrosis (p = 0.0004) compared to those with no chemotherapy. Compared to nipple-sparing mastectomies in patients with no chemotherapy, those with adjuvant chemotherapy were more likely to have a hematoma (p = 0.0021). Those that received both neoadjuvant and adjuvant chemotherapy were more likely to have complete nipple-areola complex necrosis compared with both the neoadjuvant chemotherapy-only and adjuvant chemotherapy-only groups (p < 0.0001). Nipple-sparing mastectomy is safe to perform in the setting of neoadjuvant and adjuvant chemotherapy. As a whole, neoadjuvant (with or without adjuvant) chemotherapy increases risk of complications. Therapeutic, III.

  2. Truncated Autoinducing Peptides as Antagonists of Staphylococcus lugdunensis Quorum Sensing.

    Science.gov (United States)

    Gordon, Christopher P; Olson, Shondra D; Lister, Jessica L; Kavanaugh, Jeffrey S; Horswill, Alexander R

    2016-10-13

    Competitive quorum sensing (QS) antagonism offers a novel strategy for attenuating current multidrug resistant staphylococcal infections. To this end, a series of 10 truncated analogues based on the parent autoinducing peptides (AIPs) of Staphylococcus lugdunensis (groups I and II) and Staphylococcus epidermidis (groups I-III) were sequentially assessed against a newly developed Staphylococcus lugdunensis group I QS reporter strain. The truncated analogues based upon Staphylococcus lugdunensis AIP-1 (1) and AIP-2 (2) displayed respective IC50 values of 0.2 ± 0.01 μM and 0.3 ± 0.01 μM, while the truncated analogue of the Staphylococcus epidermidis AIP-1 (3) elicited an IC50 value of 2.7 ± 0.1 μM. These findings demonstrate the potential of cognate and "crosstalk" competitive quorum sensing inhibition using truncated AIPs as a means of attenuating staphylococcal infections in species beyond Staphylococcus aureus.

  3. Catheter sepsis due to Staphylococcus epidermidis during parenteral nutrition.

    Science.gov (United States)

    Sitges-Serra, A; Puig, P; Jaurrieta, E; Garau, J; Alastrue, A; Sitges-Creus, A

    1980-10-01

    Staphylococcus epidermidis is a pathogenic organism with increasing importance in total parenteral nutrition therapy. Strict asepsis during catheter insertion prolongs the interval free from Staphylococcus epidermidis infection. Staphylococcus epidermidis colonizes the catheter after migrating from the skin. For protection, we advise a long subcutaneous tunnel for all catheters that are to be indwelling for longer than three weeks. Prompt recatheterization of a patient with Staphylococcus epidermidis sepsis can result in hematogenous seeding of the new catheter and persistence of the infection. Catheter related Staphylococcus epidermidis sepsis has subsided after catheter withdrawal, and there is no need for antibiotic therapy provided that other prosthetic materials are not placed in the vascular tree. Immunologic status of the patients is not related to the frequency or severity of Staphylococcus epidermidis infections, or both.

  4. Volatiles produced by Staphylococcus xylosus and Staphylococcus carnosus during growth in sausage minces

    DEFF Research Database (Denmark)

    Stahnke, Marie Louise Heller

    1999-01-01

    Aseptic model minces were inoculated with commercial samples of either Staphylococcus xylosus or Staphylococcus carnosus. Volatiles produced by the cultures were collected during growth by diffusive sampling onto adsorbent traps, identified by thermal desorption-gas chromatography-mass spectrometry...... and quantified by thermal desorption-gas chromatography-flame ionisation. The data were analysed by principal component analysis. The study showed that both starter cultures produced a large number of volatiles in concentrations of sensory importance. Almost all of the major volatiles resulted from amino acid...... degradation, suggesting that the effect of Staphylococcus starter cultures on flavour quality is much related to their ability of catabolizing amino acids. With the exception of diacetyl, acetoin and 2-methyl-1-butanol, both cultures formed the same volatiles. Diacetyl and acetoin were not produced...

  5. PREVALENCIA DE Staphylococcus epidermidis Y Staphylococcus aureus EN PACIENTES CON CONJUNTIVITIS

    Directory of Open Access Journals (Sweden)

    P. Hernández-Rodríguez

    2005-12-01

    Full Text Available Con el fin de establecer la prevalencia de Staphylococcus epidermidis y Staphylococcus aureus en pacientes con conjuntivitis, se evaluaron clínica y bacteriológicamente 131 pacientes con diagnóstico clínico presuntivo de conjuntivitis. A cada participante se le tomó muestra de secreción ocular, para la coloración de Gram y cultivo; además, se probó la susceptibilidad de los aislamientos frente a Oxacilina (Ox, Gentamicina (GM, Vancomicina (Va, Trimetoprim Sulfamethoxazole (SXT, Tetraciclina (Te, Cefalothin (CF, Ceftriaxone (CRO y Ciprofloxacina (CIP. El 53% de los cultivos bacteriológicos fueron positivos, donde el 87% de los aislamientos correspondieron a Gram positivos, siendo los más frecuentes Staphylococcus epidermidis (43%, Staphylococcus aureus (30%, Streptococcus sp. (15%, Enterococcus (7%, Corynebacterium sp. 5%. Se observó multirresistencia frente a 3 ó más antibióticos en S. epidermidis (44% y S.aureus (42%. La alta frecuencia de estos microorganismos y la multirresistencia encontrada en este estudio, determinan la importancia que tienen, como posibles patógenos oculares, y la necesidad de implementar las pruebas de susceptibilidad bacteriana en el ámbito oftalmológico. Este es el primer estudio publicado en Colombia sobre la prevalencia de Staphylococcus epidermidis y Staphylococcus aureus en pacientes con conjuntivitis, el cual seguramente originará la iniciación de posteriores investigaciones, encaminadas a determinar el verdadero papel de estos microorganismos, en el proceso infeccioso ocular.

  6. Aroma components from dried sausages fermented with Staphylococcus xylosus

    DEFF Research Database (Denmark)

    Stahnke, Marie Louise Heller

    1994-01-01

    an unpleasant, rancid odour compared to sausages with Staphylococcus xylosus, indicating that the esterase activity of Staphylococcus xylosus or other microorganisms is very important in order to obtain the proper fermented sausage aroma.Although sausages with Staphylococcus xylosus contained the highest...... amounts of free fatty acids, it seemed to be of no importance to aroma development. It is therefore questionable whether lipolytic activity of starter cultures has an influence on sausage flavour....

  7. Cost-utility analysis of adjuvant goserelin (Zoladex and adjuvant chemotherapy in premenopausal women with breast cancer

    Directory of Open Access Journals (Sweden)

    Cheng Tsui

    2012-01-01

    Full Text Available Abstract Background Increased health care costs have made it incumbent on health-care facilities and physicians to demonstrate both clinical and cost efficacy when recommending treatments. Though studies have examined the cost-effectiveness of adjuvant goserelin with radiotherapy for locally advanced prostate cancer, few have compared the cost-effectiveness of adjuvant goserelin to adjuvant chemotherapy alone in premenopausal breast cancer. Methods In this retrospective study at one hospital, the records of 152 patients with stage Ia to IIIa ER + breast cancer who received goserelin or chemotherapy were reviewed. Survival analysis was assessed by the Kaplan-Meier method. Patients were interviewed to evaluate their quality of life using the European Organization for Research and Treatment Quality of Life questionnaire (EORTC-QLQ-C30, version 4.0, and to obtain the utility value by the standard gamble (SG and visual scale (VS methods. Total medical cost was assessed from the (National Health Insurance NHI payer's perspective. Results Survival at 11 years was significantly better in the groserelin group (P Conclusions Goserelin therapy results in better survival and higher utility-weighted life-years, and is more cost-effective than TC or TEC chemotherapy.

  8. Gamma ray sterilization of delta inulin adjuvant particles (Advax™) makes minor, partly reversible structural changes without affecting adjuvant activity.

    Science.gov (United States)

    Cooper, P D; Barclay, T G; Ginic-Markovic, M; Petrovsky, N

    2014-01-23

    We earlier identified a developmental series of seven isoforms/polymorphs of microparticulate inulin by comparing non-covalent bonding strengths. Their pharmaceutical utility lies in the modulation of cellular immunity, exploited as vaccine adjuvants (Advax™) especially for delta inulin (DI). As such particles cannot be sterilized by filtration we explore the effect of (60)Co gamma radiation (GR) on inulin isoforms, particularly DI. Its adjuvant activity and overt physical properties were unaffected by normal GR sterilizing doses (up to 25kGy). Heating irradiated isoform suspensions near their critical dissolution temperature revealed increased solubility deduced to reflect a single lethal event in one component of a multi-component structure. Local oxidative effects of GR on DI were not found. The observed DI loss was almost halved by re-annealing at the critical temperature: surviving inulin chains apparently reassemble into smaller amounts of the original type of structure. Colorimetric tetrazolium assay revealed increases in reducing activity after GR of raw inulin powder, which yielded DI with normal physical properties but only 25% normal recovery yet 4× normal reducing ability, implying final retention of some GR-changed inulin chains. These findings suggest minimal inulin chain cleavage and confirm that GR may be a viable strategy for terminal sterilization of microparticulate inulin adjuvants.

  9. One-year mortality in coagulase-negative Staphylococcus and Staphylococcus aureus infective endocarditis

    DEFF Research Database (Denmark)

    Rasmussen, Rasmus V; Snygg-Martin, Ulrika; Olaison, Lars;

    2009-01-01

    The aim of this study was to investigate in-hospital mortality and 12-month mortality in patients with coagulase-negative Staphylococcus (CoNS) compared to Staphylococcus aureus (S. aureus) infective endocarditis (IE). We used a prospective cohort study of 66 consecutive CoNS and 170 S. aureus IE...... patients, collected at 2 tertiary university hospitals in Copenhagen (Denmark) and at 1 tertiary university hospital in Gothenburg (Sweden). Median (range) C-reactive protein at admission was higher in patients with S. aureus IE (150 mg/l (1-521) vs 94 mg/l (6-303); p

  10. Staphylococcus lugdunensis: novel organism causing cochlear implant infection

    Directory of Open Access Journals (Sweden)

    Samina Bhumbra

    2014-06-01

    Full Text Available A majority of cochlear implant infections are caused by Staphylococcus aureus or Pseudomonas aeruginosa. Reported here is a pediatric patient with a cochlear implant infection caused by methicillin-resistant Staphylococcus lugdunensis, a coagulase-negative Staphylococcus that has only recently been determined to be clinically relevant (1988. Unlike other coagulase-negative Staphylococcus, it is more aggressive, carrying a greater potential for tissue destruction. In pediatrics, the organism is uncommon, poorly described, and generally pan-susceptible. Described herein is the presentation and management of this unusual organism in a pediatric setting.

  11. Echocardiography is dispensable in uncomplicated Staphylococcus aureus bacteremia

    National Research Council Canada - National Science Library

    Khatib, Riad; Sharma, Mamta

    2013-01-01

    Current Staphylococcus aureus bacteremia (SAB) practice guidelines stratify treatment duration according to the likelihood of complications and recommend transesophageal echocardiography (TEE) in all cases...

  12. Identification of Staphylococcus spp. using (GTG)₅-PCR fingerprinting.

    Science.gov (United States)

    Svec, Pavel; Pantůček, Roman; Petráš, Petr; Sedláček, Ivo; Nováková, Dana

    2010-12-01

    A group of 212 type and reference strains deposited in the Czech Collection of Microorganisms (Brno, Czech Republic) and covering 41 Staphylococcus species comprising 21 subspecies was characterised using rep-PCR fingerprinting with the (GTG)₅ primer in order to evaluate this method for identification of staphylococci. All strains were typeable using the (GTG)₅ primer and generated PCR products ranging from 200 to 4500 bp. Numerical analysis of the obtained fingerprints revealed (sub)species-specific clustering corresponding with the taxonomic position of analysed strains. Taxonomic position of selected strains representing the (sub)species that were distributed over multiple rep-PCR clusters was verified and confirmed by the partial rpoB gene sequencing. Staphylococcus caprae, Staphylococcus equorum, Staphylococcus sciuri, Staphylococcus piscifermentans, Staphylococcus xylosus, and Staphylococcus saprophyticus revealed heterogeneous fingerprints and each (sub)species was distributed over several clusters. However, representatives of the remaining Staphylococcus spp. were clearly separated in single (sub)species-specific clusters. These results showed rep-PCR with the (GTG)₅ primer as a fast and reliable method applicable for differentiation and straightforward identification of majority of Staphylococcus spp.

  13. Development of a minimal saponin vaccine adjuvant based on QS-21

    Science.gov (United States)

    Fernández-Tejada, Alberto; Chea, Eric K.; George, Constantine; Pillarsetty, Nagavarakishore; Gardner, Jeffrey R.; Livingston, Philip O.; Ragupathi, Govind; Lewis, Jason S.; Tan, Derek S.; Gin, David Y.

    2014-07-01

    Adjuvants are materials added to vaccines to enhance the immunological response to an antigen. QS-21 is a natural product adjuvant under investigation in numerous vaccine clinical trials, but its use is constrained by scarcity, toxicity, instability and an enigmatic molecular mechanism of action. Herein we describe the development of a minimal QS-21 analogue that decouples adjuvant activity from toxicity and provides a powerful platform for mechanistic investigations. We found that the entire branched trisaccharide domain of QS-21 is dispensable for adjuvant activity and that the C4-aldehyde substituent, previously proposed to bind covalently to an unknown cellular target, is also not required. Biodistribution studies revealed that active adjuvants were retained preferentially at the injection site and the nearest draining lymph nodes compared with the attenuated variants. Overall, these studies have yielded critical insights into saponin structure-function relationships, provided practical synthetic access to non-toxic adjuvants, and established a platform for detailed mechanistic studies.

  14. Adjuvant Activity of a Novel Metabolizable Lipid Emulsion with Inactivated Viral Vaccines

    Science.gov (United States)

    1980-06-01

    hamsters, sheep, and two species of nonhuman 0 primates which demonstrate the adjuvant activity of a new metabolizable lipid emulsion with marginally...mice, hamsters, sheep, and two species of nonhuman primates . This adjuvant has several 10.000 advantages over other known adjuvant com-cpounds. It is...plaque neutralization method for arboviruses . Proc. Soc. granulomatous reaction was not observed. We Exp. Biol. Med. 125:741-747. closely observed the

  15. Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations

    OpenAIRE

    2016-01-01

    Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al3+ in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, pote...

  16. Characteristics and prognosis of patients with early-stage endometrial cancer who refuse adjuvant radiotherapy.

    Science.gov (United States)

    Koskas, Martin; Huchon, Cyrille; Amant, Frederic

    2016-06-01

    To investigate the risk factors for refusing adjuvant radiotherapy in patients who have undergone surgery for early-stage endometrial cancer, and to compare their survival rates with patients who have undergone adjuvant radiotherapy. Data from the Surveillance, Epidemiology, and End Results database for patients operated on for histologically-proven early-stage endometrioid endometrial cancer, between 1988 and 2012, were screened. Univariate and multivariate logistic regression analyses tested the associations between refusal of adjuvant radiotherapy and demographic, tumoral, and management characteristics. Overall and cancer-related survival rates were compared between 376 patients who refused adjuvant radiotherapy and 752 patients who received adjuvant radiotherapy, matched for demographics (age, race, year of diagnosis, marital status, region), tumoral (grade, FIGO stage, size), and management (lymphadenectomy performed) criteria. 434 of the 16,014 patients (2.7%) who were proposed adjuvant radiotherapy refused this treatment. Older, widowed, divorced, or separated patients, who were recently diagnosed and managed in the Northern plains or Pacific coast (USA), with limited tumoral extension, were more likely to refuse adjuvant radiotherapy. Five-year cancer-related survival was significantly lower in patients who refused adjuvant radiotherapy (88.9% vs. 95.7%, pradiotherapy. Refusing adjuvant radiotherapy increased cancer-related death but probably does not reduce overall survival. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Adjuvants and delivery systems in veterinary vaccinology: current state and future developments

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Dedieu, Laurence; Johnson, Nicholas;

    2011-01-01

    low immunogenicity themselves. The development of such adjuvants may take advantage of the increased knowledge of the molecular mechanisms and factors controlling these responses. However, knowledge of such molecular details of immune mechanisms is relatively scarce for species other than humans......Modern adjuvants should induce strong and balanced immune responses, and it is often desirable to induce specific types of immunity. As an example, efficient Th1-immunity-inducing adjuvants are highly in demand. Such adjuvants promote good cell-mediated immunity against subunit vaccines that have...

  18. Review on adjuvant chemotherapy for rectal cancer - why do treatment guidelines differ so much?

    Science.gov (United States)

    Poulsen, Laurids Ø; Qvortrup, Camilla; Pfeiffer, Per; Yilmaz, Mette; Falkmer, Ursula; Sorbye, Halfdan

    2015-04-01

    The use of postoperative adjuvant chemotherapy is controversial for rectal adenocarcinoma. Both international and national guidelines display a great span varying from recommending no adjuvant chemotherapy at all, over single drug 5-fluororuacil (5-FU), to combinations of 5-FU/oxaliplatin. A review of the literature was made identifying 24 randomized controlled trials on adjuvant treatment of rectal cancer based on about 10 000 patients. The trials were subdivided into a number of clinically relevant subgroups. As regards patients treated with preoperative (chemo) radiotherapy, four randomized studies were found where use of adjuvant chemotherapy showed no benefit in survival. Three trials were found in which a subset of patients received preoperative (chemo) radiotherapy. Two of these trials showed a statistically significant benefit of adjuvant chemotherapy. Twenty trials were identified in which the patients did not receive preoperative (chemo) radiotherapy, including five Asian studies in which a statistically significant benefit from adjuvant chemotherapy was reported. Most of the data found did not support the use of postoperative adjuvant chemotherapy for patients already treated with preoperative (chemo) radiotherapy. For patients not treated preoperatively, several studies support the use of single agent 5-FU chemotherapy. Treatment guidelines seem to differ according to if preoperative chemoradiation is considered of importance for use of adjuvant chemotherapy and if adjuvant colon cancer studies are considered transferrable to rectal cancer patients regardless of the molecular differences.

  19. Improved survival with early adjuvant chemotherapy after colonic resection for stage III colonic cancer

    DEFF Research Database (Denmark)

    Klein, Mads; Azaquoun, Najah; Jensen, Benny Vittrup

    2015-01-01

    BACKGROUND AND OBJECTIVES: In stage III colonic cancer, time from surgery to start of adjuvant chemotherapy may influence survival. In this study, we evaluated the effect of timing of adjuvant therapy on survival. METHODS: Database study from the Danish Colorectal Cancer Group's national database....... RESULTS: The final population included 1,827 patients scheduled for adjuvant chemotherapy. Adjuvant therapy started within 4 and 8 weeks improved survival when compared to start later than 8 weeks (HR [95%CI]: 1.7 [1.1-2.6]; P = 0.024 and 1.4 [1.07-1.8]; P = 0.013, respectively), whereas...

  20. Adjuvants and immunostimulants in fish vaccines: current knowledge and future perspectives.

    Science.gov (United States)

    Tafalla, Carolina; Bøgwald, Jarl; Dalmo, Roy A

    2013-12-01

    Vaccination is the most adequate method to control infectious diseases that threaten the aquaculture industry worldwide. Unfortunately, vaccines are usually not able to confer protection on their own; especially those vaccines based on recombinant antigens or inactivated pathogens. Therefore, the use of adjuvants or immunostimulants is often necessary to increase the vaccine efficacy. Traditional adjuvants such as mineral oils are routinely used in different commercial bacterial vaccines available for fish; however, important side effects may occur with this type of adjuvants. A search for alternative molecules or certain combinations of them as adjuvants is desirable in order to increase animal welfare without reducing protection levels. Especially, combinations that may target specific cell responses and thus a specific pathogen, with no or minor side effects, should be explored. Despite this, the oil adjuvants currently used are quite friendlier with respect to side effects compared with the oil adjuvants previously used. The great lack of fish antiviral vaccines also evidences the importance of identifying optimal combinations of a vaccination strategy with the use of a targeting adjuvant, especially for the promising fish antiviral DNA vaccines. In this review, we summarise previous studies performed with both traditional adjuvants as well as the most promising new generation adjuvants such as ligands for Toll receptors or different cytokines, focussing mostly on their protective efficacies, and also on what is known concerning their effects on the fish immune system when delivered in vivo.

  1. [Staphylococcus aureus prevalence among preschool- and school-aged pupils].

    Science.gov (United States)

    Pavilonyte, Zaneta; Kacerauskiene, Justina; Budryte, Brigita; Keizeris, Tadas; Junevicius, Jonas; Pavilonis, Alvydas

    2007-01-01

    To determine the prevalence and incidence of Staphylococcus aureus strains among preschool- and school-aged pupils and susceptibility of these strains to antimicrobial materials. A study of 243 preschool- and 300 school-aged pupils was conducted during 2003-2004. Identification of Staphylococcus aureus was made with plasmacoagulase and DNase tests. The resistance of Staphylococcus aureus to antibiotics, beta-lactamase activity, phagotypes, and phage groups were determined. The isolated Staphylococcus aureus strains were tested for resistance to methicillin by performing disc diffusion method using commercial discs (Oxoid) (methicillin 5 microg per disk and oxacillin 1 microg per disk). A total of 292 (53.8%) Staphylococcus aureus strains were isolated and identified (113 (46.5%) from preschool- and 179 (59.7%) from school-aged pupils). The prevalence of Staphylococcus aureus strains among preschool-aged pupils varied from 46.5% to 47%. It increased to 59.0% (P>0.05) among schoolchildren aged from 11 to 15 years and to 73.0% (Ppreschool-aged and four (2.2%) from school-aged pupils. The prevalence of Staphylococcus aureus strains with beta-lactamase activity increased from 70.7 to 76.6% in preschool-aged pupils, and it varied from 72.0 to 79.0% in school-aged pupils (P>0.05). Staphylococcus aureus strains of phage group II (32.2-43.4%) were prevailing; nontypable Staphylococcus aureus strains made up 19.2-33.6%. The prevalence of Staphylococcus aureus among preschool-aged children is 41.7 to 48.8%, and it increases among 9th-12th-grade pupils (73.0%, Ppreschool- and school-aged pupils. Pupils were colonized with methicillin-resistant Staphylococcus aureus strains belonging to phage group III phagotype 83A and 77.

  2. Staphylococcus aureus and Staphylococcus epidermidis Virulence Strains as Causative Agents of Persistent Infections in Breast Implants.

    Science.gov (United States)

    Chessa, Daniela; Ganau, Giulia; Spiga, Luisella; Bulla, Antonio; Mazzarello, Vittorio; Campus, Gian Vittorio; Rubino, Salvatore

    2016-01-01

    Staphylococcus epidermidis and Staphylococcus aureus are currently considered two of the most important pathogens in nosocomial infections associated with catheters and other medical implants and are also the main contaminants of medical instruments. However because these species of Staphylococcus are part of the normal bacterial flora of human skin and mucosal surfaces, it is difficult to discern when a microbial isolate is the cause of infection or is detected on samples as a consequence of contamination. Rapid identification of invasive strains of Staphylococcus infections is crucial for correctly diagnosing and treating infections. The aim of the present study was to identify specific genes to distinguish between invasive and contaminating S. epidermidis and S. aureus strains isolated on medical devices; the majority of our samples were collected from breast prostheses. As a first step, we compared the adhesion ability of these samples with their efficacy in forming biofilms; second, we explored whether it is possible to determine if isolated pathogens were more virulent compared with international controls. In addition, this work may provide additional information on these pathogens, which are traditionally considered harmful bacteria in humans, and may increase our knowledge of virulence factors for these types of infections.

  3. Staphylococcus aureus and Staphylococcus epidermidis Virulence Strains as Causative Agents of Persistent Infections in Breast Implants.

    Directory of Open Access Journals (Sweden)

    Daniela Chessa

    Full Text Available Staphylococcus epidermidis and Staphylococcus aureus are currently considered two of the most important pathogens in nosocomial infections associated with catheters and other medical implants and are also the main contaminants of medical instruments. However because these species of Staphylococcus are part of the normal bacterial flora of human skin and mucosal surfaces, it is difficult to discern when a microbial isolate is the cause of infection or is detected on samples as a consequence of contamination. Rapid identification of invasive strains of Staphylococcus infections is crucial for correctly diagnosing and treating infections. The aim of the present study was to identify specific genes to distinguish between invasive and contaminating S. epidermidis and S. aureus strains isolated on medical devices; the majority of our samples were collected from breast prostheses. As a first step, we compared the adhesion ability of these samples with their efficacy in forming biofilms; second, we explored whether it is possible to determine if isolated pathogens were more virulent compared with international controls. In addition, this work may provide additional information on these pathogens, which are traditionally considered harmful bacteria in humans, and may increase our knowledge of virulence factors for these types of infections.

  4. Stage IB endometrial cancer. Does lymphadenectomy replace adjuvant radiotherapy?

    Science.gov (United States)

    Bottke, Dirk; Wiegel, Thomas; Kreienberg, Rolf; Kurzeder, Christian; Sauer, Georg

    2007-11-01

    The role of surgical lymph node dissection and adjuvant radiation therapy (RT) in early stage endometrial cancer is no longer clearly defined. The increased appreciation of lymphadenectomy and the absence of survival advantage from adjuvant RT rise controversies how patients should adequately be treated in stage IB endometrial cancer. The aim of this review is to rule out the validity of either treatment option and determine which preference provides the best therapeutic benefit. Reports of relevant studies obtained from a search of PubMed and studies referenced in those reports were reviewed. Based on the available data in the literature, for stage IB grade 1 or 2, the risk of pelvic relapse is considered too low to justify pelvic RT. However, intravaginal RT (IVRT) should be recommended for those >or= 60 years old or with lymphovascular invasion (LVI). For patients with stage IB grade 3 (and IC all grades), the treatment recommendation is mainly based on whether surgical lymph node staging was performed. These patients have--without surgical lymph node staging--a high risk of pelvic recurrence and should therefore primarily undergo relaparotomy for lymphadenectomy or pelvic RT as second choice. If these patients had a surgical lymph node staging, then IVRT alone is a reasonable alternative to pelvic RT. Overall survival may not be the only ideal endpoint for stage IB endometrial cancer since causes of death are mostly other than endometrial cancer. Conventional pelvic RT may be overtreatment in some patients, in particular in those patients with a large number of negative lymph nodes after lymphadenectomy. However, negative surgical staging should not be understood as adjuvant RT can be omitted in all patients.

  5. Treg inducing adjuvants for therapeutic vaccination against chronic inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Chantal eKeijzer

    2013-08-01

    Full Text Available Many existing therapies in autoimmune diseases are based on systemic suppression of inflammation, the observed side effects illustrate the need for more specific interventions. Regulatory T cells (Treg are pivotal controllers of (autoaggressive immune responses, and decreased Treg numbers and/or functioning have been associated with autoimmune disease. Especially antigen-specific targeting of Treg would enable tailor made interventions, while obviating negative side effects of general immuno-suppression. Self-antigens that participate in inflammation, irrespective of the etiology of the different autoimmune diseases, are held to be candidate antigens for such interventions. Rather than tolerance induction to disease inciting self-antigens, which are frequently unknown, general self-antigens expressed at sites of inflammation would allow targeting of disease independent, but inflammatory-site specific, regulatory mechanisms. Preferably, such self-antigens should be abundantly expressed and up-regulated at the inflammatory site. Heat shock proteins show several of these characteristics.The development of antigen-specific Treg inducing vaccines is a major novel goal in the field of immunotherapy in autoimmune diseases. Progress is hampered by the lack of effective antigens and by the fact that other factors such as dose, route and the presence or absence of an adjuvant, turned out to be critical unknowns, with respect to effective induction of Treg. The use of a Treg inducing adjuvant might be required to achieve effective regulatory responses, in the case of ongoing inflammation. Future goals will be the optimization of natural Treg expansion (or the induction of adaptive Treg without loss of their suppressive function or the concomitant induction of non-regulatory T cells. Here, we discuss the potential use of protein/peptide-based vaccines combined with Treg inducing adjuvants for the development of therapeutic vaccines against chronic

  6. Adjuvant Ab Interno Tumor Treatment After Proton Beam Irradiation.

    Science.gov (United States)

    Seibel, Ira; Riechardt, Aline I; Heufelder, Jens; Cordini, Dino; Joussen, Antonia M

    2017-06-01

    This study was performed to show long-term outcomes concerning globe preservation in uveal melanoma patients after proton beam therapy with the main focus on outcomes according to different adjuvant ab interno surgical procedures. Retrospective cohort study. All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma between June 1998 and June 2015 were included. A total of 2499 patients underwent primary proton beam therapy, with local tumor control and globe preservation rates of 95.9% and 94.8% after 5 years, respectively. A total of 110 (4.4%) patients required secondary enucleation. Unresponsive neovascular glaucoma was the leading cause of secondary enucleation in 78 of the 2499 patients (3.1%). The 5-year enucleation-free survival rate was 94.8% in the endoresection group, 94.3% in the endodrainage group, and 93.5% in the comparator group. The log-rank test showed P = .014 (comparator group vs endoresection group) and P = .06 (comparator group vs endodrainage-vitrectomy group). Patients treated with endoresection or endodrainage-vitrectomy developed less radiation retinopathy (30.5% and 37.4% after 5 years, P = .001 and P = .048 [Kaplan-Meier], respectively) and less neovascular glaucoma (11.6% and 21.3% after 5 years, P = .001 and P = .01 [Kaplan-Meier], respectively) compared with the comparator group (52.3% radiation retinopathy and 57.8% neovascular glaucoma after 5 years). This study suggests that in larger tumors the enucleation and neovascular glaucoma rates might be reduced by adjuvant surgical procedures. Although endoresection is the most promising adjuvant treatment option, the endodrainage-vitrectomy is recommended in patients who are ineligible for endoresection. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Beryllium, an adjuvant that promotes gamma interferon production.

    Science.gov (United States)

    Lee, J Y; Atochina, O; King, B; Taylor, L; Elloso, M; Scott, P; Rossman, M D

    2000-07-01

    Beryllium is associated with a human pulmonary granulomatosis characterized by an accumulation of CD4(+) T cells in the lungs and a heightened specific lymphocyte proliferative response to beryllium (Be) with gamma interferon (IFN-gamma) release (i.e., a T helper 1 [Th1] response). While an animal model of Be sensitization is not currently available, Be has exhibited adjuvant effects in animals. The effects of Be on BALB/c mice immunized with soluble leishmanial antigens (SLA) were investigated to determine if Be had adjuvant activity for IFN-gamma production, an indicator of the Th1 response. In this strain of Leishmania-susceptible BALB/c mice, a Th2 response is normally observed after in vivo SLA sensitization and in vitro restimulation with SLA. If interleukin-12 (IL-12) is given during in vivo sensitization with SLA, markedly increased IFN-gamma production and decreased IL-4 production are detected. We show here that when beryllium sulfate (BeSO(4)) was added during in vivo sensitization of BALB/c mice with SLA and IL-12, significantly increased IFN-gamma production and decreased IL-4 production from lymph node and spleen cells were detected upon in vitro SLA restimulation. No specific responses were observed to Be alone. Lymph node and spleen cells from all mice proliferated strongly and comparably upon in vitro restimulation with SLA and with SLA plus Be; no differences were noted among groups of mice that received different immunization regimens. In vivo, when Be was added to SLA and IL-12 for sensitization of BALB/c mice, more effective control of Leishmania infection was achieved. This finding has implications for understanding not only the development of granulomatous reactions but also the potential for developing Be as a vaccine adjuvant.

  8. Methicillin-resistant Staphylococcus aureus laryngitis.

    Science.gov (United States)

    Liakos, Tracey; Kaye, Keith; Rubin, Adam D

    2010-09-01

    Infections due to methicillin-resistant Staphylococcus aureus (MRSA) have become more prevalent, in part because of the emergence and spread of community-acquired MRSA. This trend is particularly concerning because of the significant rates of morbidity and mortality associated with MRSA infections, and because MRSA strains are often resistant to many classes of antibiotics. Reports of infections of the head and neck, including wound infections, cellulitis, sinusitis, otitis media, and otitis externa, are well documented. However, to our knowledge, there have been no reports of bacterial laryngitis due to MRSA. We report the first published case of bacterial laryngitis caused by MRSA.

  9. Epidemiology of Staphylococcus aureus during space flight

    Science.gov (United States)

    Pierson, D. L.; Chidambaram, M.; Heath, J. D.; Mallary, L.; Mishra, S. K.; Sharma, B.; Weinstock, G. M.

    1996-01-01

    Staphylococcus aureus was isolated over 2 years from Space Shuttle mission crewmembers to determine dissemination and retention of bacteria. Samples before and after each mission were from nasal, throat, urine, and feces and from air and surface sampling of the Space Shuttle. DNA fingerprinting of samples by digestion of DNA with SmaI restriction endonuclease followed by pulsed-field gel electrophoresis showed S. aureus from each crewmember had a unique fingerprint and usually only one strain was carried by an individual. There was only one instance of transfer between crewmembers. Strains from interior surfaces after flight matched those of crewmembers, suggesting microbial fingerprinting may have forensic application.

  10. Cell-surface hydrophobicity of Staphylococcus saprophyticus.

    Science.gov (United States)

    Schneider, P. F.; Riley, T. V.

    1991-01-01

    The cell-surface hydrophobicity of 100 urinary isolates of Staphylococcus saprophyticus, cultured from symptomatic females in the general population, was assessed using a two-phase aqueous:hydrocarbon system. Relatively strong cell-surface hydrophobicity was exhibited by 79 isolates using the criteria employed, while only 2 of the remaining 21 isolates failed to demonstrate any detectable hydrophobicity. Cell-surface hydrophobicity may be a virulence factor of S. saprophyticus, important in adherence of the organism to uroepithelia. Additionally, the data support the concept that cell-surface hydrophobicity may be a useful predictor of clinical significance of coagulase-negative staphylococci isolated from clinical sources. PMID:1993454

  11. METHODS COMPARISON FOR ENTEROTOXIC STAPHYLOCOCCUS AUREUS CHARACTERIZATION

    Directory of Open Access Journals (Sweden)

    L. Decastelli

    2011-01-01

    Full Text Available The aim of this study was to compare two different methods for enterotoxic Staphylococcus aureus characterization. 110 S.aureus strains was isolated from foods and tested with ELISA method able to detect toxins type A to E in culture medium and PCR protocols able to detect the presence of genes (sea to see; seg to sej; sep; ser encoding for staphylococcal enterotoxins. 27 strains came out positive with ELISA; 68 resulted to have at least one encoding gene. sea and ser genes were detected respectively in 29,1% and 27,3% of strains.

  12. Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection.

    Directory of Open Access Journals (Sweden)

    Aisling F Brown

    Full Text Available Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI. These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans.

  13. Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection

    Science.gov (United States)

    Lalor, Stephen J.; Leech, John M.; O’Keeffe, Kate M.; Mac Aogáin, Micheál; O’Halloran, Dara P.; Lacey, Keenan A.; Tavakol, Mehri; Hearnden, Claire H.; Fitzgerald-Hughes, Deirdre; Humphreys, Hilary; Fennell, Jérôme P.; van Wamel, Willem J.; Foster, Timothy J.; Geoghegan, Joan A.; Lavelle, Ed C.; Rogers, Thomas R.; McLoughlin, Rachel M.

    2015-01-01

    Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans. PMID:26539822

  14. Modulation of drug resistance in Staphylococcus aureus by a kaempferol glycoside from Herissantia tiubae (Malvaceae).

    Science.gov (United States)

    Falcão-Silva, Vivyanne S; Silva, Davi A; Souza, Maria de Fátima V; Siqueira-Junior, José P

    2009-10-01

    In an ongoing project to evaluate natural compounds isolated from plants from the Brazilian biodiversity as modulators of antibiotic resistance, kaempferol-3-O-beta-d-(6''-E-p-coumaroyl) glucopyranoside (tiliroside), isolated from Herissantia tiubae (Malvaceae) was investigated using the strain SA-1199B of Staphylococcus aureus, which overexpresses the norA gene encoding the NorA efflux protein which extrudes hydrophilic fluorquinolones and some biocides, such as benzalkonium chloride, cetrimide, acriflavine and ethidium bromide. The minimum inhibitory concentrations (MICs) of the antibiotics and biocides were determined by the microdilution assay in the absence and in the presence of sub-inhibitory concentration of tiliroside. Although tiliroside did not display relevant antibacterial activity (MIC = 256 microg/mL), it modulated the activity of antibiotics, i.e. in combination with antibiotics a reduction in the MIC was observed for norfloxacin (16-fold), ciprofloxacin (16-fold), lomefloxacin (four-fold) and ofloxacin (two-fold), and an impressive reduction in the MICs for the biocides (up to 128-fold). The results presented here represent the first report of a kaempferol glycoside as a putative efflux pump inhibitor in bacteria. The present finding indicates that H. tiubae (and broadly Malvaceae) could serve as a source of plant-derived natural products that modulate bacterial resistance, i.e. a source of potential adjuvants of antibiotics.

  15. Amidase, a cell wall hydrolase, elicits protective immunity against Staphylococcus aureus and S. epidermidis.

    Science.gov (United States)

    Nair, Nisha; Vinod, Vivek; Suresh, Maneesha K; Vijayrajratnam, Sukhithasri; Biswas, Lalitha; Peethambaran, Reshmi; Vasudevan, Anil Kumar; Biswas, Raja

    2015-01-01

    The morbidity and the mortality associated with Staphylococcus aureus and S. epidermidis infections have greatly increased due to the rapid emergence of highly virulent and antibiotic resistant strains. Development of a vaccine-based therapy is greatly desired. However, no staphylococcal vaccine is available till date. In this study, we have identified Major amidase (Atl-AM) as a prime candidate for future vaccine design against these pathogens. Atl-AM is a multi-functional non-covalently cell wall associated protein which is involved in staphylococcal cell separation after cell division, host extracellular matrix adhesion and biofilm formation. Atl-AM is present on the surface of diverse S. aureus and S. epidermidis strains. When used in combination with Freund's adjuvant, Atl-AM generated a mixed Th1 and Th2 mediated immune response which is skewed more toward Th1; and showed increased production of opsonophagocytic IgG2a and IgG2b antibodies. Significant protective immune response was observed when vaccinated mice were challenged with S. aureus or S. epidermidis. Vaccination prevented the systemic dissemination of both organisms. Our results demonstrate the remarkable efficacy of Atl-AM as a vaccine candidate against both of these pathogens.

  16. Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection.

    LENUS (Irish Health Repository)

    Brown, Aisling F

    2015-01-01

    Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans.

  17. Caffeine as an opioid analgesic adjuvant in fibromyalgia

    OpenAIRE

    Scott JR; Hassett AL; Brummett CM; Harris RE; Clauw DJ; Harte SE

    2017-01-01

    J Ryan Scott,1 Afton L Hassett,1 Chad M Brummett,1 Richard E Harris,1,2 Daniel J Clauw,1,2 Steven E Harte1,2 1Chronic Pain and Fatigue Research Center, Department of Anesthesiology, 2Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA Background: Caffeine’s properties as an analgesic adjuvant with nonsteroidal anti-inflammatory drugs/acetaminophen are well documented. However, little clinical research has explored ca­ffeine&a...

  18. Radiation Recall Reaction Induced by Adjuvant Trastuzumab (Herceptin

    Directory of Open Access Journals (Sweden)

    Caroline Chung

    2009-01-01

    trastuzumab (Herceptin administration, there has been no published case of radiation recall reaction associated with trastuzumab. This case describes a clinical presentation consistent with a radiation recall reaction following administration of adjuvant trastuzumab after neoadjuvant FEC-D chemotherapy and locoregional radiotherapy for HER2-positive, locally advanced breast cancer in a premenopausal woman. Although the mechanism and etiology of radiation recall dermatitis remain unclear, this case raises further hypotheses regarding a possible drug dose-dependence and possible predisposing risk factor for the development of radiation recall reactions.

  19. Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

    Directory of Open Access Journals (Sweden)

    Ghosn Marwan G

    2010-06-01

    Full Text Available Abstract Background Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. Methods 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. Results This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96% had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy was completed by 22 patients (91.7%. Only 7 patients (36.8% completed the total planned courses of chemotherapy. 2 local relapses (10%, 2 regional relapses (10% and 2 distant relapses (10% were recorded. Time to progression has not been reached. 9 patients (37.5% died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8% with 9 (36% patients suffering grade 3 or 4 toxicity and 5 patients (20% suffering from grade 3 or 4 neutropenia. 4 (17% patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17% and 1 patient developed a deep venous thrombosis and a pulmonary embolus. Conclusions Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the

  20. [Value of adjuvant physiotherapy in postoperative pain management].

    Science.gov (United States)

    Bullmann, V; Weber, T P; Kienle, B; Schulte, T L

    2008-10-01

    In times of limited financial and human resources the application of adjuvant physiotherapy postoperatively in orthopaedic patients requires reevaluation. In the early postoperative course physiotherapy improves the patients' mobility. However, it is not able to reduce the need for pain medication. It is intended to minimize complications and to mobilize and motivate the patients early. In contrast, massages are of minor importance in the immediate postoperative course and are applied only in a few selected cases. Cryotherapy plays a major role especially after shoulder and knee surgery. On the other hand, transcutaneous electrical nerve stimulation (TENS) and acupuncture are applied only in selected patients after orthopaedic surgery, e.g., after limb amputation.

  1. Incidence of inducible clindamycin resistance in Staphylococcus pseudintermedius from dogs.

    Science.gov (United States)

    Gold, Randi M; Lawhon, Sara D

    2013-12-01

    Clindamycin is increasingly used to treat canine pyoderma. Eight of 608 Staphylococcus pseudintermedius isolates were positive for inducible clindamycin resistance by double-disk diffusion testing and PCR detection of ermB. Staphylococcus pseudintermedius isolates that are erythromycin resistant but clindamycin susceptible by in vitro antimicrobial susceptibility testing should be tested for inducible clindamycin resistance.

  2. Incidence of Inducible Clindamycin Resistance in Staphylococcus pseudintermedius from Dogs

    OpenAIRE

    Gold, Randi M.; Lawhon, Sara D.

    2013-01-01

    Clindamycin is increasingly used to treat canine pyoderma. Eight of 608 Staphylococcus pseudintermedius isolates were positive for inducible clindamycin resistance by double-disk diffusion testing and PCR detection of ermB. Staphylococcus pseudintermedius isolates that are erythromycin resistant but clindamycin susceptible by in vitro antimicrobial susceptibility testing should be tested for inducible clindamycin resistance.

  3. Exudative epidermitis in pigs caused by toxigenic Staphylococcus chromogenes

    DEFF Research Database (Denmark)

    Andresen, Lars Ole; Ahrens, Peter; Daugaard, Lise

    2005-01-01

    Staphylococcus chromogenes is closely related to Staphylococcus hyicus, which is recognised as the causative agent of exudative epidermitis (EE) in pigs. S. chromogenes is part of the normal skin flora of pigs, cattle and poultry and has so far been considered non-pathogenic to pigs. A strain of S...

  4. Utilization and impact of adjuvant therapy in anaplastic oligodendroglioma: an analysis on 1692 patients.

    Science.gov (United States)

    Shin, Jacob Y; Diaz, Aidnag Z

    2016-09-01

    The aim of this study was to determine the utilization rates and impact of adjuvant therapy on overall survival (OS) for anaplastic oligodendroglioma (AO). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 1692 patients with AO who underwent surgery were identified. 945 (55.9 %) received adjuvant radiotherapy with concomitant chemotherapy (chemoRT), 102 (6.0 %) adjuvant radiotherapy (RT) sequentially followed by chemotherapy, 244 (14.4 %) adjuvant RT alone, and 401 (23.7 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 vs. 2004-2008 (p 70 vs. <70 (p = 0.018), had private insurance vs. Medicaid vs. no insurance (p < 0.001), or had median income ≥$63,000 vs. <$63,000 (p = 0.014). Those who received adjuvant chemoRT (concomitant or sequential) had significantly better 5-year OS than those who received adjuvant RT alone or no adjuvant therapy (59.8 % vs. 65.0 % vs. 44.9 % vs. 45.6 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age. There was no difference in OS when comparing concomitant chemoRT to sequential RT and chemotherapy (p = 0.481). On multivariate analysis, receipt of adjuvant chemoRT (concomitant or sequential) remained an independent prognostic factor for improved OS. Adjuvant chemoRT (concomitant or sequential) is an independent prognostic factor for improved OS in anaplastic oligodendroglioma and should be considered for all clinically suitable patients who have undergone surgery for the disease.

  5. Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ohri, Nitin, E-mail: ohri.nitin@gmail.com [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Garg, Madhur K. [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Aparo, Santiago; Kaubisch, Andreas [Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Tome, Wolfgang [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kennedy, Timothy J. [Department of Surgical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kalnicki, Shalom; Guha, Chandan [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)

    2013-06-01

    Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy.

  6. Survival of Staphylococcus aureus on fomites.

    Science.gov (United States)

    Cuesta, Alicia; Nastri, Natalia; Bernat, Maria; Brusca, Maria; Turcot, Liliana; Nastri, Maria; Rosa, Alcira C

    2008-01-01

    The aim of this study was to evaluate duration of survival of Staphylococcus aureus on contaminated standardized fomites, such as sterilization paper (SP) and polyester previously sterilized in a steam autoclave, and to determine the potential inhibitory effects of the substrates (fabrics used to manufacture garments and special wrapping paper used in the dental setting) using the bacteriostasis test. The test was performed on two types of sterile standardized samples (T1 and T2). Sterility of the samples was validated following the protocol in use at the Department of Microbiology, after which the samples were inoculated with 50 microl of a calibrated suspension of Staphylococcus aureus (reference strain ATCC 25923) in the exponential growth phase, in a final concentration of 10(7) cfu/ml and 10(6) cfu/ml). The samples were incubated at 27 degrees C and survival and concentration of microorganisms attached to the surface of the substrates was determined at the following experimental time points: immediately post-contamination, and 3 hours, 24 hours, 3 days, and 7 days post-contamination. Recovery was determined and expressed as a percentage; the bacteriostasis test was performed and showed negative results. Our results suggest that the quantity of recovered microorganisms varies according to the type of substrate and that there is a relation between survival and incubation time of the inoculated substrate serving as an artificial niche.

  7. Reclassification of Staphylococcus jettensis De Bel et al. 2013 as Staphylococcus petrasii subsp. jettensis subsp. nov. and emended description of Staphylococcus petrasii Pantucek et al. 2013.

    Science.gov (United States)

    De Bel, Annelies; Švec, Pavel; Petráš, Petr; Sedláček, Ivo; Pantůček, Roman; Echahidi, Fedoua; Piérard, Denis; Vandamme, Peter

    2014-12-01

    The type and clinical strains of two recently described coagulase-negative species of the genus Staphylococcus, Staphylococcus petrasii and Staphylococcus jettensis, were compared using dnaJ, tuf, gap, hsp60 and rpoB gene sequences, DNA-DNA hybridization, ribotyping, repetitive sequence-based PCR fingerprinting and extensive biochemical characterization. Based on the results, the species description of S. petrasii has been emended and S. jettensis should be reclassified as a novel subspecies within S. petrasii for which the name Staphylococcus petrasii subsp. jettensis subsp. nov. is proposed. The type strain is SEQ110(T) ( = LMG 26879(T) = CCUG 62657(T) = DSM 26618(T) = CCM 8494(T)). © 2014 IUMS.

  8. Efektivitas Ekstrak Daun Jambu Biji Buah Putih Terhadap Pertumbuhan Staphylococcus aureus Dari Abses Dan Staphylococcus aureus (ATCC® 29213™)

    OpenAIRE

    Sinurat, Jojor

    2016-01-01

    Daun jambu biji mengandung senyawa aktif seperti tanin, triterpenoid, flavonoid, saponin yang mempunyai efek antibakteri. Mekanisme tanin sebagai antibakteri dengan mengkerutkan dinding sel dan membran sel, inaktivasi enzim, inaktivasi fungsi materi genetik bakteri. Flavonoid merusak sel bakteri, denaturasi protein, inaktivasi enzim dan menyebabkan lisis. Triterpenoid dan saponin menghambat pertumbuhan Staphylococcus aureus dengan cara merusak struktur membran sel. Staphylococcus aureus adala...

  9. Preparation and evaluation of functional foods in adjuvant arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Al-Okbi, S. Y.; Mohamed, D. A.

    2012-07-01

    Adjuvant arthritis is an animal model that closely resembles rheumatoid arthritis in humans. It is a successful working model used to study new anti-inflammatory agents. In previous studies (animal and clinical) we have shown that evening primrose oil, fish oil and the methanol extract of date fruits and fenugreek seeds have anti-inflammatory activity and that the methanol extract of dates has an antioxidant effect. Based on these studies, the aim of the present study was to prepare 7 functional foods containing such bioactive fractions separately or in combination and to evaluate them in adjuvant arthritis in rats, study the stability of bioactive ingredients and evaluate their sensory properties. The studied biochemical parameters were erythrocyte sedimentation rate, erythrocyte superoxide dismutase, glutathione peroxidase and plasma copper, zinc and interlukin 2. Nutritional parameters, including body weight gain, food intake and food efficiency ratio were monitored during the feeding of the functional foods. The bioactive ingredients assessed were total phenolic contents and fatty acids. The results showed improvement in the biochemical parameters, body weight gain and food efficiency ratio of arthritic rats fed on the functional foods with different degrees. All the prepared functional foods were sensory accepted. The active ingredients showed stability during storage. In conclusion, all the tested functional foods showed promising antiinflammatory activity and were determined to be acceptable through sensory evaluation which means that their potential beneficial use as dietary supplements in rheumatoid arthritis patients may be recommended. (Author) 42 refs.

  10. Innate Immune Signaling by, Genetic Adjuvants for, DNA Vaccination

    Directory of Open Access Journals (Sweden)

    Kouji Kobiyama

    2013-07-01

    Full Text Available DNA vaccines can induce both humoral and cellular immune responses. Although some DNA vaccines are already licensed for infectious diseases in animals, they are not licensed for human use because the risk and benefit of DNA vaccines is still controversial. Indeed, in humans, the immunogenicity of DNA vaccines is lower than that of other traditional vaccines. To develop the use of DNA vaccines in the clinic, various approaches are in progress to enhance or improve the immunogenicity of DNA vaccines. Recent studies have shown that immunogenicity of DNA vaccines are regulated by innate immune responses via plasmid DNA recognition through the STING-TBK1 signaling cascade. Similarly, molecules that act as dsDNA sensors that activate innate immune responses through STING-TBK1 have been identified and used as genetic adjuvants to enhance DNA vaccine immunogenicity in mouse models. However, the mechanisms that induce innate immune responses by DNA vaccines are still unclear. In this review, we will discuss innate immune signaling upon DNA vaccination and genetic adjuvants of innate immune signaling molecules.

  11. Effects of 3% trehalose as an adjuvant treatment after LASIK

    Science.gov (United States)

    Mateo Orobia, Antonio J; Casas Pascual, Paula; Cristóbal Bescós, José Á; Perez García, Diana; Peiro Embid, Carlos; del Buey Sayas, M Ángeles; Korobko Kulikova, Valentyna; Lafuente Ojeda, Noelia

    2017-01-01

    Purpose To evaluate the effect of 3% trehalose as an adjuvant in the standard treatment after laser-assisted in situ keratomileusis. Design Interventional prospective comparative single-blind study. Setting Department of Ophthalmology, Hospital Quirón Zaragoza, Spain. Methods A total of 26 eyes (13 patients) were included, of which 12 eyes (group 1) received conventional treatment with lubricant drops of hyaluronic acid (0.15%) and 14 eyes (group 2) received, additionally, an ophthalmic solution of 3% trehalose. Pre- and postoperative quality-of-life tests and vital stains, tear breakup time, and osmolarity measurements were made. Results We obtained statistically significant differences between the groups in the Symptom Assessment in Dry Eye test in all visits with respect to severity, and in the postoperative day 1 visit with respect to frequency, in all cases favoring the trehalose treatment. The values of osmolarity were not significantly different between groups. However, we did find significant differences in the Oxford scale in day 90 for the trehalose treatment (P<0.001), and in the National Eye Institute scale in day 30 (P=0.02). Conclusion The results of this exploratory study indicate that the adjuvant treatment with 3% trehalose could be superior with respect to the standard treatment, with improvements in the objective and subjective parameters of tear quality. PMID:28243058

  12. Lipopolysaccharide contamination in intradermal DNA vaccination: toxic impurity or adjuvant?

    Science.gov (United States)

    van den Berg, Joost H; Quaak, Susanne G L; Beijnen, Jos H; Hennink, Wim E; Storm, Gert; Schumacher, Ton N; Haanen, John B A G; Nuijen, Bastiaan

    2010-05-05

    Lipopolysaccharides (LPS) are known both as potential adjuvants for vaccines and as toxic impurity in pharmaceutical preparations. The aim of this study was to assess the role of LPS in intradermal DNA vaccination administered by DNA tattooing. Mice were vaccinated with a model DNA vaccine (Luc-NP) with an increasing content of residual LPS. The effect of LPS on systemic toxicity, antigen expression and cellular immunity was studied. The presence of LPS in the DNA vaccine neither induced systemic toxicity (as reflected by IL-6 concentration in serum), nor influenced antigen expression (measured by intravital imaging). Higher LPS contents however, appeared to be associated with an elevated cytotoxic T-lymphocyte (CTL) response but without reaching statistical significance. Interestingly, the DNA tattoo procedure by itself was shown to induce a serum cytokine response that was at least as potent as that induced by parenteral LPS administration. LPS does not show toxicity in mice vaccinated by DNA tattooing at dose levels well above those encountered in GMP-grade DNA preparations. Thus, residual LPS levels in the pharmaceutical range are not expected to adversely affect clinical outcome of vaccination trials and may in fact have some beneficial adjuvant effect. The observed pro-inflammatory effects of DNA tattoo may help explain the high immunogenicity of this procedure. Copyright 2009 Elsevier B.V. All rights reserved.

  13. Use of melatonin as an adjuvant therapy in neonatal sepsis.

    Science.gov (United States)

    El Frargy, M; El-Sharkawy, H M; Attia, G F

    2015-01-01

    The objective of this study is to evaluate the therapeutic efficacy of melatonin as an adjuvant therapy in treating neonatal sepsis. A prospective clinical trial study was conducted on 50 infants with neonatal sepsis diagnosed on the basis of both clinical and laboratory criteria. Enrolled infants were divided into two groups. Intervention group (n = 25) received melatonin and antibiotics, while the control group (n = 25) was treated with antibiotics only. Melatonin was administered as a single oral dose of 20 mg and antibiotics were administered according to a standard protocol. Both groups were compared using a predefined sepsis score utilizing both clinical and laboratory parameters. There was no significant difference in sepsis score between both groups before starting melatonin (p-value = 0.99), while there was significant difference in sepsis score between groups after 24 hours, 48 hours and 72 hours of starting melatonin with (p-value = 0.008, 0.006 and 0.002, respectively). There was significant improvement sepsis score in both groups with more improvement of sepsis score in the intervention group. Administration of melatonin as an adjuvant therapy in the treatment of neonatal sepsis is associated with improvement of clinical and laboratory outcomes.

  14. Ethoxylated rapeseed oil derivatives as novel adjuvants for herbicides.

    Science.gov (United States)

    Müller, Thomas; Brancq, Bernard; Milius, Alain; Okori, Nathalie; Vaille, Claude; Gauvrit, Christian

    2002-12-01

    Ethoxylates of rapeseed oil and of methylated rapeseed oil were synthesized and tested as adjuvants for 2,4-D and phenmedipham. Provided they had less than 6 units of ethylene oxide (EO), 1.0 to 10 g litre(-1) ethoxylates in water induced droplet spreading on barley leaves. In an acetone-based medium all derivatives strongly promoted the foliar uptake of 2,4-D, with no clear influence of the ethoxylation degree. In the same medium there was a negative influence of ethoxylate chain length on the foliar uptake of phenmedipham. In a water-based medium, phenmedipham applied with rapeseed oil emulsified with ethoxylated (20 EO) rapeseed oil displayed uptake rates close to a commercial preparation. The same was true for phenmedipham applied with ethoxylated (2 EO) methylated rapeseed oil. In bioassays, phenmedipham prepared with methylated rapeseed oil emulsified with ethoxylated (20 EO) rapeseed oil was as efficacious on barley as a commercial formulation. The same was true for phenmedipham prepared with ethoxylated (2 EO) methylated rapeseed oil. However, neither rapeseed oil nor methylated rapeseed oil emulsified with ethoxylated (2 EO) methylated rapeseed oil conferred good efficacy to phenmedipham. Hence, ethoxylated rapeseed oil derivatives are promising adjuvants or formulants for herbicides.

  15. Effect of ascorbic acid and other adjuvants on manganese absorption

    Energy Technology Data Exchange (ETDEWEB)

    Papaioannou, R.; Sohler, A.; Pfeiffer, C.C.

    1986-03-01

    Animal experiments have demonstrated that manganese is poorly absorbed from the gut and that it is rapidly removed from the blood by liver uptake and bilary excretion. Zinc supplements which are readily absorbed can induce a Mn deficiency so that Mn supplementation is necessary. Supplementation with a diet rich in Mn (high in legumes, nuts, whole grains, tea) failed to influence blood Mn levels. The present study is concerned with the route of Mn administration and the effect of various adjuvants on the absorption and availability of Mn. Oral and sublingual administration of 20 mgs of Mn as the chloride failed to elicit a blood level rise. A rise was noted after the intramuscular injection of 2.5 mgs Mn as Mn Cl/sub 2/. Blood Mn levels rose to a maximum in thirty minutes and were back to basal levels within three hours. Adjuvants such as arginine, lecithin, taurine, biotin, bioflavinoids, were tested with essentially negative results. Mn orotate also failed to increase absorption. Oral absorption was obtained with ascorbic acid in five female subjects when 20 mgs of Mn as the chloride was given orally with 1 gm of ascorbic acid. This effect was not observed with five male subjects. A 30-40% increase in blood Mn after 2 hours was found when Mn was administered with ascorbic acid in the female subjects.

  16. Mucosal and systemic adjuvant activity of alphavirus replicon particles

    Science.gov (United States)

    Thompson, Joseph M.; Whitmore, Alan C.; Konopka, Jennifer L.; Collier, Martha L.; Richmond, Erin M. B.; Davis, Nancy L.; Staats, Herman F.; Johnston, Robert E.

    2006-03-01

    Vaccination represents the most effective control measure in the fight against infectious diseases. Local mucosal immune responses are critical for protection from, and resolution of, infection by numerous mucosal pathogens. Antigen processing across mucosal surfaces is the natural route by which mucosal immunity is generated, as peripheral antigen delivery typically fails to induce mucosal immune responses. However, we demonstrate in this article that mucosal immune responses are evident at multiple mucosal surfaces after parenteral delivery of Venezuelan equine encephalitis virus replicon particles (VRP). Moreover, coinoculation of null VRP (not expressing any transgene) with inactivated influenza virions, or ovalbumin, resulted in a significant increase in antigen-specific systemic IgG and fecal IgA antibodies, compared with antigen alone. Pretreatment of VRP with UV light largely abrogated this adjuvant effect. These results demonstrate that alphavirus replicon particles possess intrinsic systemic and mucosal adjuvant activity and suggest that VRP RNA replication is the trigger for this activity. We feel that these observations and the continued experimentation they stimulate will ultimately define the specific components of an alternative pathway for the induction of mucosal immunity, and if the activity is evident in humans, will enable new possibilities for safe and inexpensive subunit and inactivated vaccines. vaccine vector | Venezuelan equine encephalitis virus | viral immunology | RNA virus

  17. Innate Immune Signaling by, and Genetic Adjuvants for DNA Vaccination.

    Science.gov (United States)

    Kobiyama, Kouji; Jounai, Nao; Aoshi, Taiki; Tozuka, Miyuki; Takeshita, Fumihiko; Coban, Cevayir; Ishii, Ken J

    2013-01-01

    DNA vaccines can induce both humoral and cellular immune responses. Although some DNA vaccines are already licensed for infectious diseases in animals, they are not licensed for human use because the risk and benefit of DNA vaccines is still controversial. Indeed, in humans, the immunogenicity of DNA vaccines is lower than that of other traditional vaccines. To develop the use of DNA vaccines in the clinic, various approaches are in progress to enhance or improve the immunogenicity of DNA vaccines. Recent studies have shown that immunogenicity of DNA vaccines are regulated by innate immune responses via plasmid DNA recognition through the STING-TBK1 signaling cascade. Similarly, molecules that act as dsDNA sensors that activate innate immune responses through STING-TBK1 have been identified and used as genetic adjuvants to enhance DNA vaccine immunogenicity in mouse models. However, the mechanisms that induce innate immune responses by DNA vaccines are still unclear. In this review, we will discuss innate immune signaling upon DNA vaccination and genetic adjuvants of innate immune signaling molecules.

  18. Feasibility of a randomized trial on adjuvant radio-iodine therapy in differentiated thyroid cancer.

    NARCIS (Netherlands)

    Dragoiescu, C.; Hoekstra, O.S.; Kuik, D.J.; Lips, P.T.A.M.; Plaizier, MA; Rodrigus, PT; Huijsmans, DA; Ribot, JG; Kuijpens, J; Coebergh, J.W.; Teule, G.J.J.

    2003-01-01

    BACKGROUND: Justification for adjuvant radio-iodine (I-131) therapy in differentiated thyroid cancer (DTC) is purely based on retrospective data. This is true for ablative therapy and even more so for high-dosage adjuvant schedules. Randomized trials on the latter application are considered impossib

  19. High-risk endometrial cancer may be benefit from adjuvant radiotherapy plus chemotherapy.

    Science.gov (United States)

    Miao, Jin-Wei; Deng, Xiao-Hong

    2012-12-01

    To present patterns of practice and outcomes in the adjuvant treatment of intermediate- and high-risk endometrial cancer. Retrospective data on 224 women with intermediate-risk and high-risk endometrial cancer from 1999 to 2006 were reviewed. All patients underwent surgical staging. Patterns of adjuvant treatment, consisting of pelvic radiotherapy, chemotherapy, and radiotherapy plus chemotherapy, were assessed. The 3- and 5-year disease-specific survival (DSS) rates were calculated using the Kaplan-Meier method. The difference in 5-year DSS rate was statistically significant between adjuvant group and non-adjuvant group (80.65% vs. 63.80%, P=0.040). In 110 high-risk patients who underwent adjuvant treatment, both 5-year DSS rate and recurrent rate were significantly different in combined radiotherapy and chemotherapy group compared with radiotherapy alone and chemotherapy alone groups (DSS rate, P=0.049; recurrent rate, P=0.047). In 83 intermediate-risk women who underwent adjuvant treatment, there was no significant difference in 5-year DSS rate and recurrence rate among the combined radiotherapy and chemotherapy, radiotherapy alone and chemotherapy alone groups (DSS rate, P=0.776; recurrent rate, P=0.937). Adjuvant radiotherapy plus chemotherapy is associated with a higher 5-year DSS rate and lower recurrence rate compared with radiotherapy alone and chemotherapy alone in high-risk endometrial cancer patients. Patients with intermediate-risk endometrial cancer may be not likely to benefit from adjuvant combined radiotherapy and chemotherapy.

  20. Prognostic role of adjuvant radiotherapy in triple-negative breast cancer : A historical cohort study

    NARCIS (Netherlands)

    Bhoo Pathy, Nirmala; Verkooijen, Helena M.; Wong, Fuh-Yong; Pignol, Jean-Philippe; Kwong, Ava; Tan, Ern-Yu; Taib, Nur Aishah; Nei, Wen-Long; Ho, Gwo-Fuang; Tan, Benita; Chan, Patrick; Lee, Soo-Chin; Hartman, Mikael; Yip, Cheng-Har; Dent, Rebecca

    2015-01-01

    The value of adjuvant radiotherapy in triple-negative breast cancer (TNBC) is currently debated. We assessed the association between adjuvant radiotherapy and survival in a large cohort of Asian women with TNBC. Women diagnosed with TNBC from 2006 to 2011 in five Asian centers (N=1,138) were include

  1. Different human vaccine adjuvants promote distinct antigen-independent immunological signatures tailored to different pathogens.

    Science.gov (United States)

    Knudsen, Niels Peter H; Olsen, Anja; Buonsanti, Cecilia; Follmann, Frank; Zhang, Yuan; Coler, Rhea N; Fox, Christopher B; Meinke, Andreas; D'Oro, Ugo; Casini, Daniele; Bonci, Alessandra; Billeskov, Rolf; De Gregorio, Ennio; Rappuoli, Rino; Harandi, Ali M; Andersen, Peter; Agger, Else Marie

    2016-01-21

    The majority of vaccine candidates in clinical development are highly purified proteins and peptides relying on adjuvants to enhance and/or direct immune responses. Despite the acknowledged need for novel adjuvants, there are still very few adjuvants in licensed human vaccines. A vast number of adjuvants have been tested pre-clinically using different experimental conditions, rendering it impossible to directly compare their activity. We performed a head-to-head comparison of five different adjuvants Alum, MF59®, GLA-SE, IC31® and CAF01 in mice and combined these with antigens from M. tuberculosis, influenza, and chlamydia to test immune-profiles and efficacy in infection models using standardized protocols. Regardless of antigen, each adjuvant had a unique immunological signature suggesting that the adjuvants have potential for different disease targets. Alum increased antibody titers; MF59® induced strong antibody and IL-5 responses; GLA-SE induced antibodies and Th1; CAF01 showed a mixed Th1/Th17 profile and IC31® induced strong Th1 responses. MF59® and GLA-SE were strong inducers of influenza HI titers while CAF01, GLA-SE and IC31® enhanced protection to TB and chlamydia. Importantly, this is the first extensive attempt to categorize clinical-grade adjuvants based on their immune profiles and protective efficacy to inform a rational development of next generation vaccines for human use.

  2. The importance of adjuvant formulation in the development of a TB vaccine

    Science.gov (United States)

    Baldwin, Susan L.; Bertholet, Sylvie; Reese, Valerie A.; Ching, Lance K.; Reed, Steven G.; Coler, Rhea N.

    2011-01-01

    An effective protein based vaccine for tuberculosis (TB) will require a safe and effective adjuvant. There are few adjuvants in approved human vaccines, including Alum and the oil-in-water (o/w) based emulsions MF59 (Novartis Vaccines and Diagnostics), AS03 and AS04 (GlaxoSmith Kline Biologics, GSK) AF03 (Sanofi), and liposomes (Crucell). When used with pure, defined proteins, both Alum and emulsion adjuvants are effective at inducing primarily humoral responses. One of the newest adjuvants in approved products is AS04, which combines monophosphoryl lipid A (MPL), a TLR-4 agonist, with Alum. In this study, we compared two adjuvants, an o/w emulsion (SE), and an o/w emulsion incorporating glucopyranosyl lipid adjuvant (GLA), a synthetic TLR-4 agonist, together with a recombinant protein, ID93. Both the emulsion SE and GLA-SE adjuvants induce potent cellular responses in combination with ID93 in mice. ID93/SE induced Th2 biased immune responses, whereas ID93/GLA-SE induced multifunctional CD4+ Th1 cell responses (IFN-γ, TNF-α and IL-2). The ID93/GLA-SE vaccine candidate induced significant protection in mice and guinea pigs, whereas no protection was observed with ID93/SE, as assessed by reductions in bacterial burden, survival, and pathology. These results highlight the importance of properly formulating subunit vaccines with effective adjuvants for use against TB. PMID:22291184

  3. The importance of adjuvant formulation in the development of a tuberculosis vaccine.

    Science.gov (United States)

    Baldwin, Susan L; Bertholet, Sylvie; Reese, Valerie A; Ching, Lance K; Reed, Steven G; Coler, Rhea N

    2012-03-01

    An effective protein-based vaccine for tuberculosis will require a safe and effective adjuvant. There are few adjuvants in approved human vaccines, including alum and the oil-in-water-based emulsions MF59 (Novartis Vaccines and Diagnostics), AS03 and AS04 (GlaxoSmithKline Biologics), AF03 (Sanofi), and liposomes (Crucell). When used with pure, defined proteins, both alum and emulsion adjuvants are effective at inducing primarily humoral responses. One of the newest adjuvants in approved products is AS04, which combines monophosphoryl lipid A, a TLR-4 agonist, with alum. In this study, we compared two adjuvants: a stable oil-in-water emulsion (SE) and a stable oil-in-water emulsion incorporating glucopyranosyl lipid adjuvant, a synthetic TLR-4 agonist (GLA-SE), each together with a recombinant protein, ID93. Both the emulsion SE and GLA-SE adjuvants induce potent cellular responses in combination with ID93 in mice. ID93/SE induced Th2-biased immune responses, whereas ID93/GLA-SE induced multifunctional CD4(+) Th1 cell responses (IFN-γ, TNF-α, and IL-2). The ID93/GLA-SE vaccine candidate induced significant protection in mice and guinea pigs, whereas no protection was observed with ID93/SE, as assessed by reductions in bacterial burden, survival, and pathology. These results highlight the importance of properly formulating subunit vaccines with effective adjuvants for use against tuberculosis.

  4. Aluminium based adjuvants and their effects on mitochondria and lysosomes of phagocytosing cells.

    Science.gov (United States)

    Ohlsson, Lars; Exley, Christopher; Darabi, Anna; Sandén, Emma; Siesjö, Peter; Eriksson, Håkan

    2013-11-01

    Aluminium oxyhydroxide, Al(OH)3 is one of few compounds approved as an adjuvant in human vaccines. However, the mechanism behind its immune stimulating properties is still poorly understood. In vitro co-culture of an aluminium adjuvant and the human monocytic cell line THP-1 resulted in reduced cell proliferation. Inhibition occurred at concentrations of adjuvant several times lower than would be found at the injection site using a vaccine formulation containing an aluminium adjuvant. Based on evaluation of the mitochondrial membrane potential, THP-1 cells showed no mitochondrial rupture after co-culture with the aluminium adjuvant, instead an increase in mitochondrial activity was seen. The THP-1 cells are phagocytosing cells and after co-culture with the aluminium adjuvant the phagosomal pathway was obstructed. Primary or early phagosomes mature into phagolysosomes with an internal pH of 4.5 - 5 and carry a wide variety of hydrolysing enzymes. Co-culture with the aluminium adjuvant yielded a reduced level of acidic vesicles and cathepsin L activity, a proteolytic enzyme of the phagolysosomes, was almost completely inhibited. THP-1 cells are an appropriate in vitro model in order to investigate the mechanism behind the induction of a phagocytosing antigen presenting cell into an inflammatory cell by aluminium adjuvants. Much information will be gained by investigating the phagosomal pathway and what occurs inside the phagosomes and to elucidate the ultimate fate of phagocytosed aluminium particles. © 2013.

  5. Adjuvanted multi-epitope vaccines protect HLA-A*1101 transgenic mice against Toxoplasma gondii

    Science.gov (United States)

    We created and tested multi-epitope DNA or protein vaccines with TLR4 ligand emulsion adjuvant (gluco glucopyranosyl lipid adjuvant in a stable emulsion (GLA-SE)) for their ability to protect against Toxoplasma gondii in HLA transgenic mice. Our constructs each included five of our best down selecte...

  6. Prognostic role of adjuvant radiotherapy in triple-negative breast cancer : A historical cohort study

    NARCIS (Netherlands)

    Bhoo Pathy, Nirmala; Verkooijen, Helena M.; Wong, Fuh-Yong; Pignol, Jean-Philippe; Kwong, Ava; Tan, Ern-Yu; Taib, Nur Aishah; Nei, Wen-Long; Ho, Gwo-Fuang; Tan, Benita; Chan, Patrick; Lee, Soo-Chin; Hartman, Mikael; Yip, Cheng-Har; Dent, Rebecca

    2015-01-01

    The value of adjuvant radiotherapy in triple-negative breast cancer (TNBC) is currently debated. We assessed the association between adjuvant radiotherapy and survival in a large cohort of Asian women with TNBC. Women diagnosed with TNBC from 2006 to 2011 in five Asian centers (N=1,138) were

  7. Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial

    NARCIS (Netherlands)

    Suter, Thomas M.; Procter, Marion; van Veldhuisen, Dirk J.; Muscholl, Michael; Bergh, Jonas; Carlomagno, Chiara; Perren, Timothy; Passalacqua, Rodolfo; Bighin, Claudia; Klijn, Jan G. M.; Ageev, Fail T.; Hitre, Erika; Groetz, Juergen; Iwata, Hiroji; Knap, Malgorzata; Gnant, Michael; Muehlbauer, Susanne; Spence, Alison; Gelber, Richard D.; Piccart-Gebhart, Martine J.

    2007-01-01

    Purpose The purpose of this analysis was to investigate trastuzumab- associated cardiac adverse effects in breast cancer patients after completion of ( neo) adjuvant chemotherapy with or without radiotherapy. Patients and Methods The Herceptin Adjuvant ( HERA) trial is a three- group, multicenter, o

  8. Human prophylactic vaccine adjuvants and their determinant role in new vaccine formulations

    NARCIS (Netherlands)

    Perez, O.; Batista-Duharte, A.; Gonzalez, E.; Zayas, C.; Balbao, J.; Cuello, M.; Cabrera, O.; Lastre, M.; Schijns, V.E.J.C.

    2012-01-01

    Adjuvants have been considered for a long time to be an accessory and empirical component of vaccine formulations. However, accumulating evidence of their crucial role in initiating and directing the immune response has increased our awareness of the importance of adjuvant research in the past

  9. Long-term heart function after adjuvant epirubicin chemotherapy for breast cancer

    DEFF Research Database (Denmark)

    Appel, Jon M; Zerahn, Bo; Møller, Susanne

    2012-01-01

    Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment....

  10. Current adjuvant treatment modalities for gastric cancer:From history to the future

    Institute of Scientific and Technical Information of China (English)

    Leyla Kilic; Cetin Ordu; Ibrahim Yildiz; Fatma Sen; Serkan Keskin; Rumeysa Ciftci; Kezban Nur Pilanci

    2016-01-01

    The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world.The adjuvant treatment recommendation is generally chemoradiotherapy in the United States,perioperative chemotherapy in the United Kingdom and parts of Europe,and chemotherapy in Asia.These options mainly rely on the United States Intergroup-0116,United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy,and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials.However,the benefits were evident for only certain patients,which were not very homogeneous regarding the type of surgery,chemotherapy regimens,and stage of disease.Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate.Regardless of the extent of surgery,multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement.Moreover,in the era of individualized treatment for most of the other cancer types,identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation.The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients.

  11. Aluminum hydroxide adjuvant differentially activates the three complement pathways with major involvement of the alternative pathway

    DEFF Research Database (Denmark)

    Güven, Esin; Duus, Karen; Laursen, Inga

    2013-01-01

    Al(OH)3 is the most common adjuvant in human vaccines, but its mode of action remains poorly understood. Complement involvement in the adjuvant properties of Al(OH)3 has been suggested in several reports together with a depot effect. It is here confirmed that Al(OH)3 treatment of serum depletes c...

  12. The effect of immediate breast reconstruction on the timing of adjuvant chemotherapy: a systematic review

    NARCIS (Netherlands)

    J. Xavier Harmeling; C.A.E. Kouwenberg (Casimir A. E.); E. Bijlard (Eveline); K.N.J. Burger (Koert N. J.); A. Jager (Agnes); M.A.M. Mureau (Marc)

    2015-01-01

    textabstractAdjuvant chemotherapy is often needed to achieve adequate breast cancer control. The increasing popularity of immediate breast reconstruction (IBR) raises concerns that this procedure may delay the time to adjuvant chemotherapy (TTC), which may negatively impact oncological outcome. The

  13. Unraveling molecular signatures of immunostimulatory adjuvants in the female genital tract through systems biology.

    Directory of Open Access Journals (Sweden)

    Madelene Lindqvist

    Full Text Available Sexually transmitted infections (STIs unequivocally represent a major public health concern in both industrialized and developing countries. Previous efforts to develop vaccines for systemic immunization against a large number of STIs in humans have been unsuccessful. There is currently a drive to develop mucosal vaccines and adjuvants for delivery through the genital tract to confer protective immunity against STIs. Identification of molecular signatures that can be used as biomarkers for adjuvant potency can inform rational development of potent mucosal adjuvants. Here, we used systems biology to study global gene expression and signature molecules and pathways in the mouse vagina after treatment with two classes of experimental adjuvants. The Toll-like receptor 9 agonist CpG ODN and the invariant natural killer T cell agonist alpha-galactosylceramide, which we previously identified as equally potent vaginal adjuvants, were selected for this study. Our integrated analysis of genome-wide transcriptome data determined which signature pathways, processes and networks are shared by or otherwise exclusive to these 2 classes of experimental vaginal adjuvants in the mouse vagina. To our knowledge, this is the first integrated genome-wide transcriptome analysis of the effects of immunomodulatory adjuvants on the female genital tract of a mammal. These results could inform rational development of effective mucosal adjuvants for vaccination against STIs.

  14. Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity.

    Directory of Open Access Journals (Sweden)

    Martin Kreutz

    Full Text Available Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumour immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA and CpG oligodeoxynucleotides (ODN. We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL responses than control conjugates mixed with soluble CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumour immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumour responses.

  15. Quality of adjuvant CMF chemotherapy for node-positive primary breast cancer : a population-based study

    NARCIS (Netherlands)

    Schaapveld, M; de Vries, EGE; van der Graaf, WTA; Otter, R; Willemse, PHB

    2004-01-01

    Purpose: Adjuvant 'classical' oral cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) has long been the mainstay of adjuvant chemotherapy for premenopausal breast cancer patients. The Comprehensive Cancer Center North Netherlands (CCCN) breast cancer working group performed a retrospective

  16. Preliminary results of capecitabine metronomic chemotherapy in operable triple-negative breast cancer after standard adjuvant therapy – A single-arm phase II study

    Directory of Open Access Journals (Sweden)

    Hanan Shawky

    2014-12-01

    Conclusion: One year of capecitabine metronomic therapy preceded by standard adjuvant chemotherapy, is active and well-tolerated in TNBC patients previously treated with standard adjuvant chemotherapy.

  17. A synthetic adjuvant to enhance and expand immune responses to influenza vaccines.

    Science.gov (United States)

    Coler, Rhea N; Baldwin, Susan L; Shaverdian, Narek; Bertholet, Sylvie; Reed, Steven J; Raman, Vanitha S; Lu, Xiuhua; DeVos, Joshua; Hancock, Kathy; Katz, Jacqueline M; Vedvick, Thomas S; Duthie, Malcolm S; Clegg, Christopher H; Van Hoeven, Neal; Reed, Steven G

    2010-10-27

    Safe, effective adjuvants that enhance vaccine potency, including induction of neutralizing Abs against a broad range of variant strains, is an important strategy for the development of seasonal influenza vaccines which can provide optimal protection, even during seasons when available vaccines are not well matched to circulating viruses. We investigated the safety and ability of Glucopyranosyl Lipid Adjuvant-Stable Emulsion (GLA-SE), a synthetic Toll-like receptor (TLR)4 agonist formulation, to adjuvant Fluzone® in mice and non-human primates. The GLA-SE adjuvanted Fluzone vaccine caused no adverse reactions, increased the induction of T helper type 1 (T(H)1)-biased cytokines such as IFNγ, TNF and IL-2, and broadened serological responses against drifted A/H1N1 and A/H3N2 influenza variants. These results suggest that synthetic TLR4 adjuvants can enhance the magnitude and quality of protective immunity induced by influenza vaccines.

  18. A synthetic adjuvant to enhance and expand immune responses to influenza vaccines.

    Directory of Open Access Journals (Sweden)

    Rhea N Coler

    Full Text Available Safe, effective adjuvants that enhance vaccine potency, including induction of neutralizing Abs against a broad range of variant strains, is an important strategy for the development of seasonal influenza vaccines which can provide optimal protection, even during seasons when available vaccines are not well matched to circulating viruses. We investigated the safety and ability of Glucopyranosyl Lipid Adjuvant-Stable Emulsion (GLA-SE, a synthetic Toll-like receptor (TLR4 agonist formulation, to adjuvant Fluzone® in mice and non-human primates. The GLA-SE adjuvanted Fluzone vaccine caused no adverse reactions, increased the induction of T helper type 1 (T(H1-biased cytokines such as IFNγ, TNF and IL-2, and broadened serological responses against drifted A/H1N1 and A/H3N2 influenza variants. These results suggest that synthetic TLR4 adjuvants can enhance the magnitude and quality of protective immunity induced by influenza vaccines.

  19. Saponins from the Spanish saffron Crocus sativus are efficient adjuvants for protein-based vaccines.

    Science.gov (United States)

    Castro-Díaz, Nathaly; Salaun, Bruno; Perret, Rachel; Sierro, Sophie; Romero, Jackeline F; Fernández, Jose-Antonio; Rubio-Moraga, Angela; Romero, Pedro

    2012-01-05

    Protein and peptide-based vaccines provide rigorously formulated antigens. However, these purified products are only weakly immunogenic by themselves and therefore require the addition of immunostimulatory components or adjuvants in the vaccine formulation. Various compounds derived from pathogens, minerals or plants, possess pro-inflammatory properties which allow them to act as adjuvants and contribute to the induction of an effective immune response. The results presented here demonstrate the adjuvant properties of novel saponins derived from the Spanish saffron Crocus sativus. In vivo immunization studies and tumor protection experiments unambiguously establish the value of saffron saponins as candidate adjuvants. These saponins were indeed able to increase both humoral and cellular immune responses to protein-based vaccines, ultimately providing a significant degree of protection against tumor challenge when administered in combination with a tumor antigen. This preclinical study provides an in depth immunological characterization of a new saponin as a vaccine adjuvant, and encourages its further development for use in vaccine formulations.

  20. The Effect of Adjuvants on Penetration of beta-cypermethrin Through the Epidermis of Cabbage Leaf

    Institute of Scientific and Technical Information of China (English)

    WANG Yi; ZHANG Li-ta; ZHENG Fei-neng; CHEN Fu-liang; LIANG Wen-ping

    2002-01-01

    The effects of three types of adjuvant (mineral oil, higher aliphatic acid and nonionic surfactant) on the penetration of beta-cypermethrin through the cabbage leaf surface were studied. The results showed that the penetration was positively correlated with both the concentration of adjuvant and the time after application, in a given range of treatment. A synergistic effect of two types of adjuvant on the penetration was found. Some physical properties of emulsions were determined. The change of the structures of the cabbage leaf surface by these adjuvants was observed from photomicrographs. The mechanism concerned with the effect of these adjuvants on the penetration of beta-cypermethrin through the cabbage leaf surface was tentatively discussed.

  1. Pseudo-Mannosylated DC-SIGN Ligands as Potential Adjuvants for HIV Vaccines

    Directory of Open Access Journals (Sweden)

    Angela Berzi

    2014-01-01

    Full Text Available The development of new and effective adjuvants may play a fundamental role in improving HIV vaccine efficacy. New classes of vaccine adjuvants activate innate immunity receptors, notably toll like receptors (TLRs. Adjuvants targeting the C-Type lectin receptor DC-SIGN may be alternative or complementary to adjuvants based on TRL activation. Herein we evaluate the ability of the glycomimetic DC-SIGN ligand Polyman 19 (PM 19 to modulate innate immune responses. Results showed that PM 19 alone, or in combination with TLR agonists, induces the expression of cytokines, β chemokines and co-stimulatory molecules that may, in turn, modulate adaptive immunity and exert anti-viral effects. These results indicate that the suitability of this compound as a vaccine adjuvant should be further evaluated.

  2. Adjuvant chemoradiotherapy for adenocarcinoma of the stomach. A new progress?; Chimioradiotherapie dans le traitement adjuvant des adenocarcinomes gastriques: reelle avancee?

    Energy Technology Data Exchange (ETDEWEB)

    Mineur, L. [Institut Sainte Catherine, 84 - Avignon (France); Lacaine, F. [Hopital Tenon, 75 - Paris (France); Ychou, M. [Centre Regional de Lutte Contre le Cancer Val d' Aurelle, Service d' Oncologie, 34 - Montpellier (France); Bosset, J.F. [Centre Hospitalier Universitaire, Service de Radiotherapie, 25 - Besancon (France); Daban, A. [Centre Hospitalier Universitaire, Service de Radiotherapie, 86 - Poitiers (France)

    2002-11-01

    Frequency of local and distant failures after gastrectomy has led to extended lymph nodes dissection to obtain a better locoregional control. However, five year survival rates were not significantly different between patients undergoing D2 and D1 lymphadenectomy, and higher morbidity and post operative deaths were reported in large randomized trials (respectively 25% vs 48% and 4 vs 13%). Additionally, several met-analysis failed to demonstrate a significant survival advantage with adjuvant chemotherapy. The results of the first trial demonstrating one advantage to adjuvant post-operative chemoradiotherapy should modify the standard care. Disease free and overall survival after surgery alone and after surgery and concurrent chemoradiotherapy were respectively 31% vs 48% and 41% vs 50%. The inter-group trial demonstrate that better local control improve survival if radiation fields include stamps, tumour bed, proximal nodal chains and nodes corresponding to D2 extended lymph nodes dissection. Treatment was feasible with few severe toxic effects (1%). Of the 281 patients, 17% stopped treatment because toxic effects. Technical modalities of radiotherapy and post-operative nutrition support which are critical points of interest for this treatment, are also discussed. (authors)

  3. Antimicrobial susceptibility of Staphylococcus aureus and Staphylococcus pseudintermedius isolated from various animals.

    Science.gov (United States)

    Rubin, Joseph E; Ball, Katherine R; Chirino-Trejo, Manuel

    2011-02-01

    This study characterized the antimicrobial susceptibility of 221 Staphylococcus aureus isolated from various species, and 60 canine Staphylococcus pseudintermedius isolated from 1986 through 2000 at the Western College of Veterinary Medicine (WCVM). Resistance of S. aureus was most common to penicillin (31%) and tetracycline (14%); resistance of S. pseudintermedius to penicillin was present in 8% and to tetracycline in 34% of isolates. Resistance to trimethoprim/sulfamethoxazole was only seen among S. pseudintermedius, and there was no resistance to amoxicillin/clavulanate, ampicillin/sulbactam, cephalothin, amikacin, gentamicin, enrofloxacin, chloramphenicol, or rifampin among any isolate. Inducible clindamycin resistance was found in both S. aureus and S. pseudintermedius, highlighting the need for careful interpretation of culture and susceptibility test results. There were significant differences in the minimum inhibitory concentrations of penicillin, ciprofloxacin, enrofloxacin, clindamycin, erythromycin, chloramphenicol, and tetracycline between avian, bovine, equine, and porcine isolates.

  4. An overview of Staphylococcus epidermidis and Staphylococcus aureus with a focus on developing countries.

    Science.gov (United States)

    Chessa, Daniela; Ganau, Giulia; Mazzarello, Vittorio

    2015-07-04

    Most nosocomial infections by Staphylococcus epidermidis and Staphylococcus aureus have gained considerable attention due to an increase of infections caused by these strains that have been reported in recent years throughout the world. Most notably, it is important to underline the presence of S. epidermidis and S. aureus in the human epithelia microflora and to highlight that it is impossible to eradicate them from humans. There are various virulence factors that normally sustain the infection life cycle, such as antibiotic resistance (methicillin resistance). Furthermore, it is important to evaluate the usefulness of typing the spa gene from isolated strains in order to study genotypes and geographical distributions. In the present review, different cases related to patients infected by Staphylococci and an overview of this problem worldwide are reported.

  5. Beta-lactamase detection in Staphylococcus aureus and coagulase-negative Staphylococcus isolated from bovine mastitis

    Directory of Open Access Journals (Sweden)

    Bruno F. Robles

    2014-04-01

    Full Text Available The objectives of the study were to evaluate the presence/production of beta-lactamases by both phenotypic and genotypic methods, verify whether results are dependent of bacteria type (Staphylococcus aureus versus coagulase-negative Staphylococcus - CNS and verify the agreement between tests. A total of 200 bacteria samples from 21 different herds were enrolled, being 100 CNS and 100 S. aureus. Beta-lactamase presence/detection was performed by different tests (PCR, clover leaf test - CLT, Nitrocefin disk, and in vitro resistance to penicillin. Results of all tests were not dependent of bacteria type (CNS or S. aureus. Several S. aureus beta-lactamase producing isolates were from the same herd. Phenotypic tests excluding in vitro resistance to penicillin showed a strong association measured by the kappa coefficient for both bacteria species. Nitrocefin and CLT are more reliable tests for detecting beta-lactamase production in staphylococci.

  6. Pilot scale production of the vaccine adjuvant Proteoliposome derived Cochleates (AFCo1) from Neisseria meningitidis serogroup B

    OpenAIRE

    Zayas, Caridad; González, Domingo; Acevedo, Reinaldo; del Campo, Judith; Lastre, Miriam; González, Elizabeth; Romeu, Belkis; Cuello, Maribel; Balboa, Julio; Cabrera, Osmir; Guilherme, Luisa; Pérez, Oliver

    2013-01-01

    The use of new adjuvants in vaccine formulations is a subject of current research. Only few parenteral adjuvants have been licensed. We have developed a mucosal and parenteral adjuvant known as AFCo1 (Adjuvant Finlay Cochleate 1, derived from proteoliposomes of N. meningitidis B) using a dialysis procedure to produce them on lab scale. The immunogenicity of the AFCo1 produced by dialysis has been already evaluated, but it was necessary to demonstrate the feasibility of a larger-scale manufact...

  7. Isolation and identification of Staphylococcus sp. in powdered infant milk

    Science.gov (United States)

    Palilu, Prayolga Toban; Budiarso, Tri Yahya

    2017-05-01

    Staphylococcus sp. is one of the most dangerous bacteria that could cause food poisoning. It is a pathogenic bacterium which is able to produce enterotoxin in foods. Milk is an ideal growth medium for Staphylococcus sp., that may cause problem if it is to be consumed, especially by infant. It is the objective of this research to detect the presence of Staphylococcus sp. in powdered infant milk. As many as 14 samples obtained from market were used as samples for bacterial isolation. The isolation were done by employing enrichment step on BHI-broth, continued with Baird-Parker Agar which will produce a typical colony. It is then picked and grown on Mannitol Salt Agar, and gram staining, coagulase assay, and fermentation tests. The confirmation step was done by using API-Staph which gives the identification of Staphylococcus hemoliticus, Staphylococcus aureus and Staphylococcus epidermidis, with a percentage of identity ranging from 65.9-97.7%. Two isolates with the highest identification similarity values were then picked for molecular detection. A PCR primer pair targeting gene coding for enterotoxin A was used, and it gives positive result for the two isolates being tested. It is then concluded that the two isolates belong to Staphylococcus sp., and further research need to be done to correctly identify these isolates.

  8. Characterisation of nasal Staphylococcus delphini and Staphylococcus pseudintermedius isolates from healthy donkeys in Tunisia.

    Science.gov (United States)

    Gharsa, H; Slama, K Ben; Gómez-Sanz, E; Gómez, P; Klibi, N; Zarazaga, M; Boudabous, A; Torres, C

    2015-07-01

    Staphylococcus intermedius group (SIG) bacteria can colonise the nares of some animals but are also emerging pathogens in humans and animals. To analyse SIG nasal carriage in healthy donkeys destined for food consumption in Tunisia and to characterise recovered isolates. Nasal swabs from 100 healthy donkeys were tested for SIG recovery, and isolates were identified by biochemical and molecular methods. Antimicrobial susceptibility of isolates was tested and detection of antimicrobial resistance and virulence genes was performed. Isolates were typed at the clonal level by multilocus sequence typing and SmaI pulsed-field gel electrophoresis. Staphylococcus delphini and Staphylococcus pseudintermedius (included in SIG) were obtained in 19% and 2% of the tested samples, respectively, and one isolate per sample was characterised. All isolates were meticillin susceptible and mecA negative. Most S. delphini and S. pseudintermedius isolates showed susceptibility to all antimicrobials tested, with the exception of 2 isolates resistant to tetracycline (tet(M) gene) or fusidic acid. The following toxin genes were identified (percentage of isolates): lukS-I (100%), lukF-I (9.5%), siet (100%), se-int (90%), seccanine (19%) and expA (9.5%). Thirteen different pulsed-field gel electrophoresis profiles were identified among the 21 SIG isolates. Additionally, the following 9 different sequence types (STs) were detected by multilocus sequence typing, 6 of them new: ST219 (6 isolates), ST12 (5 isolates), ST220 (3 isolates), ST13, ST50, ST193, ST196, ST218 and ST221 (one isolate each). Staphylococcus delphini and S. pseudintermedius are common nasal colonisers of donkeys, generally susceptible to the antimicrobials tested; nevertheless, these SIG isolates contain virulence genes, including the recently described exfoliative gene (expA) and several enterotoxin genes, with potential implications for public health. This is the first description of S. delphini in Tunisia. The

  9. Problems with rapid agglutination methods for identification of Staphylococcus aureus when Staphylococcus saprophyticus is being tested.

    Science.gov (United States)

    Gregson, D B; Low, D E; Skulnick, M; Simor, A E

    1988-01-01

    Six rapid agglutination tests for identification of Staphylococcus aureus were evaluated by using 62 strains of S. aureus, 63 strains of S. saprophyticus, and 67 strains of other coagulase-negative staphylococci. S. saprophyticus was responsible for 19 of 26 false-positive results and 20 uninterpretable reactions. Thus, urinary staphylococcal isolates that are positive by rapid agglutination tests may require other confirmatory tests for the identification of possible S. saprophyticus. PMID:3410950

  10. Effect of Substance P in Staphylococcus aureus and Staphylococcus epidermidis virulence: Implication for skin homeostasis

    Directory of Open Access Journals (Sweden)

    Awa eNdiaye

    2016-04-01

    Full Text Available Staphylococcus aureus and Staphylococcus epidermidis are two major skin associated bacteria, and Substance P (SP is a major skin neuropeptide. Since bacteria are known to sense and response to many human hormones, we investigated the effects of SP on Staphylococci virulence in reconstructed human epidermis model and HaCaT keratinocytes. We show that SP is stimulating the virulence of Staphylococcus aureus and Staphylococcus epidermidis in a reconstructed human epidermis model. qRT-PCR array analysis of 64 genes expressed by keratinocytes in the response to bacterial infection revealed a potential link between the action of SP on Staphylococci and skin physiopathology. qRT-PCR and direct assay of cathelicidin and human β-defensin 2 secretion also provided that demonstration that the action of SP on bacteria is independent of antimicrobial peptide expression by keratinocytes. Considering an effect of SP on S. aureus and S. epidermidis, we observed that SP increases the adhesion potential of both bacteria on keratinocytes. However, SP modulates the virulence of S. aureus and S. epidermidis through different mechanisms. The response of S. aureus is associated with an increase in Staphylococcal Enterotoxin C2 (SEC2 production and a reduction of exolipase processing whereas in S. epidermidis the effect of SP appears mediated by a rise in biofilm formation activity. The Thermo unstable ribosomal Elongation factor Ef-Tu was identified as the SP-interacting protein in S. aureus and S. epidermidis. SP appears as an inter-kingdom communication factor involved in the regulation of bacterial virulence and essential for skin microflora homeostasis.

  11. Problems with rapid agglutination methods for identification of Staphylococcus aureus when Staphylococcus saprophyticus is being tested.

    OpenAIRE

    Gregson, D B; Low, D E; Skulnick, M; Simor, A. E.

    1988-01-01

    Six rapid agglutination tests for identification of Staphylococcus aureus were evaluated by using 62 strains of S. aureus, 63 strains of S. saprophyticus, and 67 strains of other coagulase-negative staphylococci. S. saprophyticus was responsible for 19 of 26 false-positive results and 20 uninterpretable reactions. Thus, urinary staphylococcal isolates that are positive by rapid agglutination tests may require other confirmatory tests for the identification of possible S. saprophyticus.

  12. Pathogenic Staphylococcus aureus Isolates from Postoperative Wounds of Hospitalized Patients

    Directory of Open Access Journals (Sweden)

    Smritikana Biswas

    2010-07-01

    Full Text Available Staphylococcus sp., gram positive pyogenic bacteria located on skin, nose etc, secretes toxin that causes toxic shock syndrome, abscess, food poisoning and other infectious diseases. This study was carried out to identify and characterize the type of Staphylococcus sp. bacteria especially Staphylococcus aureus in the pus from postoperative wounds of hospitalized patients. From pus samples collected from twenty-four patients from Kharagpur Hospital, Paschim Medinipur, West Bengal, twenty-eight bacterial isolates were obtained. Among them twenty-five (89.2% were appeared with golden yellow colonies which is usually formed by Staphylococcus aureus. Twenty-three (82.14% of the bacterial isolates were Gram positive. Among them twenty isolates (86.9% were further confirmed to be Staphylococcus aureus by their ability to produce Catalase enzyme (positive in Catalase test and Coagulase enzyme (positive in Coagulase Test. Eighteen (90.00% of these Staphylococcus aureus were found to liquefy gelatin (Gelatin hydrolysis test, were able to hydrolyze urea (Urea hydrolysis test and were also l positive in Mannitol Fermentation Test. But there was no growth found of these isolates on MacConkey Agar, while sixteen isolates (80.00% of Staphylococcus aureus were resistant to penicillin (50µg/ml. Moreover eighteen (90.00% Staphylococcus aureus isolates were able to elaborate Hemolysin (Hemolysis test on Blood Agar media. Hence the bacterial isolates obtained from pus of postoperative wounds were predominantly pathogenic Staphylococcus aureus. So it can be concluded that careful treatment and postoperative measures to be taken to avoid serious health problem that may often be life threatening.

  13. Staphylococcus epidermidis and Staphylococcus haemolyticus: Molecular Detection of Cytotoxin and Enterotoxin Genes.

    Science.gov (United States)

    Pinheiro, Luiza; Brito, Carla Ivo; de Oliveira, Adilson; Martins, Patrícia Yoshida Faccioli; Pereira, Valéria Cataneli; da Cunha, Maria de Lourdes Ribeiro de Souza

    2015-09-14

    Although opportunistic pathogens, coagulase-negative staphylococci (CoNS), including Staphylococcus epidermidis and Staphylococcus haemolyticus, have long been regarded as avirulent organisms. The role of toxins in the development of infections caused by CoNS is still controversial. The objective of this study was to characterize the presence of enterotoxin and cytotoxin genes in S. epidermidis and S. haemolyticus isolates obtained from blood cultures. Cytotoxin genes were detected by PCR using novel species-specific primers. Among the 85 S. epidermidis and 84 S. haemolyticus isolates, 95.3% and 79.8%, respectively, carried at least one enterotoxin gene. The most frequent enterotoxin genes were sea (53.3%), seg (64.5%) and sei (67.5%). The seg gene was positively associated with S. epidermidis (p = 0.02), and this species was more toxigenic than S. haemolyticus. The hla/yidD gene was detected in 92.9% of S. epidermidis and the hla gene in 91.7% of S. haemolyticus isolates; hlb was detected in 92.9% of the S. epidermidis isolates and hld in 95.3%. Nosocomial Staphylococcus epidermidis and S. haemolyticus isolates exhibited a high toxigenic potential, mainly producing the non-classical enterotoxins seg and sei. The previously unreported detection of hla/yidD and hlb in S. epidermidis and S. haemolyticus using species-specific primers showed that these hemolysin genes differ between CoNS species and that they are highly frequent in blood culture isolates.

  14. The role of postoperative adjuvant radiotherapy in resected esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chang Geol; Kim, Choong Bae; Chung, Kyung Young; Lee, Doo Yun; Seong Jin Sil; Kim, Gwi Eon; Suh, Chang Ok [Yonsei University College of Medicine, Yonsei Cancer Center, Seoul (Korea, Republic of)

    2002-12-15

    A retrospective study was performed to evaluate whether postoperative adjuvant radiotherapy can improve survival and decrease recurrence as compared with surgery alone in resected esophageal cancer. From Jan. 1985 to Dec. 1993, among 94 esophageal cancer patients treated with surgery, fifty-one patients were included in this study. Transthoracic esophagectomy was performed in 35 patients and transhiatal esophagectomy in 16. Postoperative adjuvant radiotherapy was performed 4 weeks after surgery in 26 among 38 patients in stage II and III. A total dose of 30 {approx} 60 Gy in 1.8 Gy daily fraction, median 54 Gy over 6 weeks, was delivered in the mediastinum + both supraclavicular lymph nodes or celiac lymph nodes according to the tumor location. Forty-seven patients (92%) had squamous histology. The median follow-up period was 38 months. The overall 2-year and 5-year survival and median survival were 56.4%, 36.8% and 45 months. Two-year and 5-year survival and median survival by stage were 92%, 60.3% for stage I, 63%, 42% and 51 months for stage II and 34%, 23% and 19 months for stage III ({rho} = 0.04). For stage II and III patients, 5-year survival and median survival were 22.8%. 45 months for the surgery alone group and 37.8%, 22 months for the postoperative RT group ({rho} = 0.89). For stage III patients, 2-year survival and median survival were 0%, 11 months for the surgery alone group and 36.5%, 20 months for the postoperative RT group ({rho} = 0.14). Local and distant failure rates for stage II and III were 50%, 16% for the surgery alone and 39%, 31% for the postoperative RT group. For N1 patients, local failure rate was 71% for the surgery alone group and 37% for the postoperative RT group ({rho} = 0.19). Among 10 local failures in the postoperative RT group, in-field failures were 2, marginal failures 1, out-field 5 and anastomotic site failures 2. There were no statistically significant differences in either the overall survival or the patterns of failure

  15. Necrotizing Fasciitis Associated with Staphylococcus lugdunensis

    Directory of Open Access Journals (Sweden)

    Tony Hung

    2012-01-01

    Full Text Available Necrotizing fasciitis is a life-threatening soft tissue infection that results in rapid local tissue destruction. Type 1 necrotizing fasciitis is characterized by polymicrobial, synergistic infections that are caused by non-Group A streptococci, aerobic and anaerobic organisms. Type 2 necrotizing fasciitis involves Group A Streptococcus (GAS with or without a coexisting staphylococcal infection. Here we provide the first report of necrotizing fasciitis jointly associated with the microbes Group B Streptococcus and Staphylococcus lugdunensis. S. lugdunensis is a commensal human skin bacterium known to cause often painful and prolonged skin and soft tissue infections. To our knowledge, however, this is the first case of Staph. lugdunensis-associated necrotizing fasciitis to be reported in the literature.

  16. Staphylococcus aureus survival in human blood.

    Science.gov (United States)

    Malachowa, Natalia; DeLeo, Frank R

    2011-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is abundant in hospitals and in the United States is a leading cause of mortality due to infectious agents. Community-associated MRSA (CA-MRSA) strains such as USA300, which typically cause disease outside of healthcare settings, are also prevalent in the United States. Although most CA-MRSA infections affect skin and soft tissue, the pathogen can enter the bloodstream and ultimately cause severe disease. In a recent paper, we used USA300-specific microarrays to generate a comprehensive view of the molecules that facilitate S. aureus immune evasion and survival in human blood. Notably, genes encoding proteins involved in iron-uptake and utilization and gamma-hemolysin (hlgABC) are highly up-regulated by USA300 during culture in human blood. Here we discuss the potential implication of these findings and the possible role of gamma-hemolysin in the success of S. aureus as a human pathogen.

  17. Genomics of Natural Populations of Staphylococcus aureus.

    Science.gov (United States)

    Fitzgerald, J Ross; Holden, Matthew T G

    2016-09-01

    Staphylococcus aureus is a major human pathogen and an important cause of livestock infections. The first S. aureus genomes to be published, 15 years ago, provided the first view of genome structure and gene content. Since then, thousands of genomes from a wide array of strains from different sources have been sequenced. Comparison of these sequences has resulted in broad insights into population structure, bacterial evolution, clone emergence and expansion, and the molecular basis of niche adaptation. Furthermore, this information is now being applied clinically in outbreak investigations to inform infection control measures and to determine appropriate treatment regimens. In this review, we summarize some of the broad insights into S. aureus biology gained from the analysis of genomes and discuss future directions and opportunities in this dynamic field of research.

  18. Evasion of Neutrophil Killing by Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Will A. McGuinness

    2016-03-01

    Full Text Available Staphylococcus aureus causes many types of infections, ranging from self-resolving skin infections to severe or fatal pneumonia. Human innate immune cells, called polymorphonuclear leukocytes (PMNs or neutrophils, are essential for defense against S. aureus infections. Neutrophils are the most prominent cell type of the innate immune system and are capable of producing non-specific antimicrobial molecules that are effective at eliminating bacteria. Although significant progress has been made over the past few decades, our knowledge of S. aureus-host innate immune system interactions is incomplete. Most notably, S. aureus has the capacity to produce numerous molecules that are directed to protect the bacterium from neutrophils. Here we review in brief the role played by neutrophils in defense against S. aureus infection, and correspondingly, highlight selected S. aureus molecules that target key neutrophil functions.

  19. Hospital strain colonization by Staphylococcus epidermidis

    Directory of Open Access Journals (Sweden)

    D. Blum-Menezes

    2009-03-01

    Full Text Available The skin and mucous membranes of healthy subjects are colonized by strains of Staphylococcus epidermidis showing a high diversity of genomic DNA polymorphisms. Prolonged hospitalization and the use of invasive procedures promote changes in the microbiota with subsequent colonization by hospital strains. We report here a patient with prolonged hospitalization due to chronic pancreatitis who was treated with multiple antibiotics, invasive procedures and abdominal surgery. We studied the dynamics of skin colonization by S. epidermidis leading to the development of catheter-related infections and compared the genotypic profile of clinical and microbiota strains by pulsed field gel electrophoresis. During hospitalization, the normal S. epidermidis skin microbiota exhibiting a polymorphic genomic DNA profile was replaced with a hospital-acquired biofilm-producer S. epidermidis strain that subsequently caused repetitive catheter-related infections.

  20. Triclosan promotes Staphylococcus aureus nasal colonization.

    Science.gov (United States)

    Syed, Adnan K; Ghosh, Sudeshna; Love, Nancy G; Boles, Blaise R

    2014-04-08

    The biocide triclosan is used in many personal care products, including toothpastes, soaps, clothing, and medical equipment. Consequently, it is present as a contaminant in the environment and has been detected in some human fluids, including serum, urine, and milk. Staphylococcus aureus is an opportunistic pathogen that colonizes the noses and throats of approximately 30% of the population. Colonization with S. aureus is known to be a risk factor for several types of infection. Here we demonstrate that triclosan is commonly found in the nasal secretions of healthy adults and the presence of triclosan trends positively with nasal colonization by S. aureus. We demonstrate that triclosan can promote the binding of S. aureus to host proteins such as collagen, fibronectin, and keratin, as well as inanimate surfaces such as plastic and glass. Lastly, triclosan-exposed rats are more susceptible to nasal colonization with S. aureus. These data reveal a novel factor that influences the ability of S. aureus to bind surfaces and alters S. aureus nasal colonization. IMPORTANCE Triclosan has been used as a biocide for over 40 years, but the broader effects that it has on the human microbiome have not been investigated. We demonstrate that triclosan is present in nasal secretions of a large portion of a test population and its presence correlates with Staphylococcus aureus nasal colonization. Triclosan also promotes the binding of S. aureus to human proteins and increases the susceptibility of rats to nasal colonization by S. aureus. These findings are significant because S. aureus colonization is a known risk factor for the development of several types of infections. Our data demonstrate the unintended consequences of unregulated triclosan use and contribute to the growing body of research demonstrating inadvertent effects of triclosan on the environment and human health.

  1. Staphylococcus capitis isolated from prosthetic joint infections.

    Science.gov (United States)

    Tevell, S; Hellmark, B; Nilsdotter-Augustinsson, Å; Söderquist, B

    2017-01-01

    Further knowledge about the clinical and microbiological characteristics of prosthetic joint infections (PJIs) caused by different coagulase-negative staphylococci (CoNS) may facilitate interpretation of microbiological findings and improve treatment algorithms. Staphylococcus capitis is a CoNS with documented potential for both human disease and nosocomial spread. As data on orthopaedic infections are scarce, our aim was to describe the clinical and microbiological characteristics of PJIs caused by S. capitis. This retrospective cohort study included three centres and 21 patients with significant growth of S. capitis during revision surgery for PJI between 2005 and 2014. Clinical data were extracted and further microbiological characterisation of the S. capitis isolates was performed. Multidrug-resistant (≥3 antibiotic groups) S. capitis was detected in 28.6 % of isolates, methicillin resistance in 38.1 % and fluoroquinolone resistance in 14.3 %; no isolates were rifampin-resistant. Heterogeneous glycopeptide-intermediate resistance was detected in 38.1 %. Biofilm-forming ability was common. All episodes were either early post-interventional or chronic, and there were no haematogenous infections. Ten patients experienced monomicrobial infections. Among patients available for evaluation, 86 % of chronic infections and 70 % of early post-interventional infections achieved clinical cure; 90 % of monomicrobial infections remained infection-free. Genetic fingerprinting with repetitive sequence-based polymerase chain reaction (rep-PCR; DiversiLab®) displayed clustering of isolates, suggesting that nosocomial spread might be present. Staphylococcus capitis has the potential to cause PJIs, with infection most likely being contracted during surgery or in the early postoperative period. As S. capitis might be an emerging nosocomial pathogen, surveillance of the prevalence of PJIs caused by S. capitis could be recommended.

  2. Uncaria tomentosa—Adjuvant Treatment for Breast Cancer: Clinical Trial

    Directory of Open Access Journals (Sweden)

    Maria do Carmo Santos Araújo

    2012-01-01

    Full Text Available Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma—Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide, were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer.

  3. Uncaria tomentosa—Adjuvant Treatment for Breast Cancer: Clinical Trial

    Science.gov (United States)

    Santos Araújo, Maria do Carmo; Farias, Iria Luiza; Gutierres, Jessie; Dalmora, Sergio L.; Flores, Nélia; Farias, Julia; de Cruz, Ivana; Chiesa, Juarez; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa

    2012-01-01

    Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma—Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer. PMID:22811748

  4. Uncaria tomentosa-Adjuvant Treatment for Breast Cancer: Clinical Trial.

    Science.gov (United States)

    Santos Araújo, Maria do Carmo; Farias, Iria Luiza; Gutierres, Jessie; Dalmora, Sergio L; Flores, Nélia; Farias, Julia; de Cruz, Ivana; Chiesa, Juarez; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa

    2012-01-01

    Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma-Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer.

  5. Hypofractionated Adjuvant Whole Breast Radiotherapy: Progress and Prospects

    Energy Technology Data Exchange (ETDEWEB)

    Yarnold, John (Section of Radiotherapy, Inst. of Cancer Research, Royal Marsden Hospital, Sutton (United Kingdom)), E-mail: john.yarnold@icr.ac.uk; Haviland, Joanne (Clinical Trials and Statistics Unit (ICR-CTSU), Section of Clinical Trials, Inst. of Cancer Research, Sutton (United Kingdom))

    2010-11-15

    Published results of randomised trials involving >7000 women confirm the safety and efficacy of hypofractionated schedules of adjuvant radiotherapy for women with early breast cancer using fraction sizes between 2 and 3 Gy assuming appropriate downward adjustments to total dose. Unnecessary concerns relating to heart tolerance, suboptimal dose distribution and duration of follow up need not discourage the routine adoption of 15- or 16-fraction schedules in women treated by breast conservation surgery for early breast cancer. Regardless of fractionation regimen, dose escalation to the index quadrant in high risk subgroups will result in a greater relative increase in late adverse effects than tumour control, a therapeutic disadvantage that can only be overcome by exploiting a marked dose-volume effect. A 15-fraction schedule of whole breast radiotherapy is unlikely to represent the lower limits of hypofractionation, and the preliminary results of a 5-fraction regimen are encouraging

  6. Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy

    DEFF Research Database (Denmark)

    Eggermont, Alexander M M; Chiarion-Sileni, Vanna; Grob, Jean-Jacques;

    2016-01-01

    Background On the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had...... undergone complete resection of stage III melanoma. Methods After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months...... patients (1.1%) died owing to immune-related adverse events. Conclusions As adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence-free survival, overall survival, and distant metastasis-free survival than placebo...

  7. Adjuvant systemic therapy in older women with breast cancer

    Science.gov (United States)

    Leone, Julieta; Leone, Bernardo Amadeo; Leone, José Pablo

    2016-01-01

    Breast cancer in the elderly is an increasing clinical problem. In addition, ~60% of deaths from breast cancer occur in women aged 65 years and older. Despite this, older women with breast cancer have been underrepresented in clinical trials, and this has led to less than optimal evidence to guide their therapy. The management of elderly women with early breast cancer is a complex process that requires careful evaluation of life expectancy, comorbidities, patient values, and risks and benefits of available treatment options. This review will focus on current adjuvant systemic therapy options for older women with breast cancer, discuss the principles in the decision-making process, and define the role of endocrine therapy, chemotherapy, and targeted agents. PMID:27524919

  8. [Endotoxin adsortion as adjuvant therapy in gram negative severe sepsis].

    Science.gov (United States)

    Candel, F J; Martínez-Sagasti, F; Borges, M; Maseda, E; Herrera-Gutiérrez, M; Garnacho-Montero, J; Maynar, F J; Zaragoza, R; Mensa, J; Azanza, J R

    2010-09-01

    The mortality rate of severe sepsis and septic shock remains still high. Within the last years a better knowledge of its physiopathology and the implementation of a group of measures addressed to a fast identification and early treatment of the septic patients have proved to reduce mortality rate. Likewise, it continues being investigated in modulating the inflammatory response and limiting the harmful action of the bacterial products on the immune system. As a result of this research some endotoxin adsorber devices have been designed to control one of the most important targets that start the inflammatory cascade when gram negative microorganisms are involved.The usefulness that these endotoxin removal devices might have as adjuvant treatment in the Septic Syndrome and its applicability are reviewed in this paper. Likewise a profile of patient that might be to the benefit of this therapy is suggested according to the current knowledge.

  9. Cardiotoxicity in Asymptomatic Patients Receiving Adjuvant 5-fluorouracil

    DEFF Research Database (Denmark)

    Nielsen, Karin; Polk, Anne; Nielsen, Dorte Lisbet

    2014-01-01

    Evolving evidence of cardiotoxicity in cancer patients treated with 5-fluorouracil (5-FU) has been reported. We report two different clinical manifestations of asymptomatic 5-FU-associated cardiotoxicity in patients operated for colorectal cancer and treated with adjuvant chemotherapy of 5-FU...... (bolus-injection and continuous infusion for 46 hours), folinic acid and oxaliplatin (FOLFOX). For a research study evaluating cardiac events during 5-FU treatment, Holter monitoring, electrocardiogram (ECG) and echocardiography were done and cardiac markers monitored before and during the first...... and hyperlipidemia as well as an incidental finding of negative T-waves in electrocardiogram years before 5-FU treatment. No subjective cardiac symptoms were described during infusion, but approximately 12 hours after infusion she suffered from cardiac arrest but was revived. Subsequent analysis of the Holter...

  10. Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy

    DEFF Research Database (Denmark)

    Eggermont, Alexander M M; Chiarion-Sileni, Vanna; Grob, Jean-Jacques

    2016-01-01

    Background On the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had...... undergone complete resection of stage III melanoma. Methods After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months...... patients (1.1%) died owing to immune-related adverse events. Conclusions As adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence-free survival, overall survival, and distant metastasis-free survival than placebo...

  11. Lactic acid bacteria as adjuvants for sublingual allergy vaccines.

    Science.gov (United States)

    Van Overtvelt, Laurence; Moussu, Helene; Horiot, Stéphane; Samson, Sandrine; Lombardi, Vincent; Mascarell, Laurent; van de Moer, Ariane; Bourdet-Sicard, Raphaëlle; Moingeon, Philippe

    2010-04-01

    We compared immunomodulatory properties of 11 strains of lactic acid bacteria as well as their capacity to enhance sublingual immunotherapy efficacy in a murine asthma model. Two types of bacterial strains were identified, including: (i) potent inducers of IL-12p70 and IL-10 in dendritic cells, supporting IFN-gamma and IL-10 production in CD4+ T cells such as Lactobacillus helveticus; (ii) pure Th1 inducers such as L. casei. Sublingual administration in ovalbumin-sensitized mice of L. helveticus, but not L. casei, reduced airways hyperresponsiveness, bronchial inflammation and proliferation of specific T cells in cervical lymph nodes. Thus, probiotics acting as a Th1/possibly Treg, but not Th1 adjuvant, potentiate tolerance induction via the sublingual route.

  12. Eccentric exercise as an adjuvant to influenza vaccination in humans.

    Science.gov (United States)

    Edwards, Kate M; Burns, Victoria E; Allen, Louise M; McPhee, Jamie S; Bosch, Jos A; Carroll, Douglas; Drayson, Mark; Ring, Christopher

    2007-02-01

    The immune response to vaccination in animals can be enhanced by exposure to acute stress at the time of vaccination. The efficacy of this adjuvant strategy for vaccination in humans requires investigation. The current study employed a randomised controlled trial design to examine the effects of eccentric exercise prior to influenza vaccination on the antibody and cell-mediated responses. Sixty young healthy adults (29 men, 31 women) performed eccentric contractions of the deltoid and biceps brachii muscles of the non-dominant arm (exercise group) or rested quietly (control group), and were vaccinated 6h later in the non-dominant arm. Change in arm circumference and pain were measured to assess the physiological response to exercise. Antibody titres were measured pre-vaccination and at 6- and 20-week follow-ups. Interferon-gamma in response to in vitro stimulation by the whole vaccine, an index of the cell-mediated response, was measured 8 weeks post-vaccination. Interferon-gamma responses were enhanced by exercise in men, whereas antibody titres were enhanced by eccentric exercise in women but not in men. Men showed greater increase in arm circumference after eccentric exercise than women but there was no difference in reported pain. The interferon-gamma response was positively associated with the percentage increase in arm circumference among the exercise group. Eccentric exercise exerted differential effects on the response to vaccination in men and women, with enhancement of the antibody response in women, but enhancement of the cell-mediated response in men. Eccentric exercise of the muscle at the site of vaccine administration should be explored further as a possible behavioural adjuvant to vaccination.

  13. Caffeine as an opioid analgesic adjuvant in fibromyalgia.

    Science.gov (United States)

    Scott, J Ryan; Hassett, Afton L; Brummett, Chad M; Harris, Richard E; Clauw, Daniel J; Harte, Steven E

    2017-01-01

    Caffeine's properties as an analgesic adjuvant with nonsteroidal anti-inflammatory drugs/acetaminophen are well documented. However, little clinical research has explored caffeine's effects on opioid analgesia. This study assessed the effects of caffeine consumption on pain and other symptoms in opioid-using and nonusing chronic pain patients meeting the survey criteria for fibromyalgia. Patients presenting to a university-based pain clinic completed validated self-report questionnaires assessing symptoms. Patients (N=962) meeting the fibromyalgia survey criteria were stratified by opioid use and further split into groups based on caffeine amount consumed per day (no caffeine, or low, moderate, high caffeine). Analysis of covariance with Dunnett's post hoc testing compared pain and symptom severity between the no caffeine group and the caffeine consuming groups. In opioid users, caffeine consumption had modest but significant effects on pain, catastrophizing, and physical function. Lower levels of pain interference were associated with low and moderate caffeine use compared to no caffeine intake. Lower pain catastrophizing and higher physical function were observed in all caffeine dose groups, relative to the no caffeine group. Lower pain severity and depression were observed only in the moderate caffeine group. In opioid nonusers, low caffeine intake was associated with higher physical function; however, no other significant effects were observed. Caffeine consumption was associated with decreased pain and symptom severity in opioid users, but not in opioid nonusers, indicating caffeine may act as an opioid adjuvant in fibromyalgia-like chronic pain patients. These data suggest that caffeine consumption concomitant with opioid analgesics could provide therapeutic benefits not seen with opioids or caffeine alone.

  14. Adjuvant Intraoperative Photodynamic Therapy in Head and Neck Cancer

    Science.gov (United States)

    Rigual, Nestor R.; Shafirstein, Gal; Frustino, Jennifer; Seshadri, Mukund; Cooper, Michele; Wilding, Gregory; Sullivan, Maureen A.; Henderson, Barbara

    2015-01-01

    IMPORTANCE There is an immediate need to develop local intraoperative adjuvant treatment strategies to improve outcomes in patients with cancer who undergo head and neck surgery. OBJECTIVES To determine the safety of photodynamic therapy with 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) in combination with surgery in patients with head and neck squamous cell carcinoma. DESIGN, SETTING, AND PARTICIPANTS Nonrandomized, single-arm, single-site, phase 1 study at a comprehensive cancer center among 16 adult patients (median age, 65 years) with biopsy-proved primary or recurrent resectable head and neck squamous cell carcinoma. INTERVENTIONS Intravenous injection of HPPH (4.0 mg/m2), followed by activation with 665-nm laser light in the surgical bed immediately after tumor resection. MAIN OUTCOMES AND MEASURES Adverse events and highest laser light dose. RESULTS Fifteen patients received the full course of treatment, and 1 patient received HPPH without intraoperative laser light because of an unrelated myocardial infarction. Disease sites included larynx (7 patients), oral cavity (6 patients), skin (1 patient), ear canal (1 patient), and oropharynx (1 patient, who received HPPH only). The most frequent adverse events related to photodynamic therapy were mild to moderate edema (9 patients) and pain (3 patients). One patient developed a grade 3 fistula after salvage laryngectomy, and another patient developed a grade 3 wound infection and mandibular fracture. Phototoxicity reactions included 1 moderate photophobia and 2 mild to moderate skin burns (2 due to operating room spotlights and 1 due to the pulse oximeter). The highest laser light dose was 75 J/cm2. CONCLUSIONS AND RELEVANCE The adjuvant use of HPPH-photodynamic therapy and surgery for head and neck squamous cell carcinoma seems safe and deserves further study. PMID:23868427

  15. Immune Adjuvant Effect of Molecularly-defined Toll-Like Receptor Ligands

    Directory of Open Access Journals (Sweden)

    Deana N. Toussi

    2014-04-01

    Full Text Available Vaccine efficacy is optimized by addition of immune adjuvants. However, although adjuvants have been used for over a century, to date, only few adjuvants are approved for human use, mostly aimed at improving vaccine efficacy and antigen-specific protective antibody production. The mechanism of action of immune adjuvants is diverse, depending on their chemical and molecular nature, ranging from non-specific effects (i.e., antigen depot at the immunization site to specific activation of immune cells leading to improved host innate and adaptive responses. Although the detailed molecular mechanism of action of many adjuvants is still elusive, the discovery of Toll-like receptors (TLRs has provided new critical information on immunostimulatory effect of numerous bacterial components that engage TLRs. These ligands have been shown to improve both the quality and the quantity of host adaptive immune responses when used in vaccine formulations targeted to infectious diseases and cancer that require both humoral and cell-mediated immunity. The potential of such TLR adjuvants in improving the design and the outcomes of several vaccines is continuously evolving, as new agonists are discovered and tested in experimental and clinical models of vaccination. In this review, a summary of the recent progress in development of TLR adjuvants is presented.

  16. STRAP Is a Strong Predictive Marker of Adjuvant Chemotherapy Benefit in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Martin Buess

    2004-11-01

    Full Text Available BACKGROUND: Molecular predictors for the effectiveness of adjuvant chemotherapy in colorectal cancer are of considerable clinical interest. To this aim, we analyzed the serine threonine receptor-associated protein (STRAP, an inhibitor of TGF-βsignaling, with regard to prognosis and prediction of adjuvant 5-FU chemotherapy benefit. i The gene copy status of STRAP was determined using quantitative realtime polymerase chain reaction in 166 colorectal tumor biopsies, which had been collected from a randomized multicenter trial of 5-fluorouracil (5-FU/mitomycin C (MMC adjuvant chemotherapy of the Swiss Group for Clinical Cancer Research (SAKK. RESULTS: Amplification of STRAP was found in 22.8% of the tumors. When left without adjuvant chemotherapy, patients bearing tumors with a STRAP amplification had a significantly better prognosis (hazard ratio for death: 0.26; P = .004. Interestingly, these patients, when receiving adjuvant treatment, had a worse survival (hazard ratio for death: 3.48; P = .019 than without chemotherapy, whereas patients carrying tumors with diploidy or deletion of STRAP benefited from the treatment (hazard ratio for death: 0.44; P = .052. This suggests the amplification of STRAP as a strong predictor of an unfavorable effect of 5-FU-based adjuvant chemotherapy. CONCLUSION: If confirmed, the STRAP gene copy status might provide a parameter to decide about the use of 5-FU-based adjuvant chemotherapy.

  17. Evolution of methicillin-resistant Staphylococcus aureus towards increasing resistance

    DEFF Research Database (Denmark)

    Strommenger, Birgit; Bartels, Mette Damkjær; Kurt, Kevin

    2014-01-01

    To elucidate the evolutionary history of Staphylococcus aureus clonal complex (CC) 8, which encompasses several globally distributed epidemic lineages, including hospital-associated methicillin-resistant S. aureus (MRSA) and the highly prevalent community-associated MRSA clone USA300....

  18. First Case of Staphylococcus pseudintermedius Infection in a Human▿

    OpenAIRE

    Van Hoovels, Lieve; Vankeerberghen, Anne; Boel, An; Van Vaerenbergh, Kristien; De Beenhouwer, Hans

    2006-01-01

    We present the first clinical report of a Staphylococcus pseudintermedius infection in a human. Biochemically, S. pseudintermedius can be easily misidentified as S. aureus. Therefore, the final microbiological identification requires the combination of phenotypic and genotypic tests.

  19. Characterisation of Staphylococcus aureus bacteraemia at Tygerberg hospital

    NARCIS (Netherlands)

    Orth, H.; Dreyer, Z.S.; Makgotlho, E.; Oosthuysen, W.; Sinha, B.; Wasserman, E.

    2013-01-01

    To elucidate the local epidemiology of Staphylococcus aureus bacteraemia, we characterised blood culture isolates using molecular methods and prospectively collected clinical data to determine the occurrence of community-acquired, methicillinresistant S. aureus (MRSA). Consecutive S. aureus blood cu

  20. Prevalence of Methicillin–Resistant Staphylococcus aureus (MRSA ...

    African Journals Online (AJOL)

    Prof. Ogunji

    3Department of Food Science and Technology, School of Technology Institute of ... antimicrobial susceptibility pattern of this pathogen is necessary for selection of appropriate .... and methicillin-resistant Staphylococcus aureus in Shiraz-Iran.

  1. Improving Diagnosis and Treatment of Staphylococcus aureus Infections : Experimental Studies

    NARCIS (Netherlands)

    S. van den Berg (Sanne)

    2015-01-01

    markdownabstract__Abstract__ Staphylococcus aureus is an opportunistic pathogen that causes a variety of infections, ranging from mild skin infections like furuncles and impetigo, to severe, lifethreatening infections including endocarditis, osteomyelitis and pneumonia. Invasive infections are freq

  2. Improving Diagnosis and Treatment of Staphylococcus aureus Infections : Experimental Studies

    NARCIS (Netherlands)

    S. van den Berg (Sanne)

    2015-01-01

    markdownabstract__Abstract__ Staphylococcus aureus is an opportunistic pathogen that causes a variety of infections, ranging from mild skin infections like furuncles and impetigo, to severe, lifethreatening infections including endocarditis, osteomyelitis and pneumonia. Invasive infections are

  3. Characterisation of Staphylococcus aureus bacteraemia at Tygerberg hospital

    NARCIS (Netherlands)

    Orth, H.; Dreyer, Z.S.; Makgotlho, E.; Oosthuysen, W.; Sinha, B.; Wasserman, E.

    2013-01-01

    To elucidate the local epidemiology of Staphylococcus aureus bacteraemia, we characterised blood culture isolates using molecular methods and prospectively collected clinical data to determine the occurrence of community-acquired, methicillinresistant S. aureus (MRSA). Consecutive S. aureus blood cu

  4. Coagulase-negative Staphylococcus sp septicemia in a lovebird.

    Science.gov (United States)

    Bounous, D I; Schaeffer, D O; Roy, A

    1989-10-15

    Gram-positive cocci were observed within phagocytes in the blood of a psittacine with clinical signs of blindness and CNS disease. A coagulase-negative Staphylococcus sp was isolated from blood cultures, and the bird was successfully treated with chloramphenicol. Although the primary route of infection was not determined, the infection spread secondarily via the hematogenous route and localized intraocularly. Usually, only coagulase-positive strains of Staphylococcus are considered pathogenic, and are seldom diagnosed before death.

  5. Methicillin resistant Staphylococcus aureus in Ethiopia: a meta-analysis.

    Science.gov (United States)

    Eshetie, Setegn; Tarekegn, Fentahun; Moges, Feleke; Amsalu, Anteneh; Birhan, Wubet; Huruy, Kahsay

    2016-11-21

    The burden of methicillin resistant Staphylococcus aureus is a major public health concern worldwide; however the overall epidemiology of multidrug resistant strains is neither coordinated nor harmonized, particularly in developing countries including Ethiopia. Therefore, the aim of this meta-analysis was to assess the burden of methicillin resistant Staphylococcos aureus and its antibiotic resistance pattern in Ethiopia at large. PubMed, Google Scholar, and lancet databases were searched and a total of 20 studies have been selected for meta-analysis. Six authors have independently extracts data on the prevalence of methicillin resistant Staphylococcus aureus among clinical isolates of Staphylococcus aureus. Statistical analysis was achieved by using Open meta-analyst (version 3.13) and Comprehensive meta-analysis (version 3.3) softwares. The overall prevalence of methicillin resistant Staphylococcus aureus and its antibiotic resistance pattern were pooled by using the forest plot, table and figure with 95% CI. The pooled prevalence of methicillin resistant Staphylococcus aureus was 32.5% (95% CI, 24.1 to 40.9%). Moreover, methicillin resistant Staphylococcus aureus strains were found to be highly resistant to penicillin, ampicillin, erythromycin, and amoxicillin, with a pooled resistance ratio of 99.1, 98.1, 97.2 and 97.1%, respectively. On the other hand, comparably low levels of resistance ratio were noted to vancomycin, 5.3%. The overall burden of methicillin resistant Staphylococcus aureus is considerably high, besides these strains showed extreme resistance to penicillin, ampicillin, erythromycin and amoxicillin. In principle, appropriate use of antibiotics, applying safety precautions are the key to reduce the spread of multidrug resistant strains, methicillin resistant Staphylococcus aureus in particular.

  6. Staphylococcus epidermidis adhesion and biofilm formation onto biomaterials

    OpenAIRE

    2009-01-01

    Tese de doutoramento em Engenharia Química e Biológica Staphylococcus epidermidis is a coagulase-negative Staphylococcus (CNS) that often colonizes the skin and mucous membranes of the human body, as part of its normal microflora. However, when a rupture of the cutaneous surface occurs, by any type of trauma or insertion of a medical device, staphylococci can enter the host and become pathogenic. Therefore, S. epidermidis has emerged in recent years as a major nosocomial pathogen associate...

  7. Long-term mortality after Staphylococcus aureus spondylodiscitis

    DEFF Research Database (Denmark)

    Aagaard, Theis; Larsen, Anders R; Roed-Petersen, Casper;

    2014-01-01

    Patients diagnosed with Staphylococcus aureus spondylodiscitis have increased long-term mortality compared with the background population mainly due to infectious, endocrine, cardiovascular, gastrointestinal and alcohol and drug abuse-related diseases.......Patients diagnosed with Staphylococcus aureus spondylodiscitis have increased long-term mortality compared with the background population mainly due to infectious, endocrine, cardiovascular, gastrointestinal and alcohol and drug abuse-related diseases....

  8. IDENTIFIKASI MIKROORGANISE STAPHYLOCOCCUS AUREUS PADA PENDERITA ANGULAR CHEILITIS

    OpenAIRE

    MINARTI, NURHAERATUL

    2012-01-01

    2011 Pada suatu penelitian tentang Angular cheilitis ditemukan Staphylococcus aureus hampir dua kali dari candida albicans. Oleh karena itu tujuan penelitian ini adalah untuk mengidentifikasi pengaruh Staphylococcus aureus pada penyakit Angular cheilitis. Sampel penelitian adalah 30 pasien yang datang ke Rumah Sakit Gigi dan Mulut Halimah Daeng Sikati Kandea Bagian Penyakit Gigi dan Mulut dalam periode waktu bulan Oktober-November 2011. Apusan pada permukaan lesi angular cheilitis dima...

  9. Identifizierung und Charakterisierung eines Sdr-Proteins von Staphylococcus saprophyticus

    OpenAIRE

    Sakinç, Türkân

    2001-01-01

    Gegenstand der vorliegenden Arbeit war es, das Oberflächenprotein Ssp zu klonieren und zu charakterisieren. Stattdessen wurde ein neues Zellwand-assoziertes Protein, das SdrI, ein MSCRAMM, kloniert. Dies sollte zur Klärung der Uropathogenität von Staphylococcus saprophyticus weiterhelfen. Die Voraussetzungen zur Untersuchung der Funktion des SdrI Protein von Staphylococcus saprophyticus wurde durch die Konstruktion einer isogenen Mutante geschaffen. Die Bedeutung der SdrI-Protein ...

  10. Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: Adjuvant 5-FU/cisplatin and chemoradiation with capecitabine

    Institute of Scientific and Technical Information of China (English)

    Hyung-Sik Lee; Min-Chan Kim; Youngmin Choi; Won-Joo Hur; Hyo-Jin Kim; Hyuk-Chan Kwon; Sung-Hyun Kim; Jae-Seok Kim; Jong-Hoon Lee; Ghap-Joong Jung

    2006-01-01

    AIM: To evaluate the efficacy and toxicity of postoperative chemoradiation using FP chemotherapy and oral capecitabine during radiation for advanced gastric cancer following curative resection.METHODS: Thirty-one patients who had underwent a potentially curative resection for Stage Ⅲ and Ⅳ (MO) gastric cancer were enrolled. Therapy consists of one cycle of FP (continuous infusion of 5-FU 1000 mg/m2 on d 1 to 5 and cisplatin 60 mg/m2 on d 1) followed by 4500 cGy (180 cGy/d) with capecitabine (1650 mg/m2 daily throughout radiotherapy). Four wk after completion of the radiotherapy, patients received three additional cycles of FP every three wk. The median follow-up duration was 22.2 mo.RESULTS: The 3-year disease free and overall survival in this study were 82.7% and 83.4%, respectively. Four patients (12.9%) showed relapse during follow-up. Eight patients did not complete all planned adjuvant therapy.Grade 3/4 toxicities included neutropenia in 50.2%, anemia in 12.9%, thrombocytopenia in 3.2% and nausea/vomiting in 3.2%. Neither grade 3/4 hand foot syndrome nor treatment related febrile neutropenia or death were observed.CONCLUSION: These preliminary results suggest that this postoperative adjuvant chemoradiation regimen of FP before and after capecitabine and concurrent radiotherapy appears well tolerated and offers a comparable toxicity profile to the chemoradiation regimen utilized in INT-0116. This treatment modality allowed successful loco-regional control rate and 3-year overall survival.

  11. Adjuvant treatment for Stage I seminoma: Why radiotherapy is better than carboplatin.

    Science.gov (United States)

    Yathiraj, Prahlad H; Sharan, Krishna; Fernandes, Donald J; Vidyasagar, M S

    2016-01-01

    Adjuvant treatment options for Stage I seminoma include active surveillance, chemotherapy, and radiotherapy. Active surveillance may not be ideal for the average Indian patient. Of the two accepted adjuvant therapy options, namely single-dose carboplatin chemotherapy and radiotherapy to the retroperitoneal nodes, though it intuitively appears more appealing, a deeper review reveals the potential drawbacks of chemotherapy. This article highlights the misconceptions regarding carboplatin and provides reasons for an argument why radiotherapy is better when a patient with Stage I seminoma chooses to undergo adjuvant treatment.

  12. Adjuvant chemotherapy for completely resected non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Toyooka,Shinichi

    2009-10-01

    Full Text Available For many years, surgery alone was the standard treatment for patients with stage I-IIIA non-small-cell lung cancer (NSCLC. However, recent studies have demonstrated that adjuvant chemotherapy provides a survival benefit. The first adjuvant chemotherapy for NSCLC was performed in the 1960s using a key drug known as cyclophosphamide. In the 1980s and early 1990s, a new anti-cancer drug, cisplatin, was developed. The first meta-analysis of this drug was conducted by the Non-small Cell Lung Cancer Collaborative Group in 1995. This analysis comparing surgery with surgery plus chemotherapy containing cisplatin produced a hazard ratio of 0.87 and suggested an absolute benefit of chemotherapy of 5% at 5 years;this difference was not statistically significant (p0.08. Several clinical trials of adjuvant chemotherapy were planned after the meta-analysis conducted in 1995, but the efficacy of adjuvant chemotherapy remained a matter of controversy. However, useful evidence was reported after 2003. The International Adjuvant Lung Cancer Collaborative Group Trial (IALT demonstrated a 4.1% improvement in survival for patients with stage I to III NSCLC. The JBR. 10 trial demonstrated a 15% improvement in 5-year survival for the adjuvant chemotherapy arm in stage IB or II (excluding T3N0 patients. The Adjuvant Navelbine International Trialist Association (ANITA trial reported that the overall survival at 5 years improved by 8.6% in the chemotherapy arm and that this survival rate was maintained at 7 years (8.4% in stage II and IIIA patients. A meta-analysis based on collected and pooled individual patient data from the 5 largest randomized trials was conducted by the Lung Adjuvant Cisplatin Evaluation (LACE. This analysis demonstrated that cisplatin-based adjuvant chemotherapy improved survival in patients with stage II or III cancer. Alterna-tively, uracil-tegafur has been developed and tested in Japan. The Japan Lung Cancer Research Group (JLCRG on Postsurgical

  13. Coagulase-Positive Staphylococcus: Prevalence and Antimicrobial Resistance.

    Science.gov (United States)

    Beça, Nuno; Bessa, Lucinda Janete; Mendes, Ângelo; Santos, Joana; Leite-Martins, Liliana; Matos, Augusto J F; da Costa, Paulo Martins

    2015-01-01

    Staphylococcus pseudintermedius is the most prevalent coagulase-positive Staphylococcus inhabitant of the skin and mucosa of dogs and cats, causing skin and soft tissue infections in these animals. In this study, coagulase-positive Staphylococcus species were isolated from companion animals, veterinary professionals, and objects from a clinical veterinary environment by using two particular culture media, Baird-Parker RPF agar and CHROMagar Staph aureus. Different morphology features of colonies on the media allowed the identification of the species, which was confirmed by performing a multiplex polymerase chain reaction (PCR). Among 23 animals, 15 (65.2%) harbored coagulase-positive Staphylococcus, being 12 Staphylococcus pseudintermedius carriers. Four out of 12 were methicillin-resistant S. pseudintermedius (MRSP). All veterinary professionals had coagulase-positive Staphylococcus (CoPS) species on their hands and two out of nine objects sampled harbored MRSP. The antimicrobial-resistance pattern was achieved for all isolates, revealing the presence of many multidrug-resistant CoPS, particularly S. pseudintermedius . The combined analysis of the antimicrobial-resistance patterns shown by the isolates led to the hypothesis that there is a possible crosscontamination and dissemination of S. aureus and S. pseudintermedius species between the three types of carriers sampled in this study that could facilitate the spread of the methicillin-resistance phenotype.

  14. BIOFILM DETECTION AND CLINICAL SIGNIFICANCE OF STAPHYLOCOCCUS EPIDERMIDIS ISOLATES

    Directory of Open Access Journals (Sweden)

    Sudha Rani

    2015-04-01

    Full Text Available CONTEXT: Isolates of Staphylococcus epidermidis . AIMS : To detect biofilm among clinical isolates of Staphylococcus epidermidis . MATERIAL AND METHODS : 50 Staphylococcus epidermidis isolates were collected from clinical samples like blood, IV catheter tips, catheterized urine, wound swabs and exudates received from various clinical departments. Biofilm formation was studied in these isolates. The study was carried out over a period o f one year i. e from March 2011 - February 2012. The specimens received were processed by conventional methods. Tissue Culture plate method was used for detection of biofilm. RESULTS: IV catheter tip samples revealed 25%, implant device associated infection s revealed 20%, the Catheterized urine samples showed 16%, blood culture 8%, ventilator associated infections 10%, post - operative wound infections 11% & exudates 5% of Staphylococcus epidermidis isolates. Isolates with O. D. values more than 0. 2 were consi dered as high biofilm producers. 40% of S. epidermidis isolates were weak biofilm producers, 24% were moderate biofilm producers and 36% were high biofilm producers. Isolates from IV catheter tips showed high biofilm formation. CONCLUSIONS: In the modern h ealth care set up, various devices such as IV catheters, urine catheters, shunts, implanted prosthetic devices etc are being increasingly used thereby causing the device associated infections particularly of Staphylococcus epidermidis. Device associated in fections caused by Staphylococcus epidermidis are mainly due to biofilm formation which ultimately makes the treatment difficult.

  15. Immunogenic potential of Rhipicephalus (Boophilus) microplus aquaporin 1 against Rhipicephalus sanguineus in domestic dogs

    Science.gov (United States)

    This study evaluated a recombinant aquaporin 1 protein of Rhipicephalus microplus (RmAQP1) as antigen in a vaccine against R. sanguineus. Five dogs were vaccinated with RmAQP1 (10 µg) + adjuvant (Montanide) (G1), and five were inoculated with adjuvant only (G2), three times. Twenty-one days after th...

  16. Antibiotic-specific differences in the response of Staphylococcus aureus to treatment with antimicrobials combined with manuka honey

    Directory of Open Access Journals (Sweden)

    Michael eLiu

    2015-01-01

    Full Text Available Skin infections caused by antibiotic resistant Staphylococcus aureus are a significant health problem worldwide; often associated with high treatment cost and mortality rate. Complex natural products like New Zealand (NZ manuka honey have been revisited and studied extensively as an alternative to antibiotics due to their potent broad-spectrum antimicrobial activity, and the inability to isolate honey-resistant S. aureus. Previous studies showing synergistic effects between manuka-type honeys and antibiotics have been demonstrated against the growth of one methicillin-resistant S. aureus (MRSA strain. We have previously demonstrated strong synergistic activity between NZ manuka-type honey and rifampicin against growth and biofilm formation of multiple S. arueus strains. Here, we have expanded our investigation using multiple S. aureus strains and four different antibiotics commonly used to treat S. aureus-related skin infections: rifampicin, oxacillin, gentamicin and clindamycin. Using checkerboard microdilution and agar diffusion assays with S. aureus strains including clinical isolates and MRSA we demonstrate that manuka-type honey combined with these four antibiotics frequently produces a synergistic effect. In some cases when synergism was not observed, there was a significant enhancement in antibiotic susceptibility. Some strains that were highly resistant to an antibiotic when present alone become sensitive to clinically-achievable concentrations when combined with honey. However, not all of the S. aureus strains tested responded in the same way to these combinational treatments. Our findings support the use of NZ manuka-type honeys in clinical treatment against S. aureus-related infections and extend their potential use as an antibiotic adjuvant in combinational therapy. Our data also suggest that manuka-type honeys may not work as antibiotic adjuvants for all strains of S. aureus, and this may help determine the mechanistic processes

  17. SAMMD: Staphylococcus aureus Microarray Meta-Database

    Directory of Open Access Journals (Sweden)

    Elasri Mohamed O

    2007-10-01

    Full Text Available Abstract Background Staphylococcus aureus is an important human pathogen, causing a wide variety of diseases ranging from superficial skin infections to severe life threatening infections. S. aureus is one of the leading causes of nosocomial infections. Its ability to resist multiple antibiotics poses a growing public health problem. In order to understand the mechanism of pathogenesis of S. aureus, several global expression profiles have been developed. These transcriptional profiles included regulatory mutants of S. aureus and growth of wild type under different growth conditions. The abundance of these profiles has generated a large amount of data without a uniform annotation system to comprehensively examine them. We report the development of the Staphylococcus aureus Microarray meta-database (SAMMD which includes data from all the published transcriptional profiles. SAMMD is a web-accessible database that helps users to perform a variety of analysis against and within the existing transcriptional profiles. Description SAMMD is a relational database that uses MySQL as the back end and PHP/JavaScript/DHTML as the front end. The database is normalized and consists of five tables, which holds information about gene annotations, regulated gene lists, experimental details, references, and other details. SAMMD data is collected from the peer-reviewed published articles. Data extraction and conversion was done using perl scripts while data entry was done through phpMyAdmin tool. The database is accessible via a web interface that contains several features such as a simple search by ORF ID, gene name, gene product name, advanced search using gene lists, comparing among datasets, browsing, downloading, statistics, and help. The database is licensed under General Public License (GPL. Conclusion SAMMD is hosted and available at http://www.bioinformatics.org/sammd/. Currently there are over 9500 entries for regulated genes, from 67 microarray

  18. Staphylococcus epidermidis ΔSortase A strain elicits protective immunity against Staphylococcus aureus infection.

    Science.gov (United States)

    Tan, Chao; Wang, Jun; Hu, Yifang; Wang, Peng; Zou, Lili

    2017-01-01

    Staphylococcus aureus and Staphylococcus epidermidis are two of the most significant opportunistic human pathogens, causing medical implant and nosocomial infections worldwide. These bacteria contain surface proteins that play crucial roles in multiple biological processes. It has become apparent that they have evolved a number of unique mechanisms by which they can immobilise proteins on their surface. Notably, a conserved cell membrane-anchored enzyme, sortase A (SrtA), can catalyse the covalent attachment of precursor bacterial cell wall-attached proteins to peptidoglycan. Considering its indispensable role in anchoring substrates to the cell wall and its effects on virulence, SrtA has attracted great attention. In this study, a 549-bp gene was cloned from a pathogenic S. epidermidis strain, YC-1, which shared high identity with srtA from other Staphylococcus spp. A mutant strain, YC-1ΔsrtA, was then constructed by allelic exchange mutagenesis. The direct survival rate assay suggested that YC-1ΔsrtA had a lower survival capacity in healthy mice blood compare with the wild-type strain, indicating that the deletion of srtA affects the virulence and infectious capacity of S. epidermidis YC-1. YC-1ΔsrtA was then administered via intraperitoneal injection and it provided a relative percent survival value of 72.7 % in mice against S. aureus TC-1 challenge. These findings demonstrate the possbility that YC-1ΔsrtA might be used as a live attenuated vaccine to produce cross-protection against S. aureus.

  19. Assessment of the efficacy of polyclonal intravenous immunoglobulin G (IVIG) against the infectivity of clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo.

    Science.gov (United States)

    Farag, N; Mahran, L; Abou-Aisha, K; El-Azizi, M

    2013-09-01

    The response to treatment of severe methicillin-resistant Staphylococcus aureus (MRSA) infections with the traditional antibiotics is sometimes unsatisfactory and multiple antibiotic resistance is common. Adjuvant therapy such as intravenous immunoglobulin G (IVIG) could possibly be helpful in the treatment of such infections. The effect of IVIG on the capacity of human neutrophils to phagocytose and kill MRSA was investigated in vitro using the MTT assay and measuring the production of reactive oxygen species (ROS) and nitric oxide (NO). The efficiency of IVIG in neutralizing α-hemolysin and coagulase of MRSA was also assessed. The capability of IVIG in the treatment and prevention of MRSA infections was also evaluated in a murine peritonitis model. IVIG significantly enhanced (p MRSA by neutrophils at all concentrations tested (0.1-5 mg/ml) by 30-80 % of control values. It significantly (p MRSA 10-fold and its coagulation capabilities by 50 %. When tested in vivo, groups receiving IVIG via tail vein infusion showed no significant improvement in their survival. Only when delivered to the same site of infection did IVIG show an improvement in the survival of mice (n = 80). These results could pave the way for a better understanding of the mechanism of action of IVIG and suggest its clinical potential as an adjuvant preventive and therapeutic agent against life-threatening infections caused by MRSA and other bacteria.

  20. Tratamento adjuvante nos GISTs Adjuvant treatment in GISTs

    Directory of Open Access Journals (Sweden)

    Laercio Gomes Lourenço

    2011-09-01

    Full Text Available INTRODUÇÃO: O tumor estromal gastrointestinal (GIST é o sarcoma mais comum do aparelho digestivo. Essa neoplasia ocorre devido à mutação do gene KIT com consequente ativação constitutiva da proteína KIT. O tratamento primário é cirúrgico e consiste na sua ressecção completa. Entretanto, alguns grupos de pacientes apresentam risco elevado de recorrência mesmo após operação com ressecção completa (R0, indicando diferenças no comportamento biológico. Estudos clínicos comprovaram a atividade clínica do mesilato de imatinibe, fazendo dele a primeira linha de tratamento padrão nos GISTs metastáticos ou irressecáveis, mudando muito o desfecho clínico dessa doença em relação aos benefícios anteriormente obtidos com a quimioterapia antineoplásica. MÉTODO: Foi realizada revisão da literatura com consulta nos periódicos das bases Medline/Pubmed, Scielo e Lilacs cruzando os descritores: tumor estromal gastrointestinal, Gist, tratamento, adjuvância. Além desta revisão foi adicionada a experiência pessoal dos autores. CONCLUSÃO: Melhor refinamento dos critérios de prognóstico tem permitido selecionar de forma mais adequada pacientes para o tratamento adjuvante com imatinibe. Os resultados de maior evidência até o momento respaldam o tratamento adjuvante por um ano, o que produz benefício significativo na sobrevida livre de recidiva, mas não na sobrevida global desses pacientes.INTRODUCTION: Gastrointestinal stromal tumor (GIST is the most common sarcoma of the digestive tract. This cancer occurs due to mutation of the KIT gene resulting in constitutive activation of KIT protein. The primary treatment is surgical and consists of complete resection. However, some groups of patients at high risk of recurrence even after surgery with complete resection (R0, indicate differences in biological behavior. Clinical studies have demonstrated the clinical activity of imatinib mesylate, making it the standard first

  1. Effects of 3% trehalose as an adjuvant treatment after LASIK

    Directory of Open Access Journals (Sweden)

    Mateo Orobia AJ

    2017-02-01

    Full Text Available Antonio J Mateo Orobia,1–3 Paula Casas Pascual,1,4 José Á Cristóbal Bescós,1 Diana Perez García,1,4 Carlos Peiro Embid,1,4 M Ángeles del Buey Sayas,1,4 Valentyna Korobko Kulikova,1 Noelia Lafuente Ojeda5 1Department of Ophthalmology, Hospital Quirón, 2Department of Ophthalmology, Hospital Universitario Miguel Servet, 3Instituto de Investigación Sanitaria de Aragón (IIS, 4Department of Ophthalmology, Hospital Clínico Universitario Lozano-Blesa, 5Department of Anesthesiology, Hospital Universitario Miguel Servet, Zaragoza, Spain Purpose: To evaluate the effect of 3% trehalose as an adjuvant in the standard treatment after laser-assisted in situ keratomileusis.Design: Interventional prospective comparative single-blind study.Setting: Department of Ophthalmology, Hospital Quirón Zaragoza, Spain.Methods: A total of 26 eyes (13 patients were included, of which 12 eyes (group 1 received conventional treatment with lubricant drops of hyaluronic acid (0.15% and 14 eyes (group 2 received, additionally, an ophthalmic solution of 3% trehalose. Pre- and postoperative quality-of-life tests and vital stains, tear breakup time, and osmolarity measurements were made.Results: We obtained statistically significant differences between the groups in the Symptom Assessment in Dry Eye test in all visits with respect to severity, and in the postoperative day 1 visit with respect to frequency, in all cases favoring the trehalose treatment. The values of osmolarity were not significantly different between groups. However, we did find significant differences in the Oxford scale in day 90 for the trehalose treatment (P<0.001, and in the National Eye Institute scale in day 30 (P=0.02.Conclusion: The results of this exploratory study indicate that the adjuvant treatment with 3% trehalose could be superior with respect to the standard treatment, with improvements in the objective and subjective parameters of tear quality. Keywords: dry eye syndrome, trehalose

  2. NVC-422 inactivates Staphylococcus aureus toxins.

    Science.gov (United States)

    Jekle, Andreas; Yoon, Jungjoo; Zuck, Meghan; Najafi, Ramin; Wang, Lu; Shiau, Timothy; Francavilla, Charles; Rani, Suriani Abdul; Eitzinger, Christian; Nagl, Markus; Anderson, Mark; Debabov, Dmitri

    2013-02-01

    Bacterial pathogens have specific virulence factors (e.g., toxins) that contribute significantly to the virulence and infectivity of microorganisms within the human hosts. Virulence factors are molecules expressed by pathogens that enable colonization, immunoevasion, and immunosuppression, obtaining nutrients from the host or gaining entry into host cells. They can cause pathogenesis by inhibiting or stimulating certain host functions. For example, in systemic Staphylococcus aureus infections, virulence factors such as toxic shock syndrome toxin 1 (TSST-1), staphylococcal enterotoxin A (SEA), and staphylococcal enterotoxin B (SEB) cause sepsis or toxic shock by uncontrolled stimulation of T lymphocytes and by triggering a cytokine storm. In vitro, these superantigens stimulate the proliferation of human peripheral blood mononuclear cells (PBMC) and the release of many cytokines. NVC-422 (N,N-dichloro-2,2-dimethyltaurine) is a broad-spectrum, fast-acting topical anti-infective agent against microbial pathogens, including antibiotic-resistant microbes. Using mass spectrometry, we demonstrate here that NVC-422 oxidizes methionine residues of TSST-1, SEA, SEB, and exfoliative toxin A (ETA). Exposure of virulence factors to 0.1% NVC-422 for 1 h prevented TSST-1-, SEA-, SEB-, and ETA-induced cell proliferation and cytokine release. Moreover, NVC-422 also delayed and reduced the protein A- and clumping factor-associated agglutination of S. aureus cultures. These results show that, in addition to its well-described direct microbicidal activity, NVC-422 can inactivate S. aureus virulence factors through rapid oxidation of methionines.

  3. Toxin-Antitoxin Systems of Staphylococcus aureus.

    Science.gov (United States)

    Schuster, Christopher F; Bertram, Ralph

    2016-05-05

    Toxin-antitoxin (TA) systems are small genetic elements found in the majority of prokaryotes. They encode toxin proteins that interfere with vital cellular functions and are counteracted by antitoxins. Dependent on the chemical nature of the antitoxins (protein or RNA) and how they control the activity of the toxin, TA systems are currently divided into six different types. Genes comprising the TA types I, II and III have been identified in Staphylococcus aureus. MazF, the toxin of the mazEF locus is a sequence-specific RNase that cleaves a number of transcripts, including those encoding pathogenicity factors. Two yefM-yoeB paralogs represent two independent, but auto-regulated TA systems that give rise to ribosome-dependent RNases. In addition, omega/epsilon/zeta constitutes a tripartite TA system that supposedly plays a role in the stabilization of resistance factors. The SprA1/SprA1AS and SprF1/SprG1 systems are post-transcriptionally regulated by RNA antitoxins and encode small membrane damaging proteins. TA systems controlled by interaction between toxin protein and antitoxin RNA have been identified in S. aureus in silico, but not yet experimentally proven. A closer inspection of possible links between TA systems and S. aureus pathophysiology will reveal, if these genetic loci may represent druggable targets. The modification of a staphylococcal TA toxin to a cyclopeptide antibiotic highlights the potential of TA systems as rather untapped sources of drug discovery.

  4. Immunopathogenesis of Staphylococcus aureus pulmonary infection

    Science.gov (United States)

    Parker, Dane; Prince, Alice

    2013-01-01

    Staphylococcus aureus is a common human pathogen highly evolved as both a component of the commensal flora and as a major cause of invasive infection. Severe respiratory infection due to staphylococci has been increasing due to the prevalence of more virulent USA300 CA-MRSA strains in the general population. The ability of S. aureus to adapt to the milieu of the respiratory tract has facilitated its emergence as a respiratory pathogen. Its metabolic versatility, the ability to scavenge iron, coordinate gene expression, and the horizontal acquisition of useful genetic elements have all contributed to its success as a component of the respiratory flora, in hospitalized patients, as a complication of influenza and in normal hosts. The expression of surface adhesins facilitates its persistence in the airways. In addition, the highly sophisticated interactions of the multiple S. aureus virulence factors, particularly the α-hemolysin and protein A, with diverse immune effectors in the lung such as ADAM10, TNFR1, EGFR, immunoglobulin, and complement all contribute to the pathogenesis of staphylococcal pneumonia. PMID:22037948

  5. Aspartate inhibits Staphylococcus aureus biofilm formation.

    Science.gov (United States)

    Yang, Hang; Wang, Mengyue; Yu, Junping; Wei, Hongping

    2015-04-01

    Biofilm formation renders Staphylococcus aureus highly resistant to conventional antibiotics and host defenses. Four D-amino acids (D-Leu, D-Met, D-Trp and D-Tyr) have been reported to be able to inhibit biofilm formation and disassemble established S. aureus biofilms. We report here for the first time that both D- and L-isoforms of aspartate (Asp) inhibited S. aureus biofilm formation on tissue culture plates. Similar biofilm inhibition effects were also observed against other staphylococcal strains, including S. saprophyticus, S. equorum, S. chromogenes and S. haemolyticus. It was found that Asp at high concentrations (>10 mM) inhibited the growth of planktonic N315 cells, but at subinhibitory concentrations decreased the cellular metabolic activity without influencing cell growth. The decreased cellular metabolic activity might be the reason for the production of less protein and DNA in the matrix of the biofilms formed in the presence of Asp. However, varied inhibition efficacies of Asp were observed for biofilms formed by clinical staphylococcal isolates. There might be mechanisms other than decreasing the metabolic activity, e.g. the biofilm phenotypes, affecting biofilm formation in the presence of Asp.

  6. Control of Staphylococcus aureus pathogenicity island excision.

    Science.gov (United States)

    Mir-Sanchis, Ignacio; Martínez-Rubio, Roser; Martí, Miguel; Chen, John; Lasa, Íñigo; Novick, Richard P; Tormo-Más, María Ángeles; Penadés, José R

    2012-09-01

    Staphylococcus aureus pathogenicity islands (SaPIs) are a group of related 15-17 kb mobile genetic elements that commonly carry genes for superantigen toxins and other virulence factors. The key feature of their mobility is the induction of SaPI excision and replication by certain phages and their efficient encapsidation into specific small-headed phage-like infectious particles. Previous work demonstrated that chromosomal integration depends on the SaPI-encoded recombinase, Int. However, although involved in the process, Int alone was not sufficient to mediate efficient SaPI excision from chromosomal sites, and we expected that SaPI excision would involve an Xis function, which could be encoded by a helper phage or by the SaPI, itself. Here we report that the latter is the case. In vivo recombination assays with plasmids in Escherichia coli demonstrate that SaPI-coded Xis is absolutely required for recombination between the SaPI att(L) and att(R) sites, and that both sites, as well as their flanking SaPI sequences, are required for SaPI excision. Mutational analysis reveals that Xis is essential for efficient horizontal SaPI transfer to a recipient strain. Finally, we show that the master regulator of the SaPI life cycle, Stl, blocks expression of int and xis by binding to inverted repeats present in the promoter region, thus controlling SaPI excision.

  7. Predictors of Mortality in Staphylococcus aureus Bacteremia

    Science.gov (United States)

    Jensen, Slade O.; Vaska, Vikram L.; Espedido, Björn A.; Paterson, David L.; Gosbell, Iain B.

    2012-01-01

    Summary: Staphylococcus aureus bacteremia (SAB) is an important infection with an incidence rate ranging from 20 to 50 cases/100,000 population per year. Between 10% and 30% of these patients will die from SAB. Comparatively, this accounts for a greater number of deaths than for AIDS, tuberculosis, and viral hepatitis combined. Multiple factors influence outcomes for SAB patients. The most consistent predictor of mortality is age, with older patients being twice as likely to die. Except for the presence of comorbidities, the impacts of other host factors, including gender, ethnicity, socioeconomic status, and immune status, are unclear. Pathogen-host interactions, especially the presence of shock and the source of SAB, are strong predictors of outcomes. Although antibiotic resistance may be associated with increased mortality, questions remain as to whether this reflects pathogen-specific factors or poorer responses to antibiotic therapy, namely, vancomycin. Optimal management relies on starting appropriate antibiotics in a timely fashion, resulting in improved outcomes for certain patient subgroups. The roles of surgery and infectious disease consultations require further study. Although the rate of mortality from SAB is declining, it remains high. Future international collaborative studies are required to tease out the relative contributions of various factors to mortality, which would enable the optimization of SAB management and patient outcomes. PMID:22491776

  8. Recognition and importance of Staphylococcus epidermidis infections.

    Science.gov (United States)

    Blum, R A; Rodvold, K A

    1987-06-01

    The bacteriology, epidemiology, pathogenesis, clinical features, antimicrobial susceptibility, and therapy of Staphylococcus epidermidis infections are reviewed. Staph. epidermidis is often regarded as a culture contaminant, but its importance as a pathogen has been recognized in recent years. Except for native-valve endocarditis, most Staph. epidermidis infections are hospital-acquired. Staph. epidermidis is a common cause of infections involving indwelling foreign devices, surgical wound infections, and bacteremia in immunocompromised patients. The occult nature of these infections and low virulence of the organism make diagnosis and treatment difficult. Staph. epidermidis isolates from nosocomial infections frequently are resistant to methicillin; however, resistant isolates often appear to be susceptible to methicillin unless reliable methods of susceptibility testing are used. Cross-resistance between methicillin and cephalosporins occurs in vitro. Virtually all Staph. epidermidis isolates are susceptible in vitro to vancomycin and rifampin. Penicillin G, semisynthetic penicillinase-resistant penicillins, and cephalosporins are effective for the treatment of methicillin-sensitive Staph. epidermidis infections. Vancomycin is the drug of choice for infections caused by methicillin-resistant organisms. Vancomycin, combined with rifampin or gentamicin, or both, is recommended for therapy of serious infections caused by methicillin-resistant strains. Staph. epidermidis is an important pathogen in immunocompromised patients and patients who develop nosocomial bacteremia; treatment usually consists of antimicrobial therapy and removal of indwelling catheters or devices.

  9. Molecular basis of Staphylococcus epidermidis infections.

    Science.gov (United States)

    Otto, Michael

    2012-03-01

    Staphylococcus epidermidis is the most important member of the coagulase-negative staphylococci and one of the most abundant colonizers of human skin. While for a long time regarded as innocuous, it has been identified as the most frequent cause of device-related infections occurring in the hospital setting and is therefore now recognized as an important opportunistic pathogen. S. epidermidis produces a series of molecules that provide protection from host defenses. Specifically, many proteins and exopolymers, such as the exopolysaccharide PIA, contribute to biofilm formation and inhibit phagocytosis and the activity of human antimicrobial peptides. Furthermore, recent research has identified a family of pro-inflammatory peptides in S. epidermidis, the phenol-soluble modulins (PSMs), which have multiple functions in immune evasion and biofilm development, and may be cytolytic. However, in accordance with the relatively benign relationship that S. epidermidis has with its host, production of aggressive members of the PSM family is kept at a low level. Interestingly, in contrast to S. aureus with its large arsenal of toxins developed for causing infection in the human host, most if not all "virulence factors" of S. epidermidis appear to have original functions in the commensal lifestyle of this bacterium.

  10. Toxin-Antitoxin Systems of Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Christopher F. Schuster

    2016-05-01

    Full Text Available Toxin-antitoxin (TA systems are small genetic elements found in the majority of prokaryotes. They encode toxin proteins that interfere with vital cellular functions and are counteracted by antitoxins. Dependent on the chemical nature of the antitoxins (protein or RNA and how they control the activity of the toxin, TA systems are currently divided into six different types. Genes comprising the TA types I, II and III have been identified in Staphylococcus aureus. MazF, the toxin of the mazEF locus is a sequence-specific RNase that cleaves a number of transcripts, including those encoding pathogenicity factors. Two yefM-yoeB paralogs represent two independent, but auto-regulated TA systems that give rise to ribosome-dependent RNases. In addition, omega/epsilon/zeta constitutes a tripartite TA system that supposedly plays a role in the stabilization of resistance factors. The SprA1/SprA1AS and SprF1/SprG1 systems are post-transcriptionally regulated by RNA antitoxins and encode small membrane damaging proteins. TA systems controlled by interaction between toxin protein and antitoxin RNA have been identified in S. aureus in silico, but not yet experimentally proven. A closer inspection of possible links between TA systems and S. aureus pathophysiology will reveal, if these genetic loci may represent druggable targets. The modification of a staphylococcal TA toxin to a cyclopeptide antibiotic highlights the potential of TA systems as rather untapped sources of drug discovery.

  11. Reduction of Staphylococcus Spp. in jerked beef samples after irradiation with Co-60

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Marcio de Albuquerque, E-mail: marcioalbuquerquesilva@gmail.com [Instituto Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ (Brazil). Laboratorio de Genomica Funcional e Bioinformatica; Costa, Maria Claudia V.Vicalvi; Junior, Carlos Eduardo de O.C.; Solidonio, Evelyne G.; Sena, Kesia Xisto F.R. de; Colaco, Waldeciro, E-mail: claudiavicalvi@hotmail.com, E-mail: oliveiracosta@msn.com, E-mail: evelyne_solidonio@yahoo.com.br, E-mail: wcolaco@ufpe.com.br, E-mail: k.xisto@gmail.com [Universidade Federal de Pernambuco (UFPE), Recife (Brazil)

    2015-07-01

    This work aimed to isolate and identify Staphylococcus genus microorganisms in jerked beef before and after radiation doses between 2, 4 and 6kGy. Jerked beef samples were obtained on a Recife-PE supermarket network and divided into three lots. Under sterile conditions, the meat was cut and weighed. Sub-samples were assigned to the control group and to the irradiation source of cobalt-60 on doses of 2, 4 and 6kGy. The sub-samples were added to an Erlenmeyer flask with 225 ml of sterile water and stirred for 15 minutes creating wash water, and another part was added to an Erlenmeyer flask with 225 ml of sterile distilled water that was at rest at room temperature for 14 hours there is the formation of a water desalting. 1μL aliquots of this water was removed and sown by depletion in sheep blood agar medium and incubated at 35 °C for 24 hours for analysis of bacterial growth. After Gram staining colonies classified as Gram positive arranged in bunches were subjected to biochemical tests for identification. Were isolated and identified 94 strains of the genus Staphylococcus being 72 (76%) of the control group and 22 (24%) after irradiation. Of the 22 isolates, after irradiation, with 2 kGy 7 species were identified as Staphylococcus succinus, Staphylococcus carnosus sub. carnosus, Staphylococcus fleurettii, Staphylococcus saprophyticus sub. saprophyticus, Staphylococcus simulans, Staphylococcus auricularis all coagulase negative and coagulase positive Staphylococcus aureus sub. anaerobius. At a dose of 4kGy were identified six species: Staphylococcus epidermidis, Staphylococcus xylosus, Staphylococcus intermedius, Staphylococcus warneri, Staphylococcus fleurettii, Staphylococcus aureus sub. anaerobius. Staphylococcus simulans, Staphylococcus saprophyticus sub. saprophyticus, and Staphylococcus lugdunensis were isolated and identified after a dose of 6 kGy. Was observed that irradiation significantly reduced microbial load, and increased dose decreased the number of

  12. Efficacy and toxicity of adjuvant chemotherapy in elderly patients with colorectal cancer

    DEFF Research Database (Denmark)

    Lund, C M; Nielsen, D; Dehlendorff, C

    2016-01-01

    BACKGROUND: Elderly patients with primary colorectal cancer (CRC) are less frequently treated with adjuvant chemotherapy than younger patients due to concerns regarding toxicity and efficiency. We investigated how age, performance status (PS) and comorbidity influence treatment outcomes. PATIENTS...

  13. Adjuvant drugs in autoimmune bullous diseases, efficacy versus safety: Facts and controversies.

    Science.gov (United States)

    Schiavo, Ada Lo; Puca, Rosa Valentina; Ruocco, Vincenzo; Ruocco, Eleonora

    2010-01-01

    During the last decades, the conventional therapy for autoimmune blistering diseases has been high-dose, long-term systemic corticosteroid and immunosuppressive agents or adjuvant drugs. Long-term, high-dose steroid therapy can result in serious adverse effects. The rationale for using adjuvant drugs is that concerns reducing the need for corticosteroids, and hence, their side effects, or it may result in better control of the disease, or both. Immunosuppressive agents are not free of adverse effects, however. Prolonged immune suppression may account for high rates of morbidity, disability, and possible death. There is no consensus about the first-choice adjuvant drug for the management of blistering autoimmune diseases. This contribution evaluates six adjuvant drugs-cyclophosphamide, azathioprine, cyclosporine, mycophenolate mofetil, intravenous immunoglobulin, and rituximab-and discusses the choice of a "winning drug" that is effective and safe.

  14. [Caprine arthritis-encephalitis: trial of an adjuvant vaccine preparation. I. Clinical and virological study].

    Science.gov (United States)

    Russo, P; Vitu, C; Fontaine, J J; Vignoni, M

    1993-04-01

    In purpose to protect goats against caprine arthritis encephalitis virus (CAEV), the first group of kids (I) was inoculated with purified, inactivated and adjuvant-treated virions, the second group (II) with adjuvant and the third one (III) with culture medium. 2-4 months later, the three groups were challenged with virulent CAEV by intraarticular route. On the clinical level, vaccinated and challenged kids show more early and severe arthritis than other groups. On the virological level, isolation of lentivirus from white blood cells and different organs is more important in group I than groups II and III. Therefore, vaccinations with inactivated and adjuvant-treated virions do not protect against a virulent challenge; there is an enhancement of lesions. We note that the adjuvant elicits a mild non-specific protection against virulent challenge.

  15. Efficacy and safety of oxaliplatin chemotherapy programs as adjuvant treatment in colorectal cancer after surgery

    Institute of Scientific and Technical Information of China (English)

    杨莉萍

    2013-01-01

    Objective To compare the efficacy and safety of 5-fluorouracil and calcium folinatc combined with oxaliplatin(FOLFOX) program with capecitabine regimen combined oxaliplatin(XELOX) program as adjuvant chemotherapy in advanced colorectal cancer after surgery.

  16. THE EFFECT OF SYNTHETIC ADJUVANT ON THE FORMATION OF THE IMMUNE RESPONSE

    Directory of Open Access Journals (Sweden)

    Savina, S.V.

    2016-08-01

    Full Text Available The paper contains experimental materials on the effects of synthetic adjuvants on the formation of the immune responses. Currently, the search continues for new effective vaccines based on polymeric compounds having immunostimulating properties (Petrov R. V. et al. 1986, V. Schijns,2000 An important condition in the development of certain carriers (adjuvants is the creation of a drug capable of long-term is in the body, with its active immune system and no local and General negative reactions in the body (Volpin O. M.,1992, etc.. We carried out experiments to study the synthetic adjuvant (BP, the raw material which is polydiallyldimethyl chloride - PES. Conducted preclinical trials to study acute and chronic toxicity in laboratory animals showed no abnormalities in physiological and Toxicological parameters, i.e. its harmlessness. The results show positive effects of synthetic adjuvants on the formation of General immune responses in animals that allow it to be used as a filler in vaccines.

  17. Intravenous or oral administration of vinorelbine in adjuvant chemotherapy with cisplatin and vinorelbine for resected NSCLC

    DEFF Research Database (Denmark)

    Sorensen, Steffen Filskov; Carus, Andreas; Meldgaard, Peter

    2015-01-01

    OBJECTIVES: Cisplatin and vinorelbine given intravenously is a well-established adjuvant chemotherapy regimen after surgery for early-stage NSCLC. Vinorelbine can also be administered orally. However, the efficacy of orally administrated vinorelbine in adjuvant treatment of NSCLC is unknown. We...... assessed the overall survival (OS) and disease-free survival (DFS) of patients treated with adjuvant i.v. vinorelbine or p.o. vinorelbine, in combination with i.v. cisplatin. MATERIALS AND METHODS: We reviewed two time-separated cohorts of patients referred to the Department of Oncology at Aarhus...... University Hospital (Denmark) from 2005 to 2012 for adjuvant chemotherapy after surgery for NSCLC. RESULTS AND CONCLUSION: Of the 265 patients included in this study, 126 patients received i.v. and 139 received p.o. vinorelbine/cisplatin. The two groups were comparable with respect to important baseline...

  18. POLYPRENYL PHOSPHATES AS ADJUVANTS, POLARIZING THE IMMUNE RESPONSE TO Th1

    Directory of Open Access Journals (Sweden)

    A. V. Pronin

    2012-01-01

    Full Text Available Abstract. The attempts to decrease a toxic action of Freund complete adjuvant have led to development of new emulsion adjuvant compositions. More often they are based on metabolizable oil (squalene with addition the Tween 80 (Polisorbate 80 as an emulsifier. The third component is an immunomodulator. Adjuvants, intended for prevention of virus infections, should include the immunomodulators polarizing the immune response to Th1. From this point of view adjuvant based on a colloidal solution prepared by means of the Tween 80 from polyprenyl phasphates of fir needles (Phosprenyl can be rather perspective. The last one, as well as squalene, is constructed by isoprene links, but has them not 6, but 16 that essentially reduces its toxicity. The obtained data shows that Phosprenyl essentially enhances efficiency of vaccination in such virus infections as tick born encephalitis, bird flu, poliomyelitis and polarizes the immune response to Th1.

  19. Psidium guajava leaves decrease arthritic symptoms in adjuvant-induced arthritic rats

    Directory of Open Access Journals (Sweden)

    Hanif Nasiatul Baroroh

    2016-04-01

    Psidium guajava leaf extract is effective in decreasing the inflammatory response and arthritic symptoms in rats with adjuvant-induced arthritis. Psidium guajava leaves can be developed into an alternative anti-arthritis treatment.

  20. Evaluation of genetically inactivated alpha toxin for protection in multiple mouse models of Staphylococcus aureus infection.

    Directory of Open Access Journals (Sweden)

    Rebecca A Brady

    Full Text Available Staphylococcus aureus is a major human pathogen and a leading cause of nosocomial and community-acquired infections. Development of a vaccine against this pathogen is an important goal. While S. aureus protective antigens have been identified in the literature, the majority have only been tested in a single animal model of disease. We wished to evaluate the ability of one S. aureus vaccine antigen to protect in multiple mouse models, thus assessing whether protection in one model translates to protection in other models encompassing the full breadth of infections the pathogen can cause. We chose to focus on genetically inactivated alpha toxin mutant HlaH35L. We evaluated the protection afforded by this antigen in three models of infection using the same vaccine dose, regimen, route of immunization, adjuvant, and challenge strain. When mice were immunized with HlaH35L and challenged via a skin and soft tissue infection model, HlaH35L immunization led to a less severe infection and decreased S. aureus levels at the challenge site when compared to controls. Challenge of HlaH35L-immunized mice using a systemic infection model resulted in a limited, but statistically significant decrease in bacterial colonization as compared to that observed with control mice. In contrast, in a prosthetic implant model of chronic biofilm infection, there was no significant difference in bacterial levels when compared to controls. These results demonstrate that vaccines may confer protection against one form of S. aureus disease without conferring protection against other disease presentations and thus underscore a significant challenge in S. aureus vaccine development.

  1. Antibacterial synergy between rosmarinic acid and antibiotics against methicillin-resistant Staphylococcus aureus

    Science.gov (United States)

    Ekambaram, Sanmuga Priya; Perumal, Senthamil Selvan; Balakrishnan, Ajay; Marappan, Nathiya; Gajendran, Sabari Srinivasan; Viswanathan, Vinodhini

    2016-01-01

    Aim/Background: Medicinal plants have ability to resist microorganisms by synthesizing secondary metabolites such as phenols. Rosmarinic acid (RA) is a phenylpropanoid widely distributed in plants and well known as therapeutic and cosmetic agent. Methicillin-resistant Staphylococcus aureus (MRSA) which is resistant to all kinds of β-lactams, threatens even most potent antibiotics. To improve the efficiency of antibiotics against multi-drug resistant bacteria and to reduce the antibiotic dose, the antibacterial activity and the synergistic effect of RA with standard antibiotics against S. aureus and MRSA was investigated. Materials and Methods: Antibacterial activity of RA against S. aureus and a clinical isolate of MRSA was evaluated by agar well diffusion method. Minimum inhibitory concentration (MIC) of RA was determined by broth dilution method. Synergism of RA with various antibiotics against S. aureus and MRSA was studied by broth checkerboard method and time-kill kinetic assay. Effect of RA on microbial surface components recognizing adhesive matrix molecules (MSCRAMM’s) of S. aureus and MRSA was studied using sodium dodecyl sulfate - polyacrylamide gel electrophoresis. Results: MIC of RA was found to be 0.8 and 10 mg/ml against S. aureus and MRSA, respectively. RA was synergistic with vancomycin, ofloxacin, and amoxicillin against S. aureus and only with vancomycin against MRSA. The time-kill analysis revealed that synergistic combinations were a more effective than individual antibiotics. MSCRAMM’s protein expression of S. aureus and MRSA was markedly suppressed by RA + vancomycin combination rather than RA alone. Conclusion: The synergistic effects of RA with antibiotics were observed against S. aureus and MRSA. RA showed inhibitory effect on the surface proteins MSCRAMM’s. Even though RA was shown to exhibit a synergistic effect with antibiotics, the MIC was found to be higher. Thus, further studies on increasing the efficacy of RA can develop it

  2. Physician Beliefs and Practices for Adjuvant and Salvage Radiation Therapy After Prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Showalter, Timothy N., E-mail: timothy.showalter@jeffersonhospital.org [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Ohri, Nitin; Teti, Kristopher G. [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Foley, Kathleen A. [Strategic Consulting, Thomson Reuters Healthcare, Cambridge, MA (United States); Keith, Scott W. [Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Trabulsi, Edouard J.; Lallas, Costas D. [Department of Urology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Dicker, Adam P. [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Hoffman-Censits, Jean [Department of Medical Oncology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Pizzi, Laura T. [School of Pharmacy, Thomas Jefferson University, Philadelphia, PA (United States); Gomella, Leonard G. [Department of Urology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States)

    2012-02-01

    Purpose: Despite results of randomized trials that support adjuvant radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer with adverse pathologic features (APF), many clinicians favor selective use of salvage RT. This survey was conducted to evaluate the beliefs and practices of radiation oncologists (RO) and urologists (U) regarding RT after RP. Methods and Materials: We designed a Web-based survey of post-RP RT beliefs and policies. Survey invitations were e-mailed to a list of 926 RO and 591 U. APF were defined as extracapsular extension, seminal vesicle invasion, or positive surgical margin. Differences between U and RO in adjuvant RT recommendations were evaluated by comparative statistics. Multivariate analyses were performed to evaluate factors predictive of adjuvant RT recommendation. Results: Analyzable surveys were completed by 218 RO and 92 U (overallresponse rate, 20%). Adjuvant RT was recommended based on APF by 68% of respondents (78% RO, 44% U, p <0.001). U were less likely than RO to agree that adjuvant RT improves survival and/or biochemical control (p < 0.0001). PSA thresholds for salvage RT were higher among U than RO (p < 0.001). Predicted rates of erectile dysfunction due to RT were higher among U than RO (p <0.001). On multivariate analysis, respondent specialty was the only predictor of adjuvant RT recommendations. Conclusions: U are less likely than RO to recommend adjuvant RT. Future research efforts should focus on defining the toxicities of post-RP RT and on identifying the subgroups of patients who will benefit from adjuvant vs. selective salvage RT.

  3. Survival after adjuvant chemoradiotherapy or surgery alone in resectable adenocarcinoma at the gastro-esophageal junction

    DEFF Research Database (Denmark)

    Kofoed, Steen Christian; Muhic, A; Jensen, Lene Bæksgaard;

    2012-01-01

    Longterm survival after curative resection for adenocarcinoma at the gastro-esophageal junction (GEJ) range between 18% and 50%. In the pivotal Intergroup-0116 Phase III trial by Macdonald et all, adjuvant chemoradiotherapy improved both disease-free and overall survival in curatively resected...... patients with mainly gastric adenocarcinoma. We compared survival data for curatively resected patients with adeno-carcinoma solely at the gastro-esophageal junction (GEJ), treated with surgery alone or surgery and adjuvant chemoradio-therapy....

  4. Postoperative Adjuvant Systemic Therapy in Completely Resected Non-Small-Cell Lung Cancer: A Systematic Review.

    Science.gov (United States)

    Bradbury, Penelope; Sivajohanathan, Duvaraga; Chan, Adrien; Kulkarni, Swati; Ung, Yee; Ellis, Peter M

    2017-05-01

    The purpose of the present review was to determine whether the use of postoperative adjuvant systemic therapy in patients with completely resected non-small-cell lung cancer (NSCLC) improves survival. Cancer Care Ontario's Program in Evidence-Based Care reviewed the evidence to update previously published recommendations for patients with completely resected NSCLC. Relevant studies were identified from a systematic MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews search of studies published from 2010 to 2016. All phase III randomized controlled trials (RCTs) and relevant systematic reviews were included. Data on overall survival (OS), disease-free survival, adverse events, and quality of life were extracted from each of the studies. Two relevant systematic reviews, 13 RCTs, and a series of pooled analyses by Lung Adjuvant Cisplatin Evaluation-Biomarker were included in the present review. Adjuvant chemotherapy statistically significantly improved OS for resected stage II-IIIA NSCLC and is recommended. For patients with stage IB NSCLC, no significant improvement was seen in OS; however, the results from subgroup analyses indicate that it would be reasonable to consider adjuvant chemotherapy for patients with larger tumors (≥ 4 cm). The present data do not support the use of adjuvant novel therapies (ie, epidermal growth factor receptor tyrosine kinase inhibitor, bevacizumab, and immunotherapy) either as an addition to, or instead of, cytotoxic chemotherapy. No predictive biomarkers are available to select patients more likely to benefit from adjuvant chemotherapy. Cytotoxic chemotherapy remains the standard of care as adjuvant therapy for patients with resected stage II-IIIA NSCLC. Additional clinical trials are needed to evaluate targeted agents in molecularly defined subgroups before these agents can be recommended in the adjuvant setting. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. The impact of chronic illnesses on the use and effectiveness of adjuvant chemotherapy for colon cancer.

    Science.gov (United States)

    Gross, Cary P; McAvay, Gail J; Guo, Zhenchao; Tinetti, Mary E

    2007-06-15

    It is unclear how noncancer conditions affect the use or effectiveness of adjuvant therapy among older patients with colon cancer. The authors conducted a cohort study of older patients with stage III colon cancer who were diagnosed from 1993 to 1999 in the Surveillance, Epidemiology, and End Results-Medicare database. The correlations between receipt of adjuvant chemotherapy and heart failure, diabetes, and chronic obstructive pulmonary disease (COPD) were assessed. Multivariable regression analysis was used to assess the risk of death and hospitalization as a function of treatment and comorbidity status. The study sample consisted of 5330 patients (median age, 76 years). The use of adjuvant therapy was related significantly to heart failure (36.2% vs 64.9% of patients with vs without heart failure, respectively; adjusted odds ratio [OR], 0.49; 95% confidence interval [95% CI], 0.40-0.60). More moderate correlations were observed for COPD (OR, 0.83; 95% CI, 0.70-0.99) and diabetes (OR, 0.81; 95% CI, 0.68-0.97). Among patients who had heart failure, the 5-year survival was significantly higher among those who received adjuvant chemotherapy (adjusted 5-year survival rate, 43%; 95% CI, 40-47%) than among those who did not receive adjuvant chemotherapy (30%; 95% CI, 27-34%). Among patients without heart failure, the 5-year survival estimates among treated and untreated patients were 54% (95% CI, 52-56%) and 41% (95% CI, 38-44%), respectively. The probability of all-cause, condition-specific, or toxicity-related hospitalization associated with adjuvant therapy was not altered by the presence of any of the 3 conditions. Although chronic conditions appeared to be a strong barrier to the receipt of adjuvant chemotherapy, adjuvant therapy appeared to provide a significant survival benefit to patients who had colon cancer with the conditions studied. Copyright 2007 American Cancer Society.

  6. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA)

    DEFF Research Database (Denmark)

    Goldhirsch, Aron; Gelber, Richard D; Piccart-Gebhart, Martine J

    2013-01-01

    Trastuzumab has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. The standard of care is 1 year of adjuvant trastuzumab, but the optimum duration of treatment is unknown. We compared 2 years of treatment with trastuzumab with 1 year of treatmen......, and updated the comparison of 1 year of trastuzumab versus observation at a median follow-up of 8 years, for patients enrolled in the HERceptin Adjuvant (HERA) trial....

  7. Vaccine adjuvants – Current status and prospects on controlled release adjuvancity

    OpenAIRE

    Sivakumar, S.M.; Safhi, Mohammed M.; Kannadasan, M.; Sukumaran, N.

    2011-01-01

    The strategy of World Health Organization is to develop efficient and inexpensive vaccine against various infectious diseases amongst children’s population. Vaccination is considered as the most cost effective health intervention known to public. Since 90 years various substances have been added in vaccine formulation but still alum is considered as the safest adjuvant for human use licensed by United States Food and Drug Administration. MF 59 and ASO4 are the adjuvants were developed recentl...

  8. High-risk endometrial cancer may be benefit from adjuvant radiotherapy plus chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Jin-Wei Miao; Xiao-Hong Deng

    2012-01-01

    Objective:To present patterns of practice and outcomes in the adjuvant treatment of intermediate-and high-risk endometrial cancer.Methods:Retrospective data on 224 women with intermediate-risk and high-risk endometrial cancer from 1999 to 2006 were reviewed.All patients underwent surgical staging.Patterns of adjuvant treatment,consisting of pelvic radiotherapy,chemotherapy,and radiotherapy plus chemotherapy,were assessed.The 3-and 5-year disease-specific survival (DSS) rates were calculated using the Kaplan-Meier method.Results:The difference in 5-year DSS rate was statistically significant between adjuvant group and non-adjuvant group (80.65% vs.63.80%,P=0.040).In 110 high-risk patients who underwent adjuvant treatment,both 5-year DSS rate and recurrent rate were significantly different in combined radiotherapy and chemotherapy group compared with radiotherapy alone and chemotherapy alone groups (DSS rate,P=0.049; recurrent rate,P=0.047).In 83 intermediate-risk women who underwent adjuvant treatment,there was no significant difference in 5-year DSS rate and recurrence rate among the combined radiotherapy and chemotherapy,radiotherapy alone and chemotherapy alone groups (DSS rate,P=0.776; recurrent rate,P=0.937).Conclusions:Adjuvant radiotherapy plus chemotherapy is associated with a higher 5-year DSS rate and lower recurrence rate compared with radiotherapy alone and chemotherapy alone in high-risk endometrial cancer patients.Patients with intermediate-risk endometrial cancer may be not likely to benefit from adjuvant combined radiotherapy and chemotherapy.

  9. Elucidating the mechanisms of protein antigen adsorption to the CAF/NAF liposomal vaccine adjuvant systems

    DEFF Research Database (Denmark)

    Hamborg, Mette; Rose, Fabrice; Jorgensen, Lene

    2014-01-01

    adjuvant CAF01 composed of cationic dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB) or ii) the neutral adjuvant formulation NAF01, where DDA was replaced with zwitterionic distearoylphosphatidylcholine (DSPC). The effect of liposome charge, bilayer rigidity, isoelectric point...... interaction with the zwitterionic liposomes. In contrast, the net cationic lysozyme showed very little interaction with either types of liposome. Adsorption of α-lactalbumin altered its tertiary structure, affected lipid membrane packing below and above the phase transition temperature, and neutralized...

  10. [The role of Lactobacillus acidophilus in the prevention and adjuvant therapy of certain infectious diseases].

    Science.gov (United States)

    Halmy, C; Halmy, L

    1998-09-27

    Authors call attention to the role of lactic acid bacteria in the prevention and adjuvant therapy of certain infective diseases. It has special importance in the prevention and adjuvant therapy of new-born and childhood enteritis, different urogenital inflammations and antibiotic associated diarrhoea. Administration of lactic acid bacteria create eubiosis between the human organism and the world of bacteria, that is, eubacteriosis is developed instead of a pathogen flora, assuring normal physiologic functions for the well-being of the organism.

  11. Unequivocal identification of intracellular aluminium adjuvant in a monocytic THP-1 cell line.

    OpenAIRE

    2014-01-01

    Aluminium-based adjuvants (ABA) are the predominant adjuvants used in human vaccinations. While a consensus is yet to be reached on the aetiology of the biological activities of ABA several studies have identified shape, crystallinity and size as critical factors affecting their adjuvanticity. In spite of recent advances, the fate of ABA following their administration remains unclear. Few if any studies have demonstrated the unequivocal presence of intracellular ABA. Herein we demonstrate for...

  12. Aluminium adjuvants and adverse events in sub-cutaneous allergy immunotherapy

    OpenAIRE

    2014-01-01

    Sub-cutaneous immunotherapy is an effective treatment for allergy. It works by helping to modify or re-balance an individual’s immune response to allergens and its efficacy is greatly improved by the use of adjuvants, most commonly, aluminium hydroxide. Aluminium salts have been used in allergy therapy for many decades and are assumed to be safe with few established side-effects. This assumption belies their potency as adjuvants and their potential for biological reactivity both at injection ...

  13. Efficacy of lytic Staphylococcus aureus bacteriophage against multidrug-resistant Staphylococcus aureus in mice.

    Science.gov (United States)

    Oduor, Joseph Michael Ochieng'; Onkoba, Nyamongo; Maloba, Fredrick; Arodi, Washingtone Ouma; Nyachieo, Atunga

    2016-11-24

    The use of bacteriophages as an alternative treatment method against multidrug-resistant bacteria has not been explored in Kenya. This study sought to determine the efficacy of environmentally obtained lytic bacteriophage against multidrug-resistant Staphylococcus aureus (MDRSA) bacterium in mice. Staphylococcus aureus bacterium and S. aureus-specific lytic phage were isolated from sewage and wastewater collected within Nairobi County, Kenya. Thirty mice were randomly assigned into three groups: MDRSA infection group (n = 20), phage-infection group (n = 5), and non-infection group (n = 5). The MDRSA infection group was further subdivided into three groups: clindamycin treatment (8 mg/kg; n = 5), lytic phage treatment (108 PFU/mL (n = 5), and a combination treatment of clindamycin and lytic phage (n = 5). Treatments were done at either 24 or 72 hours post-infection (p.i), and data on efficacy, bacterial load, and animal physical health were collected. Treatment with phage was more effective (100%) than with clindamycin (62.25% at 24 hours p.i and 87.5% at 72 hours p.i.) or combination treatment (75% at 24 hours p.i. and 90% at 72 hours p.i.) (p aureus lytic bacteriophage has therapeutic potential against MDRSA bacterium in mice.

  14. Ecological Overlap and Horizontal Gene Transfer in Staphylococcus aureus and Staphylococcus epidermidis

    Science.gov (United States)

    Méric, Guillaume; Miragaia, Maria; de Been, Mark; Yahara, Koji; Pascoe, Ben; Mageiros, Leonardos; Mikhail, Jane; Harris, Llinos G.; Wilkinson, Thomas S.; Rolo, Joana; Lamble, Sarah; Bray, James E.; Jolley, Keith A.; Hanage, William P.; Bowden, Rory; Maiden, Martin C.J.; Mack, Dietrich; de Lencastre, Hermínia; Feil, Edward J.; Corander, Jukka; Sheppard, Samuel K.

    2015-01-01

    The opportunistic pathogens Staphylococcus aureus and Staphylococcus epidermidis represent major causes of severe nosocomial infection, and are associated with high levels of mortality and morbidity worldwide. These species are both common commensals on the human skin and in the nasal pharynx, but are genetically distinct, differing at 24% average nucleotide divergence in 1,478 core genes. To better understand the genome dynamics of these ecologically similar staphylococcal species, we carried out a comparative analysis of 324 S. aureus and S. epidermidis genomes, including 83 novel S. epidermidis sequences. A reference pan-genome approach and whole genome multilocus-sequence typing revealed that around half of the genome was shared between the species. Based on a BratNextGen analysis, homologous recombination was found to have impacted on 40% of the core genes in S. epidermidis, but on only 24% of the core genes in S. aureus. Homologous recombination between the species is rare, with a maximum of nine gene alleles shared between any two S. epidermidis and S. aureus isolates. In contrast, there was considerable interspecies admixture of mobile elements, in particular genes associated with the SaPIn1 pathogenicity island, metal detoxification, and the methicillin-resistance island SCCmec. Our data and analysis provide a context for considering the nature of recombinational boundaries between S. aureus and S. epidermidis and, the selective forces that influence realized recombination between these species. PMID:25888688

  15. Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization.

    Science.gov (United States)

    Iwase, Tadayuki; Uehara, Yoshio; Shinji, Hitomi; Tajima, Akiko; Seo, Hiromi; Takada, Koji; Agata, Toshihiko; Mizunoe, Yoshimitsu

    2010-05-20

    Commensal bacteria are known to inhibit pathogen colonization; however, complex host-microbe and microbe-microbe interactions have made it difficult to gain a detailed understanding of the mechanisms involved in the inhibition of colonization. Here we show that the serine protease Esp secreted by a subset of Staphylococcus epidermidis, a commensal bacterium, inhibits biofilm formation and nasal colonization by Staphylococcus aureus, a human pathogen. Epidemiological studies have demonstrated that the presence of Esp-secreting S. epidermidis in the nasal cavities of human volunteers correlates with the absence of S. aureus. Purified Esp inhibits biofilm formation and destroys pre-existing S. aureus biofilms. Furthermore, Esp enhances the susceptibility of S. aureus in biofilms to immune system components. In vivo studies have shown that Esp-secreting S. epidermidis eliminates S. aureus nasal colonization. These findings indicate that Esp hinders S. aureus colonization in vivo through a novel mechanism of bacterial interference, which could lead to the development of novel therapeutics to prevent S. aureus colonization and infection.

  16. Adjuvant formulation structure and composition are critical for the development of an effective vaccine against tuberculosis.

    Science.gov (United States)

    Orr, Mark T; Fox, Christopher B; Baldwin, Susan L; Sivananthan, Sandra J; Lucas, Elyse; Lin, Susan; Phan, Tony; Moon, James J; Vedvick, Thomas S; Reed, Steven G; Coler, Rhea N

    2013-11-28

    One third of the world is infected with Mycobacterium tuberculosis (Mtb) with eight million new cases of active tuberculosis (TB) each year. Development of a new vaccine to augment or replace the only approved TB vaccine, BCG, is needed to control this disease. Mtb infection is primarily controlled by TH1 cells through the production of IFN-γ and TNF which activate infected macrophages to kill the bacterium. Here we examine an array of adjuvant formulations containing the TLR4 agonist GLA to identify candidate adjuvants to pair with ID93, a lead TB vaccine antigen, to elicit protective TH1 responses. We evaluate a variety of adjuvant formulations including alum, liposomes, and oil-in-water emulsions to determine how changes in formulation composition alter adjuvant activity. We find that alum and an aqueous nanosuspension of GLA synergize to enhance generation of ID93-specific TH1 responses, whereas neither on their own are effective adjuvants for generation of ID93-specific TH1 responses. For GLA containing oil-in-water emulsions, the selection of the oil component is critical for adjuvant activity, whereas a variety of lipid components may be used in liposomal formulations of GLA. The composition of the liposome formulation of ID93/GLA does alter the magnitude of the TH1 response. These results demonstrate that there are multiple solutions for an effective formulation of a novel TB vaccine candidate that enhances both TH1 generation and protective efficacy. © 2013.

  17. Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants.

    Science.gov (United States)

    Olafsdottir, Thorunn A; Lindqvist, Madelene; Nookaew, Intawat; Andersen, Peter; Maertzdorf, Jeroen; Persson, Josefine; Christensen, Dennis; Zhang, Yuan; Anderson, Jenna; Khoomrung, Sakda; Sen, Partho; Agger, Else Marie; Coler, Rhea; Carter, Darrick; Meinke, Andreas; Rappuoli, Rino; Kaufmann, Stefan H E; Reed, Steven G; Harandi, Ali M

    2016-12-13

    A better understanding of the mechanisms of action of human adjuvants could inform a rational development of next generation vaccines for human use. Here, we exploited a genome wide transcriptomics analysis combined with a systems biology approach to determine the molecular signatures induced by four clinically tested vaccine adjuvants, namely CAF01, IC31, GLA-SE and Alum in mice. We report signature molecules, pathways, gene modules and networks, which are shared by or otherwise exclusive to these clinical-grade adjuvants in whole blood and draining lymph nodes of mice. Intriguingly, co-expression analysis revealed blood gene modules highly enriched for molecules with documented roles in T follicular helper (TFH) and germinal center (GC) responses. We could show that all adjuvants enhanced, although with different magnitude and kinetics, TFH and GC B cell responses in draining lymph nodes. These results represent, to our knowledge, the first comparative systems analysis of clinically tested vaccine adjuvants that may provide new insights into the mechanisms of action of human adjuvants.

  18. Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants

    Science.gov (United States)

    Olafsdottir, Thorunn A.; Lindqvist, Madelene; Nookaew, Intawat; Andersen, Peter; Maertzdorf, Jeroen; Persson, Josefine; Christensen, Dennis; Zhang, Yuan; Anderson, Jenna; Khoomrung, Sakda; Sen, Partho; Agger, Else Marie; Coler, Rhea; Carter, Darrick; Meinke, Andreas; Rappuoli, Rino; Kaufmann, Stefan H. E.; Reed, Steven G.; Harandi, Ali M.

    2016-12-01

    A better understanding of the mechanisms of action of human adjuvants could inform a rational development of next generation vaccines for human use. Here, we exploited a genome wide transcriptomics analysis combined with a systems biology approach to determine the molecular signatures induced by four clinically tested vaccine adjuvants, namely CAF01, IC31, GLA-SE and Alum in mice. We report signature molecules, pathways, gene modules and networks, which are shared by or otherwise exclusive to these clinical-grade adjuvants in whole blood and draining lymph nodes of mice. Intriguingly, co-expression analysis revealed blood gene modules highly enriched for molecules with documented roles in T follicular helper (TFH) and germinal center (GC) responses. We could show that all adjuvants enhanced, although with different magnitude and kinetics, TFH and GC B cell responses in draining lymph nodes. These results represent, to our knowledge, the first comparative systems analysis of clinically tested vaccine adjuvants that may provide new insights into the mechanisms of action of human adjuvants.

  19. Nipple-sparing mastectomy in breast cancer patients: The role of adjuvant radiotherapy (Review).

    Science.gov (United States)

    Janssen, Stefan; Holz-Sapra, Edna; Rades, Dirk; Moser, Alexander; Studer, Gabriela

    2015-06-01

    The present study aimed to evaluate the role of adjuvant radiotherapy (RT) following nipple-sparing mastectomy (NSM) for patients with ductal carcinoma in situ and invasive breast cancer, based on the published literature. Currently, there is no standard for RT following NSM. NSM aims to spare the nipple areola complex (NAC) without compromising locoregional control. Long-term follow-up studies have begun to show promising results. A search of the English literature was performed using the Medline database and Cochrane central library, with the keywords 'nipple/areola-sparing mastectomy', 'whole skin mastectomy' and 'NAC preservation'. A total of 32 original studies with data on NSM in terms of locoregional control, NAC control, NAC necrosis and adjuvant RT were identified. The median locoregional and NAC recurrence rates were 3.2 and 1.4% (range, 0-28.4% and 0-3.7%), respectively. The volume of remaining breast tissue following NSM was reported inconsistently. In 15 studies, RT was not mentioned. In the remaining 17 studies, RT was administered in 0-100% of patients. Only 7 studies provided detailed information regarding the use of adjuvant RT. Adjuvant thoracic wall irradiation was not used in certain studies, not even for locoregionally advanced tumors. Overall, NSM appears a feasible treatment without increased risk of locoregional recurrence for selected patients. The role of adjuvant RT following NSM requires further clarification. The decision regarding adjuvant RT must be made in interdisciplinary tumor boards and with consideration of the individual situation of the patient.

  20. Mesoporous silica nanoparticles as antigen carriers and adjuvants for vaccine delivery

    Science.gov (United States)

    Mody, Karishma T.; Popat, Amirali; Mahony, Donna; Cavallaro, Antonino S.; Yu, Chengzhong; Mitter, Neena

    2013-05-01

    Vaccines have been at the forefront of improving human health for over two centuries. The challenges faced in developing effective vaccines flow from complexities associated with the immune system and requirement of an efficient and safe adjuvant to induce a strong adaptive immune response. Development of an efficient vaccine formulation requires careful selection of a potent antigen, efficient adjuvant and route of delivery. Adjuvants are immunological agents that activate the antigen presenting cells (APCs) and elicit a strong immune response. In the past decade, the use of mesoporous silica nanoparticles (MSNs) has gained significant attention as potential delivery vehicles for various biomolecules. In this review, we aim to highlight the potential of MSNs as vaccine delivery vehicles and their ability to act as adjuvants. We have provided an overview on the latest progress on synthesis, adsorption and release kinetics and biocompatibility of MSNs as next generation antigen carriers and adjuvants. A comprehensive summary on the ability of MSNs to deliver antigens and elicit both humoral and cellular immune responses is provided. Finally, we give insight on fundamental challenges and some future prospects of these nanoparticles as adjuvants.

  1. Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations.

    Science.gov (United States)

    Mold, Matthew; Shardlow, Emma; Exley, Christopher

    2016-08-12

    Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al(3+) in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain.

  2. Improved immunogenicity of tetanus toxoid by Brucella abortus S19 LPS adjuvant.

    Science.gov (United States)

    Mohammadi, Mohsen; Kianmehr, Zahra; Kaboudanian Ardestani, Sussan; Gharegozlou, Behnaz

    2014-09-01

    Adjuvants are used to increase the immunogenicity of new generation vaccines, especially those based on recombinant proteins. Despite immunostimulatory properties, the use of bacterial lipopolysaccharide (LPS) as an adjuvant has been hampered due to its toxicity and pyrogenicity. Brucella abortus LPS is less toxic and has no pyrogenic properties compared to LPS from other gram negative bacteria. To evaluate the adjuvant effect of B. abortus (vaccine strain, S19) LPS for tetanus toxoid antigen (TT) and to investigate the protective effect of different tetanus vaccine preparations. LPS was extracted and purified from B. abortus S19 and KDO, glycan, phosphate content, and protein contamination were measured. Adipic acid dihydrazide (ADH) was used as a linker for conjugation of TT to LPS. Different amounts of B. abortus LPS, TT, TT conjugated with LPS, and TT mixed with LPS or complete Freund's adjuvant (CFA) were injected into mice and antibody production against TT was measured. The protective effect of induced antibodies was determined by LD50. Immunization of mice with TT+LPS produced the highest anti-TT antibody titer in comparison to the group immunized with TT without any adjuvant or the groups immunized with TT-LPS or TT+CFA. Tetanus toxid-S19 LPS also produced a 100% protective effect against TT in immunized mice. These data indicate that B. abortus LPS enhances the immune responses to TT and suggest the possible use of B. abortus LPS as an adjuvant in vaccine preparations.

  3. Inducible nitric oxide synthase and guinea-pig ileitis induced by adjuvant

    Directory of Open Access Journals (Sweden)

    N. D. Seago

    1995-01-01

    Full Text Available We sought to establish a model of inflammatory bowel disease by augmenting the activity of the local immune system with Freund's complete adjuvant, and to determine if inducible nitric oxide synthase (iNOS expression and peroxynitrite formation accompanied the inflammatory condition. In anaesthetized guinea-pigs, a loop of distal ileum received intraluminal 50% ethanol followed by Freund's complete adjuvant. Control animals were sham operated. When the animals were killed 7 or 14 days later, loop lavage fluid was examined for nitrite and PGE2 levels; mucosal levels of granulocyte and macrophages were estimated by myeloperoxidase (MPO and N-acetyl-D-glucosaminidase (NAG activity, respectively. Cellular localization if iNOS and peroxynitrite formation were determined by immunohistochemistry with polyclonal antibodies directed against peptide epitopes of mouse iNOS and nitrotyrosine, respectfully. Adjuvant administration resulted in a persistent ileitis, featuring gut thickening, crypt hyperplasia, villus tip swelling and disruption, and cellular infiltration. Lavage levels of PGE2 and nitrite were markedly elevated by adjuvant treatment. Immunoreactive iNOS and nitrotyrosine bordered on detectability in normal animals but were markedly evident with adjuvant treatment at day 7 and particularly day 14. Immunohistochemistry suggested that enteric neurons and epithelia were major sites of iNOS activity and peroxynitrite formation. We conclude that local administration of adjuvant establishes a chronic ileitis. Inducible nitric oxide synthase may contribute to the inflammatory process.

  4. Orthotopic ileal neobladder reconstruction for bladder cancer: is adjuvant chemotherapy safe?

    Directory of Open Access Journals (Sweden)

    Murugesan Manoharan

    2006-10-01

    Full Text Available OBJECTIVE: We examined our database of patients undergoing radical cystectomy (RC with orthotopic neobladder (NB to determine whether adjuvant chemotherapy in this group is safe. MATERIALS AND METHODS: We performed a retrospective analysis of patients who underwent radical cystectomy and urinary diversion between 1992 and 2004. Relevant clinical and therapeutic data were entered into a database. High-risk bladder cancer patients who underwent NB were identified. They were stratified into 2 groups, those who received adjuvant chemotherapy and those who did not. The incidence of complications between the 2 groups was analyzed and compared. RESULTS: Over the 12-year period, 136 patients underwent RC and NB construction for bladder cancer. Of these, 83 patients were at high risk for recurrence. Nineteen patients received adjuvant chemotherapy and 64 did not. The complication rate in the adjuvant chemotherapy group was 53% and it was 23% in those who did not receive chemotherapy. There were no perioperative or treatment related death. There were 2 patients with grade 4 toxicity in the adjuvant chemotherapy group. There was a statistical difference between these two groups with regard to the incidence of complications. However, none of these complications was life-threatening, required only conservative treatment and caused no long-term disability. CONCLUSIONS: Adjuvant chemotherapy is a safe treatment for patients undergoing RC and NB substitution. Hence, the option of orthotopic NB should not be denied in selected bladder cancer patients with high risk for recurrent disease.

  5. Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity

    Directory of Open Access Journals (Sweden)

    Karen A.O. Martins

    2016-01-01

    Full Text Available Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol, MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development.

  6. Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations

    Science.gov (United States)

    Mold, Matthew; Shardlow, Emma; Exley, Christopher

    2016-08-01

    Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al3+ in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain.

  7. Aluminium adjuvants and adverse events in sub-cutaneous allergy immunotherapy.

    Science.gov (United States)

    Exley, Christopher

    2014-01-20

    Sub-cutaneous immunotherapy is an effective treatment for allergy. It works by helping to modify or re-balance an individual's immune response to allergens and its efficacy is greatly improved by the use of adjuvants, most commonly, aluminium hydroxide. Aluminium salts have been used in allergy therapy for many decades and are assumed to be safe with few established side-effects. This assumption belies their potency as adjuvants and their potential for biological reactivity both at injection sites and elsewhere in the body. There are very few data purporting to the safety of aluminium adjuvants in allergy immunotherapy and particularly so in relation to longer term health effects. There are, if only few, published reports of adverse events following allergy immunotherapy and aluminium adjuvants are the prime suspects in the majority of such incidents. Aluminium adjuvants are clearly capable of initiating unwanted side effects in recipients of immunotherapy and while there is as yet no evidence that such are commonplace it is complacent to consider aluminium salts as harmless constituents of allergy therapies. Future research should establish the safety of the use of aluminium adjuvants in sub-cutaneous allergy immunotherapy.

  8. Molecular Dynamic Analysis of Hyaluronic Acid and Phospholipid Interaction in Tribological Surgical Adjuvant Design for Osteoarthritis.

    Science.gov (United States)

    Siódmiak, Jacek; Bełdowski, Piotr; Augé, Wayne K; Ledziński, Damian; Śmigiel, Sandra; Gadomski, Adam

    2017-09-04

    Tribological surgical adjuvants constitute a therapeutic discipline made possible by surgical advances in the treatment of damaged articular cartilage beyond palliative care. The purpose of this study is to analyze interactions between hyaluronic acid and phospholipid molecules, and the formation of geometric forms, that play a role in the facilitated lubrication of synovial joint organ systems. The analysis includes an evaluation of the pathologic state to detail conditions that may be encountered by adjuvants during surgical convalescence. The synovial fluid changes in pH, hyaluronic acid polydispersity, and phospholipid concentration associated with osteoarthritis are presented as features that influence the lubricating properties of adjuvant candidates. Molecular dynamic simulation studies are presented, and the Rouse model is deployed, to rationalize low molecular weight hyaluronic acid behavior in an osteoarthritic environment of increased pH and phospholipid concentration. The results indicate that the hyaluronic acid radius of gyration time evolution is both pH- and phospholipid concentration-dependent. Specifically, dipalmitoylphosphatidylcholine induces hydrophobic interactions in the system, causing low molecular weight hyaluronic acid to shrink and at high concentration be absorbed into phospholipid vesicles. Low molecular weight hyaluronic acid appears to be insufficient for use as a tribological surgical adjuvant because an increased pH and phospholipid concentration induces decreased crosslinking that prevents the formation of supramolecular lubricating forms. Dipalmitoylphosphatidylcholine remains an adjuvant candidate for certain clinical situations. The need to reconcile osteoarthritic phenotypes is a prerequisite that should serve as a framework for future adjuvant design and subsequent tribological testing.

  9. Adjuvant Teriparatide Therapy for Surgical Treatment of Femoral Fractures; Does It Work?

    Science.gov (United States)

    Kim, Jung Taek; Jeong, Hyung Jun; Lee, Soong Joon; Kim, Hee Joong

    2016-01-01

    Purpose Atypical femoral fracture (AFF), periprosthetic femoral fracture (PPFF) and femoral nonunion (FNU) are recalcitrant challenges for orthopedic surgeons. Teriparatide (TPTD) had been demonstrated to have anabolic effects on bone in various studies. We postulated that adjuvant TPTD after operation would enhance biologic stimulation for bone formation. We investigated (1) whether the adjuvant TPTD could achieve satisfactory union rate of surgically challenging cases such as displaced AFF, PPFF and FNU; (2) whether the adjuvant TPTD could promote development of abundant callus after surgical fixation; (3) whether the adjuvant TPTD had medically serious adverse effects. Materials and Methods Thirteen patients who agreed to off label use of TPTD in combination of operation were included in this retrospective case series. Median patients' age was 68.7 years, and there were three male and ten female patients. Their diagnoses were nonunion in six patients and acute fracture in seven. Medical records and radiographic images were reviewed. Results Twelve of thirteen fractures were united both clinically and radiologically within a year after adjuvant TPTD. Union completed radiologically median 5.4 months and clinically 5.7 months after the medication, respectively. Callus appeared abundantly showing median 1.4 of fracture healing response postoperatively. There was no serious adverse reaction of medication other than itching, muscle cramp, or nausea. Conclusion Even appropriate surgical treatment is a mainstay of treatment for AFF, PPFF, and FNU, the current report suggested that adjuvant TPTD combined with stable fixation results in satisfactory outcome for the challenging fractures of femur. PMID:27777917

  10. Pushing the limits of hypofractionation for adjuvant whole breast radiotherapy.

    Science.gov (United States)

    Yarnold, John; Haviland, Joanne

    2010-06-01

    Randomised trials report no disadvantages for hypofractionation based on 2.67 Gy fractions of adjuvant whole breast radiotherapy in terms of local tumour control and late adverse effects. Current 15- or 16-fraction schedules may not represent the limits of this approach, and limited data suggest that fewer larger fractions can be delivered safely provided appropriate downward adjustments are made to the total dose. Therapeutic gain will be undermined if breast cancer proves to be, on average, significantly less sensitive to fraction size than the dose-limiting late reacting normal tissues. If so, shortening overall treatment time might wholly or partially offset these limitations, and these uncertainties are addressed in ongoing or planned trials. Meanwhile, the experience of accelerated partial breast irradiation suggests a strong volume effect for late normal tissue damage. Schedules that may be safe when delivered to small partial volumes cannot be assumed to be safe if delivered to larger partial volumes or to the whole breast. Based on current evidence, testing the effectiveness of a 5-fraction schedule of hypofractionated whole breast radiotherapy appears to be a realisable research objective.

  11. Agmatine ameliorates adjuvant induced arthritis and inflammatory cachexia in rats.

    Science.gov (United States)

    Taksande, Brijesh G; Gawande, Dinesh Y; Chopde, Chandrabhan T; Umekar, Milind J; Kotagale, Nandkishor R

    2017-02-01

    The present study investigated the pharmacological effect of agmatine in Complete Freud Adjuvant (CFA) induced arthritis and cachexia in rats. The rats were injected with CFA (0.1ml/rat) to induced symptoms of arthritis. Day 8 onwards of CFA administration, rats were injected daily with agmatine for next 7days, and arthritis score, body weights and food intake were monitored daily (g). Since cachexia is known to produce severe inflammation, malnutrition and inhibition of albumin gene expression, we have also monitored the total proteins, albumin, TNF-α and IL-6 levels in arthritic rats and its modulation by agmatine. In the present study, CFA treated rats showed a progressive reduction in both food intake and body weight. In addition analysis of blood serum of arthritis animals showed a significant reduction in proteins and albumin and significant elevation in tumor necrosis factor (TNF)-α and Interleukins (IL)-6. Chronic agmatine (20-40mg/kg, ip) treatment not only attenuated the signs of arthritis but also reverses anorexia and body weight loss in CFA treated rats. In addition, agmatine restored total protein and albumin and reduces TNF-α and IL-6 levels in arthritis rats. These results suggest that agmatine administration can prevent the body weights loss and symptoms of arthritis via inhibition of inflammatory cytokines.

  12. Adjuvant arthritis pretreatment with type II collagen and Mycobacterium butyricum.

    Science.gov (United States)

    Franch, A; Cassany, S; Castellote, C; Castell, M

    1992-11-01

    A treatment previous to adjuvant arthritis induction has been performed with type II collagen (CII) or Mycobacterium butyricum (Mb), which is the inducer of the pathology. Pretreatment was administered in two different ways: a) subcutaneously or intradermally 14 days before arthritis induction, and b) intravenously 3 days before induction. In order to relate the change in inflammation to the corresponding antigen immune response, serum antibodies and delayed type hypersensitivity (DTH) against CII or Mb were studied. Pretreatment with s.c. CII 14 days before induction produced slight protection against arthritis and significantly delayed its onset; systemic inflammation showed good positive correlation with anti-CII antibodies. The CII administered i.v. 3 days before arthritic challenge did not significantly modify the inflammatory process. The use of i.d. subarthritogenic doses of Mb 14 days before induction protected a high percentage of the animals from the posterior arthritic challenge; this protection was accompanied by high anti-Mb antibody titers and DTH reaction. When Mb was given i.v. 3 days before induction, a partial protection of inflammation was observed; arthritis was milder and its onset was delayed. These changes were accompanied by reduced humoral and cellular response to Mb.

  13. Challenges in early clinical development of adjuvanted vaccines.

    Science.gov (United States)

    Della Cioppa, Giovanni; Jonsdottir, Ingileif; Lewis, David

    2015-06-08

    A three-step approach to the early development of adjuvanted vaccine candidates is proposed, the goal of which is to allow ample space for exploratory and hypothesis-generating human experiments and to select dose(s) and dosing schedule(s) to bring into full development. Although the proposed approach is more extensive than the traditional early development program, the authors suggest that by addressing key questions upfront the overall time, size and cost of development will be reduced and the probability of public health advancement enhanced. The immunogenicity end-points chosen for early development should be critically selected: an established immunological parameter with a well characterized assay should be selected as primary end-point for dose and schedule finding; exploratory information-rich end-points should be limited in number and based on pre-defined hypothesis generating plans, including system biology and pathway analyses. Building a pharmacodynamic profile is an important aspect of early development: to this end, multiple early (within 24h) and late (up to one year) sampling is necessary, which can be accomplished by sampling subgroups of subjects at different time points. In most cases the final target population, even if vulnerable, should be considered for inclusion in early development. In order to obtain the multiple formulations necessary for the dose and schedule finding, "bed-side mixing" of various components of the vaccine is often necessary: this is a complex and underestimated area that deserves serious research and logistical support.

  14. INTRASITE VANCOMYCIN POWDER AS A PROPHYLACTIC ADJUVANT IN LUMBAR FUSION

    Directory of Open Access Journals (Sweden)

    Jorge Álvaro González Ross

    2016-03-01

    Full Text Available ABSTRACT Objective: To identify whether the use of prophylactic intrasite vancomycin as an adjuvant is a protective factor against deep tissue infection of the surgical site. Methods: Retrospective, descriptive, case-control study evaluating 210 patients, of whom 70 received intrasite vancomycin (case group and 140 were controls. It was made a follow up for at least one year, reviewing the physical and electronic records. Data were tabulated in spreadsheets (Excel including all variables and the statistical analysis was made with Epi InfoTM 7 to calculate the odds ratio. Results: Seven cases of deep infection occurred in the control group and none was found in the case group (odds ratio [95% confidence interval]: 0.1262 [0.007-2.24], P = 0.1585. Among the predisposing factors, diabetes and surgical time were the most relevant. Conclusions: Intrasite use of vancomycin has a protective effect against deep infection in patients undergoing lumbar fusion surgery without presenting considerable side effects.

  15. Postoperative adjuvant radiotherapy and 5-fluorouracil chemotherapy for rectal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chao, M.W.T.; Lim-Joon, M.; Wada, M. [Peter MacCallum Cancer Institute, Melbourne, VIC (Australia). Division of Radiation Oncology; Byram, D.; Vaughan, S.; McLennan, R.; Joseph, D. [Geelong Hospital, Geelong, VIC (Australia). Department of Radiation and Medical Oncology; Bell, R.; Bond, R. [St John of God Hospital, Ballarat, VIC (Australia). Department of Medical Oncology

    1998-02-01

    Postoperative combined modality therapy with radiotherapy and 5-fluorouracil (5FU) chemotherapy is an effective adjuvant approach that reduces locoregional and distant metastatic disease in patients with high-risk rectal carcinoma. However, this approach results in a treatment regimen of at least 6 months` duration. The present prospective study investigates the integration of radiotherapy and 5FU chemotherapy in a protocol designed to minimize toxicity and reduce the overall treatment time. A total of 40 patients with TNM stage 11 or 111 disease receives postoperative radiotherapy at four fractions per week with weekly 5FU bolus injections delivered on the fifth non radiotherapy day. Patients also received systemic chemotherapy with leucovorin both before and after pelvic irradiation, with the total treatment duration extending for only 18 weeks. Patients were able to complete radiotherapy in 90% of cases, while the delivery of full-dose chemotherapy was achievable in the vast majority. The incidence of haematologic and gastrointestinal toxicities requiring the cessation of treatment was acceptable. With a median follow-up of 20.9 months among surviving patients, the estimated progression-free and overall survival at 2 years were 71% and 79%, respectively. Copyright (1998) Blackwell Science Pty Ltd 15 refs., 7 tabs., 4 figs

  16. On the adjuvant effect of aluminum hydroxide for mice

    Directory of Open Access Journals (Sweden)

    Nelson M. Vaz

    1981-03-01

    Full Text Available Linear relationships were found between the dose of A1(OH3 adjuvant and the titer of anti-OVA antibodies formed by BDF1 mice. Mice immunized with OVA, DNP-KLH and then boosted with DNP-OVA formed anti-DNP antibodies only when A1(OH3 was added to the injection of DNP-KLH; addition of A1(OH3 to the priming injection of OVA decreased, rather than increased antibody formation.Há relações lineares entre a dose de Al (OH3 usado como adjuvante imunológico e o título de anticorpos anti-ovoalbumina (anti-OVA formado por camundongos BDFI. Camundongos que receberam OVA, depois uma imunização acessoria com dinitrofenil-hemocianina (DNP-KLH e então uma imunização secundária com DNP-OVA, só formaram anticorpos anti-DNP quando havia Al (OH3 incluído na injeção de DNP-KLH; a inclusão de Al (OH3 na injeção primária de OVA baixou em vez de elevar o título de anticorpos anti-DNP. E sugerido que a ação adjuvante do Al(OH3 se deva a ações sobre linfócitos B.

  17. Outcomes after primary or adjuvant radiotherapy for salivary gland carcinoma.

    Science.gov (United States)

    Holtzman, Adam; Morris, Christopher G; Amdur, Robert J; Dziegielewski, Peter T; Boyce, Brian; Mendenhall, William M

    2017-03-01

    We report long-term outcomes of patients treated with primary radiotherapy (RT) or surgery and adjuvant RT for salivary gland malignancies. From 1964 to 2012, 291 patients received primary RT (n = 67) or RT combined with surgery (n = 224). The 5-, 10-, and 15-year local control, local-regional control, distant metastasis-free survival, cause-specific survival and overall survival rates were 82%, 77% and 73%; 77%, 72% and 67%; 74%, 70% and 70%; 70%, 59% and 54%; and 63%, 47% and 38%, respectively. Per multivariate analysis, combined surgery and RT and T stage impacted local control; overall stage and combined surgery and RT impacted local-regional control; overall stage impacted distant metastasis-free survival; and overall stage, node positivity, clinical nerve invasion, and surgery and RT impacted cause-specific and overall survival. Five percent of patients experienced grade 3 or worse toxicity. Combined surgery and RT improves local control, local-regional control, and cause-specific survival compared with primary RT for salivary tumors.

  18. Ketamine as an adjuvant to opioids for cancer pain.

    Science.gov (United States)

    Bell, Rae F; Eccleston, Christopher; Kalso, Eija A

    2017-06-28

    This is an update of a review first published in 2003 and updated in 2012.Ketamine is a commonly used anaesthetic agent, and in subanaesthetic doses is also given as an adjuvant to opioids for the treatment of refractory cancer pain, when opioids alone or in combination with appropriate adjuvant analgesics prove to be ineffective. Ketamine is known to have psychomimetic (including hallucinogenic), urological, and hepatic adverse effects. To determine the effectiveness and adverse effects of ketamine as an adjuvant to opioids for refractory cancer pain in adults. For this update, we searched MEDLINE (OVID) to December 2016. We searched CENTRAL (CRSO), Embase (OVID) and two clinical trial registries to January 2017. The intervention considered by this review was the addition of ketamine, given by any route of administration, in any dose, to pre-existing opioid treatment given by any route and in any dose, compared with placebo or active control. We included studies with a group size of at least 10 participants who completed the trial. Two review authors independently assessed the search results and performed 'Risk of bias' assessments. We aimed to extract data on patient-reported pain intensity, total opioid consumption over the study period; use of rescue medication; adverse events; measures of patient satisfaction/preference; function; and distress. We also assessed participant withdrawal (dropout) from trial. We assessed the quality of the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). One new study (185 participants) was identified by the updated search and included in the review. We included a total of three studies in this update.Two small studies, both with cross-over design, with 20 and 10 participants respectively, were eligible for inclusion in the original review. One study with 20 participants examined the addition of intrathecal ketamine to intrathecal morphine, compared with intrathecal morphine alone. The

  19. Teaching adjuvant endocrine breast cancer treatment to medical students.

    Science.gov (United States)

    de Visser, M; Fluit, C; Timmer-Bonte, J; Ottevanger, P; Verhagen, C; Klaassen, T; van Laarhoven, H W M

    2013-05-01

    In undergraduate medical education, students are supposed to acquire knowledge and understanding about the basic principles of adjuvant breast cancer treatment. The best education method in this context is unknown. In this randomised study we assessed the effect of designing a patient education poster on knowledge, perceived participation and students' satisfaction compared with case-oriented education concerning endocrine therapy for breast cancer patients. This study was conducted in the Bachelor Oncology Course for undergraduate students in Medical Science of the Radboud University Nijmegen Medical Centre. In the experimental group, students designed and created a patient education poster in small groups. In the control group, students answered case-based questions in small groups. Knowledge was tested at different moments using multiple-choice questions. To assess perceived participation and satisfaction, students filled out questionnaires. 329 students participated in the study. No difference in knowledge was observed between the experimental and control group. However, students in the control group reported a higher perceived participation and satisfaction compared with the students in the experimental group (pstudents' perceived participation and satisfaction. Working on case-based questions may be appreciated by medical students as most relevant for their future profession. We advocate more attention to the importance of patient education in the medical curriculum, to help students realise the relevance of this aspect of medical profession.

  20. Safety evaluation of monophosphoryl lipid A (MPL): an immunostimulatory adjuvant.

    Science.gov (United States)

    Baldrick, Paul; Richardson, Derek; Elliott, Gary; Wheeler, Alan W

    2002-06-01

    Animal models have shown the potential use of monophosphoryl lipid A (MPL), a detoxified bacterial lipopolysaccharide, as a vaccine adjuvant. Immunostimulatory activity with diverse effects on the cellular elements of the immune system has been demonstrated and a range of vaccines incorporating MPL, including allergy vaccines, are currently under clinical evaluation. A series of preclinical safety investigations was performed to support clinical use of MPL as used in allergy vaccines and comprised cardiovascular/respiratory assessment in dog (up to 100 microg/kg/day); repeat-dose toxicity in rat, rabbit, and dog (up to 2500 and 1200 microg/kg/day in the rat and dog, respectively); reproduction toxicity in rat and rabbit (up to 100 microg/kg/day); and genotoxicity studies. Overall, repeat-dose toxicity studies in the rat and dog showed expected immunostimulatory effects and/or signs of toxicity associated with overstimulation of the immune system (notably increased spleen weight and white blood cell values). Studies in the rabbit with weekly doses of MPL produced no effects. MPL was shown to have no adverse effects on cardiovascular/respiratory function, reproduction, and genotoxicity.

  1. Prevalence and antibiotic susceptibility of Staphylococcus aureus from bovine mastitis

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    C. G. Unakal and B. B. Kaliwal

    2010-04-01

    Full Text Available The primary objective of this study was to determine the prevalence and antimicrobial susceptibility of mastitic Staphylococcus aureus in dairy cows. Milk samples for microbiological culture were collected from dairy herds. A total of 105 samples were screened and 68 confirmed Staphylococcus aureus were obtained. The a, ß and non haemolytic activity revealed 20.58%, 75% and 4.41% respectively in 68 isolated strains of Staphylococcus aureus. Resistance of Staphylococcus aureus against 10 antimicrobial agents was tested using the disc diffusion method. The highest 86.76% isolates were resistant to penicillin followed by ampicillin 70.50%, amoxicillin 63.23%, gentamycin 47.05%, amikacin 30.80%, erythromycin 27.94%, Ciprofloxacin 26.47%, methicillin 23.52%, cefotaxime 20.58% and the lowest resistant was shown in ceftriaxone 19.11%. The study revealed that the increase in prevalence and antibiotic resistance pattern of the Staphylococcus aureus isolated from bovine mastitis. [Vet. World 2010; 3(2.000: 65-67

  2. Double triplex real-time PCR assay for simultaneous detection of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, and Staphylococcus haemolyticus and determination of their methicillin resistance directly from positive blood culture bottles.

    Science.gov (United States)

    Kilic, Abdullah; Basustaoglu, A Celal

    2011-12-01

    We developed and validated here a double triplex real-time PCR assay to simultaneously detect and identify Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus haemolyticus and their methicillin resistance in a single reaction directly from Gram-positive cocci-in-clusters (GPCs)-positive blood culture bottles. From August 15, 2009 through February 15, 2010, 238 GPC-positive samples were collected and identified by conventional methods as 11 methicillin-resistant S. aureus (MRSA), 28 methicillin-susceptible S. aureus (MSSA), 176 MR coagulase-negative staphylococci (MRCoNS), 21 MSCoNS and two Enterococcus faecalis. The double triplex real-time PCR assay was targeted and detected tuf, nuc and mecA genes in the first tube and atlE, gap and mvaA genes in the second tube which could be run simultaneously. The detection limit of the assay was found at 10(3) CFU/ml for the atleE gene, 10(4) CFU/ml for the mva gene and 10(5) CFU/ml for gap, nuc, mecA and tuf genes based on seeding experiments. All Staphylococcus species except two S. epidermidis were correctly identified by the assay. The double triplex real-time PCR assay quickly and accurately detects S. aureus, S. epidermidis, S. hominis and S. haemolyticus and their methicillin resistance in a single reaction directly from positive blood culture bottles within 83 min.

  3. Postoperative Staphylococcus aureus infections in Medicare beneficiaries.

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    Moaven Razavi

    Full Text Available Staphylococcus aureus (S. aureus infections are important because of their increasing frequency, resistance to antibiotics, and high associated rates of disabilities and deaths. We examined the incidence and correlates of S. aureus infections following 219,958 major surgical procedures in a 5% random sample of fee-for-service Medicare beneficiaries from 2004-2007. Of these surgical patients, 0.3% had S. aureus infections during the hospitalizations when index surgical procedures were performed; and 1.7% and 2.3%, respectively, were hospitalized with infections within 60 days or 180 days following admissions for index surgeries. S. aureus infections occurred within 180 days in 1.9% of patients following coronary artery bypass graft surgery, 2.3% following hip surgery, and 5.9% following gastric or esophageal surgery. Of patients first hospitalized with any major infection reported during the first 180 days after index surgery, 15% of infections were due to S. aureus, 18% to other documented organisms, and no specific organism was reported on claim forms in 67%. Patient-level predictors of S. aureus infections included transfer from skilled nursing facilities or chronic hospitals and comorbid conditions (e.g., diabetes, congestive heart failure, chronic obstructive pulmonary disease, and chronic renal disease. In a logarithmic regression, elective index admissions with S. aureus infection stayed 130% longer than comparable patients without that infection. Within 180 days of the index surgery, 23.9% of patients with S. aureus infection and 10.6% of patients without this infection had died. In a multivariate logistic regression of death within 180 days of admission for the index surgery with adjustment for demographics, co-morbidities, and other risks, S. aureus was associated with a 42% excess risk of death. Due to incomplete documentation of organisms in Medicare claims, these statistics may underestimate the magnitude of S. aureus infection

  4. [What are we learning about Staphylococcus saprophyticus?].

    Science.gov (United States)

    Orden-Martínez, Beatriz; Martínez-Ruiz, Rocío; Millán-Pérez, Rosario

    2008-10-01

    Staphylococcus saprophyticus is frequent cause of urinary tract infection in women; hence, it is important to know the epidemiology and antibiotic susceptibility of this microorganism. A retrospective longitudinal study was performed in urine specimens from outpatients in our health area cultured in the Microbiology Laboratory of C.E. Argüelles (Madrid, Spain) over a 10-year period (1997-2006). Among 35,136 urine cultures with a significant count, we identified 331 S. saprophyticus (0.9%); 324 in women and 7 in men. Mean age of the infected patients was 32.7 years. A total of 83.9% of the strains were in women aged 15 to 44 years (37 women in this group were pregnant) and the largest numbers of isolates were found during the months of June and November. All S. saprophyticus strains were susceptible to vancomycin, rifampin, gentamicin and amoxicillin-clavulanic acid. Of note, there was a high percentage of resistance to erythromycin (37.7%) (96% consistent with the MSB phenotype) which has significantly increased since 1997 (P saprophyticus isolates were considered oxacillin-resistant. These results suggest the following: First, S. saprophyticus should be considered among agents causing urinary tract infection in women 15 to 44 years old, including pregnant women, particularly during spring and autumn. Second, cotrimoxazole may be an excellent option for treating cystitis in patients without risk factors. Third, almost half of S. saprophyticus strains were considered oxacillin-resistant, thereby denying the benefit of treatment with oral beta-lactams in urinary tract infections. This is especially important in pregnant women, who should avoid trimethoprim/sulfamethoxazole and quinolones (FDA Group C), as well as fosfomycin, with in vitro resistance.

  5. Curcumin Reverse Methicillin Resistance in Staphylococcus aureus

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    Su-Hyun Mun

    2014-11-01

    Full Text Available Curcumin, a natural polyphenolic flavonoid extracted from the rhizome of Curcuma longa L., was shown to possess superior potency to resensitize methicillin-resistant Staphylococcus aureus (MRSA to antibiotics. Previous studies have shown the synergistic activity of curcumin with β-lactam and quinolone antibiotics. Further, to understand the anti-MRSA mechanism of curcumin, we investigated the potentiated effect of curcumin by its interaction in diverse conditions. The mechanism of anti-MRSA action of curcumin was analyzed by the viability assay in the presence of detergents, ATPase inhibitors and peptidoglycan (PGN from S. aureus, and the PBP2a protein level was analyzed by western blotting. The morphological changes in the curcumin-treated MRSA strains were investigated by transmission electron microscopy (TEM. We analyzed increased susceptibility to MRSA isolates in the presence of curcumin. The optical densities at 600 nm (OD600 of the suspensions treated with the combinations of curcumin with triton X-100 and Tris were reduced to 63% and 59%, respectively, compared to curcumin without treatment. N,N'-dicyclohexylcarbodiimide (DCCD and sodium azide (NaN3 were reduced to 94% and 55%, respectively. When peptidoglycan (PGN from S. aureus was combined with curcumin, PGN (0–125 μg/mL gradually blocked the antibacterial activity of curcumin (125 μg/mL; however, at a concentration of 125 µg/mL PGN, it did not completely block curcumin. Curcumin has a significant effect on the protein level of PBP2a. The TEM images of MRSA showed damage of the cell wall, disruption of the cytoplasmic contents, broken cell membrane and cell lysis after the treatment of curcumin. These data indicate a remarkable antibacterial effect of curcumin, with membrane permeability enhancers and ATPase inhibitors, and curcumin did not directly bind to PGN on the cell wall. Further, the antimicrobial action of curcumin involved in the PBP2a-mediated resistance mechanism was

  6. Staphylococcus aureus: resistance pattern and risk factors

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    Mohammad Naghavi-Behzad

    2015-03-01

    Full Text Available Introduction: Methicillin resistant Staphylococcus aureus (MRSA has emerged as a nosocomial pathogen of major worldwide importance and is an increasingly frequent cause of community-acquired infections. In this study, different risk factors and MRSA resistance pattern were investigated. Methods: In a 24 months period, all of the patients who were confined to bed in the surgery ward were included in the study. Then they were assessed to find out as if they had MRSA infection when hospitalized and once when they were discharged. Almost 48 h after admission, when patients were discharged, social and medical histories were acquired. Acquired samples were examined. Results: During the present study of 475 patients, 108 patients (22.8% had S. aureus. About frequency of antibiotic resistance among collected S. aureus colonies, erythromycin resistance, was the most frequent antibiotic resistance, also resistance to vancomycin was 0.4% that was the least. Only hospitalization duration had statistically significant correlation with antibiotic resistance, also resistance to erythromycin had statistically significant relation with history of surgery and alcohol consumption. Of all 34 MRSA species, 22 (64.7% samples were resistant to erythromycin, 17 (50.0% resistant to cefoxitin, 5 (14.7% resistant to mupirocin, 1 (2.9% resistant to vancomycin and 1 (2.9% resistant to linezolid. Conclusion: The results of the current study show that among hospitalized patients, there is resistance against methicillin. Since based on results of the study there is resistance against oxacillin and erythromycin in most cases, administering appropriate antibiotics have an important role in minimizing the resistance burden among bacterial species.

  7. Sequential hormonal therapy for metastatic breast cancer after adjuvant tamoxifen or anastrozole.

    Science.gov (United States)

    Carlson, Robert W; Henderson, I Craig

    2003-01-01

    The use of adjuvant endocrine therapy in the treatment of hormone receptor-positive, early breast cancer has become important in both pre- and postmenopausal women. Tamoxifen has been the principal adjuvant hormonal therapy in pre- and postmenopausal women with hormone receptor-positive breast cancer for nearly 20 years. Recent data in premenopausal women suggest benefit from ovarian ablation with or without tamoxifen. Early results from the 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial have demonstrated that the third-generation, selective aromatase inhibitor (AI) anastrozole ('Arimidex') is a suitable alternative adjuvant therapy for postmenopausal women with hormone receptor-positive disease. After recurrence or relapse on adjuvant endocrine therapy, responses to the sequential use of additional endocrine agents are common. The increase in the number of options now available for adjuvant therapy will have important implications for the selection of the optimal sequence of endocrine agents in the treatment of recurrent breast cancer. Menopausal status is an important factor in determining the endocrine therapy that a patient receives. For premenopausal women, tamoxifen and/or a luteinizing hormone-releasing hormone agonist such as goserelin ('Zoladex') are both options for adjuvant endocrine treatment. After progression on adjuvant and first-line tamoxifen, ovarian ablation is an appropriate second-line therapy. For premenopausal women who have undergone ovarian ablation, the use of third-line therapy with an AI becomes possible. For postmenopausal women, a wide choice of endocrine treatment options is available and an optimal sequence has yet to be determined. Options for first-line therapy of metastatic disease include an AI for women who have received adjuvant tamoxifen or tamoxifen for patients who have received adjuvant anastrozole. In addition, data suggest that fulvestrant ('Faslodex'), a novel estrogen receptor (ER) antagonist that

  8. Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity

    NARCIS (Netherlands)

    Kreutz, M.; Giquel, B.; Hu, Q.; Abuknesha, R.; Uematsu, S.; Akira, S.; Nestle, F.O.; Diebold, S.S.

    2012-01-01

    Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC) by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is par

  9. Quality control of direct molecular diagnostics for methicillin-resistant Staphylococcus aureus.

    NARCIS (Netherlands)

    A.F. van Belkum (Alex); H.G.M. Niesters (Bert); W.G. MacKay (William); W.B. van Leeuwen (Willem)

    2007-01-01

    textabstractTen samples containing various amounts of methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible S. aureus, methicillin-resistant Staphylococcus epidermidis (MRSE), and combinations thereof were distributed to 51 laboratories for molecular diagnostics testing. Sample

  10. Quality control of direct molecular diagnostics for methicillin-resistant Staphylococcus aureus

    NARCIS (Netherlands)

    van Belkum, Alex; Niesters, Hubert G M; MacKay, William G; van Leeuwen, Willem B

    2007-01-01

    Ten samples containing various amounts of methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible S. aureus, methicillin-resistant Staphylococcus epidermidis (MRSE), and combinations thereof were distributed to 51 laboratories for molecular diagnostics testing. Samples containing

  11. Factors determining Staphylococcus aureus susceptibility to photoantimicrobial chemotherapy: RsbU activity, staphyloxanthin level and membrane fluidity.

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    Monika Kossakowska-Zwierucho

    2016-07-01

    Full Text Available Photoantimicrobial chemotherapy (PACT constitutes a particular type of stress condition, in which bacterial cells induce a pleiotropic and as yet unexplored effect. In light of this, the key master regulators are of putative significance to the overall phototoxic outcome. In Staphylococcus aureus, the alternative sigma factor σB controls the expression of genes involved in the response to environmental stress. We show that aberration of any sigB operon genes in S. aureus USA300 isogenic mutants causes a pronounced sensitization (>5 log10 reduction in CFU drop to PACT with selected photosensitizers, namely protoporphyrin diarginate, zinc phthalocyanine and rose bengal. This effect is partly due to aberration-coupled staphyloxanthin synthesis inhibition. We identified frequent mutations in RsbU, a σB activator, in PACT-vulnerable clinical isolates of S. aureus, resulting in σB activity impairment. Locations of significant changes in protein structure (IS256 insertion, early STOP codon occurrence, substitutions A230T and A276D were shown in a theoretical model of S. aureus RsbU. As a phenotypic hallmark of PACT-vulnerable S. aureus strains, we observed an increased fluidity of bacterial cell membrane, which is a result of staphyloxanthin content and other yet unidentified factors. Our research indicates σB as a promising target of adjunctive antimicrobial therapy and suggests that enhanced cell membrane fluidity may be an adjuvant strategy in photoantimicrobial chemotherapy.

  12. Amikacin resistance in Staphylococcus pseudintermedius isolated from dogs.

    Science.gov (United States)

    Gold, R M; Cohen, N D; Lawhon, S D

    2014-10-01

    Staphylococcus pseudintermedius is the most common microorganism isolated from canine pyoderma and postoperative wound infections. The prevalence of methicillin-resistant S. pseudintermedius (MRSP) has increased, and recently, isolates that are resistant not only to methicillin but also to other classes of antibiotic drugs, including aminoglycosides, have become common. A total of 422 S. pseudintermedius isolates collected from 413 dogs were analyzed for amikacin and methicillin resistance using broth microdilution and disk diffusion testing. Methicillin-resistant isolates were significantly (P Staphylococcus aureus, the most prevalent gene detected was aph(3')-IIIa found in 75% (24/32) of isolates followed by aac(6')/aph(2") and ant(4')-Ia in 12% (4/32) and 3% (1/32), respectively. Understanding the differences in antimicrobial resistance gene carriage between different species of Staphylococcus may improve antimicrobial drug selection for clinical therapy and provide insights into how resistance develops in S. pseudintermedius.

  13. Small-molecule potentiators for conventional antibiotics against Staphylococcus aureus.

    Science.gov (United States)

    Vermote, Arno; Van Calenbergh, Serge

    2017-09-11

    Antimicrobial resistance constitutes a global health problem, while the discovery and development of novel antibiotics is stagnating. Methicillin-resistant Staphylococcus aureus, responsible for the establishment of recalcitrant, biofilm-related infections, is a well known and notorious example of a highly resistant micro organism. Since resistance development is unavoidable with conventional antibiotics that target bacterial viability, it is vital to develop alternative treatment options on top. Strategies aimed at more subtle manipulation of bacterial behavior have recently attracted attention. Here, we provide a literature overview of several small molecule potentiators for antibiotics, identified for the treatment of Staphylococcus aureus infection. Typically, these potentiators are not bactericidal by themselves and function either by reversing resistance mechanisms, by attenuating Staphylococcus aureus virulence, and/or by interfering with quorum sensing.

  14. Facing antibiotic resistance: Staphylococcus aureus phages as a medical tool.

    Science.gov (United States)

    Kaźmierczak, Zuzanna; Górski, Andrzej; Dąbrowska, Krystyna

    2014-07-01

    Staphylococcus aureus is a common and often virulent pathogen in humans. This bacterium is widespread, being present on the skin and in the nose of healthy people. Staphylococcus aureus can cause infections with severe outcomes ranging from pustules to sepsis and death. The introduction of antibiotics led to a general belief that the problem of bacterial infections would be solved. Nonetheless, pathogens including staphylococci have evolved mechanisms of drug resistance. Among current attempts to address this problem, phage therapy offers a promising alternative to combat staphylococcal infections. Here, we present an overview of current knowledge on staphylococcal infections and bacteriophages able to kill Staphylococcus, including experimental studies and available data on their clinical use.

  15. Evaluation of Pyrrolidonyl Arylamidase Activity in Staphylococcus delphini.

    Science.gov (United States)

    Compton, Samantha T; Kania, Stephen A; Robertson, Amy E; Lawhon, Sara D; Jenkins, Stephen G; Westblade, Lars F; Bemis, David A

    2017-03-01

    Clinical reference textbooks lack data for pyrrolidonyl arylamidase (PYR) activity in Staphylococcus delphini This study evaluated PYR activities of 21 S. delphini strains by reference broth, rapid disc, and rapid slide methods. Species and subgroup identifications were confirmed by nucleic acid-based methods and included nine group A and 12 group B strains. Testing by rapid PYR methods with products from four manufacturers was performed at two testing locations, and, with the exception of one strain tested at one location using reagents from one manufacturer, each S. delphini strain tested positive for PYR activity. Therefore, PYR may be a useful single-test adjunct for distinguishing Staphylococcus aureus from S. delphini and other members of the Staphylococcus intermedius group. Copyright © 2017 American Society for Microbiology.

  16. Botryomycosis Due to Staphylococcus Aureus-A Case Report

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    Manjula A.Vagarali

    2012-04-01

    Full Text Available Objectives: To study Staphylococcus aureus as the causative organism of botryomycosis. Background: the botryomycosis is a chronic purulent granulomatous lesion of the skin, subcutaneous tissue and visceral organs caused by several bacterial species. This condition clinically and histopathologically resembles with that of mycetoma and Actinomycosis. Method: A 51 year old male presented to us with swelling over medial aspect of the right foot with multiple sinuses. He gave a history of trauma 3 years back at the same site. The sample was examined directly by KOH preparation and grams stain. The culture was put up on blood, chocolate, lowenstein Jensen (LJ and sabouraud dextrose agar (SDA media. Fungal culture was negative. Result: Staphylococcus aureus was isolated in aerobic culture. Conclusion: the patient with botryomycosis caused by Staphylococcus aureus was subsequently treated with antibiotics and he recovered completely.

  17. Facing Antibiotic Resistance: Staphylococcus aureus Phages as a Medical Tool

    Directory of Open Access Journals (Sweden)

    Zuzanna Kaźmierczak

    2014-07-01

    Full Text Available Staphylococcus aureus is a common and often virulent pathogen in humans. This bacterium is widespread, being present on the skin and in the nose of healthy people. Staphylococcus aureus can cause infections with severe outcomes ranging from pustules to sepsis and death. The introduction of antibiotics led to a general belief that the problem of bacterial infections would be solved. Nonetheless, pathogens including staphylococci have evolved mechanisms of drug resistance. Among current attempts to address this problem, phage therapy offers a promising alternative to combat staphylococcal infections. Here, we present an overview of current knowledge on staphylococcal infections and bacteriophages able to kill Staphylococcus, including experimental studies and available data on their clinical use.

  18. Preparation and evaluation of functional foods in adjuvant arthritis

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    Al-Okbi, S. Y.

    2012-10-01

    Full Text Available Adjuvant arthritis is an animal model that closely resembles rheumatoid arthritis in humans. It is a successful working model used to study new anti-inflammatory agents. In previous studies (animal and clinical we have shown that evening primrose oil, fish oil and the methanol extract of date fruits and fenugreek seeds have anti-inflammatory activity and that the methanol extract of dates has an antioxidant effect. Based on these studies, the aim of the present study was to prepare 7 functional foods containing such bioactive fractions separately or in combination and to evaluate them in adjuvant arthritis in rats, study the stability of bioactive ingredients and evaluate their sensory properties. The studied biochemical parameters were erythrocyte sedimentation rate, erythrocyte superoxide dismutase, glutathione peroxidase and plasma copper, zinc and interlukin 2. Nutritional parameters, including body weight gain, food intake and food efficiency ratio were monitored during the feeding of the functional foods. The bioactive ingredients assessed were total phenolic contents and fatty acids. The results showed improvement in the biochemical parameters, body weight gain and food efficiency ratio of arthritic rats fed on the functional foods with different degrees. All the prepared functional foods were sensory accepted. The active ingredients showed stability during storage. In conclusion, all the tested functional foods showed promising antiinflammatory activity and were determined to be acceptable through sensory evaluation which means that their potential beneficial use as dietary supplements in rheumatoid arthritis patients may be recommended.

    La artritis adyuvante es un modelo utilizado en animales y se caracteriza por ser muy parecida a la artritis reumatoide en humanos. Se trata de un modelo de trabajo utilizado con éxito para estudiar nuevos agentes anti-inflamatorios. En estudios previos (animales y clínica hemos demostrado que

  19. The effect of adjuvant chemotherapy on osteoarticular allografts.

    Science.gov (United States)

    Hazan, E J; Hornicek, F J; Tomford, W; Gebhardt, M C; Mankin, H J

    2001-04-01

    Two hundred lower extremity osteoarticular allografts (in 200 patients) performed for aggressive or malignant bone tumors between 1976 and 1997 included 124 grafts of the distal femur, 46 of the proximal tibia, and 30 of the proximal femur. Seventy-four patients did not receive chemotherapy, and 126 received either adjuvant or neoadjuvant therapy. The diagnoses, mean ages, and length of followup were different for the two groups because most of the patients in the chemotherapy group had osteosarcoma, whereas the largest number in the control group had chondrosarcoma or parosteal osteosarcoma. The extent of the surgery was essentially the same for both patient groups, as is reflected by a low recurrence rate (7% for the control and 6% for the chemotherapy group). A statistical comparison of the various parameters showed that the infection, fracture, and amputation rates were the same, but the nonunion rate was markedly increased in the patients who received chemotherapy (32% versus 12%). Cox regression and Kaplan-Meier studies showed that chemotherapy had a significant effect on outcome, with the success rates for the two groups being quite different (72% versus 56%). The results for the distal femur showed a greater effect than for either the proximal tibia or the proximal femur. Analysis of these data suggest the distal femur is perhaps the most prone to healing problems, possibly based in part on the extent of the surgery. A final study supports the concept that the results improved in later years, suggesting a modification or application of the drugs used, better selection of patients, and improvements in surgical technique.

  20. Concurrent Boost with Adjuvant Breast Hypofractionated Radiotherapy and Toxicity Assessment

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    Mona M. Sayed

    2015-01-01

    Full Text Available Background: The use of shorter radiotherapy schedules has an economic and logistic advantage for radiotherapy departments, as well as a high degree of patient convenience. The aim of this study is to assess the acute and short-term late toxicities of a hypofractionated radiotherapy schedule with a concomitant boost. Methods: We enrolled 57 eligible patients as group A. These patients received 42.5 Gy in 16 fractions of 2.66 Gy each to the whole breast over 3.2 weeks. A concomitant electron boost of 12 Gy in 16 fractions was also administered which gave an additional 0.75 Gy daily to the lumpectomy area for a total radiation dose of 54.5 Gy. Toxicity was recorded at three weeks and at three months for this group as well as for a control group (group B. The control group comprised 76 eligible patients treated conventionally with 50 Gy to the whole breast over five weeks followed by a sequential electron boost of 12 Gy in 2 Gy per fraction. Results: There were no statistically significant differences observed in the incidence of acute skin toxicity, breast pain, and edema recorded at three weeks or pigmentation and fibrosis recorded at three months between the two groups (P0.05. Conclusion: The results of this study suggest there are no increased acute and shortterm late toxicities affiliated with the hypofractionated schedule plus a concomitant boost as prescribed compared to the conventional fractionation of adjuvant breast radiotherapy. Large randomized trials and long-term follow-up are needed to confirm these favorable findings.

  1. Sleep aid use during and following breast cancer adjuvant chemotherapy.

    Science.gov (United States)

    Moore, Tiffany A; Berger, Ann M; Dizona, Paul

    2011-03-01

    Knowledge of sleep aid use is limited despite the high prevalence of insomnia among women before, during, and following breast cancer adjuvant chemotherapy treatments (CTX). This study's purpose was to (1) determine the frequency and characteristics of participants taking sleep aid(s); (2) identify the frequency and percentage of sleep aid use by category (prescription sedative/hypnotics, prescription anti-depressants, prescription analgesics, prescription anti-emetics, over-the-counter (OTC) analgesics, OTC cold/flu/sinus, OTC sleep, alcohol, and herbal supplements); and (3) compare sleep aid use by category in the experimental and control groups within a randomized-controlled clinical trial (RCT). Longitudinal, descriptive, secondary RCT data analysis of women (n=219) receiving out-patient CTX, and at 30, 60, and 90 days following the last CTX and 1 year following CTX1. Participants recorded daily sleep aid use on a Sleep Diary. Analyses included descriptives, chi-square, and RM-ANOVA. Approximately 20% of participants took at least one sleep aid before CTX1; usage decreased over time (12-18%); a second sleep aid was used infrequently. Prescription sedative/hypnotics (46%) and OTC analgesics (24%) were used most frequently. OTC sleep aids were most commonly used as a second aid. Prescription sedative/hypnotics [F(7,211)=4.26, p=0.00] and OTC analgesics [F(7,211)=2.38, p=0.023] use decreased significantly over time. Results reflect the natural course of CTX, recovery, and healing. Comprehensive screening for sleep-wake disturbances and sleep aid use may lead to a better understanding of the risks and benefits of pharmacologic and non-pharmacologic interventions, and ultimately lead to selection of the safest and most effective treatment. Copyright © 2010 John Wiley & Sons, Ltd.

  2. Nickel acts as an adjuvant during cobalt sensitization.

    Science.gov (United States)

    Bonefeld, Charlotte Menné; Nielsen, Morten Milek; Vennegaard, Marie T; Johansen, Jeanne Duus; Geisler, Carsten; Thyssen, Jacob P

    2015-03-01

    Metal allergy is the most frequent form of contact allergy with nickel and cobalt being the main culprits. Typically, exposure comes from metal-alloys where nickel and cobalt co-exist. Importantly, very little is known about how co-exposure to nickel and cobalt affects the immune system. We investigated these effects by using a recently developed mouse model. Mice were epicutaneously sensitized with i) nickel alone, ii) nickel in the presence of cobalt, iii) cobalt alone, or iv) cobalt in the presence of nickel, and then followed by challenge with either nickel or cobalt alone. We found that sensitization with nickel alone induced more local inflammation than cobalt alone as measured by increased ear-swelling. Furthermore, the presence of nickel during sensitization to cobalt led to a stronger challenge response to cobalt as seen by increased ear-swelling and increased B and T cell responses in the draining lymph nodes compared to mice sensitized with cobalt alone. In contrast, the presence of cobalt during nickel sensitization only induced an increased CD8(+) T cell proliferation during challenge to nickel. Thus, the presence of nickel during cobalt sensitization potentiated the challenge response against cobalt more than the presence of cobalt during sensitization to nickel affected the challenge response against nickel. Taken together, our study demonstrates that sensitization with a mixture of nickel and cobalt leads to an increased immune response to both nickel and cobalt, especially to cobalt, and furthermore that the adjuvant effect appears to correlate with the inflammatory properties of the allergen. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Soluble proteins modified with acetaldehyde and malondialdehyde are immunogenic in the absence of adjuvant.

    Science.gov (United States)

    Thiele, G M; Tuma, D J; Willis, M S; Miller, J A; McDonald, T L; Sorrell, M F; Klassen, L W

    1998-11-01

    Recent studies have shown that the alcohol metabolites malondialdehyde and acetaldehyde can combine to form a stable adduct (MAA) on proteins. This adduct has been detected in the livers of rats chronically consuming ethanol, and serum antibodies to MAA have been observed at significantly higher concentrations in ethanol-fed when compared with pair-fed or chow-fed control rats. More recently, preliminary studies have strongly suggested that the MAA adduct is capable of stimulating antibody responses to soluble proteins in the absence of adjuvants. The antibodies produced recognize either the MAA epitope or the carrier protein itself. Therefore, it was the purpose of this study to examine the potential immunogenicity of MAA-modified exogenous proteins in the absence of adjuvants. Balb/c mice were immunized in the presence or absence of adjuvant with different concentrations of unmodified or MAA-modified proteins. The antibody response to both the MAA epitope and unmodified protein epitopes were determined by ELISA. In the absence of adjuvant, significant antibody responses were induced to both the MAA epitope and nonmodified protein epitopes. Smaller immunizing doses of MAA-protein conjugate favored the production of antibodies to nonmodified proteins, whereas larger doses induced a strong anti-MAA response. In studies to begin determining a mechanism for the specificity of the response in the absence of adjuvants, peritoneal macrophages were found to bind and degrade MAA-adducted proteins through the use of a scavenger receptor. This indicated that MAA-adducted proteins may be specifically taken up and epitopes presented to the humoral immune system in the absence of adjuvants. Importantly, these are the first data showing that an alcohol-related metabolite can induce an antibody response in the absence of adjuvant and suggesting a mechanism by which antibody to the MAA adduct or its carrier (exogenous or endogenous) proteins may be generated in vivo.

  4. Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

    Directory of Open Access Journals (Sweden)

    Lima Carmen SP

    2011-03-01

    Full Text Available Abstract Background Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting. Methods Randomized controlled trials were searched comparing adjuvant therapy (chemotherapy, vaccine, immunotherapy, biochemotherapy versus no active treatment after surgery among renal cell cancer patients. Outcomes were overall survival (OS, disease-free survival (DFS, and severe toxicities. Risk ratios (RR, hazard ratios (HR and 95% confidence intervals were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by I2. Different strategies of adjuvant treatment were evaluated separately. Results Ten studies (2,609 patients were included. Adjuvant therapy provided no benefits in terms of OS (HR 1.07; 95%CI 0.89 to 1.28; P = 0.48 I2 = 0% or DFS (HR 1.03; 95%CI 0.87 to 1.21; P = 0.77 I2 = 15% when compared to no treatment. No subgroup analysis (immunotherapy, vaccines, biochemotherapy and hormone therapy had relevant results. Toxicity evaluation depicted a significantly higher frequency of serious adverse events in the adjuvant group. Conclusions This analysis provided no support for the hypothesis that the agents studied provide any clinical benefit for renal cancer patients although they increase the risk of toxic effects. Randomized trials are underway to test targeted therapies, which might open a new therapeutic frontier. Until these trials yield results, no adjuvant therapy can be recommended for patients who undergo surgical resection for renal cell cancer.

  5. Treatment burden in stage I seminoma: a comparison of surveillance and adjuvant radiation therapy.

    Science.gov (United States)

    Leung, Eric; Warde, Padraig; Jewett, Michael; Panzarella, Tony; O'Malley, Martin; Sweet, Joan; Moore, Malcolm; Sturgeon, Jeremy; Gospodarowicz, Mary; Chung, Peter

    2013-12-01

    To examine the management and outcomes of patients with stage I seminoma and to relate these to overall treatment burden. A total of 764 patients with stage I seminoma underwent surveillance or adjuvant radiation therapy (RT) at a single institution. First relapse on surveillance was managed with RT alone, or with combination chemotherapy (ChT) for more extensive recurrence. Second relapse was managed with ChT. Relapse after adjuvant RT was treated with ChT. The treatment burden was measured, according to the specific treatment undertaken after orchiectomy, by defining treatment episodes as follows: surgery - one episode; one course of RT - one episode; one course of ChT - one episode. In all, 484 patients underwent surveillance and 280 received adjuvant RT. The 5- and 10-year overall survival rates were 98.6 and 97.7% for surveillance, and 97.2 and 91.4% for adjuvant RT. A total of 72 (15%) patients in the surveillance group relapsed; treatment for relapse was RT (n = 56), ChT (n = 15) and surgery (n = 1). Second relapse occurred in six patients; these patients were treated with ChT. Of the patients in the adjuvant RT group, 14 (5%) relapsed: salvage treatment was 10 - ChT (n = 10) surgery (n = 1) and further RT (n = 3). The overall treatment burden represented by number of treatment episodes per patient was 0.16 in the surveillance group and 1.05 in the adjuvant RT group. Surveillance reduces the overall treatment burden in patients with stage I seminoma and is the preferred management option. The selective use of RT at first relapse for patients on surveillance leads to a similar requirement for subsequent ChT to that for patients on adjuvant RT. © 2013 The Authors. BJU International © 2013 BJU International.

  6. Effects of adjuvant Montanide™ ISA 763 A VG in rainbow trout injection vaccinated against Yersinia ruckeri.

    Science.gov (United States)

    Jaafar, Rzgar M; Chettri, Jiwan K; Dalsgaard, Inger; Al-Jubury, Azmi; Kania, Per W; Skov, Jakob; Buchmann, Kurt

    2015-12-01

    Enteric redmouth disease (ERM) caused by the fish pathogen Yersinia ruckeri is a major threat to freshwater production of rainbow trout (Oncorhynchus mykiss) throughout all life stages. Injection vaccination of rainbow trout against Y. ruckeri infection has been shown to confer better protection compared to the traditionally applied immersion vaccination. It may be hypothesized, based on experience from other vaccines, that adjuvants may increase the protective level of ERM injection vaccines even more. Controlled comparative vaccination studies have been performed to investigate effects of the oil adjuvant Montanide™ ISA 763 A VG (Seppic) when added to an experimental Y. ruckeri bacterin (containing both biotype 1 and 2 of serotype O1). A total of 1000 fish with mean weight 19 g was divided into five different groups (in duplicated tanks 2 × 100 fish per group) 1) non-vaccinated control fish (NonVac), 2) fish injected with a commercial vaccine (AquaVac(®) Relera™) (ComVac), 3) fish injected with an experimental vaccine (ExpVac), 4) fish injected with an experimental vaccine + adjuvant (ExpVacAdj) and 5) fish injected with adjuvant alone (Adj). Injection of the experimental vaccine (both adjuvanted and non-adjuvanted) induced a significantly higher antibody (IgM) level, increased occurrence of IgM(+) cells in spleen tissue and significant up-regulation of several immune genes. Additional experiments using a higher challenge dosage suggested an immune enhancing effect of the adjuvant as the challenge produced 100% mortality in the NonVac group, 60% mortality in both of ComVac and Adj groups and only 13 and 2.5% mortalities in the ExpVac and the ExpVacAdj groups, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. ADJUVANT CHEMOTHERAPY FOLLOWING RADICAL SURGERY FOR NON-SMALL CELL LUNG CANCER:A RANDOMIZED STUDY

    Institute of Scientific and Technical Information of China (English)

    XU Guang-chuan; RONG Tie-hua; LIN Peng

    1999-01-01

    Objective: To evaluate the efficacy of adjuvant chemotherapy after radical surgery for non-small cell lung cancer (NSCLC). Methods: Seventy patients with NSCLC (stage Ⅰ-Ⅲ) undergone radical surgery were randomized into two groups: 35 patients received adjuvant chemotherapy with cyclophosphamide (CTX)300 mg/m2, vincristine (VCR) 1.4% mg/m2, adriamycin (ADM) 50 mg/m2, lomustine (CCNU) 50 mg/m2 d1,cisplatin (DDP) 20 mg/m2, d1-5, for 4 cycles, and followed by oral Ftorafur (FT-207) 600-900 mg/d for 1year (adjuvant chemotherapy group). The other 35patients received surgical treatment only (surgery group). Results: The overall 5-year survival rate was 48.6% in the adjuvant chemotherapy group, and 31.4%in the surgery group, respectively. The difference between the two groups was not statistically significant (P>0.05). The 5-year survival rate of patients in stage Ⅲwas 44.0% and 20.8% received surgery with and without adjuvant chemotherapy, respectively. The difference between the two groups was statistically significant (P<0.025). The 5-year survival rate of patients in stage Ⅰ-Ⅱ in the two groups was 60.0% and 54.5%, respectively (P>0.75). Conclusion: Postoperative adjuvant chemotherapy in NSCLC can improve survival, for those patients in stage Ⅲ, it suggests significantly 5-year survival rate in the adjuvant chemotherapy group was higher than that in the surgery alone group.

  8. Adjuvant radiotherapy is not supported in patients with verrucous carcinoma of the oral cavity.

    Science.gov (United States)

    Mohan, Suresh; Pai, Sara I; Bhattacharyya, Neil

    2017-06-01

    To analyze the impact of adjuvant radiation therapy (RT) on overall survival (OS) and disease-specific survival (DSS) in patients with verrucous carcinoma (VC) as compared to squamous cell carcinoma (SCC) of the oral cavity. Cross-sectional population analysis. Cases of nonmetastatic VC/SCC of the oral cavity were extracted from the Surveillance, Epidemiology, and End Results (SEER) database (1988-2013). Kaplan-Meier survivals, stratified according to T stage, were compared between VC and SCC for treatment with or without adjuvant RT. A total of 18,819 VC/SCC cases were identified. There were 581 (3.1%) VC (mean age 69.6 years, 48.9% female) versus 18,238 (97.0%) SCC (mean age, 65.3, 37.1% female) patients. Verrucous carcinoma patients receiving surgery alone (N = 539) demonstrated a trend toward improved OS versus VC patients receiving surgery and RT (N = 40) (117.0 vs. 71.4 months, respectively, P = 0.119). There was a statistically significant improvement in DSS in VC patients receiving surgery alone (217.2 vs. 110.9 months, P = 0.05). Verrucous carcinoma patients treated with adjuvant RT demonstrated a trend toward a worse OS (71.4 vs. 93.0 months, P = 0.992) and DSS (110.9 vs. 162.3 months, P = 0.275) compared to SCC treated with adjuvant RT, suggesting a different biology and radiosensitivity between VC and SCC. Verrucous carcinoma treated with adjuvant RT had a worse OS and DSS compared to both VC treated with surgery alone and SCC treated with surgery and adjuvant RT. Consideration should be given to surgical re-section rather than adjuvant RT in patients with positive margins or local recurrence. 2C. Laryngoscope, 127:1334-1338, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Staphylococcus pseudintermedius expresses surface proteins that closely resemble those from Staphylococcus aureus.

    Science.gov (United States)

    Geoghegan, Joan A; Smith, Emma J; Speziale, Pietro; Foster, Timothy J

    2009-09-18

    Staphylococcus pseudintermedius is a commensal of dogs that is implicated in the pathogenesis of canine pyoderma. This study aimed to determine if S. pseudintermedius expresses surface proteins resembling those from Staphylococcus aureus and to characterise them. S. pseudintermedius strain 326 was shown to adhere strongly to purified fibrinogen, fibronectin and cytokeratin 10. It adhered to the alpha-chain of fibrinogen which, along with binding to cytokeratin 10, is the hallmark of clumping factor B of S. aureus, a surface protein that is in part responsible for colonisation of the human nares. Ligand-affinity blotting with cell-wall extracts demonstrated that S. pseudintermedius 326 expressed a cell-wall anchored fibronectin binding protein which recognised the N-terminal 29kDa fragment. The ability to bind fibronectin is an important attribute of pathogenic S. aureus and is associated with the ability of S. aureus to colonise skin of human atopic dermatitis patients. S. pseudintermedius genomic DNA was probed with labelled DNA amplified from the serine-aspartate repeat encoding region of clfA of S. aureus. This probe hybridised to a single SpeI fragment of S. pseudintermedius DNA. In the cell-wall extract of S. pseudintermedius 326, a 180kDa protein was discovered which bound to fibrinogen by ligand-affinity blotting and reacted in a Western blot with antibodies raised against the serine-aspartate repeat region of ClfA and the B-repeats of SdrD of S. aureus. It is proposed that this is an Sdr protein with B-repeats that has an A domain that binds to fibrinogen. Whether it is the same protein that binds cytokeratin 10 is not clear.

  10. Characterization of lipases from Staphylococcus aureus and Staphylococcus epidermidis isolated from human facial sebaceous skin.

    Science.gov (United States)

    Xie, Winny; Khosasih, Vivia; Suwanto, Antonius; Kim, Hyung Kwoun

    2012-01-01

    Two staphylococcal lipases were obtained from Staphylococcus epidermidis S2 and Staphylococcus aureus S11 isolated from sebaceous areas on the skin of the human face. The molecular mass of both enzymes was estimated to be 45 kDa by SDS-PAGE. S2 lipase displayed its highest activity in the hydrolysis of olive oil at 32 degrees C and pH 8, whereas S11 lipase showed optimal activity at 31 degrees C and pH 8.5. The S2 lipase showed the property of cold-adaptation, with activation energy of 6.52 kcal/mol. In contrast, S11 lipase's activation energy, at 21 kcal/mol, was more characteristic of mesophilic lipases. S2 lipase was stable up to 45° C and within the pH range from 5 to 9, whereas S11 lipase was stable up to 50 degrees C and from pH 6 to 10. Both enzymes had high activity against tributyrin, waste soybean oil, and fish oil. Sequence analysis of the S2 lipase gene showed an open reading frame of 2,067 bp encoding a signal peptide (35 aa), a pro-peptide (267 aa), and a mature enzyme (386 aa); the S11 lipase gene, at 2,076 bp, also encoded a signal peptide (37 aa), pro-peptide (255 aa), and mature enzyme (399 aa). The two enzymes maintained amino acid sequence identity of 98-99% with other similar staphylococcal lipases. Their microbial origins and biochemical properties may make these staphylococcal lipases isolated from facial sebaceous skin suitable for use as catalysts in the cosmetic, medicinal, food, or detergent industries.

  11. Phenazine antibiotic inspired discovery of potent bromophenazine antibacterial agents against Staphylococcus aureus and Staphylococcus epidermidis.

    Science.gov (United States)

    Borrero, Nicholas V; Bai, Fang; Perez, Cristian; Duong, Benjamin Q; Rocca, James R; Jin, Shouguang; Huigens, Robert W

    2014-02-14

    Nearly all clinically used antibiotics have been (1) discovered from microorganisms (2) using phenotype screens to identify inhibitors of bacterial growth. The effectiveness of these antibiotics is attributed to their endogenous roles as bacterial warfare agents against competing microorganisms. Unfortunately, every class of clinically used antibiotic has been met with drug resistant bacteria. In fact, the emergence of resistant bacterial infections coupled to the dismal pipeline of new antibacterial agents has resulted in a global health care crisis. There is an urgent need for innovative antibacterial strategies and treatment options to effectively combat drug resistant bacterial pathogens. Here, we describe the implementation of a Pseudomonas competition strategy, using redox-active phenazines, to identify novel antibacterial leads against Staphylococcus aureus and Staphylococcus epidermidis. In this report, we describe the chemical synthesis and evaluation of a diverse 27-membered phenazine library. Using this microbial warfare inspired approach, we have identified several bromophenazines with potent antibacterial activities against S. aureus and S. epidermidis. The most potent bromophenazine analogue from this focused library demonstrated a minimum inhibitory concentration (MIC) of 0.78-1.56 μM, or 0.31-0.62 μg mL(-1), against S. aureus and S. epidermidis and proved to be 32- to 64-fold more potent than the phenazine antibiotic pyocyanin in head-to-head MIC experiments. In addition to the discovery of potent antibacterial agents against S. aureus and S. epidermidis, we also report a detailed structure-activity relationship for this class of bromophenazine small molecules.

  12. Evaluation of an Immunochromatographic Assay for Rapid Detection of Penicillin-Binding Protein 2a in Human and Animal Staphylococcus intermedius Group, Staphylococcus lugdunensis, and Staphylococcus schleiferi Clinical Isolates.

    Science.gov (United States)

    Arnold, A R; Burnham, C-A D; Ford, B A; Lawhon, S D; McAllister, S K; Lonsway, D; Albrecht, V; Jerris, R C; Rasheed, J K; Limbago, B; Burd, E M; Westblade, L F

    2016-03-01

    The performance of a rapid penicillin-binding protein 2a (PBP2a) detection assay, the Alere PBP2a culture colony test, was evaluated for identification of PBP2a-mediated beta-lactam resistance in human and animal clinical isolates of Staphylococcus intermedius group, Staphylococcus lugdunensis, and Staphylococcus schleiferi. The assay was sensitive and specific, with all PBP2a-negative and PBP2a-positive strains testing negative and positive, respectively.

  13. Evaluation of an Immunochromatographic Assay for Rapid Detection of Penicillin-Binding Protein 2a in Human and Animal Staphylococcus intermedius Group, Staphylococcus lugdunensis, and Staphylococcus schleiferi Clinical Isolates

    OpenAIRE

    Arnold, A. R.; Burnham, C.-A. D.; Ford, B. A.; Lawhon, S. D.; McAllister, S K; Lonsway, D.; Albrecht, V; Jerris, R C; Rasheed, J K; Limbago, B.; Burd, E M; Westblade, L. F.

    2016-01-01

    The performance of a rapid penicillin-binding protein 2a (PBP2a) detection assay, the Alere PBP2a culture colony test, was evaluated for identification of PBP2a-mediated beta-lactam resistance in human and animal clinical isolates of Staphylococcus intermedius group, Staphylococcus lugdunensis, and Staphylococcus schleiferi. The assay was sensitive and specific, with all PBP2a-negative and PBP2a-positive strains testing negative and positive, respectively.

  14. Epidemic Increase in Methicillin-resistant Staphylococcus aureus in Copenhagen

    DEFF Research Database (Denmark)

    Westh, Henrik; Boye, Kit; Bartels, Mette Damkjær;

    2006-01-01

    in 2004. All isolates have been spa-typed and epidemiologic information collected. RESULTS: The number of MRSA cases has a doubling time of about six months. The epidemic has been caused by many different MRSA types and 31 staphylococcus protein A genotypes (spa types). MRSA has caused several hospital......INTRODUCTION: We have found an epidemic increase in methicillin-resistant Staphylococcus aureus (MRSA) in Copenhagen. The increase has a complex background and involves hospitals, nursing homes and persons nursed in their own home. MATERIAL AND METHODS: We found 33 MRSA patients in 2003 and 121...

  15. A porcine model of haematogenous brain infectionwith staphylococcus aureus

    DEFF Research Database (Denmark)

    Astrup, Lærke Boye; Agerholm, Jørgen Steen; Nielsen, Ole Lerberg;

    2012-01-01

    A PORCINE MODEL OF HAEMATOGENOUS BRAIN INFECTION WITH STAPHYLOCOCCUS AUREUS Astrup Lærke1, Agerholm Jørgen1, Nielsen Ole1, Jensen Henrik1, Leifsson Páll1, Iburg Tine2. 1: Faculty of Health and Medical Sciences, University of Copenhagen, Denmark boye@life.ku.dk 2: National Veterinary Institute......, Uppsala, Sweden Introduction Staphylococcus aureus (S.aureus) is a common cause of sepsis and brain abscesses in man and a frequent cause of porcine pyaemia. Here we present a porcine model of haematogenous S. aureus-induced brain infection. Materials and Methods Four pigs had two intravenous catheters...

  16. Threat of multidrug resistant Staphylococcus aureus in Western Nepal

    DEFF Research Database (Denmark)

    Bhatta, Dharm R.; Cavaco, Lina; Nath, Gopal

    2015-01-01

    ObjectiveTo determine the prevalence of methicillin resistant Staphylococcus aureus (MRSA) and antimicrobial susceptibility patterns of the isolates from Manipal Teaching Hospital, Pokhara, Nepal. MethodsThis study was conducted over a period of 11 months (September 2012–August 2013) at the Manipal...... using disc diffusion test by cefoxitin (30 μg) and oxacillin (1 μg) disc, further confirmation was done by detection of mecA gene using PCR. ResultsOut of 400 Staphylococcus aureus strains, 139 (34.75%) were found to be MRSA. Among the MRSA isolates, 74 (53.2%) were from inpatient departments, 58 (41...

  17. Staphylococcus aureus sternal osteomyelitis: a rare cause of chest pain

    Directory of Open Access Journals (Sweden)

    Kaur M

    2015-10-01

    Full Text Available Chest pain is a common presenting symptom with a broad differential. Life-threatening cardiac and pulmonary etiologies of chest pain should be evaluated first. However, it is critical to perform a thorough assessment for other sources of chest pain in order to limit morbidity and mortality from less common causes. We present a rare case of a previously healthy 45 year old man who presented with focal, substernal, reproducible chest pain and Staphylococcus aureus bacteremia who was later found to have primary Staphylococcus aureus sternal osteomyelitis.

  18. [Study on processing adjuvant medicines in Lei Gong's treatise on preparation and broiling of materia medica (Leigong Paozhi Lun)].

    Science.gov (United States)

    Zhang, Wei; Zhang, Ruixian

    2010-09-01

    There were 268 kinds of medicines recorded in the book of Lei Gong's Treatise on preparation and broiling of materia medica (Leigong Paozhi Lun). Among these medicines, 178 medicines were prepared with adjuvant medicines, including general and special compatible adjuvant medicines. These adjuvant medicines used in this book can be explained by the theory of "seven-relation compatibility". The author tried to explain the usage and their compatibility of these adjuvant medicines and put forward that attention should be paid to the changes in functions of medicines and the influences of society should be paid attention.

  19. Modern Vaccines/Adjuvants Formulation--Session 2 (Plenary II): May 15-17, 2013--Lausanne, Switzerland.

    Science.gov (United States)

    Collin, Nicolas

    2013-09-01

    On the 15-17th May 2013, the Fourth International Conference on Modern Vaccines/Adjuvants Formulation was organized in Lausanne, Switzerland, and gathered stakeholders from academics and from the industry to discuss several challenges, advances and promises in the field of vaccine adjuvants. Plenary session 2 of the meeting was composed of four different presentations covering: (1) the recent set-up of an adjuvant technology transfer and training platform in Switzerland, (2) the proposition to revisit existing paradigms of modern vaccinology, (3) the properties of polyethyleneimine as potential new vaccine adjuvant, and (4) the progresses in the design of HIV vaccine candidates able to induce broadly neutralizing antibodies.

  20. Adjuvanted rush immunotherapy using CpG oligodeoxynucleotides in experimental feline allergic asthma.

    Science.gov (United States)

    Reinero, Carol R; Cohn, Leah A; Delgado, Cherlene; Spinka, Christine M; Schooley, Elizabeth K; DeClue, Amy E

    2008-02-15

    Allergic asthma is driven by relative overexpression of Th2 cell-derived cytokines in response to aeroallergens. In independent studies, both allergen-specific rush immunotherapy (RIT) and CpG oligodeoxynucleotides (ODN) showed promise in blunting eosinophilic inflammation in a model of feline allergic asthma. We hypothesized that RIT using allergen and CpG ODN would work synergistically to dampen the asthmatic phenotype in experimentally asthmatic cats. Twelve cats with asthma induced using Bermuda grass allergen (BGA) were studied. Of these, six were administered adjuvanted BGA RIT using CpG ODN #2142; six were administered placebo (saline) RIT and later crossed over to adjuvanted RIT. Over 2 days, subcutaneous CpG ODN (0.5ng/kg) with BGA (increasing doses every 2h from 20 to 200microg) was administered. Adverse events were recorded and compared with historical controls. Percentage of eosinophils in bronchoalveolar lavage fluid (BALF), % peripheral CD4+CD25+ T regulatory cells (Tregs), lymphocyte proliferation in response to ConA, and cytokine concentrations in BALF were measured over 2 months. Group mean BALF % eosinophils for the adjuvanted RIT cats were significantly lower at week 1 and month 1 (p=0.03 for both), and marginally significantly lower at month 2 (p=0.09) compared with placebo RIT cats. By the end of the study, 8/12 treated cats had BALF % eosinophils within the reference range for healthy cats. Adjuvanted RIT, but not placebo RIT, cats had significant decreases in the ConA stimulation index over time (p=0.05). BALF IL-4 concentrations were significantly higher at week 1 in adjuvanted RIT cats compared with baseline and month 2, and also with placebo RIT cats at week 1. No significant differences were detected between treatments or over time for IL-10 or IFN-gamma concentrations in BALF or for %Tregs cells in peripheral blood. Adjuvanted RIT using CpG ODN in experimental feline asthma dampens eosinophilic airway inflammation. Adverse effects