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Sample records for quimioterapia adjuvante baseada

  1. Assessment of potential adjuvanticity of Cry proteins.

    PubMed

    Joshi, Saurabh S; Barnett, Brian; Doerrer, Nancy G; Glenn, Kevin; Herman, Rod A; Herouet-Guicheney, Corinne; Hunst, Penny; Kough, John; Ladics, Gregory S; McClain, Scott; Papineni, Sabitha; Poulsen, Lars K; Rascle, Jean-Baptiste; Tao, Ai-Lin; van Ree, Ronald; Ward, Jason; Bowman, Christal C

    2016-08-01

    Genetically modified (GM) crops have achieved success in the marketplace and their benefits extend beyond the overall increase in harvest yields to include lowered use of insecticides and decreased carbon dioxide emissions. The most widely grown GM crops contain gene/s for targeted insect protection, herbicide tolerance, or both. Plant expression of Bacillus thuringiensis (Bt) crystal (Cry) insecticidal proteins have been the primary way to impart insect resistance in GM crops. Although deemed safe by regulatory agencies globally, previous studies have been the basis for discussions around the potential immuno-adjuvant effects of Cry proteins. These studies had limitations in study design. The studies used animal models with extremely high doses of Cry proteins, which when given using the ig route were co-administered with an adjuvant. Although the presumption exists that Cry proteins may have immunostimulatory activity and therefore an adjuvanticity risk, the evidence shows that Cry proteins are expressed at very low levels in GM crops and are unlikely to function as adjuvants. This conclusion is based on critical review of the published literature on the effects of immunomodulation by Cry proteins, the history of safe use of Cry proteins in foods, safety of the Bt donor organisms, and pre-market weight-of-evidence-based safety assessments for GM crops. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Alum adjuvanticity: unraveling a century old mystery.

    PubMed

    De Gregorio, Ennio; Tritto, Elaine; Rappuoli, Rino

    2008-08-01

    The development of vaccine adjuvants for human use has been one of the slowest processes in the history of medicine. For almost one century, aluminium hydroxide (alum) has been the only vaccine adjuvant approved worldwide. Only in the past decade have two oil-in-water emulsions and one TLR agonist been approved by the European authorities as new vaccine adjuvants. Despite the fact that alum has been injected into billions of people, its mechanism of action is not fully understood. Recently, several reports have greatly increased our knowledge of the molecular and cellular events triggered by alum; however, the contribution of each of these processes to alum adjuvanticity is still unclear. A study published in this issue of the European Journal of Immunology, together with two recent publications, have demonstrated that the NOD-like receptor, pyrin domain containing 3 (Nlrp3)-inflammasome is the molecular target of alum immunostimulatory activity in vitro. Surprisingly, these three studies reported conflicting results on the requirement of the Nlrp3 inflammasome complex for alum adjuvant effects in vivo. This commentary attempts to resolve some of these discrepancies.

  3. In vitro studies on the adjuvanticity of Brucella fractions.

    PubMed Central

    Serre, A; Vendrell, J P; Huguet, M F; Cannat, A

    1982-01-01

    Two Brucella fractions, the murein-linked fraction PI and the murein-free fraction SF, behave as in vitro adjuvants for primary anti-sheep erythrocyte responses: added to Mishell and Dutton-type cultures of spleen cells from B6/DB F1 mice they significantly enhance the number of direct anti-sheep erythrocyte PFC observed on day 5. They exert both nonspecific, polyclonal activating effects and antigen-dependent specific adjuvanticity. These two functions, however, differ in their dose responses and in their cellular requirements and can therefore be dissociated. Thus, polyclonal activation requires high doses of the "adjuvant fraction," is enhanced by adherent-cell depletion, and is not impaired by T-cell depletion. Specific adjuvanticity, on the other hand, requires lower doses of the adjuvant fractions (very high doses are in fact suppressive) and is T-cell and adherent-cell dependent. Moreover, adjuvanticity can be transferred to unstimulated spleen cells (or restored in adherent-cell-depleted populations) by PI- or SF-stimulated adherent cells or by the filtered supernatants of such cultures; adjuvant-soluble factors are therefore involved in the phenomena of adherent, T- and B-cell cooperation required for the adjuvanticity of Brucella fractions. PMID:6982864

  4. Studies on adjuvanticity of sodium houttuyfonate and its mechanism.

    PubMed

    Wang, Dayong; Yu, Qinghai; Eikstadt, Peggy; Hammond, Darcy; Feng, Yun; Chen, Na

    2002-09-01

    The adjuvanticity of sodium houttuyfonate (SH) and its mechanism were studied in this research. Significant enhancement of antibody production was observed when co-injected with antigen. The levels of anti-BSA antibodies were measured by enzyme-linked immunosorbent assay (ELISA). The possible mechanism of this phenomenon was also investigated in this research, which included the effects of SH on the phagocytosis of macrophages, the production of lysozyme, acid phosphotase and IL-1beta generated by macrophages, the proliferation of the lymphocytes in spleen and the production of IL-2 generated by lymphocytes. IL-1beta is a co-stimulator in activating Th cells, which manifests its activity together with LFA-1, ICAM-1 and ICAM-2. These observations suggested that SH could be used as a new adjuvant.

  5. A Comparative Study of Stress-mediated Immunological Functions with the Adjuvanticity of Alum*

    PubMed Central

    Wang, Yufei; Rahman, Durdana; Lehner, Thomas

    2012-01-01

    The efficacy of a vaccine is generally dependent on an adjuvant, which enhances the immune functions and alum has been widely used in human immunization. Alum activates the intracellular stress sensors inflammasomes, but whether these are responsible for the adjuvanticity is controversial. The objectives of this investigation were to examine the hypothesis that alum-mediated adjuvanticity is a function of stress and conversely that stress agents will elicit adjuvanticity. The investigation was carried out in BALB/c mice by SC immunization with ovalbumin (OVA) mixed with alum. This elicited inflammasomes, with significant activation of caspase 1, production of IL-1β, and adjuvanticity, demonstrated by enhancing OVA-specific serum IgG antibodies, CD4+ T cells, and proliferation. The novel finding that alum induced HSP70 suggests that stress is involved in the mechanism of adjuvanticity. This was confirmed by inhibition studies with PES (phenylethynesulfonamide), which disrupts inducible HSP70 function, and inhibited both inflammasomes and the adjuvant function. Parallel studies were pursued with an oxidative agent (sodium arsenite), K-releasing agent (Gramicidin) and a metal ionophore (dithiocarbamate). All 3 stress agents induced HSP70, inflammasomes, and the adjuvant functions. Furthermore, up-regulation of membrane associated IL-15 on DC and CD40L on T cells in the animals treated with alum or the stress agents mediate the interactions between splenic CD11c DC and CD4+ or CD8+ T cells. The results suggest that the three stress agents elicit HSP70, a hallmark of stress, as well as inflammasomes and adjuvanticity, commensurate with those of alum, which may provide an alternative strategy in developing novel adjuvants. PMID:22474329

  6. Cysteine Peptidases as Schistosomiasis Vaccines with Inbuilt Adjuvanticity

    PubMed Central

    El Ridi, Rashika; Tallima, Hatem; Selim, Sahar; Donnelly, Sheila; Cotton, Sophie; Gonzales Santana, Bibiana; Dalton, John P.

    2014-01-01

    Schistosomiasis is caused by several worm species of the genus Schistosoma and afflicts up to 600 million people in 74 tropical and sub-tropical countries in the developing world. Present disease control depends on treatment with the only available drug praziquantel. No vaccine exists despite the intense search for molecular candidates and adjuvant formulations over the last three decades. Cysteine peptidases such as papain and Der p 1 are well known environmental allergens that sensitize the immune system driving potent Th2-responses. Recently, we showed that the administration of active papain to mice induced significant protection (P<0.02, 50%) against an experimental challenge infection with Schistosoma mansoni. Since schistosomes express and secrete papain-like cysteine peptidases we reasoned that these could be employed as vaccines with inbuilt adjuvanticity to protect against these parasites. Here we demonstrate that sub-cutaneous injection of functionally active S. mansoni cathepsin B1 (SmCB1), or a cathepsin L from a related parasite Fasciola hepatica (FhCL1), elicits highly significant (P<0.0001) protection (up to 73%) against an experimental challenge worm infection. Protection and reduction in worm egg burden were further increased (up to 83%) when the cysteine peptidases were combined with other S. mansoni vaccine candidates, glyceraldehyde 3-phosphate dehydrogenase (SG3PDH) and peroxiredoxin (PRX-MAP), without the need to add chemical adjuvants. These studies demonstrate the capacity of helminth cysteine peptidases to behave simultaneously as immunogens and adjuvants, and offer an innovative approach towards developing schistosomiasis vaccines PMID:24465551

  7. [Analysis of the continuity, circulation and productivity of the Revista Española de Quimioterapia].

    PubMed

    Gimeno Sieres, E

    2007-06-01

    The primary objective of this study was to compare some of the bibliometric indicators of the continuity, circulation and productivity of the Revista Espanola de Quimioterapia up to 2003 with other spanish journals of Pharmacy and Pharmacology. This was done by reviewing periodicals directories, such as the ISSN (International Standard Serial Number/Número Internacional Normalizado de Publicaciones Seriadas) and ULRICH'S (Periodicals Directory), as well as the CDU (Classification Universal Decimal), national and international databases including IME (Indice Médico Español), ICYT (Indice Espanol de Ciencia y Tecnologia), IPA (International Pharmaceutical Abstracts), SCI Expanded (Science Citation Index Expanded), MEDLINE (Index Medicus), EMBASE (Excerpta Medica), BIOSIS PREVIEWS, ANALYTICAL ABSTRACTS, FSTA (Food Science and Technology Abstracts), SCIFINDER SCHOLAR and CHEMISTRY CITATION INDEX. According to the results, the Revista Española de Quimioterapia, in publication for 15 years, is widely distributed and has a good rating among other scientific journals of the same discipline.

  8. Potent adjuvantic activity of a CCR1-agonistic bis-quinoline.

    PubMed

    Ukani, Rehman; Lewis, Tyler C; Day, Timothy P; Wu, Wenyan; Malladi, Subbalakshmi S; Warshakoon, Hemamali J; David, Sunil A

    2012-01-01

    A bis-quinoline compound, (7-chloro-N-(4-(7-chloroquinolin-4-ylamino)butyl)quinolin-4-amine; RE-660) was found to have C-C chemokine receptor type 1 (CCR1)-agonistic properties. RE-660 displayed strong adjuvantic activity in mice when co-administered with bovine α-lactalbumin used as a model subunit protein antigen. RE-660 evoked a balanced Th1 (IgG2)/Th2 (IgG1) antibody profile, and the quality of antibodies elicited by the bis-quinoline was found to be superior to that evoked by glucopyranosyl lipid A by surface plasmon resonance experiments. No evidence of proinflammatory activity was observed in human blood ex vivo models. In preliminary acute toxicity studies, the compound was found to be of lower toxicity than chloroquine in mice, and was non-mutagenic in an Ames screen. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Liposome can improve the adjuvanticity of astragalus polysaccharide on the immune response against ovalbumin.

    PubMed

    Fan, Yunpeng; Ma, Lin; Zhang, Weimin; Cui, Xiaoqi; Zhen, Yin; Suolangzhaxi; Song, Xiaoping

    2013-09-01

    In vitro, the effects of astragalus polysaccharide liposome (APSL) on splenocyte proliferation of mice were determined. The results showed that APSL could significantly promote splenocyte proliferation synergistically with PHA and LPS and the efficacy were superior to those of astragalus polysaccharide (APS) and blank liposome (BL). In immune response experiment, the adjuvant effect of APSL at three doses, APS, BL and aluminum hydroxide (alum) were compared on mice immunized subcutaneously with ovalbumin (OVA). The results showed that APSL could significantly promote splenocyte proliferation, enhance specific IgG, IgG1 and IgG2a antibody responses, promote IFN-γ and IL-6 secretion, and the efficacy were significantly better than alum at most time points. These results indicated that APSL could significantly improve the adjuvanticity and drug action of APS, and its high and medium doses possessed the best efficacy. Therefore, the liposome would be expected to exploit into a new-type preparation of APS. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  10. Structure-Based Design of Human TLR8-Specific Agonists with Augmented Potency and Adjuvanticity

    PubMed Central

    2016-01-01

    Human Toll-like receptor 8 (hTLR8) is expressed in myeloid dendritic cells, monocytes, and monocyte-derived dendritic cells. Engagement by TLR8 agonists evokes a distinct cytokine profile which favors the development of type 1 helper T cells. Crystal structures of the ectodomain of hTLR8 cocrystallized with two regioisomers of a dual TLR7/8-agonistic N1-substituted imidazoquinolines showed subtle differences in their interactions in the binding site of hTLR8. We hypothesized that the potency of a previously reported best-in-class pure TLR8 agonist, 3-pentylquinoline-2-amine, could be further enhanced by “designing in” functional groups that would mimic key intermolecular interactions that we had observed in the crystal structures. We performed a focused exploration of decorating the quinoline core with alkylamino groups at all possible positions. These studies have led to the identification of a novel TLR8 agonist that was ∼20-fold more potent than the parent compound and displays prominent adjuvantic activity in a rabbit model of immunization. PMID:26351878

  11. A role of IgM antibodies in monosodium urate crystal formation and associated adjuvanticity

    PubMed Central

    Kanevets, Uliana; Sharma, Karan; Dresser, Karen; Shi, Yan

    2008-01-01

    Uric acid is released from injured cells and can act as an adjuvant signal to the immune system. Uric acid crystals invoke strong inflammatory responses in tissues. While their biological effects are evident and the associated signalling mechanisms are becoming clear, it remains unexplained as to why uric acid precipitates rapidly in vivo, in sharp contrast to the minimal crystallization in vitro. We report here that a group of IgM antibodies are able to bind to these crystals, which is interesting in light that B cell deficient mice do not sense the proinflammatory adjuvant effect of uric acid. The titers of these antibodies increase upon immunization with uric acid crystals. We have produced large quantities of such monoclonal antibodies. The purified IgM antibodies can significantly facilitate uric acid precipitation to form the inflammatory crystals in vitro. Infusion of these antibodies into B cell deficient mice significantly increases the basal level of inflammation in these recipients and restores the host’s ability to sense uric acid’s adjuvanticity. Therefore, we have identified a factor in determining uric acid precipitation and possibly its ability to function as an endogenous adjuvant. This finding suggests a new mechanism of the pathogenesis of gouty arthritis and uric acid induced immune activation. PMID:19201844

  12. Freund's adjuvants: relationship of arthritogenicity and adjuvanticity in rats to vehicle composition

    PubMed Central

    Whitehouse, M. W.; Orr, K. J.; Beck, Frances W. J.; Pearson, C. M.

    1974-01-01

    Over a hundred compounds and natural materials were examined for their ability to induce arthritis in rats when mixed with heat-killed delipidated Mycobacteria tuberculosis. Many of these materials were also assessed for (CMI) adjuvant activity by their ability to induce allergic encephalomyelitis (EAE) in rats when mixed with guinea-pig spinal cord, both with and without added M. tuberculosis. Cyclization and/or the presence of oxygen atoms, or double bonds reduced (or abolished) the arthritogenic potential and adjuvanticity of alkanes>C10. Esters/triglycerides of fatty acids >C12, retinol acetate (not palmitate) and vitamins E and K showed co-arthritogenic and adjuvant activity. Other active lipids included squalene and cholesterol oleate, which are both present in human sebum. Sebaceous lipids may therefore perhaps function as natural adjuvants if resorbed during abrasion and infection. Squalane (perhydrosqualene), pristane and hexadecane were excellent substitutes for mineral oil in preparing arthritogenic adjuvants from various mycobacteria, C. rubrum and N. asteroides. These oily compounds were also very effective adjuvants per se, in the absence of bacterial material or emulsifier, for inducing EAE in Lewis rats. PMID:4214125

  13. Mucosal Adjuvanticity and Immunogenicity of LTR72, a Novel Mutant of Escherichia coli Heat-labile Enterotoxin with Partial Knockout of ADP-ribosyltransferase Activity

    PubMed Central

    Giuliani, Marzia Monica; Del Giudice, Giuseppe; Giannelli, Valentina; Dougan, Gordon; Douce, Gill; Rappuoli, Rino; Pizza, Mariagrazia

    1998-01-01

    Heat-labile Escherichia coli enterotoxin (LT) has the innate property of being a strong mucosal immunogen and adjuvant. In the attempt to reduce toxicity and maintain the useful immunological properties, several LT mutants have been produced. Some of these are promising mucosal adjuvants. However, so far, only those that were still toxic maintained full adjuvanticity. In this paper we describe a novel LT mutant with greatly reduced toxicity that maintains most of the adjuvanticity. The new mutant (LTR72), that contains a substitution Ala → Arg in position 72 of the A subunit, showed only 0.6% of the LT enzymatic activity, was 100,000-fold less toxic than wild-type LT in Y1 cells in vitro, and was at least 20 times less effective than wild-type LT in the rabbit ileal loop assay in vivo. At a dose of 1 μg, LTR72 exhibited a mucosal adjuvanticity, similar to that observed with wild-type LT, better than that induced by the nontoxic, enzymatically inactive LTK63 mutant, and much greater than that of the recombinant B subunit. This trend was consistent for both the amounts and kinetics of the antibody induced, and priming of antigen-specific T lymphocytes. The data suggest that the innate high adjuvanticity of LT derives from the independent contribution of the nontoxic AB complex and the enzymatic activity. LTR72 optimizes the use of both properties: the enzymatic activity for which traces are enough, and the nontoxic AB complex, the effect of which is dose dependent. In fact, in dose–response experiments in mice, 20 μg of LTR72 were a stronger mucosal adjuvant than wild-type LT. This suggests that LTR72 may be an excellent candidate to be tested in clinical trials. PMID:9529328

  14. Different adjuvanticity of incomplete freund's adjuvant derived from beef or vegetable components in melanoma patients immunized with a peptide vaccine.

    PubMed

    Rosenberg, Steven A; Yang, James C; Kammula, Udai S; Hughes, Marybeth S; Restifo, Nicholas P; Schwarz, Susan L; Morton, Kathleen E; Laurencot, Carolyn M; Sherry, Richard M

    2010-01-01

    Adjuvants are requisite components of many vaccines designed to elicit T-cell immunity although the exact components of commonly used adjuvants are not always fully defined. In 2006, owing to concerns of prion contamination, the formulation of Montanide ISA 51 Incomplete Freund's Adjuvant (IFA) was changed from using oleic acid isolated from beef tallow to that isolated from olives. In sequential clinical trials in the Surgery Branch, NCI patients at high risk for recurrence of melanoma were immunized with the gp100 melanoma/melanocyte antigenic peptide, gp100: 209-217 (210M), emulsified in the beef-derived IFA or the olive-derived IFA. The in vivo generation of gp100 reactive T cells was significantly less in patients receiving the olive compared with the beef IFA as assessed by both ELISPOT (P2=0.0001) and in vitro sensitization assays (P2=0.0001). Local skin reactions to the peptide emulsion were also far less severe using the olive IFA (P2=0.0003). Thus it seems likely that contaminants in the beef-derived IFA played an important role in the increased adjuvanticity of this preparation compared with the olive-derived IFA. These findings raise serious concerns related to the use of the available olive-derived IFA for immunization in clinical trials. A survey of ongoing clinical trials listed in ClinicalTrials.gov revealed 36 trials currently accruing patients that are using the olive-derived Montanide ISA 51 IFA.

  15. Adjuvanticity of the oil-in-water emulsion MF59 is independent of Nlrp3 inflammasome but requires the adaptor protein MyD88

    PubMed Central

    Seubert, Anja; Calabro, Samuele; Santini, Laura; Galli, Barbara; Genovese, Alessia; Valentini, Sara; Aprea, Susanna; Colaprico, Annalisa; D'Oro, Ugo; Giuliani, Marzia M.; Pallaoro, Michele; Pizza, Mariagrazia; O'Hagan, Derek T.; Wack, Andreas; Rappuoli, Rino; De Gregorio, Ennio

    2011-01-01

    Oil-in-water emulsions have been successfully used to increase the efficacy, immunogenicity, and cross-protection of human vaccines; however, their mechanism of action is still largely unknown. Nlrp3 inflammasome has been previously associated to the activity of alum, another adjuvant broadly used in human vaccines, and MyD88 adaptor protein is required for the adjuvanticity of most Toll-like receptor agonists. We compared the contribution of Nlrp3 and MyD88 to the adjuvanticity of alum, the oil-in-water emulsion MF59, and complete Freund's adjuvant in mice using a three-component vaccine against serogroup B Neisseria meningitidis (rMenB). Although the basal antibody responses to the nonadjuvanted rMenB vaccine were largely dependent on Nlrp3, the high-level antibody responses induced by alum, MF59, or complete Freund's adjuvant did not require Nlrp3. Surprisingly, we found that MF59 requires MyD88 to enhance bactericidal antibody responses to the rMenB vaccine. Because MF59 did not activate any of the Toll-like receptors in vitro, we propose that MF59 requires MyD88 for a Toll-like receptor-independent signaling pathway. PMID:21690334

  16. A truncated fragment of Ov-ASP-1 consisting of the core pathogenesis-related-1 (PR-1) domain maintains adjuvanticity as the full-length protein.

    PubMed

    Guo, Jingjing; Yang, Yi; Xiao, Wenjun; Sun, Weilai; Yu, Hong; Du, Lanying; Lustigman, Sara; Jiang, Shibo; Kou, Zhihua; Zhou, Yusen

    2015-04-15

    The Onchocerca volvulus activation-associated secreted protein-1 (Ov-ASP-1) has good adjuvanticity for a variety of antigens and vaccines, probably due to its ability activate antigen-processing cells (APCs). However, the functional domain of Ov-ASP-1 as an adjuvant is not clearly defined. Based on the structural prediction of this protein family, we constructed a 16-kDa recombinant protein of Ov-ASP-1 that contains only the core pathogenesis-related-1 (PR-1) domain (residues 10-153), designated ASPPR. We found that ASPPR exhibits adjuvanticity similar to that of the full-length Ov-ASP-1 (residues 10-220) for various antigens, including ovalbumin (OVA), HBsAg protein antigen, and the HIV peptide 5 (Pep5) antigen, but it is more suitable for vaccine design in ASPPR-antigen fusion proteins, and more stable in PBS than Ov-ASP-1 stored at -70 °C. These results suggest that ASPPR might be the functional region of Ov-ASP-1 as an adjuvant, and therefore could be developed as an adjuvant for human use.

  17. Comparison of PLA microparticles and alum as adjuvants for H5N1 influenza split vaccine: adjuvanticity evaluation and preliminary action mode analysis.

    PubMed

    Zhang, Weifeng; Wang, Lianyan; Liu, Yuan; Chen, Xiaoming; Li, Jiahui; Yang, Tingyuan; An, Wenqi; Ma, Xiaowei; Pan, Ruowen; Ma, Guanghui

    2014-04-01

    To compare the adjuvanticity of polymeric particles (new-generation adjuvant) and alum (the traditional and FDA-approved adjuvant) for H5N1 influenza split vaccine, and to investigate respective action mode. Vaccine formulations were prepared by incubating lyophilized poly(lactic acid) (PLA) microparticles or alum within antigen solution. Antigen-specific immune responses in mice were evaluated using ELISA, ELISpot, and flow cytometry assay. Adjuvants' action modes were investigated by determining antigen persistence at injection sites, local inflammation response, antigen transport into draining lymph node, and activation of DCs in secondary lymphoid organs (SLOs). Alum promoted antigen-specific humoral immune response. PLA microparticles augmented both humoral immune response and cell-mediated-immunity which might enhance cross-protection of influenza vaccine. With regard to action mode, alum adjuvant functions by improving antigen persistence at injection sites, inducing severe local inflammation, slightly improving antigen transport into draining lymph nodes, and improving the expression of MHC II on DCs in SLOs. PLA microparticles function by slightly improving antigen transport into draining lymph nodes, and promoting the expression of both MHC molecules and co-stimulatory molecules on DCs in SLOs. Considering the adjuvanticity and side effects (local inflammation) of both adjuvants, we conclude that PLA microparticles are promising alternative adjuvant for H5N1 influenza split vaccine.

  18. The adjuvanticity of an O. volvulus-derived rOv-ASP-1 protein in mice using sequential vaccinations and in non-human primates.

    PubMed

    Wang, Jing; Tricoche, Nancy; Du, Lanying; Hunter, Meredith; Zhan, Bin; Goud, Gaddam; Didier, Elizabeth S; Liu, Jing; Lu, Lu; Marx, Preston A; Jiang, Shibo; Lustigman, Sara

    2012-01-01

    Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. With a few vaccine antigens, it also promoted a Th1-biased response based on pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the upregulated production of Th1 cytokines, including IL-2, IFN-γ, TNF-α and IL-6. However, because it is a protein, the rOv-ASP-1 adjuvant may also induce anti-self-antibodies. Therefore, it was important to verify that the host responses to self will not affect the adjuvanticity of rOv-ASP-1 when it is used in subsequent vaccinations with the same or different vaccine antigens. In this study, we have established rOv-ASP-1's adjuvanticity in mice during the course of two sequential vaccinations using two vaccine model systems: the receptor-binding domain (RBD) of SARS-CoV spike protein and a commercial influenza virus hemagglutinin (HA) vaccine comprised of three virus strains. Moreover, the adjuvanticity of rOv-ASP-1 was retained with an efficacy similar to that obtained when it was used for a first vaccination, even though a high level of anti-rOv-ASP-1 antibodies was present in the sera of mice before the administration of the second vaccine. To further demonstrate its utility as an adjuvant for human use, we also immunized non-human primates (NHPs) with RBD plus rOv-ASP-1 and showed that rOv-ASP-1 could induce high titres of functional and protective anti-RBD antibody responses in NHPs. Notably, the rOv-ASP-1 adjuvant did not induce high titer antibodies against self in NHPs. Thus, the present study provided a sound scientific foundation for future strategies in the development of this novel protein adjuvant.

  19. The Adjuvanticity of an O. volvulus-Derived rOv-ASP-1 Protein in Mice Using Sequential Vaccinations and in Non-Human Primates

    PubMed Central

    Wang, Jing; Tricoche, Nancy; Du, Lanying; Hunter, Meredith; Zhan, Bin; Goud, Gaddam; Didier, Elizabeth S.; Liu, Jing; Lu, Lu; Marx, Preston A.; Jiang, Shibo; Lustigman, Sara

    2012-01-01

    Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. With a few vaccine antigens, it also promoted a Th1-biased response based on pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the upregulated production of Th1 cytokines, including IL-2, IFN-γ, TNF-α and IL-6. However, because it is a protein, the rOv-ASP-1 adjuvant may also induce anti-self-antibodies. Therefore, it was important to verify that the host responses to self will not affect the adjuvanticity of rOv-ASP-1 when it is used in subsequent vaccinations with the same or different vaccine antigens. In this study, we have established rOv-ASP-1's adjuvanticity in mice during the course of two sequential vaccinations using two vaccine model systems: the receptor-binding domain (RBD) of SARS-CoV spike protein and a commercial influenza virus hemagglutinin (HA) vaccine comprised of three virus strains. Moreover, the adjuvanticity of rOv-ASP-1 was retained with an efficacy similar to that obtained when it was used for a first vaccination, even though a high level of anti-rOv-ASP-1 antibodies was present in the sera of mice before the administration of the second vaccine. To further demonstrate its utility as an adjuvant for human use, we also immunized non-human primates (NHPs) with RBD plus rOv-ASP-1 and showed that rOv-ASP-1 could induce high titres of functional and protective anti-RBD antibody responses in NHPs. Notably, the rOv-ASP-1 adjuvant did not induce high titer antibodies against self in NHPs. Thus, the present study provided a sound scientific foundation for future strategies in the development of this novel protein adjuvant. PMID

  20. A comparative study of the adjuvanticity of Hansenula polymorpha, Saccharomyces cerevsiae and Yarrowia lipolytica in oral and nasal immunization with virus capsid antigens.

    PubMed

    Lee, Jae Young; Xu, Mei Ling; Kim, Hyoung Jin; Kang, Hyun Ah; Kim, Hong-Jin

    2013-11-01

    The adjuvanticity of Hansenula polymorpha, Saccharomyces cerevsiae and Yarrowia lipolytica were compared for oral and nasal immunization with virus capsid antigens. Mice were immunized orally with human papillomavirus type 16 L1 virus-like particles (HPV16 L1 VLPs), or intra-nasally with formalin-inactivated influenza A virus (FIV), in combination with one or other yeast. Mice receiving HPV16 L1 VLPs combined with H. polymorpha had a significantly higher titer for serum anti-HPV16 L1 IgG and neutralizing activity than those receiving HPV16 L1 VLPs combined with either of the other two yeasts. Also, mice receiving FIV combined with H. polymorpha had not only a markedly higher anti-influenza A virus IgG titer but also a higher survival rate after a potentially lethal influenza A virus challenge. We suggest that H. polymorpha thus will be useful for enhancing immune responses in mucosal immunizations.

  1. Adjuvanticity of a Recombinant Calreticulin Fragment in Assisting Anti-β-Glucan IgG Responses in T Cell-Deficient Mice

    PubMed Central

    Li, Wei-Ji; Long, Kai; Dong, Hong-Liang

    2013-01-01

    Polysaccharide-encapsulated fungi are the chief source of diseases in immunocompromised hosts such as those infected with human immunodeficiency virus or neutropenia patients. Currently available polysaccharide-protein conjugate vaccines are mainly T cell dependent and are usually ineffective in weakened immune systems. In this study, laminarin, a well-characterized β-1,3-glucan, was conjugated with a prokaryotically expressed recombinant fragment (amino acids [aa] 39 to 272) of calreticulin (rCRT/39–272), which exhibits extraordinarily potent immunogenicity and adjuvanticity in experimental animals. The resultant conjugate reserves the immunostimulatory effect of rCRT/39–272 on naïve murine B cells and is capable of eliciting anti-β-glucan IgG (mostly IgG1) responses in not only BALB/c mice but also athymic nude mice. Laminarin-CRT-induced mouse antibodies (Abs) are able to bind with Candida albicans and inhibit its growth in vitro. In addition, vaccination with laminarin-CRT partially protects mice from lethal C. albicans challenge. These results imply that rCRT/39–272 could be used as an ideal carrier or adjuvant for carbohydrate vaccines aimed at inducing or boosting IgG responses to fungal infections in immunodeficient hosts. PMID:23408527

  2. Improving adjuvanticity of quaternized chitosan-based microgels for H5N1 split vaccine by tailoring the particle properties to achieve antigen dose sparing effect.

    PubMed

    Wang, Yue-Qi; Fan, Qing-Ze; Liu, Yan; Yue, Hua; Ma, Xiao-Wei; Wu, Jie; Ma, Guang-Hui; Su, Zhi-Guo

    2016-12-30

    In this study, we developed the quaternized chitosan microgels without chemical crosslinking as an adjuvant of H5N1 split vaccine. The microgels with pH-sensitivity, positive surface charge and good biocompatibility, have been demonstrated in favor of enhancing both humoral and cellular immune response. However, the detailed mechanism of the chitosan-based microgels to enhance antigen specific immune responses remains unclear. Therefore, we prepared the quaternized chitosan microgels with well defined quaternization degrees (QDs, 20-80%) and particle sizes (800nm-5μm) by the premix membrane emulsification technique, and investigated the effect of quaternization degree (QD) and size on the adjuvanticity of microgels. Results suggested that microgels with relatively smaller size (807nm) and moderate quaternization degree (QD 41% and 60%) were favorable for a maximum immune response. The mechanism was studied and explained by examining the characteristics of microgels and investigating the stimulation of bone-marrow derived dendritic cells (BMDCs). Moreover, they induced significantly stronger immune responses at lower antigen doses (known as antigen sparing effect) compared to aluminum adjuvant. These data indicated that a maximum immune response can be achieved by controlling properties of chitosan microgels, which also could serve as a significant guidance for rational design of chitosan-based particle adjuvant. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Effect of alum co-adjuvantation of oil adjuvant vaccine on emulsion stability and immune responses against haemorhagic septicaemia in mice.

    PubMed

    Kumar, Sujeet; Chaturvedi, Vinod Kumar; Kumar, Bablu; Kumar, Pankaj; Somarajan, Sudha Rani; Mishra, Anil Kumar; Sharma, Bhaskar

    2015-04-01

    Haemorrhagic septicaemia (HS), caused by Pasteurella multocida, is the most important bacterial disease of cattle and buffaloes in India. Oil adjuvant vaccine (OAV) is the most potent vaccine available for the control of HS. The study aims to evaluate the effect of alum co-adjuvantation of OAV on emulsion stability and immune response. Two different oil adjuvant vaccines viz., standard oil adjuvant vaccine (OAV) and alum precipitated oil adjuvant vaccine (A-OAV) were prepared with Pasteurella multocida antigen. Emulsion stability was tested by centrifugation, storage at 37 °C for 3 months and microscopy. Immune responses were evaluated by ELISA antibody titer, CD4, CD8 T cell populations and survival post challenge by P. multocida in mice. The separation of aqueous and oil phase of emulsion by centrifugation and storage test were 0 and 6.76% in A-OAV as compared to 11.00 and 26.39% in OAV, respectively. The mean droplet size was significantly smaller (p<0.01) in A-OAV as compared to OAV. The A-OAV recorded higher ELISA antibody titer (p<0.05) up to 21st days post vaccination, and higher CD4 (p>0.05) and CD8 T cell (p<0.05) populations compared to OAV. The A-OAV group conferred 100% protection after challenge with both 100 LD50 and 1000 LD50 as compared to 100 and 60% respective protection by OAV group. The results indicates that A-OAV had better emulsion stability, produces higher level of CD4, CD8 T cells and antibody titer with better protection compared to oil adjuvant vaccine.

  4. Effect of alum co-adjuvantation of oil adjuvant vaccine on emulsion stability and immune responses against haemorhagic septicaemia in mice

    PubMed Central

    Kumar, Sujeet; Chaturvedi, Vinod Kumar; Kumar, Bablu; Kumar, Pankaj; Somarajan, Sudha Rani; Mishra, Anil Kumar; Sharma, Bhaskar

    2015-01-01

    Background and Objectives: Haemorrhagic septicaemia (HS), caused by Pasteurella multocida, is the most important bacterial disease of cattle and buffaloes in India. Oil adjuvant vaccine (OAV) is the most potent vaccine available for the control of HS. The study aims to evaluate the effect of alum co-adjuvantation of OAV on emulsion stability and immune response. Materials and Methods: Two different oil adjuvant vaccines viz., standard oil adjuvant vaccine (OAV) and alum precipitated oil adjuvant vaccine (A–OAV) were prepared with Pasteurella multocida antigen. Emulsion stability was tested by centrifugation, storage at 37 °C for 3 months and microscopy. Immune responses were evaluated by ELISA antibody titer, CD4, CD8 T cell populations and survival post challenge by P. multocida in mice. Results: The separation of aqueous and oil phase of emulsion by centrifugation and storage test were 0 and 6.76% in A-OAV as compared to 11.00 and 26.39% in OAV, respectively. The mean droplet size was significantly smaller (p<0.01) in A–OAV as compared to OAV. The A–OAV recorded higher ELISA antibody titer (p<0.05) up to 21st days post vaccination, and higher CD4 (p>0.05) and CD8 T cell (p<0.05) populations compared to OAV. The A–OAV group conferred 100% protection after challenge with both 100 LD50 and 1000 LD50 as compared to 100 and 60% respective protection by OAV group. Conclusion: The results indicates that A–OAV had better emulsion stability, produces higher level of CD4, CD8 T cells and antibody titer with better protection compared to oil adjuvant vaccine. PMID:26622968

  5. Fusion proteins of flagellin and the major birch pollen allergen Bet v 1 show enhanced immunogenicity, reduced allergenicity, and intrinsic adjuvanticity.

    PubMed

    Kitzmüller, Claudia; Kalser, Julia; Mutschlechner, Sonja; Hauser, Michael; Zlabinger, Gerhard J; Ferreira, Fatima; Bohle, Barbara

    2017-04-26

    Recombinant fusion proteins of flagellin and antigens have been demonstrated to induce strong innate and adaptive immune responses. Such fusion proteins can enhance the efficacy of allergen-specific immunotherapy. We sought to characterize different fusion proteins of flagellin and the major birch pollen allergen Bet v 1 for suitability as allergy vaccines. A truncated version of flagellin (NtCFlg) was genetically fused to the N- or C-terminus of Bet v 1. Toll-like receptor (TLR) 5 binding was assessed with HEK293 cells expressing TLR5. Upregulation of CD40, CD80, CD83, and CD86 on monocyte-derived dendritic cells from allergic patients was analyzed by using flow cytometry. The T cell-stimulatory capacity of the fusion proteins was assessed with naive and Bet v 1-specific T cells. IgE binding was tested in inhibition ELISAs and basophil activation tests. Mice were immunized with the fusion proteins in the absence and presence of aluminum hydroxide. Cellular and antibody responses were monitored. Murine antibodies were tested for blocking capacity in basophil activation tests. Both fusion proteins matured monocyte-derived dendritic cells through TLR5. Compared with Bet v 1, the fusion proteins showed stronger T cell-stimulatory and reduced IgE-binding capacity and induced murine Bet v 1-specific antibodies in the absence of aluminum hydroxide. However, only antibodies induced by means of immunization with NtCFlg fused to the C-terminus of Bet v 1 inhibited binding of patients' IgE antibodies to Bet v 1. Bet v 1-flagellin fusion proteins show enhanced immunogenicity, reduced allergenicity, and intrinsic adjuvanticity and thus represent promising vaccines for birch pollen allergen-specific immunotherapy. However, the sequential order of allergen and adjuvant within a fusion protein determines its immunologic characteristics. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. A new intranasal influenza vaccine based on a novel polycationic lipid-ceramide carbamoyl-spermine (CCS). II. Studies in mice and ferrets and mechanism of adjuvanticity.

    PubMed

    Even-Or, Orli; Joseph, Aviva; Itskovitz-Cooper, Noga; Samira, Sarit; Rochlin, Eli; Eliyahu, Hagit; Goldwaser, Itzik; Balasingam, Shobana; Mann, Alex J; Lambkin-Williams, Rob; Kedar, Eli; Barenholz, Yechezkel

    2011-03-16

    We recently showed that lipid assemblies comprised of a novel polycationic sphingolipid (ceramide carbamoyl-spermine, CCS) are an effective adjuvant/carrier when complexed with cholesterol (CCS/C) for influenza and other vaccines administered parenterally and intranasally (i.n.) in mice. Here we expand these studies to ferrets, an established model of influenza infection. We also address the question of why the CCS/C-based liposomal vaccine (also known as VaxiSome™) in mice is superior to vaccines based on liposomes of other lipid compositions (neutral, anionic or cationic). Ferrets immunized i.n. with CCS/C-influenza vaccine produced significantly higher hemagglutination inhibition (HI) antibody titers compared to ferrets immunized intramuscularly with the unadjuvanted influenza vaccine, indicating that the CCS/C-based vaccine is very immunogenic. Furthermore, the i.n. adjuvanted vaccine was shown to significantly reduce the severity of influenza virus infection in ferrets following homologous viral challenge as determined by weight loss, temperature rise and viral titer. No adverse reactions were observed. Pharmacokinetic and biodistribution studies following i.n. administration in mice of CCS/C-based vaccine showed that both the lipids and antigens are retained in the nose and lung for at least 24h, and it appears that this retention correlates with the superior immunogenicity elicited by the adjuvanted vaccine formulation. The CCS lipid also increases production of cytokines (mainly IFN gamma, IL-2 and IL-12) and co-stimulatory molecules' expression, which might further explain the robust adjuvantation of this liposome-based vaccine. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Radio-chimiothérapie adjuvante des adénocarcinomes gastriques: à propos de 34 cas et d'une revue de la literature

    PubMed Central

    James, Laurianne; Dossou, Sepos; Bellfiq, Sarah; Irigo, Joëlle; Ogandaga, Etienne; Mouden, Karima; Loughmari, Saïda; Filali, Dounia; El Majjaoui, Sanaa; Kebdani, Tayeb; Ahid, Samir; Benjafaar, Nourredine

    2014-01-01

    Notre étude consistera en l’évaluation du pronostic des patients porteurs d'un adénocarcinome gastrique opérés et traités par radio-chimiothérapie adjuvante en technique conformationnelle. Entre Janvier 2007 et Décembre 2011, 34 patients ont reçu après une chirurgie radicale (R0 ou R1), un à trois cycles de 5-Fluoro-uracile associé à de l'Elvorine en adjuvant, suivi d'une radio-chimiothérapie selon le même protocole à la dose de 45Gy, puis de deux cycles de chimiothérapie à un mois d'intervalle après la radio-chimiothérapie concomitante. Dans le groupe d’étude, il y avait 34 patients d’âge médian 50 ans (47-58), avec un sexe ratio (H/F) de 2,4. Une chirurgie de type R1 a été réalisée dans 26,5% des cas, et 53% des patients étaient de stade III-IV. Le rapport nombres de ganglions positifs, sur nombre de ganglions prélevés étaient > 0,4 dans 26,5% des cas. Durant le traitement mené à terme, une neutropénie de grade III a été observée chez quatre patients, avec des troubles digestifs (nausées, vomissement, ou diarrhée) de grade I/II dans la majorité des cas. Après un suivi médian de 20 mois, 70,6% des patients étaient en survie sans rechute, et 29,4% ont présenté une récidive métastatique; la survie globale à 5 ans était de 35,4% et la survie sans progression de 58,7%. La radio-chimiothérapie concomitante postopératoire pourrait être un régime efficace et sûre chez les patients ayant bénéficié d'une gastrectomie à visée curative dans le cancer de l'estomac localement avancé. PMID:25709728

  8. Réponse radiologique complète d'un hémangiopéricytome méningé après radiothérapie adjuvante à une exérèse incomplète

    PubMed Central

    Bazine, Amine; Ogandaga, Etienne; Dossou, Serpos; Aissa, Abdellah; Oumellal, Jamal; Lalya, Issam; Saidi, Amar; Kebdani, Tayeb; Benjaafar, Noureddine

    2014-01-01

    L'hémangiopéricytome méningé (HM) est une tumeur vasculaire rare qui représente moins de 1% des tumeurs intracrâniennes. Son traitement reste à ce jour mal codifié et n'est basé que sur des données rétrospectives. La place de la radiothérapie adjuvante après chirurgie d'exérèse n'est pas bien établie. Ce présent travail décrit un cas d'HM chez une patiente de 42 ans, traité par chirurgie incomplète et radiothérapie adjuvante, avec réponse radiologique complète notée 1 an après la fin du traitement. PMID:25379118

  9. The adjuvanticity of Ganoderma lucidum polysaccharide for Newcastle disease vaccine.

    PubMed

    Zhang, Ping; Ding, Ronglong; Jiang, Shanxiang; Ji, Liwei; Pan, Mingming; Liu, Li; Zhang, Wei; Gao, Xiuge; Huang, Wenjuan; Zhang, Guanjun; Peng, Lin; Ji, Hui

    2014-04-01

    The adjuvant activity of GLP was investigated in vitro and in vivo. In vitro experiment, the effects of GLP on chicken peripheral lymphocytes proliferation were compared by MTT assay. The results showed that GLP could significantly enhance lymphocytes proliferation singly or synergistically with ConA. The interferon-gamma (IFN-γ) mRNA levels of chicken peripheral lymphocytes stimulated by GLP synergistically with ConA were measured using fluorescent quantitative PCR. The results showed that GLP could promote interferon-γ mRNA levels in peripheral lymphocytes. In vivo experiment, 175 14-day-old chickens were randomly divided into 7 groups. The chickens except blank control (BC) group were vaccinated with Newcastle disease vaccine, repeated vaccination at 28 days old. At the same time of the first vaccination, the chickens in experimental groups were orally administrated with 5 different doses of GLP respectively, whereas vaccination control (VC) and BC groups were treated with physiological saline, once a day for three successive days. On Day 7, 14, 21 and 28 after the first vaccination, the peripheral lymphocytes proliferation and serum ND antibody titer were determined. The results showed that GLP could significantly promote lymphocyte proliferation and enhance serum antibody titer. The results indicated that GLP may be a novel immunomodulator.

  10. Innate Immune Memory: The Latest Frontier of Adjuvanticity.

    PubMed

    Töpfer, Elfi; Boraschi, Diana; Italiani, Paola

    2015-01-01

    Recent findings in the field of immune memory have demonstrated that B and T cell mediated immunity following infections are enhanced by the so-called trained immunity. This effect has been most extensively investigated for the tuberculosis vaccine strain Bacillus Calmette-Guérin (BCG). Epidemiological studies suggest that this vaccine is associated with a substantial reduction in overall child mortality that cannot be solely explained by prevention of the target disease but that it seems to rely on inducing resistance to other infections. Upon infection or vaccination, monocytes/macrophages can be functionally reprogrammed so as to display an enhanced defensive response against unrelated infections. Epigenetic modifications seem to play a key role in the induction of this "innate memory." These findings are revolutionising our knowledge of the immune system, introducing the concept of memory also for mammalian innate immunity. Thus, vaccines are likely to nonspecifically affect the overall immunological status of individuals in a clinically relevant manner. As a consequence, future vaccine strategies ought to take into account the contribution of innate memory through appropriate design of formulations and administration scheduling.

  11. Genetic Adjuvantation of a Cell-Based Therapeutic Vaccine for Amelioration of Chagasic Cardiomyopathy.

    PubMed

    Konduri, Vanaja; Halpert, Matthew M; Liang, Dan; Levitt, Jonathan M; Cruz-Chan, Julio Vladimir; Zhan, Bin; Bottazzi, Maria Elena; Hotez, Peter J; Jones, Kathryn M; Decker, William K

    2017-09-01

    Chagas disease, caused by infection with the protozoan parasite Trypanosoma cruzi, is a leading cause of heart disease ("chagasic cardiomyopathy") in Latin America, disproportionately affecting people in resource-poor areas. The efficacy of currently approved pharmaceutical treatments is limited mainly to acute infection, and there are no effective treatments for the chronic phase of the disease. Preclinical models of Chagas disease have demonstrated that antigen-specific CD8(+) gamma interferon (IFN-γ)-positive T-cell responses are essential for reducing parasite burdens, increasing survival, and decreasing cardiac pathology in both the acute and chronic phases of Chagas disease. In the present study, we developed a genetically adjuvanted, dendritic cell-based immunotherapeutic for acute Chagas disease in an attempt to delay or prevent the cardiac complications that eventually result from chronic T. cruzi infection. Dendritic cells transduced with the adjuvant, an adenoviral vector encoding a dominant negative isoform of Src homology region 2 domain-containing tyrosine phosphatase 1 (SHP-1) along with the T. cruzi Tc24 antigen and trans-sialidase antigen 1 (TSA1), induced significant numbers of antigen-specific CD8(+) IFN-γ-positive cells following injection into BALB/c mice. A vaccine platform transduced with the adenoviral vector and loaded in tandem with the recombinant protein reduced parasite burdens by 76% to >99% in comparison to a variety of different controls and significantly reduced cardiac pathology in a BALB/c mouse model of live Chagas disease. Although no statistical differences in overall survival rates among cohorts were observed, the data suggest that immunotherapeutic strategies for the treatment of acute Chagas disease are feasible and that this approach may warrant further study. Copyright © 2017 American Society for Microbiology.

  12. Adjuvanticity of compound astragalus polysaccharide and sulfated epimedium polysaccharide per os.

    PubMed

    Chen, Xingying; Chen, Xiaolan; Qiu, Shulei; Hu, Yuanliang; Wang, Deyun; Liu, Xu; Zhao, Xiaojuan; Liu, Cui; Chen, Xinghui

    2013-11-01

    On the basis of previous researches, compound astragalus polysaccharide (APS) and sulfated epimedium polysaccharide (sEPS) oral liquid (AEO) was prepared. Three hundred and twenty 14-day-old chickens were randomly assigned into eight groups and vaccinated with ND vaccine except for blank control (BC) group, repeated vaccination at 28 days old. At the same time of each vaccination, the chickens in three experimental groups were taken orally with AEO, respectively, at three doses, in two component control groups with APS and sEPS, once a day for three successive days; in injection control group were injected with AEI once, and in vaccination control (VC) and BC groups were not administrated. On days 7, 14, 21, 28 and 35 after the first vaccination, peripheral lymphocyte proliferation, the serum antibody titer, IFN-γ and IL-2 concentrations and on day 35 immune organ index were measured. The results showed that AEO at high and medium doses could significantly promote lymphocyte proliferation and development of immune organ, enhance antibody titer and IFN-γ and IL-2 concentration, which was stronger than actions of AEI and two components. The results confirmed that AEO possessed reliable immunoenhancement and could be exploited into an oral immunopotentiator. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Alum interaction with dendritic cell membrane lipids is essential for its adjuvanticity.

    PubMed

    Flach, Tracy L; Ng, Gilbert; Hari, Aswin; Desrosiers, Melanie D; Zhang, Ping; Ward, Sandra M; Seamone, Mark E; Vilaysane, Akosua; Mucsi, Ashley D; Fong, Yin; Prenner, Elmar; Ling, Chang Chun; Tschopp, Jurg; Muruve, Daniel A; Amrein, Matthias W; Shi, Yan

    2011-04-01

    As an approved vaccine adjuvant for use in humans, alum has vast health implications, but, as it is a crystal, questions remain regarding its mechanism. Furthermore, little is known about the target cells, receptors, and signaling pathways engaged by alum. Here we report that, independent of inflammasome and membrane proteins, alum binds dendritic cell (DC) plasma membrane lipids with substantial force. Subsequent lipid sorting activates an abortive phagocytic response that leads to antigen uptake. Such activated DCs, without further association with alum, show high affinity and stable binding with CD4(+) T cells via the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1). We propose that alum triggers DC responses by altering membrane lipid structures. This study therefore suggests an unexpected mechanism for how this crystalline structure interacts with the immune system and how the DC plasma membrane may behave as a general sensor for solid structures.

  14. Comparative in vivo Study of gp96 Adjuvanticity in the Frog Xenopus laevis

    PubMed Central

    Nedelkovska, Hristina; Cruz-Luna, Tanya; McPherson, Pamela; Robert, Jacques

    2010-01-01

    We have developed in the amphibian Xenopus laevis a unique non-mammalian model to study the ability of certain heat shock proteins (hsps) such as gp96 to facilitate cross-presentation of chaperoned antigens and elicit innate and adaptive T cell responses. Xenopus skin graft rejection provides an excellent platform to study the ability of gp96 to elicit classical MHC class Ia (class Ia) restricted T cell responses. Additionally, the Xenopus model system also provides an attractive alternative to mice for exploring the ability of gp96 to generate responses against tumors that have down-regulated their class Ia molecules thereby escaping immune surveillance. Recently, we have developed an adoptive cell transfer assay in Xenopus clones using peritoneal leukocytes as antigen presenting cells (APCs), and shown that gp96 can prime CD8 T cell responses in vivo against minor histocompatibility skin antigens as well as against the Xenopus thymic tumor 15/0 that does not express class Ia molecules. We describe here the methodology involved to perform these assays including the elicitation, pulsing and adoptive transfer of peritoneal leukocytes, as well as the skin graft and tumor transplantation assays. Additionally we are also describing the harvesting and separation of peripheral blood leukocytes used for flow cytometry and proliferation assays which allow for further characterization of the effector populations involved in skin rejection and anti-tumor responses. PMID:20972386

  15. Use of inactivated E.Coli enterotoxins to enhance respiratory mucosal adjuvanticity during vaccination in swine

    USDA-ARS?s Scientific Manuscript database

    In order to augment responses to respiratory vaccines in swine, various adjuvants were intranasally co-administered with an antigen to pigs. Detoxified E. coli enterotoxins LTK63 and LTR72 enhanced mucosal and systemic immunity to the model peptide, exhibiting their efficacy as mucosal adjuvants for...

  16. Synthesis, Formulation, and Adjuvanticity of Monodesmosidic Saponins with Olenanolic Acid, Hederagenin and Gypsogenin Aglycones, and some C‐28 Ester Derivatives†

    PubMed Central

    Greatrex, Ben W.; Daines, Alison M.; Hook, Sarah; Lenz, Dirk H.; McBurney, Warren; Rades, Thomas

    2015-01-01

    Abstract In an attempt to discover a new synthetic vaccine adjuvant, the glycosylation of hederagenin, gypsogenin, and oleanolic acid acceptors with di‐ and trisaccharide donors to generate a range of mimics of natural product QS‐21 was carried out. The saponins were formulated with phosphatidylcholine and cholesterol, and the structures analyzed by transmission electron microscopy. 3‐O‐(Manp(1→3)Glcp)hederagenin was found to produce numerous ring‐like micelles when formulated, while C‐28 choline ester derivatives preferred self‐assembly and did not interact with the liposomes. When alone and in the presence of cholesterol and phospholipid, the choline ester derivatives produced nanocrystalline rods or helical micelles. The effects of modifying sugar stereochemistry and the aglycone on the immunostimulatory effects of the saponins was then evaluated using the activation markers MHC class II and CD86 in murine bone marrow dendritic cells. The most active saponin, 3‐O‐(Manp(1→3)Glcp)hederagenin, was stimulatory at high concentrations in cell culture, but this did not translate to strong responses in vivo. PMID:27308200

  17. Topical CpG Adjuvantation of a Protein-Based Vaccine Induces Protective Immunity to Listeria monocytogenes

    PubMed Central

    Cheng, Wing Ki; Wee, Kathleen; Kollmann, Tobias R.

    2014-01-01

    Robust CD8+ T cell responses are essential for immune protection against intracellular pathogens. Using parenteral administration of ovalbumin (OVA) protein as a model antigen, the effect of the Toll-like receptor 9 (TLR9) agonist, CpG oligodeoxynucleotide (ODN) 1826, as an adjuvant delivered either topically, subcutaneously, or intramuscularly on antigen-specific CD8+ T cell responses in a mouse model was evaluated. Topical CpG adjuvant increased the frequency of OVA-specific CD8+ T cells in the peripheral blood and in the spleen. The more effective strategy to administer topical CpG adjuvant to enhance CD8+ T cell responses was single-dose administration at the time of antigen injection with a prime-boost regimen. Topical CpG adjuvant conferred both rapid and long-lasting protection against systemic challenge with recombinant Listeria monocytogenes expressing the cytotoxic T lymphocyte (CTL) epitope of OVA257–264 (strain Lm-OVA) in a TLR9-dependent manner. Topical CpG adjuvant induced a higher proportion of CD8+ effector memory T cells than parenteral administration of the adjuvant. Although traditional vaccination strategies involve coformulation of antigen and adjuvant, split administration using topical adjuvant is effective and has advantages of safety and flexibility. Split administration of topical CpG ODN 1826 with parenteral protein antigen is superior to other administration strategies in enhancing both acute and memory protective CD8+ T cell immune responses to subcutaneous protein vaccines. This vaccination strategy induces rapid and persistent protective immune responses against the intracellular organism L. monocytogenes. PMID:24391136

  18. Central Role of CD169+ Lymph Node Resident Macrophages in the Adjuvanticity of the QS-21 Component of AS01

    PubMed Central

    Detienne, Sophie; Welsby, Iain; Collignon, Catherine; Wouters, Sandrine; Coccia, Margherita; Delhaye, Sophie; Van Maele, Laurye; Thomas, Séverine; Swertvaegher, Maëlle; Detavernier, Aurélie; Elouahabi, Abdelatif; Goriely, Stanislas; Didierlaurent, Arnaud M.

    2016-01-01

    Saponins represent a promising class of vaccine adjuvant. Together with the TLR4-ligand MPL, QS-21 is part of the Adjuvant System AS01, a key component of the malaria and zoster candidate vaccines that display demonstrated clinical efficacy. However, the mechanism of action of QS-21 in this liposomal formulation is poorly understood. Upon intra-muscular immunisation, we observed that QS-21 rapidly accumulated in CD169+ resident macrophages of the draining lymph node where it elicited a local innate immune response. Depletion of these cells abrogated QS-21-mediated innate cell recruitment to the lymph node, dendritic cell (DC) phenotypic maturation as well as the adjuvant effect on T-cell and antibody responses to co-administered antigens. DCs rather than lymph node-resident macrophages were directly involved in T-cell priming by QS-21, as revealed by the decrease in antigen-specific T-cell response in Batf3−/− mice. Further analysis showed that the adjuvant effect of QS-21 depended on the integration of Caspase-1 and MyD88 pathways, at least in part through the local release of HMGB1. Taken together, this work unravels the key role of lymph node sentinel macrophage in controlling the adjuvant effect of a molecule proven to improve vaccine response in humans. PMID:27996000

  19. Protein transfer-mediated surface engineering to adjuvantate virus-like nanoparticles for enhanced anti-viral immune responses.

    PubMed

    Patel, Jaina M; Kim, Min-Chul; Vartabedian, Vincent F; Lee, Yu-Na; He, Sara; Song, Jae-Min; Choi, Hyo-Jick; Yamanaka, Satoshi; Amaram, Nikhil; Lukacher, Anna; Montemagno, Carlo D; Compans, Richard W; Kang, Sang-Moo; Selvaraj, Periasamy

    2015-07-01

    Recombinant virus-like nanoparticles (VLPs) are a promising nanoparticle platform to develop safe vaccines for many viruses. Herein, we describe a novel and rapid protein transfer process to enhance the potency of enveloped VLPs by decorating influenza VLPs with exogenously added glycosylphosphatidylinositol-anchored immunostimulatory molecules (GPI-ISMs). With protein transfer, the level of GPI-ISM incorporation onto VLPs is controllable by varying incubation time and concentration of GPI-ISMs added. ISM incorporation was dependent upon the presence of a GPI-anchor and incorporated proteins were stable and functional for at least 4weeks when stored at 4°C. Vaccinating mice with GPI-granulocyte macrophage colony-stimulating factor (GM-CSF)-incorporated-VLPs induced stronger antibody responses and better protection against a heterologous influenza virus challenge than unmodified VLPs. Thus, VLPs can be enriched with ISMs by protein transfer to increase the potency and breadth of the immune response, which has implications in developing effective nanoparticle-based vaccines against a broad spectrum of enveloped viruses. The inherent problem with current influenza vaccines is that they do not generate effective cross-protection against heterologous viral strains. In this article, the authors described the development of virus-like nanoparticles (VLPs) as influenza vaccines with enhanced efficacy for cross-protection, due to an easy protein transfer modification process. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Antigen delivery by filamentous bacteriophage fd displaying an anti-DEC-205 single-chain variable fragment confers adjuvanticity by triggering a TLR9-mediated immune response

    PubMed Central

    Sartorius, Rossella; D'Apice, Luciana; Trovato, Maria; Cuccaro, Fausta; Costa, Valerio; De Leo, Maria Giovanna; Marzullo, Vincenzo Manuel; Biondo, Carmelo; D'Auria, Sabato; De Matteis, Maria Antonietta; Ciccodicola, Alfredo; De Berardinis, Piergiuseppe

    2015-01-01

    Filamentous bacteriophage fd particles delivering antigenic determinants via DEC-205 (fdsc-αDEC) represent a powerful delivery system that induces CD8+ T-cell responses even when administered in the absence of adjuvants or maturation stimuli for dendritic cells. In order to investigate the mechanisms of this activity, RNA-Sequencing of fd-pulsed dendritic cells was performed. A significant differential expression of genes involved in innate immunity, co-stimulation and cytokine production was observed. In agreement with these findings, we demonstrate that induction of proinflammatory cytokines and type I interferon by fdsc-αDEC was MYD88 mediated and TLR9 dependent. We also found that fdsc-αDEC is delivered into LAMP-1-positive compartments and co-localizes with TLR9. Thus, phage particles containing a single-strand DNA genome rich in CpG motifs delivered via DEC-205 are able to intercept and trigger the active TLR9 innate immune receptor into late endosome/lysosomes and to enhance the immunogenicity of the displayed antigenic determinants. These findings make fd bacteriophage a valuable tool for immunization without administering exogenous adjuvants. PMID:25888235

  1. A dose-ranging study of a subunit Respiratory Syncytial Virus subtype A vaccine with and without aluminum phosphate adjuvantation in adults > or =65 years of age.

    PubMed

    Langley, Joanne M; Sales, Valerie; McGeer, Allison; Guasparini, Roland; Predy, Gerald; Meekison, William; Li, Minran; Capellan, Jose; Wang, Elaine

    2009-09-25

    We studied the safety and immunogenicity of a Respiratory Syncytial Virus (RSV)-A vaccine containing subunit antigens F, G and M in older persons, and its effect on influenza vaccine immunogenicity. In a dose-ranging, placebo-controlled, blinded trial 561 adults > or =65 years of age at five Canadian sites were randomized to one intramuscular injection of either 100, 50 or 25 microg RSV-A-alum vaccine or 100 microg non-adjuvanted RSV-A vaccine, or alum-placebo. All participants were offered inactivated influenza vaccine on day 32. Immunization was well tolerated and reactogenicity was similar between the RSV and influenza vaccines and the alum-placebo. Only the 100 microg non-adjuvanted RSV vaccine achieved the primary immunogenicity outcome of eliciting a > or =4-fold rise in neutralizing antibody (NA) titres against RSV-A in > or =50% of participants at day 32. Geometric mean titres against RSV-A and -B at all points were comparable in 100 microg adjuvanted and non-adjuvanted groups. At day 32, a > or =4-fold haemagluttinin inhibition (HI) antibody response or HI > or =40 to Influenza (A-H3N2) was seen in >74% of participants; no difference was seen between groups. A subunit non-alum-containing RSV-A vaccine was well tolerated in a large population > or =65 years and did not interfere with influenza vaccine immunogenicity. This RSV-A-based vaccine demonstrated NA rise which could provide seasonal protection against severe RSV illnesses from RSV-A or -B and warrants further testing to determine its efficacy in the prevention of clinical illness in elderly persons.

  2. The increasingly anti-tumor effect of a colonic carcinoma DNA vaccine carrying HER2 by the adjuvanticity of IL-12.

    PubMed

    Gao, Ping; Zhang, Chunhua; Bian, Xiaoxia; Guo, Yanjun; Wei, Yueguang; Zhang, Li; Liu, Zhaoyang; Wang, Xiuying; Huang, Shumin

    2016-09-23

    The present study aimed to determine the effect of recombinant DNA vaccine-based human epidermal growth factor receptor-2 (HER2) and Interleukin 12 (IL-12) on the development of colonic carcinoma in mice and the potential immune mechanisms involved. Recombinant plasmids pVAX1-HER2, pVAX1-IL-12 and pVAX1-HER2-IL-12 were constructed, and injected into female mice intramuscularly (i.m.) followed by an electric pulse. The humoral and cellular immune responses after immunization were examined by enzyme linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT), respectively. To evaluate the anti-tumor efficacy of the plasmids, a mouse model with a HER2-expressing tumor was designed. Mice vaccinated with the HER2-IL-12 plasmid generated the strongest inhibition efficacy on the growth of HER2-expressing tumors and prolonged mouse survival. These observations emphasized the potential of IL-12 as an adjuvant for DNA vaccines and of vaccines based on HER2 and IL-12 as a promising treatment for colonic carcinoma.

  3. Comparison of in vivo Adjuvanticity of Liposomal PO CpG ODN with Liposomal PS CpG ODN: Soluble Leishmania Antigens as a Model

    PubMed Central

    Golali, Ensieh; Jaafari, Mahmoud Reza; Khamesipour, Ali; Abbasi, Azam; Saberi, Zahra; Badiee, Ali

    2012-01-01

    Objective(s) CpG oligodeoxynucleotides (CpG ODNs) have been shown to have potent immunostimulatory adjuvant activity for a wide range of antigens. Due to susceptibility of phosphodiester CpG ODNs (PO CpG) to nuclease degradation, nuclease-resistant phosphorothioate CpG ODNs (PS CpG) were currently utilized in an in vivo model. In this study, according to some recently reported drawbacks with PS CpG, the adjuvant potential of liposomal PO CpG as a substitute for PS CpG was evaluated. Materials and Methods Soluble Leishmania antigens (SLA) as a model antigen and distearoylphosphatidylcoline (DSPC) as a neutral lipid were employed to prepare liposomes. Susceptible BALB/c mice received buffer, SLA, Lip-SLA, Lip-SLA-PS CpG, Lip-SLA-PO CpG, SLA+PS CpG, or SLA+PO CpG subcutaneously 3 times with 3 weeks intervals and then were challenged with Leishmania major’s live promastigotes. Blood and spleen samples were analyzed to determine the level and type of antibodies and cytokines. The number of live parasites in the spleen of immunized mice was determined. Moreover, the lesion size progress was assessed weekly by footpad swelling measurement. Results The results showed that mice immunized with Lip-SLA-PS CpG or Lip-SLA-PO CpG developed a significantly smaller footpad swelling, higher level of anti SLA IgG antibodies before and after challenge, and lower spleen parasite burden compared with the control groups. However, there was no significant difference between mice received Lip-SLA-PS CpG and those received Lip-SLA-PO CpG. Conclusion The results demonstrated that liposomal PO CpG ODN could be used instead of PS CpG ODN to overcome the possible drawbacks. PMID:23493437

  4. ANÁLISE DA INSERÇÃO DOS TEMAS DE HUMANIDADES E ÉTICA, COM METODOLOGIA DE APRENDIZAGEM BASEADA EM PROBLEMAS, EM CURRICULO MÉDICO INTEGRADO EM ESCOLA PÚBLICA NO DISTRITO FEDERAL, BRASIL

    PubMed Central

    Novaes, Maria Rita Carvalho Garbi; Novaes, Luiz Carlos Garcez; Guilhem, Dirce; Lolas, Fernando; Silveira, Carla; Guiotti, Murilo

    2009-01-01

    Objetivo Realizar uma análise da inserção da ética e humanidades no currículo do Curso de Medicina da Escola Superior em Ciências da Saúde - ESCS, escola pública do Distrito Federal, Brasil, de forma a contribuir com o processo de gestão curricular. Metodologia O Estudo é de coorte e documental. Foram pesquisados 37 termos relacionados à ética e 36 referentes à humanização nos objetivos educacionais e conteúdo dos módulos temáticos, habilidades e atitudes e interação ensino-serviço-comunidade, de 1a a 4a série e no programa do internato no currículo (ano 2006) e no projeto pedagógico do Curso de Medicina (2001). Resultados Maior inserção da humanização, ética e bioética na 1a e 2a série, quando comparado à inserção na 3a e 4a série e no internato, (IC95%-α=0,034, pvalue=0,007). Unidade de habilidades e atitudes: freqüência das 3 temáticas no currículo da 1a a 4a séries (IC95%-α=0,026, pvalue=0,013). Quando comparada a inserção entre o internato e as quatro primeiras séries, observa-se que nestas a inserção da temática humanização é superior (IC95%-α=0,042, pvalue=0,029). Conclusão O currículo desenvolvido no ano de 2006 na ESCS apresentou correlação com o projeto pedagógico do curso e contemplou a temática de forma abrangente, em todas as séries e internato. PMID:20396594

  5. Anxiety and coping in women with breast cancer in chemotherapy.

    PubMed

    Silva, Araceli Vicente da; Zandonade, Eliana; Amorim, Maria Helena Costa

    2017-06-05

    to identify the coping strategies used by women with breast cancer in chemotherapy and to verify the association with the anxiety profile presented by them. cross-sectional study of the analytical type. We used a random sample of 307 women with cancer in previous chemotherapy, adjuvant or palliative treatment. The data was collected using an interview technique with form registration, active search in medical records, Scale of Mode of Confronting Problems and Inventory of Anxiety and State. The Statistical Package for Social Sciences 19.0, Pearson correlation coefficient and the test Mann-Whitney were used. there was a significant association of the anxiety trait and problem-focused coping strategies with a focus on emotion (p<0,000) and the anxiety state with problem-focused coping (p=0,001) and with focus on emotion (p=0,004). The results demonstrate weak associations between different coping strategies. the coping strategy chosen by women with breast cancer is directly related to anxiety. Patients with low-level anxiety tend to use problem-solving strategies while emotion-focused coping is applied if the level is medium to high. identificar as estratégias de enfrentamento utilizadas por mulheres com câncer de mama em quimioterapia e verificar a associação com o perfil de ansiedade por elas apresentado. estudo de corte transversal do tipo analítico. Utilizou-se amostra aleatória de 307 mulheres com câncer em tratamento quimioterápico prévio, adjuvante ou paliativo. Coletou-se os dados com técnica de entrevista com registro em formulário, busca ativa nos prontuários, Escala de Modo de Enfrentamento de Problemas e Inventário de Ansiedade e Estado. Utilizou-se para análise o Pacote Estatístico para Ciências Sociais 19.0, coeficiente de correlação de Pearson e o teste Mann-Whitney. existiu associação significante do traço de ansiedade e as estratégias de enfrentamento com foco no problema e com foco na emoção (p<0,000) e o estado de ansiedade

  6. DO PROXIMAL AND DISTAL GASTRIC TUMOURS BEHAVE DIFFERENTLY?

    PubMed

    Costa, Laurence Bedin da; Toneto, Marcelo Garcia; Moreira, Luis Fernando

    2016-01-01

    os grupos quanto à mortalidade (p=0.661), emprego de quimioterapia adjuvante (p=0.661) e de radioterapia (p=1.000). Entretanto, houve diferença significativa no grau de dissecção linfonodal empregada (p=0.002) e no número de linfonodos positivos ressecados (p=0.038) entre os dois grupos. A razão de chances para morte em cinco anos nos casos de dissecção D0 foi três vezes maior (2,78; IC95% de 1,33 a 5,82) do que a D2, enquanto que para dissecção D1, ela foi apenas 1,41 vezes maior (95%CI 0.71-2.83) quando comparado à D2. Ainda que não se tenha observado diferenças significativas entre o câncer gástrico proximal e o distal, o risco de morte aumentado nos casos de D0 e D1, claramente demonstra o papel preponderante da linfadenectomia radical D2 no tratamento dessa doença.

  7. Practical aspects of the use of intrathecal chemotherapy.

    PubMed

    Olmos-Jiménez, Raquel; Espuny-Miró, Alberto; Cárceles Rodríguez, Carlos; Díaz-Carrasco, María Sacramento

    2017-01-01

    Introducción: La quimioterapia intratecal es utilizada frecuentemente, en la practica clinica, para el tratamiento y prevencion de la meningitis neoplasica. A pesar de su uso extendido, existe poca informacion acerca de aspectos practicos tales como el volumen de farmaco a administrar o la forma de preparacion y administracion. Objetivo: Realizar una revision de la literatura acerca de aspectos practicos de la utilizacion de la quimioterapia intratecal.

  8. [High-intensity chemotherapy versus palliative chemotherapy in patients over 60 years with acute myeloid leukemia].

    PubMed

    Medrano-Contreras, Jesús; Talavera-Piña, Juan Osvaldo; Guerrero-Rivera, Susana; Gutiérrez-Espíndola, Guillermo Rodolfo; Gómez-Cortés, Cynthia; Pérez-Rocha, Juan Fernando; Terreros-Muñoz, Eduardo; Meillón-García, Luis Antonio

    2016-01-01

    Introducción: el tratamiento con quimioterapia intensa (QTI) en pacientes con leucemia mieloblástica (LMA) mayores de 60 años es controversial. En el presente estudio se evaluó la remisión completa y la supervivencia global de pacientes con LMA mayores de 60 años, tratados con QTI o quimioterapia paliativa. Métodos: los pacientes con adecuada función orgánica y ECOG ≤ 2 recibieron QTI a base de citarabina por cinco o siete días más un antracíclico por tres días y terapia de soporte. En caso de lograr remisión completa de la leucemia recibieron uno o dos ciclos de consolidación con citarabina. El tratamiento paliativo consistió en medidas de soporte o quimioterapia oral o intravenosa en dosis bajas. Resultados: del grupo de QTI siete pacientes alcanzaron remisión completa, comparados con uno del grupo de quimioterapia paliativa. La supervivencia global fue de 13.25 meses para los pacientes con QTI y de 3.35 meses para los pacientes de quimioterapia paliativa (p < 0.05). Conclusión: es posible que los pacientes con LMA mayores de 60 años de edad se beneficien de recibir QTI, comparada con la quimioterapia paliativa.

  9. [Esophageal cancer: surgical strategies].

    PubMed

    Costa, Paulo; Esteves, Rui; Lages, Patrícia; Ferreira, Filipa

    2014-01-01

    Introdução: A ressecção transmediastínica e a ressecção transtorácica têm mortalidade hospitalar (1,4% -14%) e sobrevivência (± 25% aos cinco anos) semelhantes. A terapêutica neo-adjuvante é opção em estádios avançados. A intenção deste trabalho é apresentar uma série consecutiva de 52 doentes - opção operatória baseada na localização anatómica: tumores infra-carinais e cervicais submetidos a ressecção transmediastínica e restantes ressecções transtorácicas.Material e Métodos: O estudo incluiu 52 doentes consecutivos, sete mulheres e 45 homens, mediana de idade: 64 anos [46- 85]. Localização: cervical – um; montante da carina - 22; jusante da carina -19; cárdia tipo I –10. Histologia: 19 adenocarcinomas, 32 carcinomas pavimento-celulares, um linfoma. Vinte doentes (40%) - terapêutica neoadjuvante. Abordagem tóraco-abdominal – três, tóraco-abdómino-cervical – 20, transhiatal – 27, toracotomia exploradora – dois. Transposição gástrica 49 (anastomose cervical – 46; torácica - três); esofagocoloplastia cervical - um.Resultados: Estadiamento patológico: regressão completa - 8; Ib – 3; IIa – 9; IIb - 4; IIa – 11; IIIb -2; IIIc – 10; IV – 1; linfoma - um; não classificáveis – três. Complicações major: 37%. Ressecabilidade: 96% (50/52). Mortalidade: quatro semanas - 6%; hospitalar - 14%. Sobrevida mediana 18 meses [3-80]. Curvas de sobrevida (Kaplan-Meier): dois anos - 47%; cinco anos - 19%.Discussão: Não tendo sido demonstrada vantagem oncológica para a ressecção transtorácica ou a ressecção transmediastínica,basear a opção operatória na localização do tumor permitiu-nos com segurança e eficácia, planear e executar as ressecções esofágicas desta série.Conclusão: As curvas de sobrevida foram sobreponíveis para ressecção transtorácica e ressecção transmediastínica e bastantefavoráveis numa população com 52 % de estádios p

  10. [Effect of metformin addition to an acute lymphoblastic leukemia chemotherapy treatment].

    PubMed

    Ramos-Peñafiel, Christian Omar; Martínez-Murillo, Carlos; Santoyo-Sánchez, Adrián; Jiménez-Ponce, Fiacro; Rozen-Fuller, Etta; Collazo-Jaloma, Juan; Olarte-Carrillo, Irma; Martínez-Tovar, Adolfo

    2014-01-01

    INTRODUCCIÓN: se ha informado efecto benéfico con metformina en pacientes con cáncer. El objetivo de esta investigación fue evaluar el efecto de adicionar metformina a la quimioterapia sobre las recaídas tempranas en pacientes con leucemia linfoblástica aguda. MÉTODOS: estudio prospectivo, longitudinal y experimental de pacientes portadores de leucemia linfoblástica aguda de novo, realizado en el Hospital General de Mexico. La muestra fue dividida en dos brazos de tratamiento: uno recibió metformina (850 mg cada ocho horas) + quimioterapia; otro recibió únicamente quimioterapia estándar. La distribución de los pacientes fue aleatoria, 3:1 a favor del segundo brazo.

  11. [Pulmonary carcinoid: analysis of a single institutional experience and prognostic factors].

    PubMed

    Correia, Silvia da Silva; Pinto, Carlos; Bernardo, João

    2014-01-01

    IntroduçÉo: Os tumores carcinóides pulmonares sÉo tumores raros com origem nas células neuro-endócrinas do pulmÉo. Classificam-se de acordo com os critérios da OMS em carcinóides típicos ou atípicos. Quando comparados com outros tipos de neoplasia pulmonar, os tumores carcinóides apresentam melhor prognóstico.Objetivos: CaracterizaçÉo dos doentes com diagnóstico histológico de tumor carcinóide observados numa instituiçÉo. Análise dos fatores que influenciaram o prognóstico.Material e Métodos: Análise retrospetiva incluindo todos os doentes com diagnóstico histológico de tumor carcinóide pulmonar durante um período de 11 anos numa instituiçÉo. Os tumores foram classificados em típicos e atípicos de acordo com a classificaçÉo da OrganizaçÉo Mundial de Saúde de 2004. O estadiamento foi feito com base na classificaçÉo TNM de 2009 para o carcinoma do pulmÉo de nÉo pequenas células: T (Tumor); N (Ganglionar); M (Metástase).Resultados: Foram incluídos 59 doentes: 53 carcinóides típicos e seis carcinóides atípicos. Destes, 90% foram submetidos a cirurgia. O follow-up médio foi de 57 meses. A mortalidade operatória foi de 2% (n = 1) tratando-se de cirurgia paliativa para um doente em estádio IV. Em 49 doentes nÉo se verificou envolvimento ganglionar (N0), um doente apresentava doença N1, oito doença N2 e um doente doença N3. A sobrevivência global aos cinco anos foi de 79,2%: 80,2% nos carcinóides típicos e 66,7% nos carcinóides atípicos (p < 0,05). Nos doentes T1, a sobrevivência foi de 88,1% e de 58,2% nos T2-T4 (p < 0,01). Nos doentes N0 a sobrevivência aos cinco anos de 89,7% e de 36% para os doentes N1-N3 (p < 0,001). Os doentes com doença M0 apresentaram uma sobrevivência aos cinco anos de 85,9% sendo de 0% nos doentes M1 (p < 0,01). Dos 11 doentes que necessitaram de quimioterapia adjuvante, 45,4% eram carcinóides atípicos.DiscussÉo: Na nossa série, a cirurgia no tumor carcinóide pulmonar demonstrou

  12. CpG oligodeoxynucleotides are a potent adjuvant for an inactivated polio vaccine produced from Sabin strains of poliovirus.

    PubMed

    Yang, Chunting; Shi, Huiying; Zhou, Jun; Liang, Yanwen; Xu, Honglin

    2009-11-05

    Poliovirus transmission is controlled globally through world-wide use of a live attenuated oral polio vaccine (OPV). However, the imminence of global poliovirus eradication calls for a switch to the inactivated polio vaccine (IPV). Given the limited manufacturing capacity and high cost of IPV, this switch is unlikely in most developing and undeveloped countries. Adjuvantation is an effective strategy for antigen sparing. In this study, we evaluated the adjuvanticity of CpG oligodeoxynucleotides (CpG-ODN) for an experimental IPV produced from Sabin strains of poliovirus. Our results showed that CpG-ODN, alone or in combination with alum, can significantly enhance both the humoral and cellular immune responses to IPV in mice, and, consequently, the antigen dose could be reduced substantially. Therefore, our study suggests that the global use of IPV could be facilitated by using CpG-ODN or other feasible adjuvants.

  13. Synthesis of QS-21-Based Immunoadjuvants

    PubMed Central

    Dai, Qipu; Thogaripally, Punith; Zhang, Ping; Michalek, Suzanne M.

    2014-01-01

    Three structurally defined QS-21-based immune adjuvant candidates (2a-2c) have been synthesized. Application of the two-stage activation glycosylation approach utilizing allyl glycoside building blocks improved the synthetic accessibility of the new adjuvants. The efficient synthesis and establishment of the stand-alone adjuvanticity of the examined synthetic adjuvant (2b) open the door to the pursuit of a new series of structurally defined QS-saponin based synthetic adjuvants. PMID:24147602

  14. GPRC6A mediates Alum-induced Nlrp3 inflammasome activation but limits Th2 type antibody responses

    PubMed Central

    Quandt, Dagmar; Rothe, Kathrin; Baerwald, Christoph; Rossol, Manuela

    2015-01-01

    Alum adjuvanticity is still an unknown mechanism despite the frequent use as vaccine adjuvant in humans. Here we show that Alum-induced inflammasome activation in vitro and in vivo is mediated by the G protein-coupled receptor GPRC6A. The Alum-induced humoral response in vivo was independent of the inflammasome because Nlrp3−/− and ASC−/− mice responded normally to Alum and blockade of IL-1 had no effect on antibody production. In contrast, Alum adjuvanticity was increased in GPRC6A−/− mice resulting in increased antibody responses and increased Th2 cytokine concentrations compared to wildtype mice. In vitro activation of GPRC6A−/− splenic B cells also induced increased IgG1 concentrations compared to wildtype B cells. For the first time, we show GPRC6A expression in B cells, contributing to the direct effects of Alum on those cells. B cell produced immunostimulatory IL-10 is elevated in GPRC6A−/− B cells in vitro and in vivo. Our results demonstrate a dual role of GPRC6A in Alum adjuvanticity. GPCR6A activation by Alum leads to the initiation of innate inflammatory responses whereas it is an important signal for the limitation of adaptive immune responses induced by Alum, partially explained by B cell IL-10. PMID:26602597

  15. Predicting the influence of liposomal lipid composition on liposome size, zeta potential and liposome-induced dendritic cell maturation using a design of experiments approach.

    PubMed

    Soema, Peter C; Willems, Geert-Jan; Jiskoot, Wim; Amorij, Jean-Pierre; Kersten, Gideon F

    2015-08-01

    In this study, the effect of liposomal lipid composition on the physicochemical characteristics and adjuvanticity of liposomes was investigated. Using a design of experiments (DoE) approach, peptide-containing liposomes containing various lipids (EPC, DOPE, DOTAP and DC-Chol) and peptide concentrations were formulated. Liposome size and zeta potential were determined for each formulation. Moreover, the adjuvanticity of the liposomes was assessed in an in vitro dendritic cell (DC) model, by quantifying the expression of DC maturation markers CD40, CD80, CD83 and CD86. The acquired data of these liposome characteristics were successfully fitted with regression models, and response contour plots were generated for each response factor. These models were applied to predict a lipid composition that resulted in a liposome with a target zeta potential. Subsequently, the expression of the DC maturation factors for this lipid composition was predicted and tested in vitro; the acquired maturation responses corresponded well with the predicted ones. These results show that a DoE approach can be used to screen various lipids and lipid compositions, and to predict their impact on liposome size, charge and adjuvanticity. Using such an approach may accelerate the formulation development of liposomal vaccine adjuvants.

  16. [Experience of off-label use of Eltrombopag in the treatment of thrombocytopenia associated with solid tumors].

    PubMed

    García Lagunar, María Henar; Cerezuela Fuentes, Pablo; Martínez Penella, Mónica; Gutiérrez-Meca Maestre, Dolores Paula; García Coronel, María; Martínez Ortiz, María José

    2015-05-01

    Objetivo: Describir los resultados del uso fuera de indicación de eltrombopag en pacientes con trombocitopenia limitante de tratamiento quimioterápico y tumores sólidos. Método: Estudio observacional retrospectivo en el que se incluyeron todos los pacientes con tumores sólidos tratados con eltrombopag por trombocitopenia durante el tratamiento con quimioterapia entre enero de 2012 y diciembre de 2014. Resultados: Seis pacientes, con tumores sólidos y trombocitopenia limitante de tratamiento, recibieron eltrombopag durante el periodo de estudio con una disminución en el retraso de ciclos de quimioterapia (4,83 ± 4,79 ciclos retrasados antes del inicio de eltrombopag vs 2,50 ± 4,32 ciclos durante el tratamiento con eltrombopag, p=0,492) y un aumento en el porcentaje de dosis real administrada (89,29 ± 13,36% vs 91,43 ± 10,69%, p=0,682). Así mismo, se produjo un aumento en el nadir de plaquetas (55,29 ± 16,45x109/L vs 76,14 ± 36,38x109/L, p=0,248) sin requerir en ningún paciente soporte transfusional con plaquetas durante el tratamiento con eltrombopag. Conclusiones: eltrombopag ha resultado ser una alternativa de tratamiento para pacientes con trombocitopenia limitante de tratamiento con quimioterapia, siendo necesarios ensayos clínicos con mayor número de pacientes que confirmen estos resultados.

  17. Effects of zinc supplementation on fatigue and quality of life in patients with colorectal cancer.

    PubMed

    Ribeiro, Sofia Miranda de Figueiredo; Braga, Camila Bitu Moreno; Peria, Fernanda Maris; Martinez, Edson Zangiacomi; Rocha, José Joaquim Ribeiro da; Cunha, Selma Freire Carvalho

    2017-01-01

    To investigate the effects of oral zinc supplementation on fatigue intensity and quality of life of patients during chemotherapy for colorectal cancer. A prospective, randomized, double-blinded, placebo-controlled study was conducted with 24 patients on chemotherapy for colorectal adenocarcinoma in a tertiary care public hospital. The study patients received zinc capsules 35mg (Zinc Group, n=10) or placebo (Placebo Group, n=14) orally, twice daily (70mg/day), for 16 weeks, from the immediate postoperative period to the fourth chemotherapy cycle. Approximately 45 days after surgical resection of the tumor, all patients received a chemotherapeutic regimen. Before each of the four cycles of chemotherapy, the Functional Assessment of Chronic Illness Therapy-Fatigue scale was completed. We used a linear mixed model for longitudinal data for statistical analysis. The scores of quality of life and fatigue questionnaires were similar between the groups during the chemotherapy cycles. The Placebo Group presented worsening of quality of life and increased fatigue between the first and fourth cycles of chemotherapy, but there were no changes in the scores of quality of life or fatigue in the Zinc Group. Zinc supplementation prevented fatigue and maintained quality of life of patients with colorectal cancer on chemotherapy. Investigar os efeitos da suplementação oral de zinco sobre a intensidade da fadiga e a qualidade de vida de pacientes durante a quimioterapia para neoplasia colorretal. Estudo prospectivo, randomizado, controlado e duplo-cego conduzido em um hospital universitário público terciário, com 24 pacientes em regime quimioterápico para adenocarcinoma colorretal. Os pacientes receberam cápsulas de zinco 35mg (Grupo Zinco, n=10) ou placebo (Grupo Placebo, n=14) por via oral, duas vezes ao dia (70mg/dia), durante 16 semanas, desde o período pós-operatório imediato até o quarto ciclo de quimioterapia. Todos os pacientes receberam quimioterapia por

  18. Synthetic sulpholipopolysaccharides: novel adjuvants for humoral immune responses.

    PubMed

    Hilgers, L A; Snippe, H; Jansze, M; Willers, J M

    1987-01-01

    Referring to the strong immunostimulating activity of combinations of lipophilic agents and dextran sulphate, conjugates with chemical determinants of both types of adjuvants were synthesized and then examined for immunostimulatory capabilities in mice. Saturated fatty acids with varying chain lengths and sulphate groups were coupled covalently at defined ratios to the polysaccharide Ficoll (MW 400,000). Chemical analysis of 60 of the sulpholipopolysaccharides synthesized revealed that the number of sulphate groups per monosaccharide unit varied from 0 to 1.6, and the number of lipid groups from 0 to 0.8. Adjuvanticity of these conjugates for the humoral immune response was determined using sheep red blood cells (SRBC) and dinitrophenyl-haptenated bovine serum albumin (DNP-BSA) as antigens. Five days after intraperitoneal injection of adjuvant and antigen, the numbers of direct anti-SRBC plaque-forming cells (PFC) in the spleen were determined. Anti-DNP antibody titres were measured from 1 to 4 weeks after immunization. PFC responses to 2 X 10(6) SRBC were augmented up to a 100-fold by conjugates of Ficoll and sulphate (sulphopolysaccharides: SPs) or lipid groups (lipopolysaccharides: LPs). Introduction of low or moderate numbers of lipid groups in SPs reduced adjuvanticity. Adjuvant activity of sulpholipopolysaccharides (SLPs) with varying sulphate and high lipid content depended on the sulphate contents and the chain length of the lipids. Sulphate reduced adjuvanticity of the SLPs, and the number of sulphate groups required for complete annihilation increased with the chain length of the lipid. LPs and SLPs, including conjugates that did not enhance anti-SRBC PFC responses, augmented serum antibody responses to DNP-BSA while SPs were hardly effective.

  19. Seeking help: B cells adapting to flu variability.

    PubMed

    van der Most, Robbert G; Roman, François P; Innis, Bruce; Hanon, Emmanuel; Vaughn, David W; Gillard, Paul; Walravens, Karl; Wettendorff, Martine

    2014-07-23

    The study of influenza vaccines has revealed potential interactions between preexisting immunological memory and antigenic context and/or adjuvantation. In the face of antigenic diversity, the process of generating B cell adaptability is driven by cross-reactive CD4 memory cells, such as T follicular helper cells from previous infections or vaccinations. Although such "helped" B cells are capable of adapting to variant antigens, lack of CD4 help could lead to a suboptimal antibody response. Collectively, this indicates an interplay between CD4 T cells, adjuvant, and B cell adaptability.

  20. Chemotherapy near the end of life; assessment of the clinical practise in onco-hematological in adult patients.

    PubMed

    Taberner Bonastre, Pilar; Taberner Bonastre, María Teresa; Soler Company, Enrique; Pérez-Serrano Lainosa, María Dolores

    2016-01-01

    Objetivo: garantizar una buena calidad de vida en la última fase de los pacientes onco-hematológicos debería ser nuestro principal objetivo; a pesar de ello, disponemos de pocos datos a nivel europeo y los estudios publicados son contradictorios. No obstante, la mayoría coinciden en que administrar quimioterapia en la etapa final de la vida impacta de forma negativa en la calidad de vida del paciente. El objetivo principal del estudio es analizar los indicadores de no agresividad del tratamiento en pacientes onco-hematológicos. Como objetivo secundario, realizar un estudio descriptivo de las variables clínicas de los pacientes a los que se les administra quimioterapia en la fase final de la vida y los esquemas más utilizados. Método: se realizó un estudio observacional retrospectivo en un hospital de tercer nivel. Se incluyeron todos los pacientes oncológicos y hematológicos que recibieron quimioterapia (oral o intravenosa) entre enero y diciembre de 2013, a los que se les administró la última quimioterapia en los 90 días previos al fallecimiento. Resultados: se analizaron 823 pacientes que recibieron tratamiento entre enero y diciembre de 2013. De ellos, 106 (13%) cumplían los criterios de inclusión. Un 14,1% (n = 93) de los pacientes oncológicos y un 8,4% (n = 13) de los hematológicos que habían recibido quimioterapia durante el último año de vida lo seguían haciendo en los últimos tres meses. Un 21,7% (n = 23) de los pacientes recibieron quimioterapia en las dos últimas semanas, 41,5% (n = 44) en los últimos 30 días y 78,3% (n = 83) en los últimos dos meses de vida. El 67,9% (n = 72) de los pacientes ingresaron en el hospital durante los últimos tres meses de vida, el 47,2% (n = 50) lo hicieron durante el último mes, el 33% (n = 35) durante las dos últimas semanas y el 10,4% (n = 11) durante los últimos tres días de vida. El 25,5% (n = 27) de los pacientes ingresaron en más de una ocasión durante los 90 días previos al

  1. rOv-ASP-1, a recombinant secreted protein of the helminth Onchocercavolvulus, is a potent adjuvant for inducing antibodies to ovalbumin, HIV-1 polypeptide and SARS-CoV peptide antigens.

    PubMed

    MacDonald, Angus J; Cao, Long; He, Yuxian; Zhao, Qian; Jiang, Shibo; Lustigman, Sara

    2005-05-16

    We studied the adjuvanticity of recombinant Onchocerca volvulus activation associated protein-1 (rOv-ASP-1) for ovalbumin (OVA) in mice. After a single immunization and one boost, rOv-ASP-1 exceeded the efficacy of alum or MPL + TDM adjuvants in terms of end-point total IgG or IgG1 and IgG2a anti-OVA titres. Using the helminth-derived adjuvant, IgG isotype responses to OVA were of a mixed Th1/Th2 profile and spleen cell cytokines exclusively Th1-type. The potent adjuvanticity of rOv-ASP-1 was confirmed in mice vaccinated with a 37-mer peptide from the S protein of SARS-CoV and an HIV-1 gp120-CD4 chimeric polypeptide antigen. Unusually for a helminth product, the rOv-ASP-1 adjuvant augmented not only Th2 but also Th1 responses, the latter property being of potential utility in stimulating anti-viral immune responses.

  2. Strong Antibody Responses Induced by Protein Antigens Conjugated onto the Surface of Lecithin-Based Nanoparticles

    PubMed Central

    Sloat, Brian R.; Sandoval, Michael A.; Hau, Andrew M.; He, Yongqun; Cui, Zhengrong

    2009-01-01

    An accumulation of research over the years has demonstrated the utility of nanoparticles as antigen carriers with adjuvant activity. Herein we defined the adjuvanticity of a novel lecithin-based nanoparticle engineered from emulsions. The nanoparticles were spheres of around 200 nm. Model protein antigens, bovine serum albumin (BSA) or Bacillus anthracis protective antigen (PA) protein, were covalently conjugated onto the nanoparticles. Mice immunized with the BSA-conjugated nanoparticles developed strong anti-BSA antibody responses comparable to that induced by BSA adjuvanted with incomplete Freund's adjuvant and 6.5-fold stronger than that induced by BSA adsorbed onto aluminum hydroxide. Immunization of mice with the PA-conjugated nanoparticles elicited a quick, strong, and durable anti-PA antibody response that afforded protection of the mice against a lethal dose of anthrax lethal toxin challenge. The potent adjuvanticity of the nanoparticles was likely due to their ability to move the antigens into local draining lymph nodes, to enhance the uptake of the antigens by antigen-presenting cells (APCs), and to activate APCs. This novel nanoparticle system has the potential to serve as a universal protein-based vaccine carrier capable of inducing strong immune responses. PMID:19729045

  3. Integrating experimental (in vitro and in vivo) neurotoxicity studies of low-dose thimerosal relevant to vaccines.

    PubMed

    Dórea, José G

    2011-06-01

    There is a need to interpret neurotoxic studies to help deal with uncertainties surrounding pregnant mothers, newborns and young children who must receive repeated doses of Thimerosal-containing vaccines (TCVs). This review integrates information derived from emerging experimental studies (in vitro and in vivo) of low-dose Thimerosal (sodium ethyl mercury thiosalicylate). Major databases (PubMed and Web-of-science) were searched for in vitro and in vivo experimental studies that addressed the effects of low-dose Thimerosal (or ethylmercury) on neural tissues and animal behaviour. Information extracted from studies indicates that: (a) activity of low doses of Thimerosal against isolated human and animal brain cells was found in all studies and is consistent with Hg neurotoxicity; (b) the neurotoxic effect of ethylmercury has not been studied with co-occurring adjuvant-Al in TCVs; (c) animal studies have shown that exposure to Thimerosal-Hg can lead to accumulation of inorganic Hg in brain, and that (d) doses relevant to TCV exposure possess the potential to affect human neuro-development. Thimerosal at concentrations relevant for infants' exposure (in vaccines) is toxic to cultured human-brain cells and to laboratory animals. The persisting use of TCV (in developing countries) is counterintuitive to global efforts to lower Hg exposure and to ban Hg in medical products; its continued use in TCV requires evaluation of a sufficiently nontoxic level of ethylmercury compatible with repeated exposure (co-occurring with adjuvant-Al) during early life.

  4. The Mincle-Activating Adjuvant TDB Induces MyD88-Dependent Th1 and Th17 Responses through IL-1R Signaling

    PubMed Central

    Desel, Christiane; Werninghaus, Kerstin; Ritter, Manuel; Jozefowski, Katrin; Wenzel, Jens; Russkamp, Norman; Schleicher, Ulrike; Christensen, Dennis; Wirtz, Stefan; Kirschning, Carsten; Agger, Else Marie; da Costa, Clarissa Prazeres; Lang, Roland

    2013-01-01

    Successful vaccination against intracellular pathogens requires the generation of cellular immune responses. Trehalose-6,6-dibehenate (TDB), the synthetic analog of the mycobacterial cord factor trehalose-6,6-dimycolate (TDM), is a potent adjuvant inducing strong Th1 and Th17 immune responses. We previously identified the C-type lectin Mincle as receptor for these glycolipids that triggers the FcRγ-Syk-Card9 pathway for APC activation and adjuvanticity. Interestingly, in vivo data revealed that the adjuvant effect was not solely Mincle-dependent but also required MyD88. Therefore, we dissected which MyD88-dependent pathways are essential for successful immunization with a tuberculosis subunit vaccine. We show here that antigen-specific Th1/Th17 immune responses required IL-1 receptor-mediated signals independent of IL-18 and IL-33-signaling. ASC-deficient mice had impaired IL-17 but intact IFNγ responses, indicating partial independence of TDB adjuvanticity from inflammasome activation. Our data suggest that the glycolipid adjuvant TDB triggers Mincle-dependent IL-1 production to induce MyD88-dependent Th1/Th17 responses in vivo. PMID:23308247

  5. Chondrosarcome myxoïde extra-osseux: à propos d'un cas et revue de la littérature

    PubMed Central

    Sasbou, Youness; Rhanim, Abdelkarim; Mhammdi, Younes; Nkaoui, Mustapha; El Bardouni, Ahmed; Berrada, Mohammed Saleh; El Yaacoubi, Morad

    2015-01-01

    Le chondrosarcome primitif des tissus mous est beaucoup plus rare que son homonyme intra-osseux, le type myxoïde est une entité distincte sur le plan clinique, histologique, immuno-histo-chimique, cytogénétique et évolutif. Le but de cette étude est d’évaluer les caractéristiques de cette tumeur et de mettre en évidence sa difficulté diagnostique et thérapeutique. Cette étude rapporte un cas de chondrosarcome myxoïde extra-osseux atteignant les parties molles, il s'agit d'une femme âgée de 28 ans ayant une localisation au niveau de la face antéro-externe du tiers moyen de la cuisse gauche, la patiente a été explorée par une IRM. L'examen histologique a confirmé le diagnostic et la patiente a bénéficié d'une résection large complétée par une chimiothérapie adjuvante, et le suivi n'a déploré aucune récidive ni métastase. Le diagnostic des chondrosarcomes primitifs extra osseux est particulièrement histologique et leur traitement repose sur la résection chirurgicale large suivie d'une chimiothérapie adjuvante. PMID:26185552

  6. The Syk–NFAT–IL-2 Pathway in Dendritic Cells Is Required for Optimal Sterile Immunity Elicited by Alum Adjuvants

    PubMed Central

    Khameneh, Hanif Javanmard; Ho, Adrian W. S.; Spreafico, Roberto; Derks, Heidi; Quek, Hazel Q. Y.

    2017-01-01

    Despite a long history and extensive usage of insoluble aluminum salts (alum) as vaccine adjuvants, the molecular mechanisms underpinning Ag-specific immunity upon vaccination remain unclear. Dendritic cells (DCs) are crucial initiators of immune responses, but little is known about the molecular pathways used by DCs to sense alum and, in turn, activate T and B cells. In this article, we show that alum adjuvanticity requires IL-2 specifically released by DCs, even when T cell secretion of IL-2 is intact. We demonstrate that alum, as well as other sterile particulates, such as uric acid crystals, induces DCs to produce IL-2 following initiation of actin-mediated phagocytosis that leads to Src and Syk kinase activation, Ca2+ mobilization, and calcineurin-dependent activation of NFAT, the master transcription factor regulating IL-2 expression. Using chimeric mice, we show that DC-derived IL-2 is required for maximal Ag-specific proliferation of CD4+ T cells and optimal humoral responses following alum-adjuvanted immunization. These data identify DC-derived IL-2 as a key mediator of alum adjuvanticity in vivo and the Src–Syk pathway as a potential leverage point in the rational design of novel adjuvants. PMID:27895176

  7. Twenty Years of Autologous Stem Cell Transplantation in Diffuse Large B-Cell Lymphoma: A Single Portuguese Center Experience.

    PubMed

    Dantas Brito, Margarida; Campilho, Fernando; Branca, Rosa; Vaz, Carlos; Roncon, Susana; Campos, António

    2016-03-01

    Introdução: O linfoma não Hodgkin difuso de grandes células B pode ser curado em 60% - 70% dos doentes. O transplante autológo de progenitores hematopoiéticos é o tratamento de intenção curativa standard à recidiva. Este tratamento intensivo após primeira remissão num grupo selecionado de doentes de alto risco é controverso e fez parte da estratégia do nosso Serviço durante alguns anos. Material e Métodos: Estudo retrospectivo, consulta do processo clínico. Resultados: Este estudo analisa o outcome de 113 doentes transplantados entre 1992 e 2012. Formaram-se quatro grupos com base no status pré-transplante: a) primeira remissão completa após 1 ciclo de quimioterapia (n = 64); b) segunda remissão completa após ≥ duas linhas de quimioterapia (n = 15); c) segunda remissão completa (n = 15); d) doença mais avançada (n = 19). O protocolo de quimioterapia de primeira linha mais utilizado foi R-CHOP (n = 71) e CHOP (n = 28). O seguimento mediano foi de 34 meses (1 - 221). Aos cinco anos a sobrevivência global foi de 73% (± 5) e a sobrevivência livre de progressão 75% (± 5). Conclusão: A imunoquimioterapia convencional seguida de transplante autólogo é uma opção segura e eficaz no tratamento de casos selecionados de linfoma difuso de grandes células B. Na nossa casuística cerca de 70% dos doentes de alto risco atingiram remissões duráveis com esta estratégia terapêutica.

  8. [Carcinosarcoma of the breast a rare entity with fatal prognosis. One case report].

    PubMed

    Villalón-López, José Sebastián; Souto-del Bosque, Rosalía; Alonso-Briones, Marco Vinicio; Trujillo-de Anda, Ana Patricia

    2013-01-01

    Antecedentes: los carcinomas metaplásticos de la glándula mamaria son un grupo heterogéneo de neoplasias con pobre pronóstico en comparación con el carcinoma ductal invasor. Corresponden a menos de 1% del total de las neoplasias malignas de la glándula mamaria. Casi siempre se manifiestan como tumores de alto grado con menor índice de metástasis ganglionares y menor expresión de receptores de estrógeno y progesterona, Her2 y mayor expresión de Her1 y Ki-67. Caso clínico: se reporta el caso de una mujer de 52 años de edad con carcinosarcoma mamario que se manifiesta con un tumor mamario izquierdo, fungado, ulcerado, polipoide, de 18 cm de diámetro, con metástasis ganglionares al momento del diagnóstico. Recibió tratamiento multimodal con quimioterapia neoadyuvante seguida de mastectomía y quimioterapia complementaria; evolucionó con metástasis pulmonares y recurrencia local masiva. Falleció por complicaciones derivadas de la enfermedad.Conclusiones: los carcinomas metaplásticos de la glándula mamaria son padecimientos sumamente raros. Debido a la naturaleza de la enfermedad y su forma de presentación el pronóstico es pobre. Existen varios subtipos histológicos basados en estudios de hematoxilina y eosina o tinciones de inmunohistoquímica. El tratamiento debe ser multimodal (cirugía, radioterapia y quimioterapia) para obtener mejores resultados.

  9. The influence of body composition on quality of life of patients with breast cancer.

    PubMed

    Porciúncula Frenzel, Aline; Aberici Pastore, Carla; González, Maria Cristina

    2013-01-01

    Introducción: Los cambios no deseados en la composición corporal, así como el impacto de éstos en la calidad de vida de esta población, han sido poco investigados. Objetivo: Evaluar el rol de la composición corporal en la calidad de vida, y el impacto de la quimioterapia en ambos, en mujeres con cáncer de mama. Métodos: Se evaluaron prospectivamente las mujeres con cáncer de mama en una cohorte de pacientes sometidos a quimioterapia. La composición corporal se estimó mediante la impedancia bioeléctrica. La calidad de vida se evaluó mediante el cuestionario de calidad de vida de la Organización Mundial de la Salud. Resultados: Se evaluaron 70 mujeres, de las cuales el 77 y 73% tuvieron inicialmente sobrepeso y exceso de grasa corporal, respectivamente. Se observó un aumento significativo en la masa libre de grasa (p < 0,001), el índice de masa corporal (P = 0,03) y el peso (p = 0,02), mientras que la calidad de vida se mantuvo igual durante el período. Por otra parte, las mujeres con exceso de grasa corporal, mostraron una puntuación general de salud inicial significativamente menor, en comparación con aquellas con grasa corporal normal (p = 0,02). Conclusiones: La quimioterapia ha demostrado ser un inductor potencial del incremento de peso en esta población. Destacamos la importancia de nuevas investigaciones sobre el impacto de la acumulación de grasa corporal en la calidad de vida de estas mujeres.

  10. EFFECTIVENESS OF IMMUNONUTRITION ON INFLAMMATORY MARKERS IN PATIENTS WITH CANCER; RANDOMIZED CLINICAL TRIAL.

    PubMed

    Pérez Cruz, Elizabeth; Reyes Marín, Arturo; Asbun Bojalil, Juan; Arteaga Morfin, Jose Ignacio

    2015-10-01

    Antecedentes: la desnutrición es una complicación frecuente en los pacientes oncológicos y se relaciona con inmunosupresión y alteraciones en la respuesta inflamatoria. Objetivo: evaluar los efectos de la suplementación de dos fórmulas enterales sobre los marcadores inflamatorios (PCR, IL-6 y el TNF-) en pacientes con cáncer sometidos a quimioterapia. Diseño y métodos: se hizo un ensayo clínico, aleatorizado, realizado en el Hospital Juárez de México en pacientes con cáncer sometidos a quimioterapia con IRN < 97,5 y EGS B o C. Los pacientes se dividieron en dos grupos: grupo I (imunomoduladora), grupo II (ácidos -3). La intervención se inició en el primer día de la quimioterapia hasta el décimo día posterior a esta. Se valoró el estado nutricional y se determinaron los marcadores inflamatorios en los días 0, +5 y +10 de QT. Se hizo análisis paramétrico. Se aplicó t de Student, X2 y análisis de varianza para mediciones repetidas. Se consideró p < 0.05 como estadísticamente significativo. Resultados: se estudiaron 43 pacientes, 27(62,8%) mujeres y 16 (37,2%) hombres. La media de edad fue de 43,91 + 11,3 años. La prevalencia de desnutrición moderada fue de 48,8% y severa de 51,2%. El grupo II presentó un incremento en los niveles de prealbúmina con respecto a la basal vs el grupo I (p < 0,05). En ambos grupos se observó el mantenimiento del peso corporal, el porcentaje de masa magra y de masa grasa. No se observó disminución de los niveles séricos de PCR, IL-6 y TNF(p = NS). Conclusiones: la administración de suplementos enterales durante la quimioterapia inhibe el deterioro nutricional y mantiene el peso y la masa magra. No se observó disminución de los marcadores inflamatorios.

  11. [Anthracycline-induced cardiotoxicity: report of fatal cases].

    PubMed

    Vargas-Neri, Jessica Liliana; Castelán-Martínez, Osvaldo Daniel; de Jesús Estrada-Loza, María; Betanzos-Cabrera, Yadira; Rivas-Ruiz, Rodolfo

    2016-01-01

    Introducción: las antraciclinas son fármacos eficaces en el tratamiento de pacientes pediátricos con cáncer. Sin embargo, la cardiotoxicidad inducida por antraciclinas (CIA) es una reacción adversa grave que afecta la sobrevida de niños y jóvenes. Casos clínicos: el caso 1 estuvo constituido por una paciente de nueve años con linfoma de Hodgkin estadio IV con 12 ciclos de quimioterapia con epirrubicina y una dosis acumulada de 576 mg/m2. Después del último ciclo de quimioterapia, la paciente ingresó con respuesta inflamatoria sistémica, astenia y adinamia. El ecocardiograma reportó una FEVI de 22 %, FA de 11 % e insuficiencia mitral moderada. La paciente falleció dos días después con diagnóstico de cardiomiopatía dilatada secundaria a antraciclinas. El caso 2 fue el de una paciente de 15 años con linfoma no Hodgkin tipo Burkitt estadio IV, con dos ciclos de quimioterapia con epirrubicina y una dosis acumulada de 90 mg/m2. Después del último ciclo, la paciente presentó diversos focos infecciosos. El ecocardiograma reportó una FEVI de 49 %, una FA de 20 % y dilatación del ventrículo izquierdo con aplanamiento septal. La paciente falleció 13 días después del diagnóstico de cardiomiopatía dilatada por antraciclinas. Conclusión: la CIA es un problema en los pacientes pediátricos que reciben antraciclinas. El monitoreo durante y después de la quimioterapia es indispensable para detectar el inicio del daño cardiaco a fin de brindar una intervención oportuna que evite la evolución a una insuficiencia cardiaca.

  12. [Music as an adjuvant treatment for anxiety in pediatric oncologic patients].

    PubMed

    Sepúlveda-Vildósola, Ana Carolina; Herrera-Zaragoza, Octavio René; Jaramillo-Villanueva, Leonel; Anaya-Segura, Armando

    2014-01-01

    INTRODUCCIÓN: la música ha sido utilizada como adyuvante en el manejo de la ansiedad y se basa en principios científicos. Tono, ritmo, armonía y tiempo son factores determinantes para su efectividad. El estrés importante en los pacientes pediátricos, en ocasiones puede retrasar el tratamiento. Nuestro objetivo fue determinar si la musicoterapia es eficaz para disminuir el nivel de ansiedad de los pacientes con cáncer que reciben quimioterapia ambulatoria. MÉTODOS: se realizó un ensayo clínico, cuasiexperimental, tipo antes y después. Se incluyeron pacientes de ocho a 16 años de edad que acudieron a quimioterapia intravenosa ambulatoria en el Hospital de Pediatría, Centro Médico Nacional Siglo XXI. En la primera sesión recibieron su tratamiento de forma habitual y en la segunda, la maniobra con musicoterapia. Se aplicó una escala visual análoga para determinar el nivel de ansiedad al inicio y al finalizar el procedimiento en ambas fases (sin y con intervención).

  13. [Subconjunctival chemotherapy in patients with acquired immunodeficiency syndrome. Experimental study of 3 clinical cases].

    PubMed

    Melgares-Ramos, María de los Ángeles; Carnesoltas-Lázaro, Deyanira; Silveira-Melgares, Yiliam Suyen; Domínguez-Odio, Aníbal

    2015-01-01

    Introducción: el carcinoma escamoso de la conjuntiva (CEC) es un tumor maligno epitelial de la mucosa conjuntival, de etiología multifactorial. Existen varias alternativas de tratamiento para el control de esta enfermedad con diferentes resultados terapéuticos. El objetivo del trabajo fue evaluar la respuesta antitumoral de la preparación de una formulación de cisplatino en 3 pacientes con HIV y CEC recidivante, candidatos a tratamiento de enucleación y exenteración orbitaria, y evaluar los efectos adversos que se presentaron con la administración de la formulación aplicada. Métodos: fueron tratados 3 pacientes masculinos, caucásicos, con media de edad 37 años, a los que se les realizó cirugía exerética y se les administraron 3 ciclos de quimioterapia subconjuntival, con duración de 3 meses. Resultados: todos los pacientes conservaron sus ojos y la visión. No hubo persistencia ni aparecieron recidivas tumorales durante el periodo evaluado. Un paciente falleció por progresión del HIV 2 años después de finalizado el tratamiento, mantuvo visión conservada y sin actividad tumoral. Conclusión: el tratamiento con quimioterapia subconjuntival adyuvante a la cirugía resulta eficaz y es tolerable en la población de pacientes tratados.

  14. Integrative review of factors related to the nursing diagnosis nausea during antineoplastic chemotherapy.

    PubMed

    Moysés, Aline Maria Bonini; Durant, Lais Corsino; Almeida, Ana Maria de; Gozzo, Thais de Oliveira

    2016-10-10

    to identify factors related to the nursing diagnosis nausea among cancer patients undergoing chemotherapy. integrative review conducted in four electronic databases (PUBMED, EMBASE, CINAHL and LILACS) using the key words: neoplasia, antineoplastic agents and nausea. only 30 out of 1,258 papers identified met the inclusion criteria. The most frequent related factors were: being younger than 50 years old, motion sickness, being a woman, emetogenic potential of the chemotherapy, anxiety, conditioned stimulus, and expecting nausea after treatment. this review's findings, coupled with the incidence of nausea among cancer patients undergoing chemotherapy, reveal an important difference between evidence found and that used by NANDA International, Inc. Even though it provides an appropriate definition of related factors, it does not mention chemotherapy, despite the various studies addressing the topic using different designs and presenting various objectives and outcomes. identificar os fatores relacionados ao diagnóstico de enfermagem náusea entre pacientes oncológicos durante o tratamento quimioterápico. revisão integrativa de quatro bases eletrônicas de dados (PUBMED, EMBASE, CINAHL e LILACS) com as palavras-chaves neoplasia, agentes antineoplásicos e náusea. dos 1258 artigos identificados, somente 30 atenderam aos critérios de inclusão. Os fatores relacionados mais frequentes foram: idade abaixo de 50 anos, doença do movimento, sexo feminino, potencial emético do quimioterápico, ansiedade, estímulo condicionado e expectativa de náuseas depois do tratamento. diante dos resultados encontrados e da incidência de náusea entre os pacientes oncológicos em tratamento quimioterápico, observa-se diferença importante entre as evidências encontradas e as utilizadas pela NANDA International, Inc. Apesar da definição estar adequada entre os fatores relacionados, não há menção à quimioterapia mesmo com inúmeros estudos, com diferentes delineamentos

  15. Recombinant Ov-ASP-1, a Th1-biased protein adjuvant derived from the helminth Onchocerca volvulus, can directly bind and activate antigen-presenting cells.

    PubMed

    He, Yuxian; Barker, Sophie J; MacDonald, Angus J; Yu, Yu; Cao, Long; Li, Jingjing; Parhar, Ranjit; Heck, Susanne; Hartmann, Susanne; Golenbock, Douglas T; Jiang, Shibo; Libri, Nathan A; Semper, Amanda E; Rosenberg, William M; Lustigman, Sara

    2009-04-01

    We previously reported that rOv-ASP-1, a recombinant Onchocerca volvulus activation associated protein-1, was a potent adjuvant for recombinant protein or synthetic peptide-based Ags. In this study, we further evaluated the adjuvanticity of rOv-ASP-1 and explored its mechanism of action. Consistently, recombinant full-length spike protein of SARS-CoV or its receptor-binding domain in the presence of rOv-ASP-1 could effectively induce a mixed but Th1-skewed immune response in immunized mice. It appears that rOv-ASP-1 primarily bound to the APCs among human PBMCs and triggered Th1-biased proinflammatory cytokine production probably via the activation of monocyte-derived dendritic cells and the TLR, TLR2, and TLR4, thus suggesting that rOv-ASP-1 is a novel potent innate adjuvant.

  16. PLGA particulate delivery systems for subunit vaccines: Linking particle properties to immunogenicity.

    PubMed

    Silva, A L; Soema, P C; Slütter, B; Ossendorp, F; Jiskoot, W

    2016-04-02

    Among the emerging subunit vaccines are recombinant protein- and synthetic peptide-based vaccine formulations. However, proteins and peptides have a low intrinsic immunogenicity. A common strategy to overcome this is to co-deliver (an) antigen(s) with (an) immune modulator(s) by co-encapsulating them in a particulate delivery system, such as poly(lactic-co-glycolic acid) (PLGA) particles. Particulate PLGA formulations offer many advantages for antigen delivery as they are biocompatible and biodegradable; can protect the antigens from degradation and clearance; allow for co-encapsulation of antigens and immune modulators; can be targeted to antigen presenting cells; and their particulate nature can increase uptake and cross-presentation by mimicking the size and shape of an invading pathogen. In this review we discuss the pros and cons of using PLGA particulate formulations for subunit vaccine delivery and provide an overview of formulation parameters that influence their adjuvanticity and the ensuing immune response.

  17. Pathogen-associated porin turns IL-10 competent B-1a cells toward proinflammatory cytokine response.

    PubMed

    Ghosh, Amlan Kanti; Sinha, Debolina; Biswas, Ratna; Biswas, Tapas

    2016-12-01

    Shigellosis is a major problem in the developing countries causing mortality and morbidity particularly among the children. Shigella spp. harbours the epithelial cells of the human colon to infect the host and spread the disease. We analyzed the response of B-1a cells, the major component of the mucosal immune system to porin of Shigella dysenteriae type 1. We show that porin while proliferating B-1a cells, deplete Siglec-G, the inhibitory molecule present on B-1a cells. Adjuvanticity of porin has been shown to govern innate signaling for promoting host adaptive immune response. Up-regulation of CD69 and CD40 denotes activation of the cells parallel to abrogation of Siglec-G. As a result of cell activation, porin stimulated the inflammatory cytokines of CD5(+) B-1a cells, otherwise rich in IL-10. The work shows B-1a cell responses promote the immunopotentiating activity of porin.

  18. Plasmid containing CpG motifs enhances the efficacy of porcine reproductive and respiratory syndrome live attenuated vaccine.

    PubMed

    Guo, Xiaoyu; Zhang, Quan; Hou, Shaohua; Zhai, Guoqin; Zhu, Hongfei; Sánchez-Vizcaíno, J M

    2011-12-15

    Porcine reproductive and respiratory syndrome (PRRS) is now among the most important swine diseases that affect the Chinese swine industry. Both killed and live attenuated vaccines are currently used against the disease, but neither of them could provide full protection after vaccination. In the present study, the adjuvanticity of a plasmid containing CpG motifs (pUC18-CpG) was introduced to enhance the efficacy of a commercial PRRS live attenuated vaccine. After vaccination, PRRSV-specific antibodies, PRRSV-specific cytokines, and clinical parameters were studied and compared between different vaccinated groups. During a following challenge study, co-administration of pUC18-CpG with the vaccine could confer higher protection rate. Our results have shown that co-administration of pUC18-CpG with the vaccine could elicit more potent adaptive immune response and provide better protection. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Carcinome neuroendocrine du sein: à propos d'un cas et revue de la literature

    PubMed Central

    Affane, Mariam; Elmorjani, Leila; El Omrani, Abdelhamid; Abbadi, Fayçal; Rais, Hanane; Khouchani, Mouna

    2016-01-01

    Les carcinomes neuroendocrines primitifs (CNEP) du sein sont des tumeurs rares. Ils sont actuellement inclus dans la dernière classification de l'OMS des tumeurs du sein. Nous rapportons un cas de localisation mammaire chez une patiente de 39 ans. Il s'agissait d'une tumeur localement avancée ayant nécessité une mastectomie et un curage ganglionnaire axillaire homolatérale. Une chimiothérapie adjuvante était indiquée. L’évolution était marquée par une poursuite évolutive locale. La patiente est décédée dans un tableau de pancytopénie fébrile après une survie d'un an. PMID:27642417

  20. Pneumopathie interstitielle aiguë fatale sous docetaxel: à propos d'un cas et revue de la littérature

    PubMed Central

    Brahmi, Sami Aziz; Youssef, Seddik; Ziani, Fatima Zahra; Afqir, Said

    2016-01-01

    Le docetaxel est un agent de chimiothérapie appartenant à la famille des taxanes. Ce médicament est largement utilisé dans le traitement des cancers. La pneumopathie intestitielle est une toxicité rare mais redoutable du fait d'un risque de mortalité élevé. On rapporte un cas d'une patiente atteinte d'un cancer du sein qui a présenté une pneumopathie interstitielle aigue fatale à la suite d'une chimiothérapie adjuvante par docetaxel. Le clinicien doit être conscient de ce risque et doit le considérer comme un diagnostique différentiel en cas de symptômes respiratoire chez un patient recevant du docetaxel. PMID:27642457

  1. PLGA particulate delivery systems for subunit vaccines: Linking particle properties to immunogenicity

    PubMed Central

    Silva, A. L.; Soema, P. C.; Slütter, B.; Ossendorp, F.; Jiskoot, W.

    2016-01-01

    ABSTRACT Among the emerging subunit vaccines are recombinant protein- and synthetic peptide-based vaccine formulations. However, proteins and peptides have a low intrinsic immunogenicity. A common strategy to overcome this is to co-deliver (an) antigen(s) with (an) immune modulator(s) by co-encapsulating them in a particulate delivery system, such as poly(lactic-co-glycolic acid) (PLGA) particles. Particulate PLGA formulations offer many advantages for antigen delivery as they are biocompatible and biodegradable; can protect the antigens from degradation and clearance; allow for co-encapsulation of antigens and immune modulators; can be targeted to antigen presenting cells; and their particulate nature can increase uptake and cross-presentation by mimicking the size and shape of an invading pathogen. In this review we discuss the pros and cons of using PLGA particulate formulations for subunit vaccine delivery and provide an overview of formulation parameters that influence their adjuvanticity and the ensuing immune response. PMID:26752261

  2. Nanomaterials for enhanced immunity as an innovative paradigm in nanomedicine.

    PubMed

    Seth, Anushree; Oh, Doo-Byoung; Lim, Yong Taik

    2015-01-01

    Since the advent of nanoparticle technology, novel and versatile properties of nanomaterials have been introduced, which has constantly expanded their applications in therapeutics. Introduction of nanomaterials for immunomodulation has opened up new avenues with tremendous potential. Interesting properties of nanoparticles, such as adjuvanticity, capability to enhance cross-presentation, polyvalent presentation, siRNA delivery for silencing of immunesuppressive gene, targeting and imaging of immune cells have been known to have immense utility in vaccination and immunotherapy. A thorough understanding of the merits associated with nanomaterials is crucial for designing of modular and versatile nanovaccines, for improved immune response. With the emerging prerequisites of vaccination, nanomaterial-based immune stimulation, seems to be capable of taking the field of immunization to a next higher level.

  3. Treatment of retroauricular keloids: Revision of cases treated at the ENT service of HC/UFPR.

    PubMed

    Carvalho, Bettina; Ballin, Annelyse Cristine; Becker, Renata Vecentin; Ribeiro, Talita Beithum; Cavichiolo, Juliana Benthien; Ballin, Carlos Roberto; Mocellin, Marcos

    2012-04-01

    Introdução: Queloides são tumores benignos resultantes de cicatrização anômala da pele, sendo que existem diversos procedimentos disponíveis para o seu tratamento.Objetivo: O objetivo deste trabalho é avaliar os resultados de pacientes submetidos a tratamento de queloides retroauriculares após cirurgias otorrinológicas em nosso serviço.Método: Estudo retrospectivo e prospectivo, através de análise de prontuários, dos pacientes submetidos a tratamento de queloides retroauriculares em nosso serviço.Resultados: Nove pacientes foram avaliados, sendo que 6 foram submetidos a ressecção e betaterapia adjuvante, 2 foram submetidos a ressecção mais aplicação de corticoide local, 1 foi submetido apenas a ressecção sem terapia adjuvante. Não houve recidiva nos casos tratados com betaterapia no pós-operatório precoce, 1 paciente apresentou recidiva mesmo com corticoterapia e betaterapia tardia.Discussão: diversas técnicas tem sido utilizadas para tratamento dos queloides retroauriculares, sendo que a betaterapia é considerada a com melhores resultados, seguida pela utilização de corticoides intralesionais.Conclusão: o tratamento dos queloides retroauriculares continua um desafio. Enquanto novas técnicas não são desenvolvidas, a ressecção seguida de betaterapia precoce ainda é a melhor opção.

  4. Induction of Dendritic Cell Maturation and Activation by a Potential Adjuvant, 2-Hydroxypropyl-β-Cyclodextrin

    PubMed Central

    Kim, Sun Kyung; Yun, Cheol-Heui; Han, Seung Hyun

    2016-01-01

    2-Hydroxypropyl-β-cyclodextrin (HP-β-CD) is a chemically modified cyclic oligosaccharide produced from starch that is commonly used as an excipient. Although HP-β-CD has been suggested as a potential adjuvant for vaccines, its immunological properties and mechanism of action have yet to be characterized. In the present study, we investigated the maturation and activation of human dendritic cells (DCs) treated with HP-β-CD. We found that DCs stimulated with HP-β-CD exhibited a remarkable upregulation of costimulatory molecules, MHC proteins, and PD-L1/L2. In addition, the production of cytokines, such as TNF-α, IL-6, and IL-10, was modestly increased in DCs when treated with HP-β-CD. Furthermore, HP-β-CD-sensitized DCs markedly induced the proliferation and activation of autologous T lymphocytes. HP-β-CD also induced a lipid raft formation in DCs. In contrast, filipin, a lipid raft inhibitor, attenuated HP-β-CD-induced DC maturation, the cytokine expression, and the T lymphocyte-stimulating activities. To determine the in vivo relevance of the results, we investigated the adjuvanticity of HP-β-CD and the modulation of DCs in a mouse footpad immunization model. When mice were immunized with ovalbumin in the presence of HP-β-CD through a hind footpad, serum ovalbumin-specific antibodies were markedly elevated. Concomitantly, DC populations expressing CD11c and MHC class II were increased in the draining lymph nodes, and the expression of costimulatory molecules was upregulated. Collectively, our data suggest that HP-β-CD induces phenotypic and functional maturation of DCs mainly mediated through lipid raft formation, which might mediate the adjuvanticity of HP-β-CD. PMID:27812358

  5. Impact of formulation and particle size on stability and immunogenicity of oil-in-water emulsion adjuvants.

    PubMed

    Iyer, Vidyashankara; Cayatte, Corinne; Guzman, Bernardo; Schneider-Ohrum, Kirsten; Matuszak, Ryan; Snell, Angie; Rajani, Gaurav Manohar; McCarthy, Michael P; Muralidhara, Bilikallahalli

    2015-01-01

    Oil-in-water emulsions have gained consideration as vaccine adjuvants in recent years due to their ability to elicit a differentiated immunogenic response compared to traditional aluminum salt adjuvants. Squalene, a cholesterol precursor, is a natural product with immunostimulatory properties, making it an ideal candidate for such oil-in-water emulsions. Particle size is a key parameter of these emulsions and its relationship to stability and adjuvanticity has not been extensively studied. This study evaluates the effect of particle size on the stability and immunogenicity of squalene emulsions. We investigated the effect of formulation parameters such as surfactant concentration on particle size, resulting in particles with average diameter of 80 nm, 100 nm, 150 nm, 200 nm, or 250 nm. Emulsions were exposed to shear and temperature stresses, and stability parameters such as pH, osmolarity, size, and in-depth visual appearance were monitored over time. In addition, adjuvanticity of different particle size was assessed in a mouse model using Respiratory Syncytial Virus Fusion protein (RSV-F) as a model antigen. Temperature dependent phase separation appeared to be the most common route of degradation occurring in the higher particle sizes emulsions. The emulsions below 150 nm size maintained stability at either 5 °C or 25 °C, and the 80 nm diameter ones showed no measurable changes in size even after one month at 40 °C. In vivo studies using the emulsions as an adjuvant with RSV F antigen revealed that superior immunogenicity could be achieved with the 80 nm particle size emulsion.

  6. Impact of formulation and particle size on stability and immunogenicity of oil-in-water emulsion adjuvants

    PubMed Central

    Iyer, Vidyashankara; Cayatte, Corinne; Guzman, Bernardo; Schneider-Ohrum, Kirsten; Matuszak, Ryan; Snell, Angie; Rajani, Gaurav Manohar; McCarthy, Michael P; Muralidhara, Bilikallahalli

    2015-01-01

    Oil-in-water emulsions have gained consideration as vaccine adjuvants in recent years due to their ability to elicit a differentiated immunogenic response compared to traditional aluminum salt adjuvants. Squalene, a cholesterol precursor, is a natural product with immunostimulatory properties, making it an ideal candidate for such oil-in-water emulsions. Particle size is a key parameter of these emulsions and its relationship to stability and adjuvanticity has not been extensively studied. This study evaluates the effect of particle size on the stability and immunogenicity of squalene emulsions. We investigated the effect of formulation parameters such as surfactant concentration on particle size, resulting in particles with average diameter of 80 nm, 100 nm, 150 nm, 200 nm, or 250 nm. Emulsions were exposed to shear and temperature stresses, and stability parameters such as pH, osmolarity, size, and in-depth visual appearance were monitored over time. In addition, adjuvanticity of different particle size was assessed in a mouse model using Respiratory Syncytial Virus Fusion protein (RSV-F) as a model antigen. Temperature dependent phase separation appeared to be the most common route of degradation occurring in the higher particle sizes emulsions. The emulsions below 150 nm size maintained stability at either 5°C or 25°C, and the 80 nm diameter ones showed no measurable changes in size even after one month at 40°C. In vivo studies using the emulsions as an adjuvant with RSV F antigen revealed that superior immunogenicity could be achieved with the 80 nm particle size emulsion. PMID:26090563

  7. EVALUATION OF DIET ACCEPTANCE BY PATIENTS WITH HAEMATOLOGICAL CANCER DURING CHEMOTHERAPEUTIC TREATMENT.

    PubMed

    Prockmann, Stéphanie; Ruschel Freitas, Ana Helena; Gonçalves Ferreira, Marilyn; Kunradi Vieira, Francilene Gracieli; Kuerten de Salles, Raquel

    2015-08-01

    Introducción: el estado nutricional amenazado es uno de los factores que puede elevar la morbimortalidad de los pacientes sometidos a quimioterapia. El objetivo de este estudio fue evaluar la aceptación de la dieta por parte de pacientes con cáncer hematológico durante la internación para quimioterapia. Métodos: investigación transversal, descriptiva y cuantitativa llevada a cabo entre febrero y octubre de 2014 con pacientes adultos de ambos sexos diagnosticados de linfoma y leucemia. Se realizó la evaluación diaria del consumo alimentario mediante la utilización de herramientas para colección de datos preparado por el autor. Se utilizó ANOVA para medidas repetidas. Resultados: fueron evaluados 32 pacientes con edad promedio de 42 ± 11 años, siendo la mayoría mujeres (66%). Observamos trastornos gastrointestinales en el 72% de los pacientes, la mayoría de las molestias fueron náuseas (59%) además de xerostomía (34%), vómitos (28%), inapetencia (28%) y disgeusia (25%). El porcentaje de resto de ingesta alimentaria fue significativo, oscilando entre el 23% y el 35%. El mayor rechazo ocurrió en el almuerzo y la cena. Las meriendas fueron mejor aceptadas, con un porcentaje del 75% al 100%. Conclusión de la investigación: los registros de alimentos mostraron que durante los ciclos de quimioterapia se produjo un rechazo significativo de alimentos sobre todo en las comidas de mayor volumen, como el almuerzo y la cena, mientras que las comidas pequeñas, tales como aperitivos, son mejor toleradas. El uso de opciones de alimentos enumerados por los pacientes puede ser una estrategia para mejorar el cumplimiento de la dieta. Se necesitan más estudios sobre este tema para mejorar la atención a esta población, con el objetivo de prevenir y/o recuperar el estado nutricional de estos pacientes.

  8. [Serum lactate as a biomarker of severe sepsis in children with cancer, neutropenia and fever].

    PubMed

    Pacheco-Rosas, Daniel Octavio; Huelgas-Plaza, Ana Celia; Miranda-Novales, María Guadalupe

    2014-01-01

    INTRODUCCIÓN: la neutropenia es una complicación frecuente secundaria a la quimioterapia en los pacientes con cáncer, en quienes la prevalencia de sepsis es de 12.9 a 17.4 % y la letalidad es de 16 %. El objetivo de este estudio fue determinar la utilidad del lactato como biomarcador de sepsis grave en niños con cáncer, fiebre y neutropenia. MÉTODOS: se realizó un estudio de prueba diagnóstica fase II. Se midieron los niveles del lactato al ingreso. Los episodios de neutropenia se clasificaron en tres grupos: I, con sepsis II, sin sepsis; III, pacientes neutropénicos sin fiebre (controles). Se calculó sensibilidad, especificidad, valores predictivos positivo y negativo e índices de verosimilitud. El estándar de oro fue el diagnóstico clínico de sepsis grave.

  9. [Survival of patients with diffuse large B-cell lymphoma].

    PubMed

    Salas-Delgado, Arnoldo; Hernández-Pliego, Marco Antonio

    2014-01-01

    INTRODUCCIÓN: la quimioterapia actual ha incrementado la supervivencia total y la libre de recaída en los pacientes con linfoma no Hodgkin. Un recurso que permite hacer proyecciones al respecto es el Índice Pronóstico Internacional (IPI). El objetivo del presente análisis fue determinar la correspondencia entre el pronóstico determinado mediante ese índice y la supervivencia obtenida a dos años. MÉTODOS: estudio longitudinal, observacional y prospectivo. Se incluyeron pacientes diagnosticados y tratados durante un año que hubieran requerido hospitalización. Todos recibieron ciclofosfamida-doxorrubicina-vincristina- prednisona, y en algunos casos también rituximab; el seguimiento en promedio fue de 26 meses. La supervivencia se estimó mediante curvas de Kaplan-Meier.

  10. [Neuroendocrine carcinoma of the urinary bladder. A case report].

    PubMed

    Aragón-Tovar, Anel Rogelio; Pineda-Rodríguez, Marco Elí; Puente-Gallegos, Francisco Edgardo; Zavala-Pompa, Angel

    2014-01-01

    Antecedentes: el carcinoma neuroendocrino de células pequeñas primario de vejiga es una lesión maligna muy poco frecuente. Caso clínico: paciente masculino de 68 años de edad, que tuvo hematuria macroscópica de 24 horas de evolución. Estudios de imagen mostraron tumoración vesical de 218 cc, que en 20 días alcanzó un volumen de 426 cc. A la tinción con hematoxilina-eosina, histológicamente se apreció: placa sólida infiltrante de bordes irregulares, compuesta por células neoplásicas con claro predominio de núcleo y escaso citoplasma (células pequeñas). A la tinción inmunohistoquímica con cromogranina parecía difusamente positivo en células neoplásicas, en un patrón granular citoplasmático. A la tinción con citoqueratina de alto peso molecular se observó patrón negativo en células neoplásicas con control interno positivo en el urotelio acompañante en espécimen. De igual manera, la tumoración fue positiva para sinaptofisina y CD-56 y negativa para CK-7 y CK-20. El paciente recibió tratamiento a base de radioterapia y quimioterapia. Conclusión: el carcinoma neuroendocrino de células pequeñas primario de vejiga representa de 0.35 a 0.70% de los tumores vesicales primarios. Su diagnóstico se basa en el reconocimiento histológico e inmunohistoquímico. El tratamiento se fundamenta en quimioterapia con cisplatino más cistectomía radical, excepto cuando existe enfermedad metastásica.

  11. CHRONIC ENTERITIS IN PATIENTS UNDERGOING PELVIC RADIOTHERAPY: PREVALENCE, RISK FACTORS AND ASSOCIATED COMPLICATIONS.

    PubMed

    Hernández-Moreno, Ana; Vidal-Casariego, Alfonso; Calleja-Fernández, Alicia; Kyriakos, Georgios; Villar-Taibo, Rocío; Urioste-Fondo, Ana; Cano-Rodríguez, Isidoro; Ballesteros-Pomar, María D

    2015-11-01

    Introducción: la radiacion de los tumores de la cavidad pelvica puede provocar mucositis a nivel intestinal. El objetivo de nuestro estudio fue determinar la prevalencia, los factores de riesgo y las complicaciones de la enteritis radica cronica en los pacientes tratados con radioterapia pelvica. Pacientes y métodos: estudio transversal sobre 150 pacientes tratados con radioterapia pelvica durante el ano 2008 debido a un cancer de prostata, cervix, endometrio o recto. Se interrogo a los pacientes sobre la presencia de sintomas sugestivos de enteritis y sobre cambios en el peso habitual y modificaciones en su dieta. Los parametros considerados como posibles factores de riesgo de enteritis cronica (sexo, edad, tratamiento antitumoral, enteritis aguda previa y tipo de tumor) se analizaron con metodos univariantes y multivariantes. Resultados: el estudio incluyo finalmente a 100 pacientes, el 84% varones, con una mediana de edad de 72,3 anos. Se encontro una prevalencia de enteritis radica cronica del 20%, en la mayoria de grado 1 (45%). Por otra parte, el 10% referian una perdida de peso ≥ 5 kg, el 3% habian requerido hospitalizacion debido a diarrea incoercible o a obstruccion intestinal, y el 11% habian modificado su patron de alimentacion habitual, reduciendo principalmente el consumo de verduras, legumbres y dulces. Se encontro asociacion entre la enteritis radica cronica y el sexo masculino, la edad, la enteritis radica aguda previa y la quimioterapia, pero solo esta resulto asociarse de forma independiente con el desarrollo de enteritis radica cronica despues del analisis multivariante (OR = 3,59 [95% CI 1,20–10,73]). Conclusión: la enteritis cronica es una entidad frecuente en los pacientes tratados con radioterapia pelvica, sobre todo cuando se asocia con quimioterapia. La tasa de complicaciones por esta patologia es baja, pero un numero importante de pacientes realiza modificaciones en su dieta habitual para aliviar o evitar la sintomatologia derivada

  12. Le carcinome urothélial plasmocytoïde de la vessie : une entité histologique rare au pronostic sombre

    PubMed Central

    Benazzouz, Mohamed Hicham; Essatara, Younes; Elsayegh, Hachem; Iken, Ali; Benslimane, Lounis; Znati, Kaoutar; Nouini, Yassine

    2014-01-01

    Résumé Introduction : Le carcinome urothélial plasmocytoïde est une variante histologique rare du carcinome urothélial. Seule une centaine de cas ont été décrits dans la littérature. Dans cette étude, nous faisons état de deux nouvelles observations. En combinant nos résultats à ceux des différentes séries décrites dans la littérature, nous tentons de définir les caractéristiques cliniques et pathologiques ainsi que l’approche thérapeutique de cette pathologie. Observations : Deux nouveaux cas de carcinome urothélial plasmocytoïde ont été diagnostiqués et pris en charge dans notre établissement. Les 2 patients étaient des hommes de 76 ans en moyenne. L’hématurie était le principal symptôme. Les deux patients ont subi une résection transurétrale de la vessie. Le stade tumoral au moment du diagnostic était avancé dans les deux cas (respectivement T3N0M0 et T3N1M0). Les deux patients ont été traités par cystoprostatectomie. L’analyse histologique de la pièce opératoire, complétée par une étude immunohistochimique, a confirmé le diagnostic de carcinome urothélial plasmocytoïde. Le premier patient est décédé un mois plus tard des suites d’une embolie pulmonaire. Le deuxième patient est décédé au bout de deux mois après avoir reçu deux cycles de chimiothérapie adjuvante. Les données recueillies sur les différentes séries décrites dans la littérature vont dans le même sens que nos données, à savoir un stade avancé au moment du diagnostic et un pronostic sombre. Conclusion : Le carcinome urothélial plasmocytoïde est une variante histologique rare et agressive du carcinome urothélial. Le diagnostic se fait souvent à un stade avancé, et le pronostic est peu encourageant. Le traitement repose le plus souvent sur une cystectomie, suivie d’une chimiothérapie adjuvante à base de cisplatine. L’intérêt d’une chimiothérapie néo-adjuvante n’a pas encore été établi. PMID:25408815

  13. Place de la chirurgie dans la prise en charge des cancers du sein chez la femme au Centre Hospitalier Universitaire Yalgado Ouedraogo: à propos de 81 cas

    PubMed Central

    Zongo, Nayi; Millogo-Traore, Timonga Françoise Danielle; Bagre, Sidpawalmdé Carine; Bagué, Abdoul-Halim; Ouangre, Edgar; Zida, Maurice; Bambara, Aboubacar; Bambara, Tozoula Augustin; Traoré, Si Simon

    2015-01-01

    Etudier la place de la chirurgie dans la prise en charge des cancers du sein au centre hospitalier universitaire Yalgado Ouédraogo. Nous avons réalisé une étude prospective et descriptive sur dix (10) mois portant sur la place de la chirurgie dans le cancer du sein. Elle a eu pour cadre les services de gynécologie-obstétrique et de chirurgie viscérale et digestive du centre hospitalier universitaire Yalgado Ouédraogo. Ont été pris en compte les indications, les gestes et les résultats de la chirurgie. Nous avons colligé 81 cancers mammaires. Le délai moyen de consultation a été de 14,26 mois. Les tumeurs T3 à T4 représentaient 82,71% des cas. Trente-huit patientes (46,91%) ont été opérées. La chimiothérapie néo adjuvante a été réalisée dans 29,63% des cas. Trente-quatre patientes (41,97%) étaient opérables d'emblée. Il s'agissait de mastectomie selon Madden dans 94,74% des cas et de chirurgie de propreté dans 2 cas (5,26% des cas). Une chimiothérapie adjuvante a été réalisée chez 52,63% des patientes opérées. Des complications à type de lymphocèle ont été notées dans 23,68% des cas. Leur traitement a consisté en des ponctions évacuatrices. Les indications de la chirurgie sont limitées par le retard diagnostique corollaire de stades avancés des cancers du sein. L'absence de la radiothérapie rend délicate la pratique de la chirurgie conservatrice et la mastectomie occupe toujours une place importante. Un diagnostic précoce permettrait d'augmenter les indications chirurgicales. PMID:26848364

  14. Broad Clade 2 Cross-Reactive Immunity Induced by an Adjuvanted Clade 1 rH5N1 Pandemic Influenza Vaccine

    PubMed Central

    Leroux-Roels, Isabel; Bernhard, Roger; Gérard, Pascal; Dramé, Mamadou; Hanon, Emmanuel; Leroux-Roels, Geert

    2008-01-01

    Background The availability of H5N1 vaccines that can elicit a broad cross-protective immunity against different currently circulating clade 2 H5N1 viruses is a pre-requisite for the development of a successful pre-pandemic vaccination strategy. In this regard, it has recently been shown that adjuvantation of a recombinant clade 1 H5N1 inactivated split-virion vaccine with an oil-in-water emulsion-based adjuvant system also promoted cross-immunity against a recent clade 2 H5N1 isolate (A/Indonesia/5/2005, subclade 2.1). Here we further analyse the cross-protective potential of the vaccine against two other recent clade 2 isolates (A/turkey/Turkey/1/2005 and A/Anhui/1/2005 which are, as defined by WHO, representatives of subclades 2.2 and 2.3 respectively). Methods and Findings Two doses of the recombinant A/Vietnam/1194/2004 (H5N1, clade 1) vaccine were administered 21 days apart to volunteers aged 18–60 years. We studied the cross-clade immunogenicity of the lowest antigen dose (3.8 µg haemagglutinin) given with (N = 20) or without adjuvant (N = 20). Immune responses were assessed at 21 days following the first and second vaccine doses and at 6 months following first vaccination. Vaccination with two doses of 3.8 µg of the adjuvanted vaccine induced four-fold neutralising seroconversion rates in 85% of subjects against A/turkey/Turkey/1/2005 (subclade 2.2) and 75% of subjects against A/Anhui/1/2005 (subclade 2.3) recombinant strains. There was no response induced against these strains in the non-adjuvanted group. At 6 months following vaccination, 70% and 60% of subjects retained neutralising antibodies against the recombinant subclade 2.2 and 2.3 strains, respectively and 40% of subjects retained antibodies against the recombinant subclade 2.1 A/Indonesia/5/2005 strain. Conclusions In addition to antigen dose-sparing, adjuvantation of inactivated split H5N1 vaccine promotes broad and persistent cross-clade immunity which is a pre-requisite for a pre

  15. Mucosal and systemic antibody responses against an acellular pertussis vaccine in mice after intranasal co-administration with recombinant cholera toxin B subunit as an adjuvant.

    PubMed

    Isaka, Masanori; Yasuda, Yoko; Taniguchi, Tooru; Kozuka, Satoshi; Matano, Keiko; Maeyama, Jun-ichi; Morokuma, Kazunori; Ohkuma, Kunio; Goto, Norihisa; Tochikubo, Kunio

    2003-03-07

    To investigate the possibility of intranasal immunization with an acellular pertussis vaccine, groups of mice were administered intranasally with aluminium-non-adsorbed pertussis toxoid (PTd; 0.5 or 5 microg) and formalin-treated filamentous hemagglutinin (fFHA; 5 microg) with and without recombinant cholera toxin B subunit (rCTB; 10 microg) as a mucosal adjuvant. At a low concentration of PTd, the following things became clear: (1) earlier and higher elevation of serum anti-PTd and anti-FHA IgG antibody titres in the presence of rCTB than in its absence, (2) higher serum anti-PTd and anti-FHA IgG antibody titres than 200 and 100 ELISA units ml(-1) (EU ml(-1)) in all mice, respectively, in the presence of rCTB, which were obtained by calibration against a reference anti-pertussis mouse serum, and (3) in an intranasal challenge experiment with Bordetella pertussis, slightly more rapid elimination of the bacteria from the lungs of mice intranasally immunized in the presence of rCTB, suggesting the effectiveness of rCTB as a mucosal adjuvant. However, irrespective of rCTB and dose of PTd, mice which were immunized four times and sacrificed on day 35 developed high levels of anti-PTd serum IgG antibodies, high or moderate levels of anti-FHA serum IgG antibodies and mucosal anti-PTd IgA antibodies in the lungs; only a slight or no increase of anti-FHA mucosal IgA antibodies was observed in the lung. These facts suggested the immunogenicity and mucosal adjuvanticity of PTd, and therefore, the mucosal adjuvanticity of rCTB seemed to be inconspicuous. Moreover, the addition of rCTB induced higher anti-PTd serum IgE antibody responses than no addition of it depending on dose of PTd. These results show that dose of PTd included in an acellular pertussis vaccine had better be low as possible and the addition of rCTB may not be always necessary in case of this nasal vaccine alone unlike tetanus and diphtheria toxoids and hepatitis B virus vaccine reported before.

  16. Intranasal influenza vaccination using a new synthetic mucosal adjuvant SF-10: induction of potent local and systemic immunity with balanced Th1 and Th2 responses.

    PubMed

    Kimoto, Takashi; Mizuno, Dai; Takei, Tsunetomo; Kunimi, Takuya; Ono, Shinji; Sakai, Satoko; Kido, Hiroshi

    2013-11-01

    We found previously that bovine pulmonary Surfacten® used in newborns with acute respiratory distress syndrome is a safe and efficacious antigen vehicle for intranasal vaccination. The objective of this study was to industrially produce a synthetic adjuvant mimicking Surfacten® for clinical use without risk of bovine spongiform encephalopathy. We selected three Surfacten lipids and surfactant protein (SP)-C as essential constituents for adjuvanticity. For replacement of the hydrophobic SP-C, we synthesized SP-related peptides and analyzed their adjuvanticity. We evaluated lyophilization to replace sonication for the binding of influenza virus hemagglutinin (HA) to the synthetic adjuvant. We also added a carboxy vinyl polymer (CVP) to the synthetic adjuvant and named the mixture as SF-10 adjuvant. HA combined with SF-10 was administered intranasally to mice, and induction of nasal-wash HA-specific secretory IgA (s-IgA) and serum IgG with Th1-/Th2-type cytokine responses in nasal cavity and virus challenge test were assessed. Intranasal immunization with HA-SF-10 induced significantly higher levels of anti-HA-specific nasal-wash s-IgA and serum IgG than those induced by HA-poly(I:C), a reported potent mucosal vaccine, and provided highly efficient protection against lethal doses of virus challenge in mice. Anti-HA-specific serum IgG levels induced by HA-SF-10 were almost equivalent to those induced by subcutaneous immunization of HA twice. Intranasal administration of HA-SF-10 induced balanced anti-HA-specific IgG1 and IgG2a in sera and IFN-γ- and IL-4-producing lymphocytes in nasal cavity without any induction of anti-HA IgE. The results suggest that HA-SF-10 is a promising nasal influenza vaccine and that SF-10 can be supplied in large quantities commercially. © 2013 The authors. Influenza and other Respiratory Viruses published by John Wiley & Sons Ltd.

  17. Hyperbaric Oxygen Therapy for the Treatment of Fournier's Gangrene: A Review of 34 Cases.

    PubMed

    Rosa, Isabel; Guerreiro, Francisco

    2015-01-01

    Introdução: A gangrena de Fournier é uma infecção necrotizante grave, que pode levar à morte se não for tratada rapidamente. O tratamento baseia-se na combinação do desbridamento cirúrgico, antibioterapia e terapêutica de suporte. A oxigenoterapia hiperbárica surge como adjuvante quer na optimização da oxigenação dos tecidos infetados, quer através da ação bactericida e bacteriostática. Material e Métodos: Foi feita uma revisão dos processos clínicos dos doentes com gangrena de Fournier referenciados ao Centro de Medicina Subaquática e Hiperbárica da Marinha para realizar oxigenoterapia hiperbárica num período de 25 anos. Resultados: Foram tratados 34 doentes. A maioria dos doentes era do género masculino (94,1%) com idade média de 53,7 anos. A diabetes foi a comorbilidade mais frequentemente associada. O foco de infeção mais frequente foi o trato urinário. A taxa de mortalidade foi de 20,8%. Discussão: A diabetes é a comorbilidade mais frequente, sugerindo a diabetes como factor predisponente. A maioria dos doentes falecidos tinham diabetes, todavia não se conseguiu estabelecer correlação entre diabetes e morte. A área de residência dos doentes parece limitar a referenciação ao centro. Conclusões: A gangrena de Fournier, apesar de rara, é uma doença potencialmente fatal, nomeadamente em doentes com comorbilidades como a diabetes. A oxigenoterapia hiperbárica está recomendada como adjuvante à terapêutica convencional e, quando este recurso está disponível, deve ser considerado. São necessários mais estudos para melhor aferir o papel da oxigenoterapia hiperbárica no tratamento desta entidade.

  18. Nanocarriers for DNA Vaccines: Co-Delivery of TLR-9 and NLR-2 Ligands Leads to Synergistic Enhancement of Proinflammatory Cytokine Release

    PubMed Central

    Poecheim, Johanna; Heuking, Simon; Brunner, Livia; Barnier-Quer, Christophe; Collin, Nicolas; Borchard, Gerrit

    2015-01-01

    Adjuvants enhance immunogenicity of vaccines through either targeted antigen delivery or stimulation of immune receptors. Three cationic nanoparticle formulations were evaluated for their potential as carriers for a DNA vaccine, and muramyl dipeptide (MDP) as immunostimulatory agent, to induce and increase immunogenicity of Mycobacterium tuberculosis antigen encoding plasmid DNA (pDNA). The formulations included (1) trimethyl chitosan (TMC) nanoparticles, (2) a squalene-in-water nanoemulsion, and (3) a mineral oil-in-water nanoemulsion. The adjuvant effect of the pDNA-nanocomplexes was evaluated by serum antibody analysis in immunized mice. All three carriers display a strong adjuvant effect, however, only TMC nanoparticles were capable to bias immune responses towards Th1. pDNA naturally contains immunostimulatory unmethylated CpG motifs that are recognized by Toll-like receptor 9 (TLR-9). In mechanistic in vitro studies, activation of TLR-9 and the ability to enhance immunogenicity by simultaneously targeting TLR-9 and NOD-like receptor 2 (NLR-2) was determined by proinflammatory cytokine release in RAW264.7 macrophages. pDNA in combination with MDP was shown to significantly increase proinflammatory cytokine release in a synergistic manner, dependent on NLR-2 activation. In summary, novel pDNA-Ag85A loaded nanoparticle formulations, which induce antigen specific immune responses in mice were developed, taking advantage of the synergistic combinations of TLR and NLR agonists to increase the adjuvanticity of the carriers used. PMID:28347123

  19. Liposarcome paratesticulaire métastatique

    PubMed Central

    Fahsi, Otheman; Kallat, Adil; Ouazize, Hicham; Dergamoun, Hamza; Sayegh, Hachem El; Iken, Ali; Benslimane, Lounis; Nouini, Yassine

    2017-01-01

    Nous rapportons le cas dramatique d'un liposarcome à cellules rondes paratesticulaire d'emblée métastatique chez un jeune homme de 18 ans. Il s'agit d'une tumeur rare qui se développe à partir du tissu graisseux entourant le testicule et le cordon spermatique. Les signes cliniques et radiologiques sont peu spécifiques, le diagnostic n'est en général fait que sur la pièce opératoire. Le traitement consiste en une orchidéctomie radicale par voie inguinale, parfois élargie aux structures adjacentes. La radiothérapie adjuvante pourrait avoir une place en cas de masse localement avancée ou en cas de résection incomplète. Malgré une évolutivité lente, une surveillance prolongée s'impose du fait du risque élevé de récidive tardive. PMID:28819522

  20. Adjuvanted seasonal influenza vaccines and perpetual viral metamorphosis: the importance of cross-protection.

    PubMed

    Ansaldi, Filippo; Canepa, Paola; Parodi, Valentina; Bacilieri, Sabrina; Orsi, Andrea; Compagnino, Federica; Icardi, Giancarlo; Durando, Paolo

    2009-05-26

    Vaccination is considered the most effective means of reducing influenza burden, providing substantial benefits in terms of reduction of morbidity, complications, hospitalizations and deaths, even if vaccines have been associated with a reduced immune response and lower effectiveness in older adults, in particular when a mismatch between the vaccine and the circulating virus strains occurred. Several strategies have been proposed to enhance vaccine protection against drifted strains, including the use of adjuvants. Among oil-emulsion adjuvants, MF-59 was approved for human use more than a decade ago and it is largely used for adjuvantation of influenza vaccine. Recent studies have demonstrated that addition of the MF-59 to subunit influenza vaccine can lead to higher haemagglutination-inhibiting seroprotection rates and to higher neutralization antibody titers against drifted strains not included in the vaccine respect to non-adjuvanted vaccine. Promising results were obtained using a new generation of oil-in-water emulsion adjuvants, named AS, offering cross-protection against heterologous challenge in ferrets.

  1. Le carcinome neuro-endocrine cutané primitif: à propos d'un nouveau cas et revue de la littérature

    PubMed Central

    Boukind, Samira; Elatiqi, Oumkeltoum; Dlimi, Meriem; Elamrani, Driss; Benchamkha, Yassine; Ettalbi, Saloua

    2015-01-01

    Le carcinome neuro- endocrine cutané primitif (CNEC) est une tumeur cutanée rare et agressive du sujet âgé, favorisée par le soleil et l'immunodépression. Elle est caractérisée par une évolution agressive avec un fort taux de récidive, une évolution ganglionnaire régionale et un risque de métastases à distance. Nous rapportons un cas de cette tumeur chez un patient âgé de 67 ans sous forme d'un placard nodulaire hémorragique mesurant 16 /14 cm. Le patient a bénéficié d'une exérèse chirurgicale large avec couverture de la perte de substance par un lambeau musculo-cutané du muscle grand dorsal, un curage ganglionnaire axillaire et une radiothérapie adjuvante. Après un recul de 2 ans et 2 mois, le patient est toujours vivant sans métastase ni récidive. La littérature étant pauvre, la prise en charge diagnostique et thérapeutique est controversée et donc hétérogène. Globalement le pronostic est mauvais, et certains paramètres corrélés au pronostic sont précisés. PMID:26185585

  2. A current update on the phytopharmacological aspects of Houttuynia cordata Thunb

    PubMed Central

    Kumar, Manish; Prasad, Satyendra K.; Hemalatha, S.

    2014-01-01

    The present review is an attempt to put an insight into a medicinal plant Houttuynia cordata Thunb, which is indigenous to North-East India and China. It is an aromatic medicinal herb belonging to family Saururaceae and is restricted to specialized moist habitats. The review provides detailed information regarding the morphology, distribution, phytochemistry, ethnopharmacological uses and also describes various pharmacological activities reported on the plant H. cordata. The review describes therapeutic efficacy of the whole plant and its extracts, fractions and isolated compounds in different diseased condition. Among the important pharmacological activities reported includes, anti-mutagenic, anti-cancer, adjuvanticity, anti-obesity, hepatoprotective, anti-viral, anti-bacterial, anti-inflammatory, free radical scavenging, anti-microbial, anti-allergic, anti-leukemic, chronic sinusitis and nasal polyps activities. Thus, the present review will act as a source of referential information to researchers to perform clinical studies on isolated compounds that may serve the society and will help in improving human health care system. PMID:24600193

  3. Adjuvant effect of Gantrez®AN nanoparticles during oral vaccination of piglets against F4+enterotoxigenic Escherichia coli.

    PubMed

    Vandamme, Katrien; Melkebeek, Vesna; Vesna, Melkebeek; Cox, Eric; Eric, Cox; Remon, Jean Paul; Paul, Remon Jean; Vervaet, Chris; Chris, Vervaet

    2011-02-15

    In this study, the adjuvanticity of methylvinylether-co-maleic anhydride (Gantrez(®)AN) nanoparticles (NP) was investigated in an oral immunisation experiment of pigs against F4+enterotoxigenic Escherichia coli (F4+ETEC). In addition, Wheat Germ Agglutinin (WGA)-coating of the nanoparticles was tested for enterocyte-targeting. Pigs were either vaccinated with F4 fimbriae, F4 encapsulated in Gantrez(®)AN NP, F4 encapsulated in Gantrez(®)AN NP coated with WGA or F4 fimbriae mixed with empty Gantrez(®)AN NP. Only vaccination with the combination of F4 mixed with empty Gantrez(®)AN NP improved protection against F4+ETEC infection. In addition, vaccination with this formulation also resulted in an F4-specific serum antibody response prior to F4+ETEC challenge. Encapsulation of F4 in Gantrez(®)AN NP only raised the serum antibody response after F4+ETEC challenge compared to soluble F4, but did not improve protection, whereas WGA-coating almost completely abolished the serum antibody response. These data indicate that nanoparticle effects after F4 encapsulation were of lesser importance for the adjuvant effect of Gantrez(®)AN NP, contrarily to the reactivity of the Gantrez(®)AN polymer used to prepare the nanoparticles. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. From stock bottle to vaccine: Elucidating the particle size distributions of aluminum adjuvants using dynamic light scattering.

    NASA Astrophysics Data System (ADS)

    Shardlow, Emma; Mold, Matthew; Exley, Christopher

    2016-12-01

    The physicochemical properties of aluminum salts are key determinants of their resultant adjuvanticity in vivo when administered as part of a vaccine. While there are links between particle size and the efficacy of the immune response, the limited literature directly characterizing the PSD of aluminum adjuvants has stymied the elucidation of such a relationship for these materials. Hence, this comparative study was undertaken to monitor the PSD of aluminum adjuvants throughout the process of vaccine formulation using DLS. A significant proportion of the stock suspensions was highly agglomerated (>6.5µm), although a large degree of disaggregation was observed upon the dilution of all materials into saline. Adju-Phos® yielded the largest particles in this diluent (4251±137nm); however, the higher affinity of BSA for the surface of Alhydrogel® resulted in a comparable size being observed for both commercial adjuvants when this protein was included in the formulation. These results suggest that the PSD of aluminum adjuvants is greatly influenced by dilution and the degree of protein adsorption experienced within the vaccine itself. The size of the resultant antigen-adjuvant complex may be important for its immunological recognition and subsequent clearance from the injection site.

  5. Aluminum hydroxide nanoparticles show a stronger vaccine adjuvant activity than traditional aluminum hydroxide microparticles

    PubMed Central

    Li, Xinran; Aldayel, Abdulaziz M.; Cui, Zhengrong

    2013-01-01

    Aluminum hydroxide is used as a vaccine adjuvant in various human vaccines. Unfortunately, despite its favorable safety profile, aluminum hydroxide can only weakly or moderately potentiate antigen-specific antibody responses. When dispersed in an aqueous solution, aluminum hydroxide forms particulates of 1–20 µm. There is increasing evidence that nanoparticles around or less than 200 nm as vaccine or antigen carriers have a more potent adjuvant activity than large microparticles. In the present study, we synthesized aluminum hydroxide nanoparticles of 112 nm. Using ovalbumin and Bacillus anthracis protective antigen protein as model antigens, we showed that protein antigens adsorbed on the aluminum hydroxide nanoparticles induced a stronger antigen-specific antibody response than the same protein antigens adsorbed on the traditional aluminum hydroxide microparticles of around 9.3 µm. The potent adjuvant activity of the aluminum hydroxide nanoparticles was likely related to their ability to more effectively facilitate the uptake of the antigens adsorbed on them by antigen-presenting cells. Finally, the local inflammation induced by aluminum hydroxide nanoparticles in the injection sites was milder than that induced by microparticles. Simply reducing the particle size of the traditional aluminum hydroxide adjuvant into nanometers represents a novel and effective approach to improve its adjuvanticity. PMID:24188959

  6. Aluminum hydroxide nanoparticles show a stronger vaccine adjuvant activity than traditional aluminum hydroxide microparticles.

    PubMed

    Li, Xinran; Aldayel, Abdulaziz M; Cui, Zhengrong

    2014-01-10

    Aluminum hydroxide is used as a vaccine adjuvant in various human vaccines. Unfortunately, despite its favorable safety profile, aluminum hydroxide can only weakly or moderately potentiate antigen-specific antibody responses. When dispersed in an aqueous solution, aluminum hydroxide forms particulates of 1-20μm. There is increasing evidence that nanoparticles around or less than 200nm as vaccine or antigen carriers have a more potent adjuvant activity than large microparticles. In the present study, we synthesized aluminum hydroxide nanoparticles of 112nm. Using ovalbumin and Bacillus anthracis protective antigen protein as model antigens, we showed that protein antigens adsorbed on the aluminum hydroxide nanoparticles induced a stronger antigen-specific antibody response than the same protein antigens adsorbed on the traditional aluminum hydroxide microparticles of around 9.3μm. The potent adjuvant activity of the aluminum hydroxide nanoparticles was likely related to their ability to more effectively facilitate the uptake of the antigens adsorbed on them by antigen-presenting cells. Finally, the local inflammation induced by aluminum hydroxide nanoparticles in the injection sites was milder than that induced by microparticles. Simply reducing the particle size of the traditional aluminum hydroxide adjuvant into nanometers represents a novel and effective approach to improve its adjuvanticity. © 2013.

  7. Native and genetically inactivated pertussis toxins induce human dendritic cell maturation and synergize with lipopolysaccharide in promoting T helper type 1 responses.

    PubMed

    Ausiello, Clara M; Fedele, Giorgio; Urbani, Francesca; Lande, Roberto; Di Carlo, Beatrice; Cassone, Antonio

    2002-08-01

    The capacity of pertussis toxin (PT) to induce maturation and functional activities of human monocyte-derived dendritic cells (DCs) was investigated. Both native PT (nPT) and genetically detoxified PT (dPT) efficiently promoted expression on DCs of CD80, CD86, human leukocyte antigen-DR, and CD83 markers, alloreactive antigen presentation, and cytokine production, primarily interferon (IFN)-gamma. Although they did not affect interleukin (IL)-10 production by lipopolysaccharide (LPS)-stimulated DCs, both nPT and dPT strongly synergized with LPS for IL-12 production. PTs plus LPS-stimulated DCs secreted soluble factors fostering IFN-gamma but not IL-4 and IL-5 production by naive T cells. T helper type 1 (Th1) polarization was, as alloreactive antigen presentation, inhibited by anti-IL-12 monoclonal antibody. These findings support the notion that nPT, in addition to inducing specific immune response, is a potent Th1 adjuvant and that dPT fully preserves this adjuvanticity. The synergic interaction between PT and LPS in IL-12 production might be relevant for the mechanisms of vaccine-induced protection.

  8. Suppression of influenza virus infection by the orf virus isolated in Taiwan

    PubMed Central

    LIN, Fong-Yuan; TSENG, Yeu-Yang; CHAN, Kun-Wei; KUO, Shu-Ting; YANG, Cheng-Hsiung; WANG, Chi-Young; TAKASU, Masaki; HSU, Wei-Li; WONG, Min-Liang

    2015-01-01

    Orf virus (ORFV), a member of parapoxvirus, is an enveloped virus with genome of double-stranded DNA. ORFV causes contagious pustular dermatitis or contagious ecthyma in sheep and goats worldwide. In general, detection of viral DNA and observing ORFV virion in tissues of afflicted animals are two methods commonly used for diagnosis of orf infection; however, isolation of the ORFV in cell culture using virus-containing tissue as inoculum is known to be difficult. In this work, the ORFV (Hoping strain) isolated in central Taiwan was successfully grown in cell culture. We further examined the biochemical characteristic of our isolate, including viral genotyping, viral mRNA and protein expression. By electron microscopy, one unique form of viral particle from ORFV infected cellular lysate was demonstrated in the negative-stained field. Moreover, immunomodulating and anti-influenza virus properties of this ORFV were investigated. ORFV stimulated human monocytes (THP-1) secreting proinflammatory cytokines IL-8 and TNF-α. And, pre-treatment of ORFV-infected cell medium prevents A549 cells from subsequent type A influenza virus (IAV) infection. Similarly, mice infected with ORFV via both intramuscular and subcutaneous routes at two days prior to IAV infection significantly decreased the replication of IAV. In summary, the results of a current study indicated our Hoping strain harbors the immune modulator property; with such a bio-adjuvanticity, we further proved that pre-exposure of ORFV protects animals from subsequent IAV infection. PMID:25855509

  9. A novel virus-like particle based on hepatitis B core antigen and substrate-binding domain of bacterial molecular chaperone DnaK.

    PubMed

    Wang, Xue Jun; Gu, Kai; Xiong, Qi Yan; Shen, Liang; Cao, Rong Yue; Li, Ming Hui; Li, Tai Ming; Wu, Jie; Liu, Jing Jing

    2009-12-09

    Hepatitis B virus core (HBc) protein has been proved to be an attractive carrier for foreign epitopes, and can display green fluorescent protein (GFP) on its surface. The structure of substrate-binding domain of DnaK [DnaK (394-504 aa), DnaK SBD] is similar to GFP, we therefore reasoned that DnaK SBD might also be tolerated. Electron microscopic observations suggested that the chimeric proteins containing the truncated HBc (HBcDelta) and DnaK SBD could self-assemble into virus-like particle (VLP). Then the accessibility of DnaK SBD and the adjuvanticity of VLP HBcDelta-SBD were demonstrated by two recombinant peptide vaccines against gonadotropin-releasing hormone (GnRH), GhM and GhMNR. The latter carries in addition the peptide motif NRLLLTG which is known to bind to DnaK and DnaK SBD. The combination of VLP HBcDelta-SBD and GhMNR elicited stronger humoral responses and caused further testicular atrophy than the combinations of VLP HBcDelta and GhMNR or VLP HBcDelta-SBD and GhM in Balb/c mice. These findings indicate VLP HBcDelta-SBD might serve as an excellent carrier for GhMNR and some other peptide vaccines.

  10. Improving Hepatitis B Vaccine Efficacy in End-Stage Renal Diseases Patients and Role of Adjuvants

    PubMed Central

    Somi, Mohammad Hossein; Hajipour, Babak

    2012-01-01

    Hepatitis B virus (HBV) infection is a serious global health problem.The prevalence of viral hepatitis is higher in dialysis patients than in the general population because of the opportunity for exposure during the dialysis procedure. Immunization is the most effective way to prevent transmission of hepatitis B virus (HBV) and hence the development of acute or chronic hepatitis B. It is well established that patients with end-stage renal disease including dialysis-dependent patients, have an impaired immune response to hepatitis B vaccine. End stage renal diseases (ESRD) patients have lower seroconversion rates compared with the subjects with intact renal function. Moreover, even after the completion of vaccination schedule anti-hepatitis B (anti-HBs) titers of responder dialysis, patients are low and decline logarithmically with time. The impaired efficacy of HBV vaccine in patients with ESRD has been attributed to numerous factors such as immune compromise because of uremia and some other factors. One approach to improve the immunogenicity of existing HBV vaccines is adjuvantation, and it's very important to find more effective adjutants for improving HBV vaccine efficacy. In this paper we have a brief review on recently known new ways for improving HBV vaccine efficacy. PMID:23029621

  11. Induction of protection against divergent H5N1 influenza viruses using a recombinant fusion protein linking influenza M2e to Onchocerca volvulus activation associated protein-1 (ASP-1) adjuvant.

    PubMed

    Zhao, Guangyu; Du, Lanying; Xiao, Wenjun; Sun, Shihui; Lin, Yongping; Chen, Min; Kou, Zhihua; He, Yuxian; Lustigman, Sara; Jiang, Shibo; Zheng, Bo-Jian; Zhou, Yusen

    2010-10-18

    Our previous studies have shown the adjuvanticity of an Onchocerca volvulus recombinant protein, Ov-ASP-1 (ASP-1), when administered in an aqueous formulation with bystander vaccine antigens or commercial vaccines. In this study, we reported a novel formulation that took advantage of the protein nature of the ASP-1 adjuvant by creating recombinant fusion protein vaccines linking the highly conserved extracellular domain of M2 protein (M2e) consensus sequence of H5N1 influenza viruses with the ASP-1 adjuvant. Two recombinant fusion proteins designated M2e-ASP-1 and M2e3-ASP-1 were studied, in which ASP-1 was fused with one or three tandem copies of the M2e antigen. Our results show that these novel recombinant influenza vaccines, particularly M2e3-ASP-1, induced strong anti-M2e-specific humoral and cellular immune responses in the established mouse model. Furthermore, M2e3-ASP-1 was able to provide significant cross-clade protection against divergent H5N1 viruses. Consequently, this study has demonstrated a potential novel vaccine formulation that could provide a complementary prophylactic strategy in preventing the threat of future influenza outbreak resulting from rapid evolution of the H5N1 virus and co-circulation of multiple antigenic variants in various regions.

  12. The changing shape of vaccination: improving immune responses through geometrical variations of a microdevice for immunization.

    PubMed

    Crichton, Michael Lawrence; Muller, David Alexander; Depelsenaire, Alexandra Christina Isobel; Pearson, Frances Elizabeth; Wei, Jonathan; Coffey, Jacob; Zhang, Jin; Fernando, Germain J P; Kendall, Mark Anthony Fernance

    2016-06-02

    Micro-device use for vaccination has grown in the past decade, with the promise of ease-of-use, painless application, stable solid formulations and greater immune response generation. However, the designs of the highly immunogenic devices (e.g. the gene gun, Nanopatch or laser adjuvantation) require significant energy to enter the skin (30-90 mJ). Within this study, we explore a way to more effectively use energy for skin penetration and vaccination. These modifications change the Nanopatch projections from cylindrical/conical shapes with a density of 20,000 per cm(2) to flat-shaped protrusions at 8,000 per cm(2), whilst maintaining the surface area and volume that is placed within the skin. We show that this design results in more efficient surface crack initiations, allowing the energy to be more efficiently be deployed through the projections into the skin, with a significant overall increase in penetration depth (50%). Furthermore, we measured a significant increase in localized skin cell death (>2 fold), and resultant infiltrate of cells (monocytes and neutrophils). Using a commercial seasonal trivalent human influenza vaccine (Fluvax 2014), our new patch design resulted in an immune response equivalent to intramuscular injection with approximately 1000 fold less dose, while also being a practical device conceptually suited to widespread vaccination.

  13. Comparison of the adjuvant activity of aluminum hydroxide and calcium phosphate on the antibody response towards Bothrops asper snake venom.

    PubMed

    Olmedo, Hidekel; Herrera, María; Rojas, Leonardo; Villalta, Mauren; Vargas, Mariángela; Leiguez, Elbio; Teixeira, Catarina; Estrada, Ricardo; Gutiérrez, José María; León, Guillermo; Montero, Mavis L

    2014-01-01

    The adjuvanticity of aluminum hydroxide and calcium phosphate on the antibody response in mice towards the venom of the snake Bothrops asper was studied. It was found that, in vitro, most of the venom proteins are similarly adsorbed by both mineral salts, with the exception of some basic phospholipases A2, which are better adsorbed by calcium phosphate. After injection, the adjuvants promoted a slow release of the venom, as judged by the lack of acute toxicity when lethal doses of venom were administered to mice. Leukocyte recruitment induced by the venom was enhanced when it was adsorbed on both mineral salts; however, venom adsorbed on calcium phosphate induced a higher antibody response towards all tested HPLC fractions of the venom. On the other hand, co-precipitation of venom with calcium phosphate was the best strategy for increasing: (1) the capacity of the salt to couple venom proteins in vitro; (2) the venom ability to induce leukocyte recruitment; (3) phagocytosis by macrophages; and (4) a host antibody response. These findings suggest that the chemical nature is not the only one determining factor of the adjuvant activity of mineral salts.

  14. Cationic liposomes containing soluble Leishmania antigens (SLA) plus CpG ODNs induce protection against murine model of leishmaniasis.

    PubMed

    Heravi Shargh, Vahid; Jaafari, Mahmoud Reza; Khamesipour, Ali; Jalali, Seyed Amir; Firouzmand, Hengameh; Abbasi, Azam; Badiee, Ali

    2012-07-01

    Development of an effective vaccine against leishmaniasis is possible due to the fact that individuals cured from cutaneous leishmaniasis (CL) are protected from further infection. First generation Leishmania vaccines consisting of whole killed parasites reached to phase 3 clinical trials but failed to show enough efficacies mainly due to the lack of an appropriate adjuvant. In this study, an efficient liposomal protein-based vaccine against Leishmania major infection was developed using soluble Leishmania antigens (SLA) as a first generation vaccine and cytidine phosphate guanosine oligodeoxynucleotides (CpG ODNs) as an immunostimulatory adjuvant. 1, 2-Dioleoyl-3-trimethylammonium-propane was used as a cationic lipid to prepare the liposomes due to its intrinsic adjuvanticity. BALB/c mice were immunized subcutaneously (SC), three times in 2-week intervals, with Lip-SLA-CpG, Lip-SLA, SLA + CpG, SLA, or HEPES buffer. As criteria for protection, footpad swelling at the site of challenge and spleen parasite loads were assessed, and the immune responses were evaluated by determination of IFN-γ and IL-4 levels of cultured splenocytes, and IgG subtypes. The group of mice that received Lip-SLA-CpG showed a significantly smaller footpad swelling, lower spleen parasite burden, higher IgG2a antibody, and lower IL-4 level compared to the control groups. It is concluded that cationic liposomes containing SLA and CpG ODNs are appropriate to induce Th1 type of immune response and protection against leishmaniasis.

  15. Induction of protection against leishmaniasis in susceptible BALB/c mice using simple DOTAP cationic nanoliposomes containing soluble Leishmania antigen (SLA).

    PubMed

    Firouzmand, Hengameh; Badiee, Ali; Khamesipour, Ali; Heravi Shargh, Vahid; Alavizadeh, Seyedeh Hoda; Abbasi, Azam; Jaafari, Mahmoud Reza

    2013-12-01

    A suitable adjuvant and delivery system are needed to develop an effective vaccine against leishmaniasis. To induce a Th1 type of response and protection in BALB/c mice against Leishmania major infection, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) nanoliposomes bearing an intrinsic adjuvanticity, were used as an antigen delivery system and immunoadjuvant for soluble Leishmania antigens (SLA). DOTAP liposomes containing different concentrations of SLA were prepared by using lipid film method followed by sonication. The prepared vesicles showed a diameter of about 100nm, a positive zeta potential and approximately 70% encapsulation efficiency of SLA. BALB/c mice were immunized subcutaneously (SC), three times in a 3-week interval with different concentrations of liposomal SLA (12.5, 25, and 50μg of SLA/50μl/mice), free SLA and as well as free liposome. The group of mice received 50μg of SLA in DOTAP-nanoliposomes showed a significantly (p<0.001) smaller footpad swelling and the lowest spleen and footpad parasite burden after the challenge. This group also showed the highest IFN-γ production compared to the other groups, lower IL-4 level and higher IgG2a antibody titer. Taken together, the results indicated that simple DOTAP nanoliposome containing 1μg/μl SLA are appropriate delivery systems to induce a Th1 type of immune response and protection against L. major infection in BALB/c mice.

  16. Recombinant Lactobacillus plantarum induces immune responses to cancer testis antigen NY-ESO-1 and maturation of dendritic cells.

    PubMed

    Mobergslien, Anne; Vasovic, Vlada; Mathiesen, Geir; Fredriksen, Lasse; Westby, Phuong; Eijsink, Vincent G H; Peng, Qian; Sioud, Mouldy

    2015-01-01

    Given their safe use in humans and inherent adjuvanticity, Lactic Acid Bacteria may offer several advantages over other mucosal delivery strategies for cancer vaccines. The objective of this study is to evaluate the immune responses in mice after oral immunization with Lactobacillus (L) plantarum WCFS1 expressing a cell-wall anchored tumor antigen NY-ESO-1. And to investigate the immunostimulatory potency of this new candidate vaccine on human dendritic cells (DCs). L. plantarum displaying NY-ESO-1 induced NY-ESO-1 specific antibodies and T-cell responses in mice. By contrast, L. plantarum displaying conserved proteins such as heat shock protein-27 and galectin-1, did not induce immunity, suggesting that immune tolerance to self-proteins cannot be broken by oral administration of L. plantarum. With respect to immunomodulation, immature DCs incubated with wild type or L. plantarum-NY-ESO-1 upregulated the expression of co-stimulatory molecules and secreted a large amount of interleukin (IL)-12, TNF-α, but not IL-4. Moreover, they upregulated the expression of immunosuppressive factors such as IL-10 and indoleamine 2,3-dioxygenase. Although L. plantarum-matured DCs expressed inhibitory molecules, they stimulated allogeneic T cells in-vitro. Collectively, the data indicate that L. plantarum-NY-ESO-1 can evoke antigen-specific immunity upon oral administration and induce DC maturation, raising the potential of its use in cancer immunotherapies.

  17. Preparation of mucosal nanoparticles and polymer-based inactivated vaccine for Newcastle disease and H9N2 AI viruses

    PubMed Central

    Naggar, Heba M. El; Madkour, Mohamed Sayed; Hussein, Hussein Ali

    2017-01-01

    Aim: To develop a mucosal inactivated vaccines for Newcastle disease (ND) and H9N2 viruses to protect against these viruses at sites of infections through mucosal immunity. Materials and Methods: In this study, we prepared two new formulations for mucosal bivalent inactivated vaccine formulations for Newcastle and Avian Influenza (H9N2) based on the use of nanoparticles and polymer adjuvants. The prepared vaccines were delivered via intranasal and spray routes of administration in specific pathogen-free chickens. Cell-mediated and humoral immune response was measured as well as challenge trial was carried out. In addition, ISA71 water in oil was also evaluated. Results: Our results showed that the use of spray route as vaccination delivery method of polymer and nanoparticles Montanide™ adjuvants revealed that it enhanced the cell mediated immune response as indicated by phagocytic activity, gamma interferon and interleukin 6 responses and induced protection against challenge with Newcastle and Avian Influenza (H9N2) viruses. Conclusion: The results of this study demonstrate the potentiality of polymer compared to nanoparticles adjuvantes when used via spray route. Mass application of such vaccines will add value to improve the vaccination strategies against ND virus and Avian influenza viruses. PMID:28344402

  18. Harnessing self-assembled peptide nanoparticles in epitope vaccine design.

    PubMed

    Negahdaripour, Manica; Golkar, Nasim; Hajighahramani, Nasim; Kianpour, Sedigheh; Nezafat, Navid; Ghasemi, Younes

    2017-09-01

    Vaccination has been one of the most successful breakthroughs in medical history. In recent years, epitope-based subunit vaccines have been introduced as a safer alternative to traditional vaccines. However, they suffer from limited immunogenicity. Nanotechnology has shown value in solving this issue. Different kinds of nanovaccines have been employed, among which virus-like nanoparticles (VLPs) and self-assembled peptide nanoparticles (SAPNs) seem very promising. Recently, SAPNs have attracted special interest due to their unique properties, including molecular specificity, biodegradability, and biocompatibility. They also resemble pathogens in terms of their size. Their multivalency allows an orderly repetitive display of antigens on their surface, which induces a stronger immune response than single immunogens. In vaccine design, SAPN self-adjuvanticity is regarded an outstanding advantage, since the use of toxic adjuvants is no longer required. SAPNs are usually composed of helical or β-sheet secondary structures and are tailored from natural peptides or de novo structures. Flexibility in subunit selection opens the door to a wide variety of molecules with different characteristics. SAPN engineering is an emerging area, and more novel structures are expected to be generated in the future, particularly with the rapid progress in related computational tools. The aim of this review is to provide a state-of-the-art overview of self-assembled peptide nanoparticles and their use in vaccine design in recent studies. Additionally, principles for their design and the application of computational approaches to vaccine design are summarized. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Molecular cloning, expression and the adjuvant effects of interleukin-8 of channel catfish (Ictalurus Punctatus) against Streptococcus iniae

    PubMed Central

    Wang, Erlong; Wang, Jun; Long, Bo; Wang, Kaiyu; He, Yang; Yang, Qian; Chen, Defang; Geng, Yi; Huang, Xiaoli; Ouyang, Ping; Lai, Weimin

    2016-01-01

    Interleukin-8 (IL-8) as an important cytokine involving in inflammatory and immune response, has been studied as effective adjuvants for vaccines in mammals. However, there are fewer reports about the characterization and adjuvant effects of IL-8 in fish. In this study, cloning and sequence analysis of IL-8 coding region of channel catfish (Ictalurus punctatus) were conducted, mature IL-8(rtIL-8) was expressed and evaluated for its adjuvant effects on the immunoprotection of subunit vaccine encoding α-enolase (rENO) of Streptococcus iniae from several aspects in channel catfish. The results showed co-vaccination of rENO with rtIL-8 enhanced immune responses including humoral and cellular immunity, with higher relative percent survival(RPS,71.4%) compared with the moderate RPS of rENO alone(50%) against S. iniae infection at 4 week post vaccination. While rtIL-8 failed to maintain long-lasting immune protection, only with RPS of 26.67% in rENO + rtIL-8-vaccinated fish compared with that of rENO alone(20%) at 8 week, signifying that IL-8 hold promise for use as potential immunopotentiator in vaccines against bacterial infections in fish, whereas it is insufficient to extend the immunoprotection for long time, and further studies are required to understand the mechanisms of IL-8 used as an adjuvant and seek for more effective way to strengthen the adjuvanticity of IL-8. PMID:27373470

  20. Impact of antibody quality and anamnestic response on viremia control post-challenge in a combined Tat/Env vaccine regimen in rhesus macaques

    PubMed Central

    Demberg, Thorsten; Brocca-Cofano, Egidio; Kuate, Seraphin; Aladi, Stanley; Vargas-Inchaustegui, Diego A.; Venzon, David; Kalisz, Irene; Kalyanaraman, V.S.; Lee, Eun Mi; Pal, Ranajit; DiPasquale, Janet; Ruprecht, Ruth M.; Montefiori, David C.; Srivastava, Indresh; Barnett, Susan W.; Robert-Guroff, Marjorie

    2013-01-01

    Previously, priming rhesus macaques with Adenovirus type 5 host range mutant-recombinants encoding Tat and Env and boosting with Tat and Env protein in MPL-SE controlled chronic viremia by 4 logs following homologous intravenous SHIV89.6P challenge. Here we evaluated Tat, Env, and Tat/Env regimens for immunogenicity and protective efficacy using clade C Env, alum adjuvant, and a heterologous intrarectal SHIV1157ipd3N4 challenge. Despite induction of strong cellular and humoral immunity, Tat/Env group T and B-cell memory responses were not significantly enhanced over Tat- or Env-only groups. Lack of viremia control post-challenge was attributed to lower avidity Env antibodies and no anamnestic ADCC response or SHIV1157ipd3N4 neutralizing antibody development post-challenge. Poor biologic activity of the Tat immunogen may have impaired Tat immunity. In the absence of sterilizing immunity, strong anamnestic responses to heterologous virus can help control viremia. Both antibody breadth and optimal adjuvanticity are needed to elicit high-quality antibody for protective efficacy. PMID:23528732

  1. Un cas d’angiosarcome de l’oreille externe

    PubMed Central

    Issara, Karima; Boughaleb, Zouhour; Tawfiq, Nezha; Bouchbika, Zineb; Benchakroun, Nadia; Jouhadi, Hassan; Sahraoui, Souha; Benider, Abdellatif

    2016-01-01

    L’angiosarcome de l’oreille est une tumeur maligne très rare, et localement très agressive. Elle représente 4-5% des sarcomes cutanés et moins de 1% de tous les sarcomes. Notre objectif est de décrire et de discuter les modalités diagnostiques et thérapeutiques de cette tumeur maligne. A travers le cas clinique d’une patiente âgée de 31 ans reçue pour une masse bourgeonnante du pavillon de l’oreille gauche. Le scanner était en faveur d’une tumeur du pavillon d’oreille avec envahissement de la parotide homolatérale. Le diagnostic histologique était en faveur d’un angiosarcome. Le traitement a consisté en une chirurgie d’exérèse complète suivie d’une radiothérapie adjuvante. Elle est en rémission compléte avec un recul d’une année. PMID:27795774

  2. Formulation and Evaluation of Niosomes

    PubMed Central

    Okore, V. C.; Attama, A. A.; Ofokansi, K. C.; Esimone, C. O.; Onuigbo, E. B.

    2011-01-01

    Span 20-based niosome was prepared by lipid film hydration technique and loaded with Newcastle disease vaccine. Three batches with Span 20, cholesterol and dicetyl phosphate in micro molar ratios of 10:10:1; 15:15:1 and 20:20:1 were prepared and evaluated for encapsulation efficiency using haemagglutination test. The morphology of the vesicles was studied by means of transmission electron microscopy. Particle size, zeta potential and polydispersity index were determined by photon correlation spectroscopy using a nanosizer. Adjuvanticity was assessed using haemagglutination inhibition test. The vesicles of Span 20-based niosomes were distinct, near spherical large unilamellar vesicles. The vesicles were of varied sizes (<1000 nm) with the entrapped Newcastle disease vaccine in the core of the vaccine. The zeta potential had a peak at -50 mV. The polydispersity index was 0.68. Haemagglutination inhibition test showed a 71% increment in immune response over that of the marketed La Sota® vaccine which had a 60% increment in immune response. The niosomal vaccine did not alter but rather enhanced the immunogenicity of the Newcastle disease vaccine. PMID:22457561

  3. Induction of lupus autoantibodies by adjuvants

    USGS Publications Warehouse

    Satoh, M.; Kuroda, Y.; Yoshida, H.; Behney, K.M.; Mizutani, A.; Akaogi, J.; Nacionales, D.C.; Lorenson, T.D.; Rosenbauer, R.J.; Reeves, W.H.

    2003-01-01

    Exposure to the hydrocarbon oil pristane induces lupus specific autoantibodies in non-autoimmune mice. We investigated whether the capacity to induce lupus-like autoimmunity is a unique property of pristane or is shared by other adjuvant oils. Seven groups of 3-month-old female BALB/cJ mice received a single intraperitoneal injection of pristane, squalene (used in the adjuvant MF59), incomplete Freund's adjuvant (IFA), three different medicinal mineral oils, or saline, respectively. Serum autoantibodies and peritoneal cytokine production were measured. In addition to pristane, the mineral oil Bayol F (IFA) and the endogenous hydrocarbon squalene both induced anti-nRNP/Sm and -Su autoantibodies (20% and 25% of mice, respectively). All of these hydrocarbons had prolonged effects on cytokine production by peritoneal APCs. However, high levels of IL-6, IL-12, and TNF?? production 2-3 months after intraperitoneal injection appeared to be associated with the ability to induce lupus autoantibodies. The ability to induce lupus autoantibodies is shared by several hydrocarbons and is not unique to pristane. It correlates with stimulation of the production of IL-12 and other cytokines, suggesting a relationship with a hydrocarbon's adjuvanticity. The potential to induce autoimmunity may complicate the use of oil adjuvants in human and veterinary vaccines. ?? 2003 Elsevier Ltd. All rights reserved.

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

    PubMed Central

    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

  5. Liposomes containing recombinant E protein vaccine against duck Tembusu virus in ducks.

    PubMed

    Ma, Tengfei; Liu, Yongxia; Cheng, Jia; Liu, Yanhan; Fan, Wentao; Cheng, Ziqiang; Niu, Xudong; Liu, Jianzhu

    2016-04-27

    To obtain an effective vaccine candidate against duck Tembusu viral (DTMUV) disease which causes egg-drop and great economical loss in the Chinese duck industry, liposome vaccines containing recombinant E protein were prepared and assessed in this study. The recombinant plasmid (PET28a-E) was constructed and transformed into BL21 (DE3) cells to produce E proteins. The recombinant E proteins were purified and entrapped by liposomes through reverse-phase evaporation. Eighty-four cherry valley ducks were randomly divided into seven groups and inoculated intramuscularly at one- or seven-day-old with liposomes-E protein or Freund's adjuvant-E protein vaccine. Blood samples were collected from the first week to the tenth week for serum antibody, plasma for viremia, as well as oropharyngeal and cloacal swabs for virus shedding analyses after being challenged with a 10(2.4) 50% tissue culture infective dose (TCID50) of duck Tembusu virus. Results showed that serum antibody level of the liposomes vaccine was higher than the Freund's adjuvant vaccine, and inoculating twice was superior to once; furthermore, the viremia and virus shedding tests also proved that the liposomes vaccine can provide complete protection against DTMUV challenge. These results demonstrated that the liposomes-E protein vaccine could be used as a potential candidate vaccine to prevent DTMUV infection in ducks.

  6. Trehalose diester glycolipids are superior to the monoesters in binding to Mincle, activation of macrophages in vitro and adjuvant activity in vivo

    PubMed Central

    Huber, Alexandra; Kallerup, Rie S; Korsholm, Karen S; Franzyk, Henrik; Lepenies, Bernd; Christensen, Dennis

    2016-01-01

    The T-cell adjuvanticity of mycobacterial cord factor trehalose 6,6'-dimycolate (TDM) is well established. The identification of the C-type lectin Mincle on innate immune cells as the receptor for TDM and its synthetic analogue trehalose 6,6'-dibehenate (TDB) has raised interest in development of synthetic Mincle ligands as novel adjuvants. Trehalose mono- (TMXs) and diesters (TDXs) with symmetrically shortened acyl chains [denoted by X: arachidate (A), stearate (S), palmitate (P), and myristate (M)] were tested. Upon stimulation of murine macrophages, G-CSF secretion and NO production were strongly augmented by all TDXs tested, in a wide concentration range. In contrast, the TMXs triggered macrophage activation only at high concentrations. Macrophage activation by all TDXs required Mincle, but was independent of MyD88. The superior capacity of TDXs for activating macrophages was paralleled by direct binding of TDXs, but not of TMXs, to a Mincle-Fc fusion protein. Insertion of a short polyethylene glycol between the sugar and acyl chain in TDS reduced Mincle-binding and macrophage activation. Immunization of mice with cationic liposomes containing the analogues demonstrated the superior adjuvant activity of trehalose diesters. Overall, immune activation in vitro and in vivo by trehalose esters of simple fatty acids requires two acyl chains of length and involves Mincle. PMID:27252171

  7. Exposure to Mercury and Aluminum in Early Life: Developmental Vulnerability as a Modifying Factor in Neurologic and Immunologic Effects

    PubMed Central

    Dórea, José G.

    2015-01-01

    Currently, ethylmercury (EtHg) and adjuvant-Al are the dominating interventional exposures encountered by fetuses, newborns, and infants due to immunization with Thimerosal-containing vaccines (TCVs). Despite their long use as active agents of medicines and fungicides, the safety levels of these substances have never been determined, either for animals or for adult humans—much less for fetuses, newborns, infants, and children. I reviewed the literature for papers reporting on outcomes associated with (a) multiple exposures and metabolism of EtHg and Al during early life; (b) physiological and metabolic characteristics of newborns, neonates, and infants relevant to xenobiotic exposure and effects; (c) neurobehavioral, immunological, and inflammatory reactions to Thimerosal and Al-adjuvants resulting from TCV exposure in infancy. Immunological and neurobehavioral effects of Thimerosal-EtHg and Al-adjuvants are not extraordinary; rather, these effects are easily detected in high and low income countries, with co-exposure to methylmercury (MeHg) or other neurotoxicants. Rigorous and replicable studies (in different animal species) have shown evidence of EtHg and Al toxicities. More research attention has been given to EtHg and findings have showed a solid link with neurotoxic effects in humans; however, the potential synergic effect of both toxic agents has not been properly studied. Therefore, early life exposure to both EtHg and Al deserves due consideration. PMID:25625408

  8. A novel non-toxic combined CTA1-DD and ISCOMS adjuvant vector for effective mucosal immunization against influenza virus.

    PubMed

    Eliasson, Dubravka Grdic; Helgeby, Anja; Schön, Karin; Nygren, Caroline; El-Bakkouri, Karim; Fiers, Walter; Saelens, Xavier; Lövgren, Karin Bengtsson; Nyström, Ida; Lycke, Nils Y

    2011-05-23

    Here we demonstrate that by using non-toxic fractions of saponin combined with CTA1-DD we can achieve a safe and above all highly efficacious mucosal adjuvant vector. We optimized the construction, tested the requirements for function and evaluated proof-of-concept in an influenza A virus challenge model. We demonstrated that the CTA1-3M2e-DD/ISCOMS vector provided 100% protection against mortality and greatly reduced morbidity in the mouse model. The immunogenicity of the vector was superior to other vaccine formulations using the ISCOM or CTA1-DD adjuvants alone. The versatility of the vector was best exemplified by the many options to insert, incorporate or admix vaccine antigens with the vector. Furthermore, the CTA1-3M2e-DD/ISCOMS could be kept 1 year at 4°C or as a freeze-dried powder without affecting immunogenicity or adjuvanticity of the vector. Strong serum IgG and mucosal IgA responses were elicited and CD4 T cell responses were greatly enhanced after intranasal administration of the combined vector. Together these findings hold promise for the combined vector as a mucosal vaccine against influenza virus infections including pandemic influenza. The CTA1-DD/ISCOMS technology represents a breakthrough in mucosal vaccine vector design which successfully combines immunomodulation and targeting in a safe and stable particulate formation.

  9. Modulation of the immune response by the cholera-like enterotoxins.

    PubMed

    Plant, Andrea; Williams, Neil A

    2004-01-01

    Cholera toxins and heat labile enterotoxin from E. coli differ from most soluble proteins in eliciting systemic immunity both against themselves and unrelated admixed antigens, rather than tolerance following administration to a mucosal surface. Several reports have also demonstrated preferential induction of Th2-type responses when these molecules are used as adjuvants. Conversely, these proteins and their non-toxic derivatives, including the B sub-units are also able prevent and alleviate autoimmune diseases in naïve and systemically immune hosts demonstrating wide-ranging effects on the immune system. The recent observation that amelioration of autoimmune disease is associated with the generation of regulatory T cells which inhibit pathogenic Th1 responses may also help to consolidate these two apparently contradictory outcomes of exposure to the cholera-like enterotoxins. Furthermore, the observation that EtxB is able to alleviate autoimmune disease in the absence of conjugation to autoantigen highlights its potential for use in the clinical setting where the target antigen is often unknown. Direct effects on T cells, B cells and APC have been demonstrated in vitro which have provided insights into how these molecules may elicit these diverse effects. Further investigation is required for elucidation of the mechanisms of action of adjuvanticity and tolerance induction by these molecules to realise their potential for use in vaccines and therapies for autoimmune disease in humans.

  10. Fractionation, structural studies, and immunological characterization of the semi-synthetic Quillaja saponins derivative GPI-0100.

    PubMed

    Marciani, Dante J; Reynolds, Robert C; Pathak, Ashish K; Finley-Woodman, Kyra; May, Richard D

    2003-09-08

    Unfractionated GPI-0100 (UFGPI-0100) containing semi-synthetic derivatives of deacylated Quillaja saponins (DS saponins) modified at the glucuronic acid residue was resolved by reverse phase low-pressure liquid chromatography (RP-LPLC) into two fractions, RP18-1 and RP18-2, with different compositions and adjuvanticity. The fraction RP18-1 contained DS saponin adducts of N-dicyclohexylurea, and stimulated Th2 immunity with production of IgG1, while the RP18-2 fraction contained the dodecylamide derivatives of DS saponins and stimulated Th1 immunity with production of IgG2a, IFN-gamma, IL-2, and CTL. The strong immune stimulatory properties of RP18-2, relative to RP18-1, and the formation of RP18-1/RP18-2 mixed micelles may account for the effective stimulation of Th1 immunity by UFGPI-0100. UFGPI-0100 was free of acylated quillaja saponin components, including the more stable QS-7.

  11. Enhancement of Mucosal Immunization with Virus-Like Particles of Simian Immunodeficiency Virus

    PubMed Central

    Kang, Sang-Moo; Compans, Richard W.

    2003-01-01

    Cholera toxin (CT) is the most potent known mucosal adjuvant, but its toxicity precludes its use in humans. Here, in an attempt to develop safe and effective mucosal adjuvants, we compared immune responses to simian immunodeficiency virus (SIV) virus-like particles (VLPs) after intranasal coimmunization with RANTES, CpG oligodeoxynucleotides (ODN), or CT. Antibody analysis demonstrated that RANTES and CpG ODN had capacities for mucosal adjuvanticity, i.e., for enhancing serum and vaginal antibodies specific to SIV Env, similar to those for CT. RANTES and CpG ODN skewed serum antibodies predominantly to the immunoglobulin G2a isotype. Most importantly, RANTES and CpG ODN were more effective than CT in increasing neutralizing titers of both serum and vaginal antibodies. After intranasal coadministration with VLPs, RANTES or CpG ODN also induced increased levels of gamma interferon (IFN-γ)-producing lymphocyte and cytotoxic T-lymphocyte activities in both spleen and lymph nodes but did not increase the levels of interleukin-4-producing lymphocytes. The results suggest that RANTES and CpG ODN enhance immune responses in a T-helper-cell-type-1 (Th1)-oriented manner and that they can be used as effective mucosal adjuvants for enhancing both humoral and cellular immune responses in the context of VLPs, which are particulate antigens. PMID:12610137

  12. Immunogenic and adjuvant properties of Haemophilus ducreyi lipooligosaccharides.

    PubMed

    Lundqvist, Annika; Kubler-Kielb, Joanna; Teneberg, Susann; Ahlman, Karin; Lagergård, Teresa

    2009-03-01

    Haemophilus ducreyi, the chancroid-causing bacterium, produces lipooligosaccharides (HdLOS) that comprise 5-11 partially sialylated monosaccharides. Subcutaneous immunisation of mice with 5 microg of HdLOS purified from H. ducreyi strains 4438 and 7470 induced high levels of anti-HdLOS IgG. The antibody responses displayed T-cell-independent features, and were dependent upon Toll-like receptor 4/MyD88 signalling pathways as demonstrated using knockout mice. The immunogenicity of HdLOS was found to require the intact lipid A moiety. The specificity studies of the anti-HdLOS antibodies, as revealed by absorption studies, antibody detection in ELISA, and immune thin-layer chromatography, indicated that the majority of the anti-LOS antibodies were specific for the inner core of the HdLOS. Antibodies to HdLOS failed to inhibit LOS induction of TNF-alpha release from human mononuclear cells. The adjuvanticity of HdLOS7470 was assessed in BALB/c mice that were immunised with bovine serum albumin (BSA) with or without the addition of HdLOS. The addition of 5 microg HdLOS resulted in a 10-fold increase in the total anti-BSA IgG antibody level as estimated by ELISA. The highest increase was noted for IgG2b, which contrasted with the predominantly IgG1 subclass response to immunisation with BSA alone, indicating an immunomodulatory activity of the HdLOS.

  13. Adjuvant effect of Lactobacillus casei in a mouse model of gluten sensitivity.

    PubMed

    D'Arienzo, Rossana; Maurano, Francesco; Luongo, Diomira; Mazzarella, Giuseppe; Stefanile, Rosita; Troncone, Riccardo; Auricchio, Salvatore; Ricca, Ezio; David, Chella; Rossi, Mauro

    2008-08-15

    Probiotic strains have been reported to exert immunomodulatory activities in the gut-associated lymphoid tissue. In this study we explored the effect of Lactobacillus casei in transgenic mice expressing the human DQ8 heterodimer, a HLA molecule linked to Celiac Disease (CD). DQ8 mice, mucosally immunized with the gluten component gliadin, mounted an intestinal Th1-like response as observed in CD, without developing enteropathy. Co-administration of L. casei in sensitized mice specifically enhanced the gliadin-specific response mediated by CD4(+) T cells. Notably, both a strong increase of the gliadin-specific IFNgamma expression and a pro-inflammatory polarization of the cytokine milieu in the small intestinal mucosa were associated to the presence of the probiotic strain. However, this condition did not bring on any mucosal alteration. These findings suggest that the gliadin-specific enteropathy is not merely related to the HLA DQ8-restricted massive production of IFNgamma, but additional parameters are involved. Moreover, our data imply that the intrinsic adjuvanticity of L. casei can be exploited to further enhance both mucosal and systemic T cell-mediated responses.

  14. IL-1–induced Bhlhe40 identifies pathogenic T helper cells in a model of autoimmune neuroinflammation

    PubMed Central

    Lin, Chih-Chung; Bradstreet, Tara R.; Schwarzkopf, Elizabeth A.; Jarjour, Nicholas N.; Chou, Chun; Archambault, Angela S.; Sim, Julia; Zinselmeyer, Bernd H.; Carrero, Javier A.; Wu, Gregory F.; Taneja, Reshma; Artyomov, Maxim N.; Russell, John H.

    2016-01-01

    The features that define autoreactive T helper (Th) cell pathogenicity remain obscure. We have previously shown that Th cells require the transcription factor Bhlhe40 to mediate experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Here, using Bhlhe40 reporter mice and analyzing both polyclonal and TCR transgenic Th cells, we found that Bhlhe40 expression was heterogeneous after EAE induction, with Bhlhe40-expressing cells displaying marked production of IFN-γ, IL-17A, and granulocyte-macrophage colony-stimulating factor. In adoptive transfer EAE models, Bhlhe40-deficient Th1 and Th17 cells were both nonencephalitogenic. Pertussis toxin (PTX), a classical co-adjuvant for actively induced EAE, promoted IL-1β production by myeloid cells in the draining lymph node and served as a strong stimulus for Bhlhe40 expression in Th cells. Furthermore, PTX co-adjuvanticity was Bhlhe40 dependent. IL-1β induced Bhlhe40 expression in polarized Th17 cells, and Bhlhe40-expressing cells exhibited an encephalitogenic transcriptional signature. In vivo, IL-1R signaling was required for full Bhlhe40 expression by Th cells after immunization. Overall, we demonstrate that Bhlhe40 expression identifies encephalitogenic Th cells and defines a PTX–IL-1–Bhlhe40 pathway active in EAE. PMID:26834156

  15. Combination of TLR1/2 and TLR3 ligands enhances CD4+ T cell longevity and antibody responses by modulating type I IFN production

    PubMed Central

    Lee, Bo Ryeong; Jeong, Soo Kyung; Ahn, Byung Cheol; Lee, Byeong-Jae; Shin, Sung Jae; Yum, Jung Sun; Ha, Sang-Jun

    2016-01-01

    Despite the possibility of combining Toll-like receptor (TLR) ligands as adjuvants to improve vaccine efficacy, it remains unclear which combinations of TLR ligands are effective or what their underlying mechanisms may be. Here, we investigated the mechanism of action of L-pampo, a proprietary adjuvant composed of TLR1/2 and TLR3 ligands. L-pampo dramatically increased humoral immune responses against the tested target antigens, which was correlated with an increase in follicular helper T cells and the maintenance of antigen-specific CD4+ T cells. During the initial priming phase, in contrast to the induction of type I interferon (IFN) and pro-inflammatory cytokines stimulated by polyI:C, L-pampo showed a greatly diminished induction of type I IFN, but not of other cytokines, and remarkably attenuated IRF3 signaling, which appeared to be critical to L-pampo-mediated adjuvanticity. Collectively, our results demonstrate that the adjuvant L-pampo contributes to the promotion of antigen-specific antibodies and CD4+ T cell responses via a fine regulation of the TLR1/2 and TLR3 signaling pathways, which may be helpful in the design of improved vaccines. PMID:27580796

  16. The changing shape of vaccination: improving immune responses through geometrical variations of a microdevice for immunization

    PubMed Central

    Crichton, Michael Lawrence; Muller, David Alexander; Depelsenaire, Alexandra Christina Isobel; Pearson, Frances Elizabeth; Wei, Jonathan; Coffey, Jacob; Zhang, Jin; Fernando, Germain J. P.; Kendall, Mark Anthony Fernance

    2016-01-01

    Micro-device use for vaccination has grown in the past decade, with the promise of ease-of-use, painless application, stable solid formulations and greater immune response generation. However, the designs of the highly immunogenic devices (e.g. the gene gun, Nanopatch or laser adjuvantation) require significant energy to enter the skin (30–90 mJ). Within this study, we explore a way to more effectively use energy for skin penetration and vaccination. These modifications change the Nanopatch projections from cylindrical/conical shapes with a density of 20,000 per cm2 to flat-shaped protrusions at 8,000 per cm2, whilst maintaining the surface area and volume that is placed within the skin. We show that this design results in more efficient surface crack initiations, allowing the energy to be more efficiently be deployed through the projections into the skin, with a significant overall increase in penetration depth (50%). Furthermore, we measured a significant increase in localized skin cell death (>2 fold), and resultant infiltrate of cells (monocytes and neutrophils). Using a commercial seasonal trivalent human influenza vaccine (Fluvax 2014), our new patch design resulted in an immune response equivalent to intramuscular injection with approximately 1000 fold less dose, while also being a practical device conceptually suited to widespread vaccination. PMID:27251567

  17. The Human Pathogen Streptococcus pyogenes Releases Lipoproteins as Lipoprotein-rich Membrane Vesicles.

    PubMed

    Biagini, Massimiliano; Garibaldi, Manuela; Aprea, Susanna; Pezzicoli, Alfredo; Doro, Francesco; Becherelli, Marco; Taddei, Anna Rita; Tani, Chiara; Tavarini, Simona; Mora, Marirosa; Teti, Giuseppe; D'Oro, Ugo; Nuti, Sandra; Soriani, Marco; Margarit, Immaculada; Rappuoli, Rino; Grandi, Guido; Norais, Nathalie

    2015-08-01

    Bacterial lipoproteins are attractive vaccine candidates because they represent a major class of cell surface-exposed proteins in many bacteria and are considered as potential pathogen-associated molecular patterns sensed by Toll-like receptors with built-in adjuvanticity. Although Gram-negative lipoproteins have been extensively characterized, little is known about Gram-positive lipoproteins. We isolated from Streptococcus pyogenes a large amount of lipoproteins organized in vesicles. These vesicles were obtained by weakening the bacterial cell wall with a sublethal concentration of penicillin. Lipid and proteomic analysis of the vesicles revealed that they were enriched in phosphatidylglycerol and almost exclusively composed of lipoproteins. In association with lipoproteins, a few hypothetical proteins, penicillin-binding proteins, and several members of the ExPortal, a membrane microdomain responsible for the maturation of secreted proteins, were identified. The typical lipidic moiety was apparently not necessary for lipoprotein insertion in the vesicle bilayer because they were also recovered from the isogenic diacylglyceryl transferase deletion mutant. The vesicles were not able to activate specific Toll-like receptor 2, indicating that lipoproteins organized in these vesicular structures do not act as pathogen-associated molecular patterns. In light of these findings, we propose to name these new structures Lipoprotein-rich Membrane Vesicles. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. The changing shape of vaccination: improving immune responses through geometrical variations of a microdevice for immunization

    NASA Astrophysics Data System (ADS)

    Crichton, Michael Lawrence; Muller, David Alexander; Depelsenaire, Alexandra Christina Isobel; Pearson, Frances Elizabeth; Wei, Jonathan; Coffey, Jacob; Zhang, Jin; Fernando, Germain J. P.; Kendall, Mark Anthony Fernance

    2016-06-01

    Micro-device use for vaccination has grown in the past decade, with the promise of ease-of-use, painless application, stable solid formulations and greater immune response generation. However, the designs of the highly immunogenic devices (e.g. the gene gun, Nanopatch or laser adjuvantation) require significant energy to enter the skin (30–90 mJ). Within this study, we explore a way to more effectively use energy for skin penetration and vaccination. These modifications change the Nanopatch projections from cylindrical/conical shapes with a density of 20,000 per cm2 to flat-shaped protrusions at 8,000 per cm2, whilst maintaining the surface area and volume that is placed within the skin. We show that this design results in more efficient surface crack initiations, allowing the energy to be more efficiently be deployed through the projections into the skin, with a significant overall increase in penetration depth (50%). Furthermore, we measured a significant increase in localized skin cell death (>2 fold), and resultant infiltrate of cells (monocytes and neutrophils). Using a commercial seasonal trivalent human influenza vaccine (Fluvax 2014), our new patch design resulted in an immune response equivalent to intramuscular injection with approximately 1000 fold less dose, while also being a practical device conceptually suited to widespread vaccination.

  19. Biologically active components from mycobacterial cell walls. III. Production of experimental allergic encephalomyelitis in guinea-pigs.

    PubMed

    Meyer, T J; Azuma, I; Ribi, E E

    1975-02-01

    The efficacy of various fractions of mycobacterial cell walls in producing experimental ahlergic encephalomyelitis (EAE) has been evaluated. BCG (Bacillus-Calmette-Buérin) cell walls were effective in producing EAE in all animals at dose levels as low as 40 mug. Study of subfractions of these cell walls revealed the following: (1) wax D was active, but required larger doses than BCG cell walls; (2) the chloroform-methanol-soluble (CMS) portion of wax D and P3 (a mycolic acid-trehalose ester contained therein) were inactive; (3) the chloroform-methanol-insoluble (CMI) portion of wax D was active; (4) exhaustively delipidated cell wass skeletons of BCG, Nocardia asteroides, Mycobacterium smegmatis, Corynebacterium diphtheriae and M. kansaii were active; (5) two water-soluble adjuvants prepared from mycobacteria were active. These results suggest that the mycobacterial structure responsible for EAE adjuvanticity is present in the organic solvent-insoluble cell wall skeleton framework. The activity of wax D may be due to the presence of cell-wall skeleton constituents which are found in varying quanity in most wax D preparations. Wax D components soluble in a solution of chloroform:methanol (diluted 2:1 v/v) do not produce EAE.

  20. The potential of adjuvants to improve immune responses against TdaP vaccines: A preclinical evaluation of MF59 and monophosphoryl lipid A.

    PubMed

    Agnolon, Valentina; Bruno, Cristina; Leuzzi, Rosanna; Galletti, Bruno; D'Oro, Ugo; Pizza, Mariagrazia; Seubert, Anja; O'Hagan, Derek T; Baudner, Barbara C

    2015-08-15

    The successful approach of combining diphtheria, tetanus and pertussis antigens into a single vaccine has become a cornerstone of immunization programs. Yet, even if vaccination coverage is high, a resurgence of pertussis has been reported in many countries suggesting current vaccines may not provide adequate protection. To induce better tailored and more durable immune responses against pertussis vaccines different approaches have been proposed, including the use of novel adjuvants. Licensed aP vaccines contain aluminum salts, which mainly stimulate humoral immune responses and might not be ideal for protecting against Bordetella pertussis infection. Adjuvants inducing more balanced T-helper profiles or even Th1-prone responses might be more adequate. In this study, two adjuvants already approved for human use have been tested: MF59 emulsion and the combination of aluminum hydroxide with the Toll-Like Receptor 4 agonist MPLA. Adjuvanticity was evaluated in a mouse model using a TdaP vaccine containing three B. pertussis antigens: genetically detoxified pertussis toxin (PT-9K/129G), filamentous hemagglutinin (FHA) and pertactin (PRN) The physico-chemical compatibility of TdaP antigens with the proposed adjuvants, together with a quicker onset and changed quality of the antibody responses, fully supports the replacement of aluminum salts with a new adjuvant to enhance aP vaccines immunogenicity. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. A micro-sterile inflammation array as an adjuvant for influenza vaccines

    PubMed Central

    Ji, Wang; Shah, Dilip; Chen, Xinyuan; Anderson, R. Rox; Wu, Mei X.

    2015-01-01

    There is an urgent need of adjuvants for cutaneous vaccination. Here we report that micro-sterile inflammation induced at inoculation sites can augment immune responses to influenza vaccines in animal models. The inoculation site is briefly illuminated with a handheld, non-ablative fractional laser before the vaccine is intradermally administered, which creates an array of self-healing microthermal zones (MTZs) in the skin. The dying cells in the MTZs send “danger” signals that attract a large number of antigen-presenting cells, in particular, plasmacytoid dendritic cells (pDCs) around each MTZ forming a micro-sterile inflammation array. A pivotal role for pDCs in the adjuvanticity is ascertained by significant abrogation of the immunity after systemic depletion of pDCs, local application of a TNF-α inhibitor, or null mutation of IFN regulatory factor7 (IRF7). In contrast to conventional adjuvants that cause persistent inflammation and skin lesions, micro-sterile inflammation enhances efficacy of influenza vaccines, yet with diminished adverse effects. PMID:25033973

  2. Successful immunization with a totally synthetic diphtheria vaccine.

    PubMed Central

    Audibert, F; Jolivet, M; Chedid, L; Arnon, R; Sela, M

    1982-01-01

    Three peptides corresponding to fragments of diphtheria toxin have been synthesized. They include the previously described tetradecapeptide and two structural analogs, the hexadecapeptide and the octadecapeptide. Conjugates of these peptides to proteins or a synthetic carrier have induced in guinea pig protection against the dermonecrotic activity of diphtheria toxin. All of the conjugates were immunogenic when administered either in complete Freund's adjuvant or with N-acetylmuramyl-L-alanyl-D-isoglutamine in aqueous medium. Positive immune response toward the octadecapeptide was obtained in mice as well. In this case, the immunogenic combinations were conjugates with bovine serum albumin administered either in Freund's adjuvant or with the muramyl dipeptide and a complete synthetic conjugate comprising both the octadecapeptide and the muramyl dipeptide covalently attached to a synthetic carrier, multichain poly(DLAla). This last immunogen, which induced the most effective immune response, is a completely synthetic immunogen with built-in adjuvanticity and induces protective antitoxic immunity when administered in a physiological medium. PMID:6956913

  3. Role of Metallic Nanoparticles in Vaccinology: Implications for Infectious Disease Vaccine Development

    PubMed Central

    Marques Neto, Lázaro Moreira; Kipnis, André; Junqueira-Kipnis, Ana Paula

    2017-01-01

    Subunit vaccines are safer but less immunogenic than live-attenuated vaccines or whole cell inactivated vaccines. Adjuvants are used to enhance and modulate antigen (Ag) immunogenicity, aiming to induce a protective and long-lasting immune response. Several molecules and formulations have been studied for their adjuvanticity, but only seven have been approved to formulate human vaccines. Metallic nanoparticles (MeNPs), particularly those containing gold and iron oxides, are widely used in medicine for diagnosis and therapy and have been used as carriers for drugs and vaccines. However, little is known about the immune response elicited by MeNPs or about their importance in the development of new vaccines. There is evidence that these particles display adjuvant characteristics, promoting cell recruitment, antigen-presenting cell activation, cytokine production, and inducing a humoral immune response. This review focuses on the characteristics of MeNPs that could facilitate the induction of a cellular immune response, particularly T-helper 1 and T-helper 17, and their potential functions as adjuvants for subunit vaccines. PMID:28337198

  4. Immunogenicity of a reduced-dose whole killed rabies vaccine is significantly enhanced by ISCOMATRIX™ adjuvant, Merck amorphous aluminum hydroxylphosphate sulfate (MAA) or a synthetic TLR9 agonist in rhesus macaques.

    PubMed

    DiStefano, Daniel; Antonello, Joseph M; Bett, Andrew J; Medi, Muneeswara B; Casimiro, Danilo R; ter Meulen, Jan

    2013-10-01

    There is a need for novel rabies vaccines suitable for short course, pre- and post-exposure prophylactic regimens which require reduced doses of antigen to address the current worldwide supply issue. We evaluated in rhesus macaques the immunogenicity of a quarter-dose of a standard rabies vaccine formulated with Merck's amorphous aluminum hydroxylphosphate sulfate adjuvant, the saponin-based ISCOMATRIX™ adjuvant, or a synthetic TLR9 agonist. All adjuvants significantly increased the magnitude and durability of the humoral immune response as measured by rapid fluorescent focus inhibition test (RFFIT). Several three-dose vaccine regimens resulted in adequate neutralizing antibody of ≥ 0.5 IU/ml earlier than the critical day seven post the first dose. Rabies vaccine with ISCOMATRIX™ adjuvant given at days 0 and 3 resulted in neutralizing antibody titers which developed faster and were up to one log10 higher compared to WHO-recommended intramuscular and intradermal regimens and furthermore, passive administration of human rabies immunoglobulin did not interfere with immunogenicity of this reduced dose, short course vaccine regimen. Adjuvantation of whole-killed rabies vaccine for intramuscular injection may therefore be a viable alternative to intradermal application of non-adjuvanted vaccine for both pre- and post-exposure regimens.

  5. The Human Pathogen Streptococcus pyogenes Releases Lipoproteins as Lipoprotein-rich Membrane Vesicles*

    PubMed Central

    Biagini, Massimiliano; Garibaldi, Manuela; Aprea, Susanna; Pezzicoli, Alfredo; Doro, Francesco; Becherelli, Marco; Taddei, Anna Rita; Tani, Chiara; Tavarini, Simona; Mora, Marirosa; Teti, Giuseppe; D'Oro, Ugo; Nuti, Sandra; Soriani, Marco; Margarit, Immaculada; Rappuoli, Rino; Grandi, Guido; Norais, Nathalie

    2015-01-01

    Bacterial lipoproteins are attractive vaccine candidates because they represent a major class of cell surface-exposed proteins in many bacteria and are considered as potential pathogen-associated molecular patterns sensed by Toll-like receptors with built-in adjuvanticity. Although Gram-negative lipoproteins have been extensively characterized, little is known about Gram-positive lipoproteins. We isolated from Streptococcus pyogenes a large amount of lipoproteins organized in vesicles. These vesicles were obtained by weakening the bacterial cell wall with a sublethal concentration of penicillin. Lipid and proteomic analysis of the vesicles revealed that they were enriched in phosphatidylglycerol and almost exclusively composed of lipoproteins. In association with lipoproteins, a few hypothetical proteins, penicillin-binding proteins, and several members of the ExPortal, a membrane microdomain responsible for the maturation of secreted proteins, were identified. The typical lipidic moiety was apparently not necessary for lipoprotein insertion in the vesicle bilayer because they were also recovered from the isogenic diacylglyceryl transferase deletion mutant. The vesicles were not able to activate specific Toll-like receptor 2, indicating that lipoproteins organized in these vesicular structures do not act as pathogen-associated molecular patterns. In light of these findings, we propose to name these new structures Lipoprotein-rich Membrane Vesicles. PMID:26018414

  6. Synthesis of synthetic mannan backbone polysaccharides found on the surface of Mycobacterium tuberculosis as a vaccine adjuvant and their immunological properties.

    PubMed

    Wattanasiri, Chakree; Paha, Jiraporn; Ponpuak, Marisa; Ruchirawat, Somsak; Boonyarattanakalin, Siwarutt

    2017-11-01

    Surface components of Mycobacterium tuberculosis (Mtb) play crucial roles in modulating host immune responses. Thorough understandings of immunological properties of the Mtb's surface components are essential for the development of tuberculosis treatment and prevention. Unfortunately, the accessibility to the molecules on the surface of Mtb is limited by the structural complexity due to their various macromolecular nature and the hazard of culturing Mtb. In this study, we reveal a practical synthesis of lipomannan (LM) backbone polysaccharides - the core glycans found on Mtb's surface. A rapid synthetic approach based on a controlled polymerization was developed for the chemical synthesis of mannopyranans, the core structure of LM. The size of the LM glycans can be controlled by using specific monomer concentrations in addition to stereo- and regioselectivity derived from the versatile tricyclic orthoester mannose monomer. The immunological properties of the synthesized mannopyranans were investigated and their adjuvant potential was revealed. The adjuvanticity mechanism of the synthetic mannopyranans appears to involve the NF-κB and inflammasome pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. [Pseudomyxoma peritonei. Two-case-report].

    PubMed

    Carranza-Martínez, Ixchel; Cornejo-López, Gilberto; Monroy-Argumedo, Montserrat; Villanueva-Sáenz, Eduardo

    2014-01-01

    Antecedentes: el pseudomixoma peritoneal se caracteriza por la diseminación celular intraperitoneal de un tumor adenomucinoso; el apéndice cecal es la etiología más frecuente. Objetivo: reportar la experiencia de un grupo de Cirugía General y revisar la bibliografía. Casos clínicos: 1: paciente femenina de 74 años de edad, que cuatro días previos inició con dolor abdominal tipo cólico en el mesogastrio y fosa iliaca derecha, evacuaciones diarreicas y fiebre. A su ingreso al hospital se la encontró con datos de irritacion peritoneal y resistencia muscular, leucocitosis de 14,500 células por mm3, neutrófilos 89%, bandas 1%. Se diagnosticó: apendicitis aguda y se programó para laparoscopia diagnóstica, con distensión importante de asas, por lo que se decidió convertir a laparotomía. Caso 2: paciente masculino de 73 años de edad; el padecimiento actual se inició con dolor intermitente en la fosa iliaca derecha e hipogastrio, de un año de evolución. Al cuadro se agregaron: disnea, estreñimiento alternado con periodos de diarrea, plenitud gástrica, y pirosis. A la exploración física se encontró un tumor palpable en el mesogastrio y ambas fosas iliacas. Por eso se le realizó la laparotomía exploradora. En ambos casos el diagnóstico se estableció en el transoperatorio con el hallazgo de múltiples implantes tumorales mucinosos multilobulados diseminados en la cavidad peritoneal, el diagnóstico se confirmó con el reporte histopatológico de pseudomixoma peritoneal. Conclusiones: el pseudomixoma peritoneal es una neoplasia poco frecuente y de difícil diagnóstico, caracterizada por producción copiosa de ascitis mucinosa y de múltiples implantes tumorales en la serosa de las vísceras intracavitarias. El tratamiento ideal es la cirugía citorreductiva y la quimioterapia intraperitoneal perioperatoria o la quimioterapia postoperatoria, o ambas.

  8. [Nutritional status of patients with cancer of oral cavity].

    PubMed

    Pérez Camargo, Dana Aline; De Nicola Delfín, Luigina; Ñamendys-Silva, Silvio A; Copca Mendoza, Erika Thalia; Hernández Méndez, Margarita; Herrera Gómez, Ángel; Meneses García, Abelardo

    2013-01-01

    Introducción: El cáncer de cavidad oral ocupa el doceavo lugar a nivel mundial. El tratamiento del cáncer de cavidad oral es habitualmente cirugía seguida de radioterapia, la cual puede estar indicada sola o con quimioterapia; este tipo de terapias tienen importantes efectos secundarios funcionales sobre el estado nutricio del paciente. Objetivo: El objetivo de este trabajo es conocer el impacto de los diferentes tratamientos sobre el estado nutricional de los pacientes con cáncer de cavidad oral atendidos en el Instituto Nacional de Cancerología durante el período comprendido del 2009 al 2011. Material y métodos: Se realizó un estudio descriptivo, y retrospectivo. Se incluyeron 99 pacientes con cáncer de cavidad oral. Se registraron las siguientes variables; género, edad, tipo de tratamiento (cirugía, quimioterapia, radioterapia), complicaciones más importantes secundarias a tratamiento, pérdida de peso, índice de masa corporal (IMC) y albumina. Resultados y discusión: La prevalencia de cáncer de cavidad oral fue mayor en mujeres (58,6%); la edad promedio fue de 61,22 años. Las complicaciones secundarias al tratamiento fueron xerostomía (20%) seguida de odinofagia y mucositis (19%), la relación de pérdida de peso y sintomatología se observó en el (54%) de los pacientes, debido al tipo de alimentación previo, durante y después del tratamiento en los cuales tuvo mayor predominio el uso de papillas. Conclusión: Se observó una pérdida de peso debido a las complicaciones del tratamiento médico que afectaron el estado nutricio, por ello es importante tener un monitoreo continuo que apoye el éxito del tratamiento multidisciplinario.

  9. [Evaluation of two closed-system drug transfer device in the antineoplastic drug elaboration process].

    PubMed

    Gómez-Álvarez, Sandra; Porta-Oltra, Begoña; Hernandez-Griso, Marta; Pérez-Labaña, Francisca; Climente-Martí, Mónica

    2016-01-01

    Objetivo: evaluar el impacto del uso de dos sistemas cerrados sobre el proceso de preparación de quimioterapia parenteral, con respecto al sistema estándar, en términos de contaminación local y ambiental, y tiempos de preparación. Método: estudio observacional prospectivo. Se compararon dos proveedores distintos de sistemas cerrados, Icu Medical® y Care Fusion®, frente al sistema estándar de preparación de quimioterapia parenteral. Quince enfermeros del Servicio de Farmacia elaboraron cada uno de ellos 5 preparaciones, una siguiendo el procedimiento estándar y cuatro usando los sistemas cerrados. Para evaluar la aparición de contaminación se elaboró una solución de fluoresceína al 0,5%. Se evaluaron dos tipos de contaminación: local (en tres puntos: sistema acoplado a vial, jeringa y envase final) y ambiental (guantes y mesa de trabajo), obteniéndose el porcentaje de preparaciones contaminadas en cada uno de ellos. Se registró el tiempo empleado por cada enfermero en cada una de las preparaciones. Resultados: se elaboraron 75 preparaciones. Se produjo una reducción global de la contaminación local para los SC Icu Medical® y Care Fusion® del 24% y 74%, respectivamente. En el sistema cerrado Care Fusion® la contaminación local fue significativamente menor que en el sistema estándar en vial, jeringa y envase final; mientras que en el sistema cerrado Icu Medical® solo fue significativamente menor en la conexión al vial. Se produjo un incremento significativo del tiempo de preparación con la utilización de sistemas cerrados de los entre 23,4 y 30,5 segundos. Conclusiones: ambos sistemas cerrados han mostrado un beneficio con respecto a la utilización del sistema estándar. Sin embargo, se han visto incrementados significativamente los tiempos de preparación con ambos sistemas.

  10. [Synchronous bilateral breast cancer in a male].

    PubMed

    García-Mejido, José Antonio; Delgado-Jiménez, Carmen; Gutiérrez-Palomino, Laura; Sánchez-Sevilla, Miguel; Iglesias-Bravo, Eva; Caballero-Fernández, Virginia

    2013-01-01

    antecedentes: el cáncer de mama en el hombre es una enfermedad con baja incidencia, que se reduce aún más cuando es bilateral sincrónica. Existen pocas publicaciones en los últimos años. Objetivo: establecer pautas para el tratamiento de este cáncer, aunque sea infrecuente. Caso clínico: paciente masculino de 75 años de edad, con tumores en ambas mamas, que se le resecaron completamente con exéresis de ganglios palpables. El estudio histopatológico informó que se trataba de un carcinoma ductal infiltrante no especificado. Se indicó tratamiento adyuvante con tamoxifeno y radioterapia; en la actualidad está libre de enfermedad. Conclusiones: el carcinoma mamario bilateral sincrónico en el varón es una enfermedad poco frecuente. Su tratamiento principal es la cirugía, de ahí la importancia del diagnóstico temprano. En la mayoría de los casos se requiere quimioterapia y radioterapia adyuvante porque suelen diagnosticarse en un estadio avanzado.

  11. [Recommendations from MENSURA for selection of antimicrobial agents for susceptibility testing and criteria for the interpretation of antibiograms].

    PubMed

    2000-03-01

    This document includes the recommendations from the Spanish antibiogram committee (The MENSURA group, Mesa Española de Normalización de la Sensibilidad y Resistencia a los Antimicrobianos, under the auspices of the Sociedad Española de Quimioterapia and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica) for the selection of antimicrobials for susceptibility testing. Separate tables for each group of organism with proposed susceptibility and resistance breakpoints are updated and comparatively presented with those of other groups, such us NCCLS, CA-SFM and BSAC. The susceptibility breakpoint tends to identify the fully susceptible population, which probably lacks any specific resistance mechanism. The analysis of MIC distributions for different homogeneous populations (same species) is used to define breakpoints for susceptibility. The resistance breakpoint is based on pharmacological and clinical data obtained when the corresponding antibiotic is administered with a conventional schedule. The primary objective of the Spanish MENSURA group is to contribute to the international consensus on the establishment of breakpoints.

  12. [Pineal anlage tumor in a 8-month-old boy. The first case reported in Spanish language].

    PubMed

    Rodríguez-Velasco, Alicia; Ramírez-Reyes, Alma Griselda

    2014-01-01

    INTRODUCCIÓN: el tumor pineal anlage es una neoplasia maligna muy poco frecuente. Aunque ya ha sido informado en la literatura, aún no se encuentra listado en la última clasificación de los tumores del sistema nervioso central de la Organización Mundial de la Salud publicada en 2007. Es un tumor primario de la pineal con diferenciación neuroepitelial y ectomesenquimal. Debido a su poca frecuencia, el entendimiento de su comportamiento biológico y su tratamiento apropiado son incompletos. En una búsqueda realizada en PubMed como pineal anlage tumor solo se identificaron siete casos informados entre 1989 y 2011. CASO CLÍNICO: niño de ocho meses de edad que fue llevado a consulta por aumento progresivo del perímetro cefálico y estrabismo convergente de dos meses de evolución. Se identificó tumor pineal conformado por glia, células ganglionares, neuroepitelio pigmentado y células musculares estriadas. Se realizó derivación ventrículo-peritoneal para mitigar la hidrocefalia y resección quirúrgica completa. El paciente recibió dos cursos de quimioterapia con carboplatino, ifosfamida y mesna. Al año permanecía asintomático.

  13. Paragangliome malin orbitaire, à propos d’un cas

    PubMed Central

    Andaloussi, Idriss Benatiya; Maaroufi, Mustapha; Benzagmout, Mohammed; Harmouch, Taoufiq; Abdellaoui, Meryem; Bhallil, Salima; Tizniti, Siham; Elfaiz, Mohammed Chaoui; Amarti, Afaf; Tahri, Hicham

    2012-01-01

    Les paragangliomes sont des tumeurs neuroendocrines développées aux dépens du système nerveux parasympathique. Ils peuvent se localiser n’ importe où dans l’organisme depuis la tète et cou jusqu’au pelvis. La localisation orbitaire de cette tumeur est très rare. Nous présentons le cas d’un patient âgé de 37 ans qui présente depuis 4 mois une exophtalmie unilatérale droite, d’installation progressive, sans douleur ni baisse de l’acuité visuelle associés. L’examen général montre une tuméfaction sous le cuire chevelu, sans adénopathies locorégionales ni hépato ou splénomégalie. La tomodensitométrie retrouve un processus tumoral occupant le cadran supéro-externe de l’orbite droite, mesurant 38 mm de grand axe, envahissant la paroi supérieure et externe de l’orbite avec une importante ostéolyse. Un body scan révèle alors une métastase pulmonaire. L’examen histopathologique complétés par l’immunohistochimie, réalisé après biopsie, révèle un marquage cytoplasmique par l’anticorps anti-chromogranin, l’anticorps anti-synaptophysine et un marquage des vaisseaux par l’anticorps anti-CD31 soulignant l’architecture en zellbalen des nids tumoraux. Cet aspect est en faveur d’un paragangliome malin. Une exérèse chirurgicale incomplète suivie d’une radiothérapie adjuvante, sont alors réalisés. L’origine exacte de cette tumeur au sein de l’orbite reste très controversée. L’exophtalmie reste le principal signe révélateur. La tomodensitométrie, l’imagerie par résonnance magnétique et la scintigraphie au Metaiodobenzylguanidine radioinonisée à l’iode (MIBG-I131) permettent d’orienter le diagnostic et faire un bilan d’extension de la tumeur. Le diagnostic de certitude repose sur l’histopathologie et l’immunohistochimie. L’excision totale de la lésion est le traitement de choix pour les lésions bien délimitées. Dans les formes plus étendues le traitement repose sur l

  14. Place de la radiothérapie dans les séminomes testiculaires de stade I: à propos de 25 cas

    PubMed Central

    Aissa, Abdellah; Marnouche, Elamin; Elkacemi, Hanan; Kebdani, Tayeb; Benjaafar, Noureddine

    2016-01-01

    Notre travail se proposait de rapporter les résultats d’une étude rétrospective, descriptive, portant sur 25 séminomes testiculaires de stade I et de préciser la place de la radiothérapie dans la prise en charge de cette entité. Entre janvier 2001 et décembre 2009, 25 patients atteints d'un séminome testiculaire de stade I ont été pris en charge au service de radiothérapie de l’institut national d’oncologie de Rabat. L’orchidectomie première a été réalisée par voie inguinale. Le bilan d’extension initial comportait un dosage de bHCG totale, d’alphafoetoprotéine, et une exploration des aires ganglionnaires sus- et sous-diaphragmatiques par une tomodensitométrie. L’irradiation adjuvante a été délivrée au moyen d’un accélérateur linéaire. L'âge médian est de 33 ans (18-52 ans). La tumeur testiculaire siégeait à droite chez 16 malades et à gauche chez les 9 autres. La radiothérapie était délivrée dans les aires ganglionnaires lomboaortiques pour 18 patients, lomboaortiques et iliaques homolatérales pour les 7 autres et ceci par deux faisceaux antéropostérieurs, délivrant une dose de 20 à 25 Gy en 10 à 14 fractions. La tolérance immédiate était excellente. La durée médiane de surveillance était de 73 mois. Vingt trois patients sont actuellement vivants, en situation de rémission complète. Un patient a rechuté au niveau pulmonaire 22 mois après la fin de sa radiothérapie. Un patient a été perdu de vue. Il n’a pas été observé de toxicité à long terme, en particulier gastro-intestinale. Aucune tumeur ou pathologie hématologique secondaire n’a été rapportée. La radiothérapie prophylactique reste le traitement adjuvant de référence des séminomes de stade I. La tolérance immédiate est satisfaisante et l’augmentation du risque de cancer secondaire est négligeable par rapport au bénéfice thérapeutique. Toutefois une surveillance armée ainsi qu’une chimiothérapie adjuvante avec un

  15. Migration intra-péritonéal d'un dispositif intra utérin diagnostiqué 20 ans après l'insertion: à propos d'un cas

    PubMed Central

    Bouzouba, Wail; Alaoui, Fatime Zahra Fdili; Jayi, Sofia; Bouguern, Hakima; Melhouf, Moulay Abdelilah

    2014-01-01

    Le dispositif intra-utérin (DIU) est une des méthodes contraceptives les plus efficaces et les plus utilisé à travers le monde: environ 100 millions d'utilisatrices. La perforation reste exceptionnelle âpres la pose d'un DIU cependant c'est une des complications les plus graves. Nous rapportant le cas d'une patiente de 49 ans, notion de pose de stérilet il y a 20 ans, suivie en oncologie pour un carcinome canalaire infiltrant du sein ayant bénéficiée d'un patey puis chimiothérapie adjuvante actuellement sous hormonothérapie, qui dans le cadre du bilan d'extension, un scanner thoraco-abdomino-pelvienne a objectivé la présence d'un DIU en sous hépatique. Sous guidage coelioscopique, on a réussie à retirer le DIU qui était enchâssé dans l’épiploon au niveau de la gouttière pariéto-colique droite. Nous insistons à travers cette observation et sous la lumière de la revue de la littérature sur l'efficacité et l'innocuité du DIU lorsque la technique et les indications sont rigoureusement respectées, mais aussi sur une des complications rarissime de la pose du DIU, et à mettre en évidence le rôle diagnostic et thérapeutique de la cœlioscopie dans la prise en charge de ces migrations. PMID:25184024

  16. Differential outcome of TRIF-mediated signaling in TLR4 and TLR3 induced DC maturation.

    PubMed

    Hu, Wei; Jain, Aakanksha; Gao, Yajing; Dozmorov, Igor M; Mandraju, Rajakumar; Wakeland, Edward K; Pasare, Chandrashekhar

    2015-11-10

    Recognition of pathogen-associated molecular patterns by Toll-like receptors (TLRs) on dendritic cells (DCs) leads to DC maturation, a process involving up-regulation of MHC and costimulatory molecules and secretion of proinflammatory cytokines. All TLRs except TLR3 achieve these outcomes by using the signaling adaptor myeloid differentiation factor 88. TLR4 and TLR3 can both use the Toll-IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF)-dependent signaling pathway leading to IFN regulatory factor 3 (IRF3) activation and induction of IFN-β and -α4. The TRIF signaling pathway, downstream of both of these TLRs, also leads to DC maturation, and it has been proposed that the type I IFNs act in cis to induce DC maturation and subsequent effects on adaptive immunity. The present study was designed to understand the molecular mechanisms of TRIF-mediated DC maturation. We have discovered that TLR4-TRIF-induced DC maturation was independent of both IRF3 and type I IFNs. In contrast, TLR3-mediated DC maturation was completely dependent on type I IFN feedback. We found that differential activation of mitogen-activated protein kinases by the TLR4- and TLR3-TRIF axes determined the type I IFN dependency for DC maturation. In addition, we found that the adjuvanticity of LPS to induce T-cell activation is completely independent of type I IFNs. The important distinction between the TRIF-mediated signaling pathways of TLR4 and TLR3 discovered here could have a major impact in the design of future adjuvants that target this pathway.

  17. Characterization and optimization of the glucan particle-based vaccine platform.

    PubMed

    Huang, Haibin; Ostroff, Gary R; Lee, Chrono K; Specht, Charles A; Levitz, Stuart M

    2013-10-01

    Glucan particles (GPs) are hollow porous Saccharomyces cerevisiae cell walls that are treated so that they are composed primarily of β-1,3-d-glucans. Our previous studies showed that GPs can serve as an effective vaccine platform. Here, we characterize CD4(+) T-cell and antibody responses in immunized mice as a function of antigen (ovalbumin) encapsulation, antigen dose, particle numbers, time, immunization schedule, and trapping methods. Although we found that GPs served as an effective adjuvant when admixed with free antigens for IgG1 antibody production, stronger CD4(+) T-cell and IgG2c antibody responses were stimulated when antigens were encapsulated inside GPs, suggesting that the GP platform acts as both an adjuvant and a delivery system. Vigorous T-cell and antibody responses were stimulated even at submicrogram antigen doses, as long as the number of GPs was kept at 5 × 10(7) particles per immunization. One prime and one boost were sufficient to elicit robust immune responses. In addition, strong antigen-specific antibody and T-cell responses prevailed up to 20 months following the last immunization, including those of gamma interferon (IFN-γ), interleukin 17A (IL-17A), and dual IFN-γ/IL-17A-secreting CD4(+) T cells. Finally, robust immune responses were observed using generally recognized as safe (GRAS) materials (alginate and calcium, with or without chitosan) to trap antigens within GPs. Thus, these studies demonstrate that antigens encapsulated into GPs make an effective vaccine platform that combines adjuvanticity and antigen delivery to elicit strong durable immune responses at relatively low antigen doses using translationally relevant formulations.

  18. TLR7/8 adjuvant overcomes newborn hyporesponsiveness to pneumococcal conjugate vaccine at birth

    PubMed Central

    Dowling, David J.; van Haren, Simon D.; Scheid, Annette; Bergelson, Ilana; Kim, Dhohyung; Mancuso, Christy J.; Foppen, Willemina; Fresh, Lynn; Theriot, Terese B.; Lackner, Andrew A.; Fichorova, Raina N.; Smirnov, Dmitri; Vasilakos, John P.; Beaurline, Joe M.; Tomai, Mark A.; Midkiff, Cecily C.; Alvarez, Xavier; Blanchard, James L.; Gilbert, Margaret H.; Aye, Pyone Pyone

    2017-01-01

    Infection is the most common cause of mortality in early life, and immunization is the most promising biomedical intervention to reduce this burden. However, newborns fail to respond optimally to most vaccines. Adjuvantation is a key approach to enhancing vaccine immunogenicity, but responses of human newborn leukocytes to most candidate adjuvants, including most TLR agonists, are functionally distinct. Herein, we demonstrate that 3M-052 is a locally acting lipidated imidazoquinoline TLR7/8 agonist adjuvant in mice, which, when properly formulated, can induce robust Th1 cytokine production by human newborn leukocytes in vitro, both alone and in synergy with the alum-adjuvanted pneumococcal conjugate vaccine 13 (PCV13). When admixed with PCV13 and administered i.m. on the first day of life to rhesus macaques, 3M-052 dramatically enhanced generation of Th1 CRM-197–specific neonatal CD4+ cells, activation of newborn and infant Streptococcus pneumoniae polysaccharide–specific (PnPS-specific) B cells as well as serotype-specific antibody titers, and opsonophagocytic killing. Remarkably, a single dose at birth of PCV13 plus 0.1 mg/kg 3M-052 induced PnPS-specific IgG responses that were approximately 10–100 times greater than a single birth dose of PCV13 alone, rapidly exceeding the serologic correlate of protection, as early as 28 days of life. This potent immunization strategy, potentially effective with one birth dose, could represent a new paradigm in early life vaccine development. PMID:28352660

  19. Intranasal Immunization Using Mannatide as a Novel Adjuvant for an Inactivated Influenza Vaccine and Its Adjuvant Effect Compared with MF59

    PubMed Central

    Sun, Li-Juan; Guo, Xue; Tian, Tian; Zhang, Jian; Guo, Qi-Yuan; Li, Xue; Guo, Li-Jun; Che, Jin; Wang, Bing; Zhang, Hui

    2017-01-01

    Intranasal vaccination is more potent than parenteral injection for the prevention of influenza. However, because the poor efficiency of antigen uptake across the nasal mucosa is a key issue, immunostimulatory adjuvants are essential for intranasal vaccines. The immunomodulator mannatide or polyactin (PA) has been used for the clinical treatment of impaired immunity in China, but its adjuvant effect on an inactivated trivalent influenza vaccine (ITIV) via intranasal vaccination is unclear. To explore the adjuvant effect of PA, an inactivated trivalent influenza virus with or without PA or MF59 was instilled intranasally once a week in BALB/c mice. Humoral immunity was assessed by both the ELISA and hemagglutination inhibition (HI) methods using antigen-specific antibodies. Splenic lymphocyte proliferation and the IFN-γ level were measured to evaluate cell-mediated immunity. The post-vaccination serum HI antibody geometric mean titers (GMTs) for the H1N1 and H3N2 strains, antigen-specific serum IgG and IgA GMTs, mucosal SIgA GMT, splenic lymphocyte proliferation, and IFN-γ were significantly increased in the high-dose PA-adjuvanted vaccine group. The seroconversion rate and the mucosal response for the H3N2 strain were significantly elevated after high-dose PA administration. These adjuvant effects of high-dose PA for the influenza vaccine were comparable with those of the MF59 adjuvant, and abnormal signs or pathological changes were not found in the evaluated organs. In conclusion, PA is a novel mucosal adjuvant for intranasal vaccination with the ITIV that has safe and effective mucosal adjuvanticity in mice and successfully induces both serum and mucosal antibody responses and a cell-mediated response. PMID:28052136

  20. TLR2-dependent modulation of dendritic cells by LT-IIa-B5, a novel mucosal adjuvant derived from a type II heat-labile enterotoxin

    PubMed Central

    Lee, Chang Hoon; Masso-Welch, Patricia; Hajishengallis, George; Connell, Terry D.

    2011-01-01

    A host of human pathogens invades the body at mucosal surfaces. Yet, strong, protective mucosal immune responses directed against those pathogens routinely cannot be induced without the use of adjuvants. Although the strongest mucosal adjuvants are members of the family of HLTs, the inherent toxicities of HLT holotoxins preclude their clinical use. Herein, it is shown that LT-IIa-B5 enhances mucosal immune responses by modulating activities of DCs. i.n. immunization of mice with OVA in the presence of LT-IIa-B5 recruited DCs to the NALT and significantly increased uptake of OVA by those DCs. Furthermore, LT-IIa-B5 increased expression of CCR7 by DCs, which mediated enhanced migration of the cells from the NALT to the draining CLNs. LT-IIa-B5 also enhanced maturation of DCs, as revealed by increased surface expression of CD40, CD80, and CD86. Ag-specific CD4+ T cell proliferation was augmented in the CLNs of mice that had received i.n. LT-IIa-B5. Finally, when used as an i.n. adjuvant, LT-IIa-B5 dramatically increased the levels of OVA-specific salivary IgA and OVA-specific serum IgG. Strikingly, each of the activities induced by LT-IIa-B5 was strictly TLR2-dependent. The data strongly suggest that the immunomodulatory properties of LT-IIa-B5 depend on the productive modulation of mucosal DCs. Notably, this is the first report for any HLT to demonstrate in vivo the elicitation of strong, TLR2-dependent modulatory effects on DCs with respect to adjuvanticity. PMID:21791597

  1. Local application of bacteria improves safety of Salmonella-mediated tumor therapy and retains advantages of systemic infection

    PubMed Central

    Schauer, Tim; Frahm, Michael; Heise, Ulrike; Zimmermann, Kurt; Erhardt, Marc; Weiss, Siegfried

    2017-01-01

    Cancer is a devastating disease and a large socio-economic burden. Novel therapeutic solutions are on the rise, although a cure remains elusive. Application of microorganisms represents an ancient therapeutic strategy, lately revoked and refined via simultaneous attenuation and amelioration of pathogenic properties. Salmonella Typhimurium has prevailed in preclinical development. Yet, using virulent strains for systemic treatment might cause severe side effects. In the present study, we highlight a modified strain based on Salmonella Typhimurium UK-1 expressing hexa-acylated Lipid A. We corroborate improved anti-tumor properties of this strain and investigate to which extent an intra-tumoral (i.t.) route of infection could help improve safety and retain advantages of systemic intravenous (i.v.) application. Our results show that i.t. infection exhibits therapeutic efficacy against CT26 and F1.A11 tumors similar to a systemic route of inoculation. Moreover, i.t. application allows extensive dose titration without compromising tumor colonization. Adverse colonization of healthy organs was generally reduced via i.t. infection and accompanied by less body weight loss of the murine host. Despite local application, adjuvanticity remained, and a CT26-specific CD8+ T cell response was effectively stimulated. Most interestingly, also secondary tumors could be targeted with this strategy, thereby extending the unique tumor targeting ability of Salmonella. The i.t. route of inoculation may reap the benefits of systemic infection and aid in safety assurance while directing potency of an oncolytic vector to where it is most needed, namely the primary tumor. PMID:28637010

  2. From Stock Bottle to Vaccine: Elucidating the Particle Size Distributions of Aluminum Adjuvants Using Dynamic Light Scattering.

    PubMed

    Shardlow, Emma; Mold, Matthew; Exley, Christopher

    2016-01-01

    The physicochemical properties of aluminum salts are key determinants of their resultant adjuvanticity in vivo when administered as part of a vaccine. While there are links between particle size and the efficacy of the immune response, the limited literature directly characterizing the PSD of aluminum adjuvants has stymied the elucidation of such a relationship for these materials. Hence, this comparative study was undertaken to monitor the PSD of aluminum adjuvants throughout the process of vaccine formulation using DLS. A significant proportion of the stock suspensions was highly agglomerated (>9 μm) and Alhydrogel® exhibited the smallest median size (2677 ± 120 nm) in comparison to Adju-Phos® or Imject alum® (7152 ± 308 and 7294 ± 146 nm respectively) despite its large polydispersity index (PDI). Dilution of these materials induced some degree of disaggregation within all samples with Adju-Phos® being the most significantly affected. The presence of BSA caused the median size of Alhydrogel® to increase but these trends were not evident when model vaccines were formulated with either Adju-Phos® or Imject alum®. Nevertheless, Alhydrogel® and Adju-Phos® exhibited comparable median sizes in the presence of this protein (4194 ± 466 and 4850 ± 501 nm respectively) with Imject alum® being considerably smaller (2155 ± 485 nm). These results suggest that the PSD of aluminum adjuvants is greatly influenced by dilution and the degree of protein adsorption experienced within the vaccine itself. The size of the resultant antigen-adjuvant complex may be important for its immunological recognition and subsequent clearance from the injection site.

  3. From Stock Bottle to Vaccine: Elucidating the Particle Size Distributions of Aluminum Adjuvants Using Dynamic Light Scattering

    PubMed Central

    Shardlow, Emma; Mold, Matthew; Exley, Christopher

    2017-01-01

    The physicochemical properties of aluminum salts are key determinants of their resultant adjuvanticity in vivo when administered as part of a vaccine. While there are links between particle size and the efficacy of the immune response, the limited literature directly characterizing the PSD of aluminum adjuvants has stymied the elucidation of such a relationship for these materials. Hence, this comparative study was undertaken to monitor the PSD of aluminum adjuvants throughout the process of vaccine formulation using DLS. A significant proportion of the stock suspensions was highly agglomerated (>9 μm) and Alhydrogel® exhibited the smallest median size (2677 ± 120 nm) in comparison to Adju-Phos® or Imject alum® (7152 ± 308 and 7294 ± 146 nm respectively) despite its large polydispersity index (PDI). Dilution of these materials induced some degree of disaggregation within all samples with Adju-Phos® being the most significantly affected. The presence of BSA caused the median size of Alhydrogel® to increase but these trends were not evident when model vaccines were formulated with either Adju-Phos® or Imject alum®. Nevertheless, Alhydrogel® and Adju-Phos® exhibited comparable median sizes in the presence of this protein (4194 ± 466 and 4850 ± 501 nm respectively) with Imject alum® being considerably smaller (2155 ± 485 nm). These results suggest that the PSD of aluminum adjuvants is greatly influenced by dilution and the degree of protein adsorption experienced within the vaccine itself. The size of the resultant antigen-adjuvant complex may be important for its immunological recognition and subsequent clearance from the injection site. PMID:28119911

  4. Amyloidosis and the serum amyloid A protein response to muramyl dipeptide analogs and different mycobacterial species.

    PubMed Central

    McAdam, K P; Foss, N T; Garcia, C; DeLellis, R; Chedid, L; Rees, R J; Wolff, S M

    1983-01-01

    Serum amyloid A protein (SAA) elevation accompanies induction of secondary amyloidosis in mice given Mycobacterium butyricum in Freund adjuvant. The synthesis of SAA by cultured hepatocytes is induced by a macrophage-derived mediator, which has been identified as interleukin 1. In these studies, SAA synthesis has been used as an index of macrophage activation to examine the in vivo response of mice to challenge with seven different mycobacteria and with synthetic analogs of the immunoadjuvant N-acetylmuramyl-L-alanyl-D-isoglutamine [MDP(L-D)]. SAA synthesis was stimulated by administration (by the intraperitoneal route) of the mycobacteria dissolved in saline, with Mycobacterium vaccae being the most active and Mycobacterium leprae being the least stimulatory. MDP(L-D), which is the minimal structure (molecular weight, 492) able to substitute for mycobacteria in Freund adjuvant, stimulated SAA synthesis, whereas the MDP(D-D) isomer was inactive. The butyl ester of MDP, which induces no detectable pyrogenicity but retains adjuvanticity, required a 100-fold greater dosage than MDP(L-D) in stimulating SAA synthesis. Amyloidosis was detected histologically only when active SAA inducers MDP(L-D), M. vaccae, and M. butyricum, were administered in incomplete Freund adjuvant, with amyloid-enhancing factor. These studies demonstrated that SAA elevation was a sensitive in vivo marker of the capacity of antigens to stimulate macrophages to produce interleukin 1. A point of considerable relevance to the human use of MDP was the observation that repeated injections of the adjuvant MDP in saline did not induce secondary amyloidosis. PMID:6601620

  5. Low-dose Thimerosal in pediatric vaccines: Adverse effects in perspective.

    PubMed

    Dórea, José G

    2017-01-01

    Vaccines are prophylactics used as the first line of intervention to prevent, control and eradicate infectious diseases. Young children (before the age of six months) are the demographic group most exposed to recommended/mandatory vaccines preserved with Thimerosal and its metabolite ethylmercury (EtHg). Particularly in the less-developed countries, newborns, neonates, and young children are exposed to EtHg because it is still in several of their pediatric vaccines and mothers are often immunized with Thimerosal-containing vaccines (TCVs) during pregnancy. While the immunogenic component of the product has undergone more rigorous testing, Thimerosal, known to have neurotoxic effects even at low doses, has not been scrutinized for the limit of tolerance alone or in combination with adjuvant-Al during immaturity or developmental periods (pregnant women, newborns, infants, and young children). Scientific evidence has shown the potential hazards of Thimerosal in experiments that modeled vaccine-EtHg concentrations. Observational population studies have revealed uncertainties related to neurological effects. However, consistently, they showed a link of EtHg with risk of certain neurodevelopment disorders, such as tic disorder, while clearly revealing the benefits of removing Thimerosal from children's vaccines (associated with immunological reactions) in developed countries. So far, only rich countries have benefited from withdrawing the risk of exposing young children to EtHg. Regarding Thimerosal administered to the very young, we have sufficient studies that characterize a state of uncertainty: the collective evidence strongly suggests that Thimerosal exposure is associated with adverse neurodevelopmental outcomes. It is claimed that the continued use of Thimerosal in the less-developed countries is due to the cost to change to another preservative, such as 2-phenoxyethanol. However, the estimated cost increase per child in the first year of life is lower than

  6. Liposomal SLA co-incorporated with PO CpG ODNs or PS CpG ODNs induce the same protection against the murine model of leishmaniasis.

    PubMed

    Shargh, Vahid Heravi; Jaafari, Mahmoud Reza; Khamesipour, Ali; Jaafari, Iman; Jalali, Seyed Amir; Abbasi, Azam; Badiee, Ali

    2012-06-06

    First generation Leishmania vaccines consisting of whole killed parasites with or without adjuvants have reached phase 3 trial and failed to show enough efficacy mainly due to the lack of an appropriate adjuvant. In this study, the nuclease-resistant phosphorothioate CpG oligodeoxynucleotides (PS CpG) or nuclease-sensitive phosphodiester CpG ODNs (PO CpG) were used as adjuvants to enhance immunogenicity and rate of protection against leishmaniasis. Due to the susceptibility of PO CpG to nuclease degradation, an efficient liposomal delivery system was developed to protect them from degradation. 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) as a cationic lipid was used because of its unique adjuvanticity and electrostatic interaction with negatively charged CpG ODNs. To evaluate the role of liposomal formulation in protection rate and enhanced immune response, BALB/c mice were immunized subcutaneously with liposomal soluble Leishmania antigens (SLA) co-incorporated with PO CpG (Lip-SLA-PO CpG), Lip-SLA-PS CpG, SLA+PO CpG, SLA+PS CpG, SLA or buffer. As criteria for protection, footpad swelling at the site of challenge, parasite loads, the levels of IFN-γ and IL-4, and the IgG subtypes were evaluated. The groups of mice receiving Lip-SLA-PO CpG or Lip-SLA-PS CpG showed a high protection rate compared with the control groups. In addition, there was no significant difference in immune response generation between mice immunized with PS CpG and the group receiving PO CpG when incorporated into the liposomes. The results suggested that liposomal form of PO CpG might be used instead of PS CpG in future vaccine formulations as an efficient adjuvant.

  7. Enhanced humoral and cellular immune responses after sublingual immunization against human papillomavirus 16 L1 protein with adjuvants.

    PubMed

    Cho, Hee-Jeong; Kim, Ji-Yeon; Lee, Young; Kim, Jung Mogg; Kim, Young Bong; Chun, Taehoon; Oh, Yu-Kyoung

    2010-03-19

    Needle-free nonparenteral vaccines offer a number of practical advantages, especially in developing countries. To address the effects of vaccine administration route, we tested mucosal and systemic immune responses against human papillomavirus 16 L1(HPV16L1) protein using intranasal, intravaginal, transdermal, sublingual (SL) and intramuscular routes. The SL route provided the most effective mucosal secretory IgA (sIgA) and serum IgG responses. After a 150 microg antigen dose via the SL route, saliva sIgA levels were 7.2- and 5.8-fold higher than those achieved via intravaginal and transdermal routes, respectively. Notably, SL administration even produced 4.6-fold higher levels of vaginal sIgA levels than did intravaginal delivery of 150 microg antigen. To enhance the immunogenicity of SL vaccines, we tested the adjuvanticity of nine molecules: three toll-like receptor agonists, three nucleotide-binding oligomerization-domain agonists, vitamin D3, poly-gamma-glutamic acid and cholera toxin subunit B (CTB). Among the molecules tested, CTB provided the most enhanced mucosal sIgA and systemic IgG induction. SL-applied CTB enhanced the production of interleukin-4 and interferon-gamma from stimulated CD4+ T cells. Moreover, interferon-gamma-producing CD8+ T cell responses were increased 1.7-fold after co-treatment with SL CTB and HPV16L1. These results suggest the potential of the SL route for delivery of HPV16L1 vaccines using CTB as an adjuvant.

  8. Is fucose the answer to the immunomodulatory paradox of Quillaja saponins?

    PubMed

    Marciani, Dante J

    2015-12-01

    Quillaja saponins, e.g. QS-21, are immunomodulating aldehyde-carrying triterpene glycosides, which depending on the acylation state of their single fucosyl residue (Fucp) induce either Th1/Th2 or Th2 immunity. Indeed, their changes in immunomodulation or adjuvanticity from Th1/Th2 to sole Th2 immunity, correlate with the presence of acylated and de-acylated Fucp residues, respectively. Thus, it is possible to infer that the single Fucp residue is responsible for the Th2 immunity biasing induced by de-acylated Q. saponins (QT-0101). That removal of the fucosylated oligosaccharide from de-acylated Q. saponins results once more in the induction of Th1/Th2 immunity supports the Fucp role in polarizing the response toward Th2 immunity. From structural and functional analogies with the helminths' fucosylated glycans, it is possible to infer that these saponins' Fucp must bind to the lectin DC-SIGN on dendritic cells (DC). This binding to DC-SIGN, a C-type lectin that shows significant pliability in its binding interactions, must result in polarization toward Th2 while inhibiting Th1 immunity. Apparently, acylation of the Fucp by large fatty acids sterically hinders this sugar from binding to DC-SIGN, preventing a biasing to Th2 immunity. Evidently, de-acylation of Q. saponins may negatively affect vaccines requiring Th1 immunity for immune protection, particularly those against pathogens that use DC-SIGN to infect DCs and modulate Th2 immunity. However, it could be valuable in vaccines that require a sole Th2 immunity, like those against proteinopathies, e.g. Alzheimer's disease. Hence, it would valuable to elucidate the possible interactions between DC-SIGN and the QT-0101 immunomodulator. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Recombinant outer membrane vesicles carrying Chlamydia muridarum HtrA induce antibodies that neutralize chlamydial infection in vitro.

    PubMed

    Bartolini, Erika; Ianni, Elvira; Frigimelica, Elisabetta; Petracca, Roberto; Galli, Giuliano; Berlanda Scorza, Francesco; Norais, Nathalie; Laera, Donatello; Giusti, Fabiola; Pierleoni, Andrea; Donati, Manuela; Cevenini, Roberto; Finco, Oretta; Grandi, Guido; Grifantini, Renata

    2013-01-01

    Outer membrane vesicles (OMVs) are spheroid particles released by all Gram-negative bacteria as a result of the budding out of the outer membrane. Since they carry many of the bacterial surface-associated proteins and feature a potent built-in adjuvanticity, OMVs are being utilized as vaccines, some of which commercially available. Recently, methods for manipulating the protein content of OMVs have been proposed, thus making OMVs a promising platform for recombinant, multivalent vaccines development. Chlamydia muridarum DO serine protease HtrA, an antigen which stimulates strong humoral and cellular responses in mice and humans, was expressed in Escherichia coli fused to the OmpA leader sequence to deliver it to the OMV compartment. Purified OMVs carrying HtrA (CM rHtrA-OMV) were analyzed for their capacity to induce antibodies capable of neutralizing Chlamydia infection of LLC-MK2 cells in vitro. CM rHtrA-OMV immunization in mice induced antibodies that neutralize Chlamydial invasion as judged by an in vitro infectivity assay. This was remarkably different from what observed with an enzymatically functional recombinant HtrA expressed in, and purified from the E. coli cytoplasm (CM rHtrA). The difference in functionality between anti-CM rHtrA and anti-CM rHtrA-OMV antibodies was associated to a different pattern of protein epitopes recognition. The epitope recognition profile of anti-CM HtrA-OMV antibodies was similar to that induced in mice during Chlamydial infection. When expressed in OMVs HtrA appears to assume a conformation similar to the native one and this results in the elicitation of functional immune responses. These data further support the potentiality of OMVs as vaccine platform.

  10. Recombinant outer membrane vesicles carrying Chlamydia muridarum HtrA induce antibodies that neutralize chlamydial infection in vitro

    PubMed Central

    Bartolini, Erika; Ianni, Elvira; Frigimelica, Elisabetta; Petracca, Roberto; Galli, Giuliano; Berlanda Scorza, Francesco; Norais, Nathalie; Laera, Donatello; Giusti, Fabiola; Pierleoni, Andrea; Donati, Manuela; Cevenini, Roberto; Finco, Oretta; Grandi, Guido; Grifantini, Renata

    2013-01-01

    Background Outer membrane vesicles (OMVs) are spheroid particles released by all Gram-negative bacteria as a result of the budding out of the outer membrane. Since they carry many of the bacterial surface-associated proteins and feature a potent built-in adjuvanticity, OMVs are being utilized as vaccines, some of which commercially available. Recently, methods for manipulating the protein content of OMVs have been proposed, thus making OMVs a promising platform for recombinant, multivalent vaccines development. Methods Chlamydia muridarum DO serine protease HtrA, an antigen which stimulates strong humoral and cellular responses in mice and humans, was expressed in Escherichia coli fused to the OmpA leader sequence to deliver it to the OMV compartment. Purified OMVs carrying HtrA (CM rHtrA-OMV) were analyzed for their capacity to induce antibodies capable of neutralizing Chlamydia infection of LLC-MK2 cells in vitro. Results CM rHtrA-OMV immunization in mice induced antibodies that neutralize Chlamydial invasion as judged by an in vitro infectivity assay. This was remarkably different from what observed with an enzymatically functional recombinant HtrA expressed in, and purified from the E. coli cytoplasm (CM rHtrA). The difference in functionality between anti-CM rHtrA and anti-CM rHtrA-OMV antibodies was associated to a different pattern of protein epitopes recognition. The epitope recognition profile of anti-CM HtrA-OMV antibodies was similar to that induced in mice during Chlamydial infection. Conclusions When expressed in OMVs HtrA appears to assume a conformation similar to the native one and this results in the elicitation of functional immune responses. These data further support the potentiality of OMVs as vaccine platform. PMID:24009891

  11. Genetic conjugation of components in two pneumococcal fusion protein vaccines enhances paediatric mucosal immune responses.

    PubMed

    Pope, Caroline; Oliver, Elizabeth H; Ma, Jiangtao; Langton Hewer, Claire; Mitchell, Tim J; Finn, Adam

    2015-03-30

    Streptococcus pneumoniae colonises the upper respiratory tract and can cause pneumonia, meningitis and otitis media. Existing pneumococcal conjugate vaccines are expensive to produce and only protect against 13 of the 90+ pneumococcal serotypes; hence there is an urgent need for the development of new vaccines. We have shown previously in mice that pneumolysin (Ply) and a non-toxic variant (Δ6Ply) enhance antibody responses when genetically fused to pneumococcal surface adhesin A (PsaA), a potentially valuable effect for future vaccines. We investigated this adjuvanticity in human paediatric mucosal primary immune cell cultures. Adenoidal mononuclear cells (AMNC) from children aged 0-15 years (n=46) were stimulated with conjugated, admixed or individual proteins, cell viability and CD4+ T-cell proliferative responses were assessed using flow cytometry and cytokine secretion was measured using multiplex technology. Proliferation of CD4+ T-cells in response to PsaAPly, was significantly higher than responses to individual or admixed proteins (p=0.002). In contrast, an enhanced response to PsaAΔ6Ply compared to individual or admixed proteins only occurred at higher concentrations (p<0.01). Evaluation of cytotoxicity suggested that responses occurred when Ply-induced cytolysis was inhibited, either by fusion or mutation, but importantly an additional toxicity independent immune enhancing effect was also apparent as a result of fusion. Responses were MHC class II dependent and had a Th1/Th17 profile. Genetic fusion of Δ6Ply to PsaA significantly modulates and enhances pro-inflammatory CD4+ T-cell responses without the cytolytic effects of some other pneumolysoids. Membrane binding activity of such proteins may confer valuable adjuvant properties as fusion may assist Δ6Ply to deliver PsaA to the APC surface effectively, contributing to the initiation of anti-pneumococcal CD4+ T-cell immunity.

  12. Gene expression profiles identify both MyD88-independent and MyD88-dependent pathways involved in the maturation of dendritic cells mediated by heparan sulfate: A novel adjuvant

    PubMed Central

    Wu, Meini; Wang, Haixuan; Shi, Jiandong; Sun, Jing; Duan, Zhiqing; Li, Yanhan; Li, Jianfang; Hu, Ningzhu; Wei, Yiju; Chen, Yang; Hu, Yunzhang

    2015-01-01

    The traditional vaccine adjuvant research is mainly based on the trial and error method, and the mechanisms underlying the immune system stimulation remaining largely unknown. We previously demonstrated that heparan sulfate (HS), a TLR-4 ligand and endogenous danger signal, effectively enhanced humoral and cellular immune responses in mice immunized by HBsAg. This study aimed to evaluate whether HS induces better humoral immune responses against inactivated Hepatitis A or Rabies Vaccines, respectively, compared with traditional adjuvants (e.g. Alum and complete Freund's adjuvant). In order to investigate the molecular mechanisms of its adjuvanticity, the gene expression pattern of peripheral blood monocytes derived DCs (dendritic cells) stimulated with HS was analyzed at different times points. Total RNA was hybridized to Agilent SurePrint G3 Human Gene Expression 8 × 60 K one-color oligo-microarray. Through intersection analysis of the microarray results, we found that the Toll-like receptor signaling pathway was significantly activated, and NF-kB, TRAF3 and IRF7 were activated as early as 12 h, and MyD88 was activated at 48 h post-stimulation. Furthermore, the expression of the surface marker CD83 and the co-stimulatory molecules CD80 and CD86 was up-regulated as early as 24 h. Therefore, we speculated that HS-induced human monocyte-derived DC maturation may occur through both MyD88-independent and dependent pathways, but primarily through the former (TRIF pathway). These data provide an important basis for understanding the mechanisms underlying HS enhancement of the immune response. PMID:25668674

  13. Differential Adjuvant Activities of TLR7 and TLR9 Agonists Inversely Correlate with Nitric Oxide and PGE2 Production

    PubMed Central

    Lee, Jinhee; Martinez, Nuria; West, Kim; Kornfeld, Hardy

    2015-01-01

    Activation of different pattern recognition receptors causes distinct profiles of innate immune responses, which in turn dictate the adaptive immune response. We found that mice had higher CD4+ T cell expansion to an immunogen, ovalbumin, when coadministered with CpG than with CL097 in vivo. To account for this differential adjuvanticity, we assessed the activities of CpG and CL097 on antigen-specific CD4+ T cell expansion in vitro using an OT-II CD4+ T cell/bone marrow-derived dendritic cell (DC) co-culture system. Unexpectedly, ovalbumin-stimulated expansion of OT-II CD4+ T cells in vitro was potently suppressed by both TLR agonists, with CL097 being stronger than CpG. The suppression was synergistically reversed by co-inhibition of cyclooxygenases 1 and 2, and inducible nitric oxide (NO) synthase. In addition, stimulation of OT-II CD4+ T cell/DC cultures with CL097 induced higher levels of CD4+ T cell death than stimulation with CpG, and this CD4+ T cell turnover was reversed by NO and PGE2 inhibition. Consistently, the co-cultures stimulated with CL097 produced higher levels of prostaglandin E2 (PGE2) and NO than stimulation with CpG. CL097 induced higher PGE2 production in DC cultures and higher IFN-γ in the OT-II CD4+ T cell/DC cultures, accounting for the high levels of PGE2 and NO. This study demonstrates that the adjuvant activities of immunostimulatory molecules may be determined by differential induction of negative regulators, including NO and PGE2 suppressing clonal expansion and promoting cell death of CD4+ T cells. PMID:25875128

  14. Lactococcus lactis as an adjuvant and delivery vehicle of antigens against pneumococcal respiratory infections.

    PubMed

    Medina, Marcela; Vintiñi, Elisa; Villena, Julio; Raya, Raul; Alvarez, Susana

    2010-01-01

    Most studies of Lactococcus lactis as delivery vehicles of pneumococcal antigens are focused on the effectiveness of mucosal recombinant vaccines against Streptococcus pneumoniae in animal models. At present, there are three types of pneumococcal vaccines: capsular polysaccharide pneumococcal vaccines (PPV), protein-polysaccharide conjugate pneumococcal vaccines (PCV) and protein-based pneumococcal vaccines (PBPV). Only PPV and PCV have been licensed. These vaccines, however, do not represent a definitive solution. Novel, safe and inexpensive vaccines are necessary, especially in developing countries. Probiotic microorganisms such as lactic acid bacteria (LAB) are an interesting alternative for their use as vehicles in pneumococcal vaccines due to their GRAS (Generally Recognized As Safe) status. Thus, the adjuvanticity of Lactococcus lactis by itself represents added value over the use of other bacteria, a question dealt with in this review. In addition, the expression of different pneumococcal antigens as well as the use of oral and nasal mucosal routes of administration of lactococcal vaccines is considered. The advantages of nasal live vaccines are evident; nonetheless, oral vaccines can be a good alternative when the adequate dose is used. Another point addressed here is the use of live versus inactivated vaccines. In this sense, few researchers have focused on inactivated strains to be used as vaccines against pneumoccoccus. The immunogenicity of live vaccines is better than the one afforded by inactivated ones; however, the probiotic-inactivated vaccine combination has improved this matter considerably. The progress made so far in the protective immune response induced by recombinant vaccines, the successful trials in animal models and the safety considerations of their application in humans suggest that the use of recombinant vaccines represents a good short-term option in the control of pneumococcal diseases. © 2010 Landes Bioscience

  15. Lactococcus lactis as an adjuvant and delivery vehicle of antigens against pneumococcal respiratory infections

    PubMed Central

    Vintiñi, Elisa; Villena, Julio; Raya, Raul

    2010-01-01

    Most studies of Lactococcus lactis as delivery vehicles of pneumococcal antigens are focused on the effectiveness of mucosal recombinant vaccines against Streptococcus pneumoniae in animal models. At present, there are three types of pneumococcal vaccines: capsular polysaccharide pneumococcal vaccines (PPV), protein-polysaccharide conjugate pneumococcal vaccines (PCV) and protein-based pneumococcal vaccines (PBPV). Only PPV and PCV have been licensed. These vaccines, however, do not represent a definitive solution. Novel, safe and inexpensive vaccines are necessary, especially in developing countries. Probiotic microorganisms such as lactic acid bacteria (LAB) are an interesting alternative for their use as vehicles in pneumococcal vaccines due to their GRAS (Generally Recognized As Safe) status. Thus, the adjuvanticity of Lactococcus lactis by itself represents added value over the use of other bacteria, a question dealt with in this review. In addition, the expression of different pneumococcal antigens as well as the use of oral and nasal mucosal routes of administration of lactococcal vaccines is considered. The advantages of nasal live vaccines are evident; nonetheless, oral vaccines can be a good alternative when the adequate dose is used. Another point addressed here is the use of live versus inactivated vaccines. In this sense, few researchers have focused on inactivated strains to be used as vaccines against pneumoccoccus. The immunogenicity of live vaccines is better than the one afforded by inactivated ones; however, the probiotic-inactivated vaccine combination has improved this matter considerably. The progress made so far in the protective immune response induced by recombinant vaccines, the successful trials in animal models and the safety considerations of their application in humans suggest that the use of recombinant vaccines represents a good short-term option in the control of pneumococcal diseases. PMID:21326831

  16. Quantitative Proteomic Analysis of Escherichia coli Heat-Labile Toxin B Subunit (LTB) with Enterovirus 71 (EV71) Subunit VP1.

    PubMed

    Liu, Lin; Ma, Yongping; Zhou, Huicong; Wu, Mingjun

    2016-08-27

    The nontoxic heat-labile toxin (LT) B subunit (LTB) was used as mucosal adjuvant experimentally. However, the mechanism of LTB adjuvant was still unclear. The LTB and enterovirus 71 (EV71) VP1 subunit (EVP1) were constructed in pET32 and expressed in E. coli BL21, respectively. The immunogenicity of purified EVP1 and the adjuvanticity of LTB were evaluated via intranasal immunization EVP1 plus LTB in Balb/c mice. In order to elucidate the proteome change triggered by the adjuvant of LTB, the proteomic profiles of LTB, EVP1, and LTB plus EVP1 were quantitatively analyzed by iTRAQ-LC-MS/MS (isobaric tags for relative and absolute quantitation; liquid chromatography-tandem mass spectrometry) in murine macrophage RAW264.7. The proteomic data were analyzed by bioinformatics and validated by western blot analysis. The predicted protein interactions were confirmed using LTB pull-down and the LTB processing pathway was validated by confocal microscopy. The results showed that LTB significantly boosted EVP1 specific systematic and mucosal antibodies. A total of 3666 differential proteins were identified in the three groups. Pathway enrichment of proteomic data predicted that LTB upregulated the specific and dominant MAPK (mitogen-activated protein kinase) signaling pathway and the protein processing in endoplasmic reticulum (PPER) pathway, whereas LTB or EVP1 did not significantly upregulate these two signaling pathways. Confocal microscopy and LTB pull-down assays confirmed that the LTB adjuvant was endocytosed and processed through endocytosis (ENS)-lysosomal-endoplasmic reticulum (ER) system.

  17. Modulation of Primary Immune Response by Different Vaccine Adjuvants

    PubMed Central

    Ciabattini, Annalisa; Pettini, Elena; Fiorino, Fabio; Pastore, Gabiria; Andersen, Peter; Pozzi, Gianni; Medaglini, Donata

    2016-01-01

    Adjuvants contribute to enhancing and shaping the vaccine immune response through different modes of action. Here early biomarkers of adjuvanticity after primary immunization were investigated using 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 toward 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 center 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. PMID:27781036

  18. A CpG-containing oligodeoxynucleotide as an efficient adjuvant counterbalancing the Th1/Th2 immune response in diphtheria-tetanus-pertussis vaccine.

    PubMed

    Sugai, Toshiyuki; Mori, Masaaki; Nakazawa, Masatoshi; Ichino, Motohide; Naruto, Takuya; Kobayashi, Naoki; Kobayashi, Yoshinori; Minami, Mutsuhiko; Yokota, Shumpei

    2005-11-16

    Adjuvants in vaccines are immune stimulants that play an important role in the induction of effective and appropriate immune responses to vaccine component(s). Diphtheria-tetanus-pertussis (DPT) vaccine contains not only aluminum hydrate (alum) to enhance the immune response to the vaccine ingredients, but also, both for that purpose and as a principal ingredient, pertussis toxin (PT). However, both adjuvants strongly promote T helper (Th) 2 type immune responses. Th1 and Th2 type immune responses are counterbalanced in vivo, and a Th2-prone immune response is not effective against intracellular infections but promotes IgE production, which is related to allergic disease. In this study, we used the CpG motif contained in oligodeoxynucleotide (CpG-ODN), which has an adjuvant effect and also induces the Th1 response, as an adjuvant to this vaccine, and we investigated its adjuvanticity and its potential to modulate immune responses to DPT vaccine. Administration of DPT vaccine with CpG-ODN (DPT-alum/ODN) to mice significantly reduced the total IgE levels and increased the anti-PT specific IgG2a titer in serum, in comparison with ordinary DPT vaccine (DPT-alum). Moreover, we investigated the antibody response to orally administrated ovalbumin (OVA) after vaccine administration. In the DPT-alum/ODN-administered group, the OVA specific IgE production in serum greatly decreased in comparison with that in the DPT-alum-administered group. These data indicate that CpG-ODN was not useful only as an efficient vaccine adjuvant but also shifted the immune responses substantially toward Th1 and modulated the Th1/Th2 immune response in DPT vaccine. These data suggested new applications of CpG-ODN as adjuvants in DPT vaccine.

  19. Low-dose intraperitoneal Freund's adjuvant: toxicity and immunogenicity in mice using an immunogen targeting amyloid-beta peptide.

    PubMed

    Oscherwitz, Jon; Hankenson, F C; Yu, Fen; Cease, Kemp B

    2006-04-05

    Complete Freund's adjuvant (CFA) is effective for potentiating immune responses in mice when administered subcutaneously, and is often more potent when given intraperitoneally (i.p.). However, the the potential toxicity of i.p. administration in mice has led investigators and Institutional Animal Care and Use committees to increasingly view the use of CFA i.p. with reservation. We evaluated whether an 80% reduction in the dose of CFA administered i.p. to mice, compared to the i.p. doses used in a previous analysis, could abrogate the untoward effects associated with its use, while still maintaining adjuvanticity. Using a novel immunogen targeting the N-terminus of the 42-amino acid amyloid-beta peptide, we compared low dose CFA administered i.p., with three other commonly used adjuvants given i.p.: alum, incomplete Freunds adjuvant (IFA) and monophoshoryl lipid A + trehalose dicorynomycolate (MPL + TDM). The results of the study showed that, though the reduction in intraperitoneal dose of CFA mitigated transient weight loss and leukocytosis observed previously with higher doses of i.p. CFA, all mice administered CFA or IFA i.p. developed abdominal adhesions and granulomatous peritonitis. Mice from all adjuvant groups, however, appeared to tolerate the respective adjuvants well and excellent comparative immunogenicity was observed in mice immunized with the Freunds and MPL + TDM adjuvants. Consequently, we conclude that though a high-titered, humoral response may be generated using low dose CFA administered i.p., the accompanying toxicity remains significant, and thus alternative adjuvants and/or routes should be considered.

  20. Quantitative Proteomic Analysis of Escherichia coli Heat-Labile Toxin B Subunit (LTB) with Enterovirus 71 (EV71) Subunit VP1

    PubMed Central

    Liu, Lin; Ma, Yongping; Zhou, Huicong; Wu, Mingjun

    2016-01-01

    The nontoxic heat-labile toxin (LT) B subunit (LTB) was used as mucosal adjuvant experimentally. However, the mechanism of LTB adjuvant was still unclear. The LTB and enterovirus 71 (EV71) VP1 subunit (EVP1) were constructed in pET32 and expressed in E. coli BL21, respectively. The immunogenicity of purified EVP1 and the adjuvanticity of LTB were evaluated via intranasal immunization EVP1 plus LTB in Balb/c mice. In order to elucidate the proteome change triggered by the adjuvant of LTB, the proteomic profiles of LTB, EVP1, and LTB plus EVP1 were quantitatively analyzed by iTRAQ-LC-MS/MS (isobaric tags for relative and absolute quantitation; liquid chromatography-tandem mass spectrometry) in murine macrophage RAW264.7. The proteomic data were analyzed by bioinformatics and validated by western blot analysis. The predicted protein interactions were confirmed using LTB pull-down and the LTB processing pathway was validated by confocal microscopy. The results showed that LTB significantly boosted EVP1 specific systematic and mucosal antibodies. A total of 3666 differential proteins were identified in the three groups. Pathway enrichment of proteomic data predicted that LTB upregulated the specific and dominant MAPK (mitogen-activated protein kinase) signaling pathway and the protein processing in endoplasmic reticulum (PPER) pathway, whereas LTB or EVP1 did not significantly upregulate these two signaling pathways. Confocal microscopy and LTB pull-down assays confirmed that the LTB adjuvant was endocytosed and processed through endocytosis (ENS)-lysosomal-endoplasmic reticulum (ER) system. PMID:27618897

  1. The role of ISCOMATRIX bilayer composition to induce a cell mediated immunity and protection against leishmaniasis in BALB/c mice

    PubMed Central

    Mehravaran, Ahmad; Jaafari, Mahmoud Reza; Jalali, Seyed Amir; Khamesipour, Ali; Ranjbar, Reza; Hojatizade, Mansure; Badiee, Ali

    2016-01-01

    Objective(s): Development of new generation of vaccines against leishmaniasis is possible because long-term protection is usually seen after recovery from cutaneous leishmaniasis. ISCOMATRIX is particulate antigen delivery system composed of antigen, cholesterol, phospholipid and saponin. In this study, the role of ISCOMATRIX bilayer composition made by different phase transition temperature (Tc) to induce a type of immune response and protection against leishmaniasis was assessed. Materials and Methods: ISCOMATRIX formulations with different bilayer compositions consisting of EPC (Tc <0 °C), DMPC (Tc 23 °C) and DSPC (Tc 54 °C) were prepared. Different ISCOMATRIX formulations were mixed with soluble Leishmania antigens (SLA). BALB/c mice were immunized subcutaneously, three times with 2-week intervals. As criteria for protection, footpads swelling, parasite burden, determination of IgG isotypes and the level of IFN-γ and IL-4 were assessed. Results: Although the groups of mice immunized with ISCOMATRIX DMPC or ISCOMATRIX DSPC showed the smallest footpad swelling and least parasite burden compared with the buffer group, the difference was not significant. Moreover, the highest level of IFN- γ and IL-4 was observed in the splenocytes of mice immunized with ISCOMATRIX DMPC or ISCOMATRIX DSPC, respectively. After challenge, the mice immunized with ISCOMATRIX DSPC showed the highest elevation of IgG, IgG1 and IgG2a antibodies (P<0.01) compared with control group. However, our results indicated that ISCOMATRIX EPC, DMPC or DSPC generated a mixed Th1/Th2 response that was not protective. Conclusion: Our results showed that the adjuvanticity of prepared ISCOMATRIX doesn’t influence with different phospholipids at least in our mice model. PMID:27081463

  2. Gene expression profiles identify both MyD88-independent and MyD88-dependent pathways involved in the maturation of dendritic cells mediated by heparan sulfate: a novel adjuvant.

    PubMed

    Wu, Meini; Wang, Haixuan; Shi, Jiandong; Sun, Jing; Duan, Zhiqing; Li, Yanhan; Li, Jianfang; Hu, Ningzhu; Wei, Yiju; Chen, Yang; Hu, Yunzhang

    2014-01-01

    The traditional vaccine adjuvant research is mainly based on the trial and error method, and the mechanisms underlying the immune system stimulation remaining largely unknown. We previously demonstrated that heparan sulfate (HS), a TLR-4 ligand and endogenous danger signal, effectively enhanced humoral and cellular immune responses in mice immunized by HBsAg. This study aimed to evaluate whether HS induces better humoral immune responses against inactivated Hepatitis A or Rabies Vaccines, respectively, compared with traditional adjuvants (e.g. Alum and complete Freund's adjuvant). In order to investigate the molecular mechanisms of its adjuvanticity, the gene expression pattern of peripheral blood monocytes derived DCs (dendritic cells) stimulated with HS was analyzed at different times points. Total RNA was hybridized to Agilent SurePrint G3 Human Gene Expression 8×60 K one-color oligo-microarray. Through intersection analysis of the microarray results, we found that the Toll-like receptor signaling pathway was significantly activated, and NF-kB, TRAF3 and IRF7 were activated as early as 12 h, and MyD88 was activated at 48 h post-stimulation. Furthermore, the expression of the surface marker CD83 and the co-stimulatory molecules CD80 and CD86 was up-regulated as early as 24 h. Therefore, we speculated that HS-induced human monocyte-derived DC maturation may occur through both MyD88-independent and dependent pathways, but primarily through the former (TRIF pathway). These data provide an important basis for understanding the mechanisms underlying HS enhancement of the immune response.

  3. CD40 Ligand enhances immunogenicity of vector-based vaccines in immunocompetent and CD4+ T cell deficient individuals

    PubMed Central

    Auten, Matthew W.; Huang, Weitao; Dai, Guixiang; Ramsay, Alistair J.

    2012-01-01

    Impairment of host immunity, particularly CD4+ T cell deficiency, presents significant complications for vaccine immunogenicity and efficacy. CD40 ligand (CD40L or CD154), a member of the tumor necrosis factor superfamily (TNFSF), is an important co-stimulatory molecule and, through interactions with its cognate receptor CD40, plays a pivotal role in the generation of host immune responses. Exploitation of CD40L and its receptor CD40 could provide a means to enhance and potentially restore protective immune responses in CD4+ T cell deficiency. To investigate the potential adjuvanticity of CD40L, we constructed recombinant plasmid DNA and adenoviral (Ad) vaccine vectors expressing murine CD40L and the mycobacterial protein antigen 85B (Ag85B). Co-immunization of mice with CD40L and Ag85B by intranasal or intramuscular prime-boosting led to route-dependent enhancement of the magnitude of vaccine-induced circulating and lung mucosal CD4+ and CD8+ T cell responses in both normal (CD4-replete) and CD4+ T cell deficient animals, including polyfunctional T cell responses. The presence of CD40L alone was insufficient to enhance or restore CD4+ T cell responses in CD4-ablated animals; however, in partially-depleted animals, co-immunization with Ag85B and CD40L was capable of eliciting enhanced T cell responses, similar to those observed in normal animals, when compared to those given vaccine antigen alone. In summary, these findings show that CD40L has the capacity to enhance the magnitude of vaccine-induced polyfunctional T cell responses in CD4+ T cell deficient mice, and warrants further study as an adjuvant for immunization against opportunistic pathogens in individuals with CD4+ T cell deficiency. PMID:22349523

  4. [Secondary hypothyroidism after cervical irradiation: systematic evaluation of thyroid function in follow-up].

    PubMed

    Gonçalves, Sara Monteiro; Ferreira, Brígida Costa; Guardado, Maria João; Marques, Rui; Serra, Tânia; Serra, Maria João; Roda, Domingos; Brandão, Joana; Melo, Gilberto; Lopes, Maria Carmo; Khouri, Leila

    2014-01-01

    Introdução: A disfunção tiroideia constitui uma consequência, por vezes subestimada, da exposição à radiação. O mecanismo subjacente não está claramente esclarecido, mas terá uma origem multifatorial. Os fatores de risco específicos para o desenvolvimento de hipotiroidismo secundário à radioterapia permanecem indeterminados. A irradiação direta da glândula tiroideia pode resultar, com maior frequência, em hipotiroidismo. Este é uma condição irreversível, requerendo monitorização e tratamento permanente. Objetivos: Avaliar a incidência de hipotiroidismo nos doentes portadores de neoplasias da cabeça e pescoço submetidos a irradiação cervical, a título intensivo ou adjuvante, bem como determinar se é justificável a integração no protocolo de seguimento Institucional, de parâmetros laboratoriais (TSH, T3 Livre e T4 Livre) para avaliação da função tiroideia neste grupo de doentes e qual a sua periodicidade. Material e Métodos: Este é um estudo observacional, descritivo, retrospetivo, que engloba um grupo de 376 doentes portadores de neoplasias da cabeça e pescoço, submetidos a tratamento de radioterapia, a título adjuvante ou intensivo, entre os anos de 2007 e 2012, no Instituto Português de Oncologia de Coimbra Francisco Gentil E.P.E. Cumpriram todos os critérios de inclusão 145 doentes. Foram utilizadas escalas de avaliação padronizadas para a definição de hipotiroidismo – LENT-SOMA scales (Late Effects Normal Tissues Subjective Objective Management Analysis). Foi considerada como complicação o hipotiroidismo Grau 1 ou superior. Resultados: Procedeu-se à análise de um grupo de 145 doentes. A localização tumoral mais frequente foi a Laringe (26,9%). Trinta e dois doentes efetuaram radioterapia adjuvante e 113 efetuaram esquemas intensivos. A técnica de radioterapia mais utilizada foi a intensidade modulada (IMRT), efetuada em 86,2% doentes. A taxa de incidência global de hipotiroidismo aos 12 meses foi de

  5. Pulmonary Embolism in Ambulatory Oncologic Patients.

    PubMed

    Silva, Patrícia; Rosales, Maria; Milheiro, Maria João; Santos, Luísa L

    2015-01-01

    Introdução: A associação entre a doença oncológica e a doença tromboembólica venosa é conhecida. O doente oncológico apresenta um risco de evento trombótico seis a sete vezes superior à população em geral. O tromboembolismo pulmonar é uma importante causa de morbilidade e mortalidade neste grupo de doentes, encontrando-se a sua prevalência subestimada. Material e Métodos: Estudo retrospetivo de todos os episódios de tromboembolismo pulmonar referenciados num período de cinco anos. Selecionaram-se os doentes oncológicos em regime de ambulatório, tendo sido revistos os dados demográficos, fatores de risco, presença de sintomatologia ao diagnóstico, estratificação de risco de doença tromboembólica venosa pelo modelo de Khorana, probabilidade de mortalidade aos 30 dias e sobrevivência global. O trabalho elaborado está de acordo com a declaração de Helsínquia. Resultados: Avaliaram-se 186 doentes, 55,9% do sexo feminino, mediana de idade de 64 anos. As neoplasias mais prevalentes foram a colo-rectal (24,2%) e a pulmonar (17,7%), sendo que a maioria apresentava metástases (66,1%) ou realizaram quimioterapia (69,4%). O tromboembolismo pulmonar foi um achado imagiológico em 69,4%, sendo que nenhum dado clínico analisado no nosso estudo mostrou ter significado estatístico na apresentação de tromboembolismo pulmonar com sintomatologia clínica evidente. Observou-se uma mortalidade aos 30 dias resultante do tromboembolismo pulmonar de 7,5%, tendo-se verificado que os doentes sintomáticos apresentaram uma sobrevivência média inferior relativamente aos assintomáticos (12 vs. 20 meses; p = 0,029). A aplicação retrospetiva do modelo preditivo de Khorana para doença tromboembólica venosa nos doentes sob quimioterapia permitiu identificar 11% dos indivíduos em alto risco. Discussão: O tromboembolismo pulmonar foi um achado imagiológico na maioria dos doentes, sendo que nenhuma variável clínica se associou à presença ou aus

  6. [Effectiveness of plerixafor in patients undergoing mobilization autologous haematopoietic progenitor cell].

    PubMed

    Ruano Camps, R; Ortiz Pareja, M; Vidales Mancha, I; Muñoz Castillo, I M; Heiniger Mazo, A I

    2013-01-01

    Objetivo: Evaluar efectividad del tratamiento con plerixafor en pacientes sometidos a movilización para posterior autotrasplante de progenitores hematopoyéticos en nuestro hospital. Métodos: Estudio retrospectivo de todos los pacientes que hasta septiembre 2012, recibieron plerixafor en su esquema de movilización de progenitores hematopoyéticos a sangre periférica. Se revisaron las historias clínicas y los registros de dispensación de medicamentos de la consulta de pacientes externos. Las variables de efectividad utilizadas fueron: CD34/kg en producto de aféresis obtenidas, dosis y días recibidos de factor estimulante de colonias (G-CSF) y de plerixafor. Para cada paciente se comparó los resultados de efectividad del fármaco con los obtenidos para anteriores esquemas de movilización en los que no se utilizó plerixafor, en caso de tenerlos. Los datos se analizaron mediante IBM spss v19. Resultados: Un total de 24 pacientes recibieron plerixafor en nuestro hospital. Los diagnósticos se distribuyeron: 15 linfoma no Hodgkin , 6 pacientes con mieloma múltiple, 2 enfermedad de Hodgkin, y 1 coriocarcinoma diseminado. Los resultados de efectividad fueron: Movilización sin plerixafor (n = 18): 5 pacientes se movilizaron sólo con G-CSGF, 13 con G-CSF y quimioterapia. La dosis de G-CSF /día fue de 931,1 mcg (± 179,5), durante 9,5 días (± 4,7). El promedio de CD34/kg en producto obtenido fue de 0,2 células (± 0,5). Ningún paciente obtuvo producto suficiente (≥?2 x 106 células/kg) para el posterior autotrasplante. El 100 % de las movilizaciones fracasaron. Movilización con plerixafor (n = 24): 13 pacientes se movilizaron sólo con G-CSGF, 11 con G-CSF y quimioterapia. La dosis de G-CSF /día y de plerixafor promedio fue de 885,1 mcg (± 240,1) y 19,8 (± 4,4), respectivamente, administrados durante 8,9 (± 5,1) y 1,5 (± 0,6) días, respectivamente. El promedio de CD34/kg en producto obtenido fue de 2,3x106 células (±1,7) (p = 0,014, en relaci

  7. Successful treatment of post-transplant relapsed acute myeloid leukemia with FLT3 internal tandem duplication using the combination of induction chemotherapy, donor lymphocyte infusion, sorafenib and azacitidine. Report of three cases.

    PubMed

    Campregher, Paulo Vidal; Mattos, Vinicius Renan Pinto de; Salvino, Marco Aurélio; Santos, Fabio Pires de Souza; Hamerschlak, Nelson

    2017-07-24

    tandem de FLT3 que recidivaram depois do transplante alogênico de células-tronco hematopoiéticas e que foram tratados com combinação de quimioterapia de reindução, infusão de linfócitos de doador, sorafenib e azacitidina. São descritos três casos, e todos os pacientes apresentaram remissão completa prolongada com a terapia combinada. A combinação de quimioterapia de indução, seguida de infusão de linfócitos do doador, e a manutenção com azacitidina e sorafenib podem ser abordagens eficazes no tratamento da recorrência pós-transplante em pacientes com leucemia mieloide aguda e duplicação em tandem de FLT3. Essa estratégia deve ser mais explorada no contexto de ensaios clínicos.

  8. [Surgical treatment of spinal tuberculosis: an orthopedic service experience].

    PubMed

    Soares do Brito, Joaquim; Batista, Nuno; Tirado, António; Fernandes, Pedro

    2013-01-01

    Introdução: A espondilodiscite de etiologia tuberculosa é responsável por mais de 40% do universo destas infeções. Enquanto a quimioterapia tuberculostática se mantém como gold-standard da terapêutica desta patologia, o tratamento cirúrgico tem lugar em situações muito específicas. Neste trabalho apresentam-se os resultados de 33 doentes com espondilodiscite tuberculosa operados no nosso serviço durante os últimos 15 anos.Objetivo: Avaliar retrospetivamente doentes com diagnóstico de espondilodiscite tuberculosa operados num período de 15 anos(1996 a 2011); avaliar opções cirúrgicas tomadas e respetivos resultados relativamente à resolução da infeção, controlo da deformidade e evolução da lesão neurológica.Material e Métodos: Análise retrospetiva dos processos clínicos e avaliações imagiológicas de doentes com diagnóstico de espondilodiscite tuberculosa operados entre 1996 e 2011. Foram identificados 33 doentes com idade média de 46,7 anos; 17 doentes apresentavam infeção torácica, 11 lombar e cinco toraco-lombar. O abcesso paravertebral foi identificado em 26 dos casos estudados, existindo extensão intracanalar em 16 doentes. Nove dos doentes avaliados apresentavam lesão neurológica. A abordagem cirúrgica por via anterior foi utilizada em sete casos, a via posterior em 11 e a abordagem combinada foi a preferida em 15 ocasiões. A quimioterapia antibacilar foi mantida em média por 14 meses, com seguimento médio de 24 meses.Resultados: Verificámos cura da infeção em todos os doentes, sendo documentados critérios de fusão óssea, em média, 10,6 meses pós-cirurgia. A abordagem anterior isolada não permitiu obter correção da deformidade inicial, enquanto a via posterior permitiu uma correção média de 12,7º e a via combinada uma correção média de 8,7º. Cinco dos doentes com lesão neurológica melhoraram 2 a 3 níveis na escala ASIA durante o seguimento pós-operatório. Como complicações referem-se 2

  9. Yolk sac primary tumor of mediastino: a rare case in a young adult.

    PubMed

    Silva, Lorena Luryann Cartaxo da; Vergilio, Fernanda Sasaki; Yamaguti, Diva Carvalho Collarile; Cruz, Isabela Azevedo Nicodemos da; Queen, Joana Angrisani Granato

    2017-09-21

    . Havia ainda aumento dos níveis séricos da alfafetoproteína. Após quimioterapia neoadjuvante pré-operatória, o paciente foi submetido à ressecção cirúrgica, seguida de estudo anatomopatológico da peça, no qual demonstrou tratar-se de um tumor de saco vitelínico primário do mediastino. Os tumores de saco vitelínicos primários do mediastino têm prognóstico reservado, apesar do avanço na terapêutica com a ressecção cirúrgica e a quimioterapia à base de cisplatina. Isto se deve ao grau de invasão e de irressecabilidade na maioria dos pacientes no momento do diagnóstico.

  10. The Inflammatory-Nutritional Index; assessing nutritional status and prognosis in gastrointestinal and lung cancer patients.

    PubMed

    Pastore, Carla Alberici; Orlandi, Silvana Paiva; Gonzalez, Maria Cristina

    2014-03-01

    Objetivo: Evaluar la capacidad pronostica del Índice Inflamatorio-Nutricional (INI) en pacientes con cáncer del tracto gastrointestinal y pulmón. Métodos: Estudio longitudinal, con pacientes de un servicio de quimioterapia en Brasil, entre Julio de 2008 y Mayo de 2010. INI (Albúmina/CRP) y el estadio nutricional (Valoración Global Subjetiva-SGA) fueran evaluados. INI de riesgo fue definido como menor que 0.35. El tiempo medio de acompañamiento fue 1.6 año. Analices estadísticas fueran realizadas con el programa Stata 11.1™. Resultados: Fueron evaluados 74 pacientes, con edad media de 63.4 años, la mayoría hombres (58%) e con cáncer gastrointestinal (71%). Desnutrición fue identificada en 87% de los pacientes (22% con desnutrición grave). El INI medio fue 2.67 y 54% de los individuos presentaban INI de riesgo. Durante el acompañamiento hubieran 49 óbitos (66%). El tiempo mediano de sobrevida de los pacientes con INI de riesgo fue significantemente más corto que de los pacientes con INI normal (p = 0.002). El grupo con INI de riesgo llevó 0.78 año para decaer 50%, en cuanto el grupo con INI normal llevó 2.78 año (p = 0.001). INI de riesgo y desnutrición grave fueron factores independientes de peor sobrevida. Conclusión: El INI demostró capacidad pronostica en esta amuestra y puede ser una herramienta útil, basada testes rutineros y disponibles, para evaluar pacientes con cáncer.

  11. BRAZILIAN CONSENSUS FOR MULTIMODAL TREATMENT OF COLORECTAL LIVER METASTASES. MODULE 3: CONTROVERSIES AND UNRESECTABLE METASTASES.

    PubMed

    Torres, Orlando Jorge Martins; Marques, Márcio Carmona; Santos, Fabio Nasser; Farias, Igor Correia de; Coutinho, Anelisa Kruschewsky; Oliveira, Cássio Virgílio Cavalcante de; Kalil, Antonio Nocchi; Mello, Celso Abdon Lopes de; Kruger, Jaime Arthur Pirola; Fernandes, Gustavo Dos Santos; Quireze, Claudemiro; Murad, André M; Silva, Milton José de Barros E; Zurstrassen, Charles Edouard; Freitas, Helano Carioca; Cruz, Marcelo Rocha; Weschenfelder, Rui; Linhares, Marcelo Moura; Castro, Leonaldson Dos Santos; Vollmer, Charles; Dixon, Elijah; Ribeiro, Héber Salvador de Castro; Coimbra, Felipe José Fernandez

    2016-01-01

    In the last module of this consensus, controversial topics were discussed. Management of the disease after progression during first line chemotherapy was the first discussion. Next, the benefits of liver resection in the presence of extra-hepatic disease were debated, as soon as, the best sequence of treatment. Conversion chemotherapy in the presence of unresectable liver disease was also discussed in this module. Lastly, the approach to the unresectable disease was also discussed, focusing in the best chemotherapy regimens and hole of chemo-embolization. RESUMO Neste último módulo do consenso, abordou-se alguns temas controversos. O primeiro tópico discutido foi o manejo da doença após progressão na primeira linha de quimioterapia, com foco em se ainda haveria indicação cirúrgica neste cenário. A seguir, o painel debruçou-se sobre as situações de ressecção da doença hepática na presença de doença extra-hepática, assim como, qual a melhor sequência de tratamento. O tratamento de conversão para doença inicialmente irressecável também foi abordado neste módulo, incluindo as importantes definições de quando se pode esperar que a doença se torne ressecável e quais esquemas terapêuticos seriam mais efetivos à luz dos conhecimentos atuais sobre a biologia tumoral e taxas de resposta objetiva. Por último, o tratamento da doença não passível de ressecção foi discutida, focando-se nos melhores esquemas a serem empregados e seu sequenciamento, bem como o papel da quimioembolização no manejo destes pacientes.

  12. Oral physiology and quality of life in cancer patients.

    PubMed

    Pereira, Luciano J; Braga Caputo, Júnior; Midori Castelo, Paula; Francelino Andrade, Eric; Silva Marques, Leandro; Martins de Paiva, Saul; Márcia Pereira, Stela; Vicente Pereira, Cássio

    2015-05-01

    Introdución: El tratamiento del cáncer puede afectar la salud de los dientes y estructuras de apoyo, que son esenciales para el proceso de masticación, que pueden cambiar el estado nutricional del paciente. Objetivo: El objetivo de este estudio fue evaluar el impacto de los cambios fisiológicos orales sobre la calidad de vida (QoL) de los pacientes sometidos a tratamiento contra el cáncer. Metodos: Inicialmente 84 pacientes con cáncer fueron examinados y sólo los que presentan al menos 15 dientes naturales fueron seleccionados para la fisiología oral y la calidad de las pruebas de la vida. La muestra final quedó conformado por 30 pacientes. Veinte sujetos fueron seleccionados como controles emparejados por edad y sexo. Dental estado de la caries, el flujo salival, rendimiento masticatorio (MP), la ubicación del tumor, la duración de la quimioterapia y la radioterapia y lo cuestionario de La Organización Mundial de la Salud Calidad de Vida (WHOQOL-BREF) cuestionario fueron evaluados. Se utilizaron modelos de regresión lineal para probar la relación entre los dominios del WHOQOL-BREF (psicológicos relación física,, social, ambiental y de calidad de vida en general) y variables independientes bajo estudio. Resultados y Discusión: Número de dientes, MP y el flujo salival fueron menores en los pacientes de cáncer, así como para las puntuaciones obtenidas en la relación social, medio ambiente y dominios de calidad de vida general (p.

  13. The role of surgery in the management of women with gestational trophoblastic disease.

    PubMed

    Lima, Lana DE Lourdes Aguiar; Padron, Lílian; Câmara, Raphael; Sun, Sue Yazaki; Rezende, Jorge; Braga, Antônio

    2017-01-01

    The Gestational Trophoblastic Disease includes an interrelated group of diseases originating from placental tissue, with distinct behaviors concerning local invasion and metastasis. The high sensitivity of the serial dosages of human chorionic gonadotrophin, combined with advances in chemotherapy treatment, have made gestational trophoblastic neoplasia curable, most often through chemotherapy. However, surgery remains of major importance in the management of patients with gestational trophoblastic disease, improving their prognosis. Surgery is necessary in the control of the disease's complications, such as hemorrhage, and in cases of resistant/relapsed neoplasia. This review discusses the indications and the role of surgical interventions in the management of women with molar pregnancy and gestational trophoblastic neoplasia. RESUMO Doença trofoblástica gestacional inclui um grupo interrelacionado de doenças originadas do tecido placentário, com tendências distintas de invasão local e metástase. A alta sensibilidade das dosagens seriadas de gonadotrofina coriônica humana aliada aos avanços do tratamento quimioterápico tornou a neoplasia trofoblástica gestacional, curável, na maioria das vezes, através da quimioterapia. No entanto, a cirurgia permanece ainda, da maior importância na condução de pacientes com doença trofoblástica gestacional, melhorando seu prognóstico. A cirurgia é necessária no controle de complicações da doença, tais como hemorragia, e em casos de neoplasia resistente/recidivada. Esta revisão discute as indicações e o papel das intervenções cirúrgicas durante o manejo de mulheres com gravidez molar e neoplasia trofoblástica gestacional.

  14. [Lapatinib plus transtuzumab for HER-2 positiva metastatic breast cancer: experience of use].

    PubMed

    García-Muñoz, C; Cortijo-Cascajares, S; Cañamares-Orbis, I; Goyache-Goñi, M P; Ferrari-Piquero, J M

    2014-04-01

    Objetivo: Describir los resultados obtenidos con la utilización conjunta de dos inhibidores del receptor HER2 (lapatinib y trastuzumab) en el tratamiento del cáncer de mama metastático HER 2 positivo. Método: Estudio observacional retrospectivo. Se seleccionaron pacientes en tratamiento con trastuzumab y lapatinib entre enero de 2010 y mayo de 2012. Se recogieron datos demográficos y clínicos. Resultados: Se incluyeron 23 pacientes con cáncer de mama metastático (edad media de 59,3 ± 13,3 años). Todos ellos habían recibido una media de 5 líneas de tratamiento previo con al menos una línea de tratamiento con trastuzumab. La mediana de supervivencia libre de progresión con lapatinib + trastuzumab combinado con o sin otra quimioterapia asociada fue de 7 meses (IC 95%: 2,78-11,21) y de 3 meses para las pacientes que sólo recibieron lapatinib y trastuzumab. Siete pacientes tuvieron efectos adversos y en cuatro pacientes se suspendió el tratamiento por toxicidad. Conclusiones: El tratamiento con dos inhibidores del receptor HER2 en nuestras pacientes ha resultado en una supervivencia libre de progresión similar a la de los ensayos clínicos publicados cuando las pacientes recibieron lapatinib + trastuzumab y no se combinó con otra terapia antineoplásica, con buena tolerancia al tratamiento.

  15. [Intracranial tumor behavior of plasma cell neoplasms. Report of 2 cases and literature review].

    PubMed

    López-Elizalde, Ramiro; Lemus-Rodríguez, Yazmín; Godínez-Rubí, Marisol; Madrigal-Saray, Arturo; Muñoz-Serrano, José Antonio; Velásquez-Santana, Héctor

    2013-01-01

    Antecedentes: el mieloma múltiple es una neoplasia de células plasmáticas caracterizada por destrucción ósea, insuficiencia renal, anemia e hipercalcemia. Los plasmacitomas de los huesos del cráneo representan menos de 1% de los tumores de cabeza y cuello. Se manifiestan como lesión primaria o secundaria a mieloma múltiple en 20-30%, incluso pueden aparecer varios años después del diagnóstico. Los autores comunicamos dos casos de pacientes mexicanas con lesiones plasmocíticas intracraneales, asociadas con mieloma múltiple.Casos clínicos: el primer caso es el de una paciente de 24 años de edad, con diagnóstico de mieloma múltiple e infiltración ósea que fue extirpado en 90%. Experimentó una recidiva local que requirió otra intervención para su remoción. El segundo caso es el de una mujer de 62 años de edad con un tumor intracraneal de células plasmáticas que se resecó en su totalidad. Ambas recibieron terapia adyuvante con quimio y radioterapia con resultados favorables. Las pacientes fallecieron a los 5 y 1.5 años, respectivamente, por insuficiencia renal como consecuencia de la enfermedad sistémica. Conclusiones: se propone a la quimioterapia y radioterapia como parte esencial del tratamiento de este tumor porque su comportamiento natural agresivo puede complicar la evolución, a pesar de ser accesibles quirúrgicamente.

  16. Ependimoma myxopapilar sacro gigante con osteolisis

    PubMed Central

    Ajler, Pablo; Landriel, Federico; Goldschmidt, Ezequiel; Campero, Álvaro; Yampolsky, Claudio

    2014-01-01

    Objetivo: la presentación de un caso de una paciente con un ependimoma sacro con extensa infiltración y destrucción ósea local. Descripción del caso: una mujer de 53 años acudió a la consulta por dolor lumbosacro y alteraciones sensitivas perineales y esfinterianas. La imágenes por Resonancia Magnética (IRM) y la Tomografía Axial Computada (TAC) mostraron una lesión expansiva gigante a nivel S2-S4 con extensa osteólisis e invasión de tejidos adyacentes. Se realizó una exéresis tumoral completa con mejoría del estatus funcional. La anatomía patológica informó ependimoma mixopapilar. Discusión: la extensión de la resección quirúrgica es el mejor predictor de buen pronóstico. El tratamiento radiante se reserva como opción adyuvante para las resecciones incompletas y recidiva tumoral. La quimioterapia sólo debería utilizarse en casos en que la cirugía y la radioterapia estén contraindicadas. Conclusión: Los ependimomas mixopapilares sacros con destrucción ósea y presentación intra y extradural son muy infrecuentes y deben ser tenidos en cuenta entre los diagnósticos diferenciales preoperatorios. Su resección total, siempre que sea posible, es la mejor alternativa terapéutica. PMID:25165615

  17. Reliability of nutritional assessment in patients with gastrointestinal tumors.

    PubMed

    Poziomyck, Aline Kirjner; Fruchtenicht, Ana Valeria Gonçalves; Kabke, Georgia Brum; Volkweis, Bernardo Silveira; Antoniazzi, Jorge Luiz; Moreira, Luis Fernando

    2016-01-01

    Patients with gastrointestinal cancer and malnutrition are less likely to tolerate major surgical procedures, radiotherapy or chemotherapy. In general, they display a higher incidence of complications such as infection, dehiscence and sepsis, which increases the length of stay and risk of death, and reduces quality of life. The aim of this review is to discuss the pros and cons of different points of view to assess nutritional risk in patients with gastrointestinal tract (GIT) tumors and their viability, considering the current understanding and screening approaches in the field. A better combination of anthropometric, laboratory and subjective evaluations is needed in patients with GIT cancer, since malnutrition in these patients is usually much more severe than in those patients with tumors at sites other than the GIT. RESUMO Pacientes com neoplasia gastrointestinal e desnutridos são menos propensos a tolerar procedimentos cirúrgicos de grande porte, radioterapia ou quimioterapia. Em geral, apresentam maior incidência de complicações, como infecção, deiscência e sepse, o que aumenta o tempo de internação e o risco de morte, e reduz a qualidade de vida. O objetivo desta revisão é abordar os prós e contras de diferentes pontos de vista que avaliam risco nutricional em pacientes com tumores do Trato Gastrointestinal (TGI) e sua viabilidade, considerando o atual entendimento e abordagens de triagem neste campo. Melhor combinação de avaliações antropométricas, laboratoriais e subjetivas se faz necessária em pacientes com câncer do TGI, uma vez que a desnutrição nestes pacientes costuma ser muito mais grave do que naqueles indivíduos com tumores em outros sítios que não o TGI.

  18. [Neurological complications in the population of children with leukaemia].

    PubMed

    Martínez-Cayuelas, Elena; Domingo-Jiménez, Rosario; Pascual-Gázquez, Juan F; Martínez-Salcedo, Eduardo; Alarcón-Martínez, Helena; Bermúdez-Cortés, Mar; Fuster-Soler, José L; Pérez-Fernández, Virginia

    2015-02-01

    Introduccion. La leucemia es el cancer mas frecuente en edad pediatrica. Su tasa de curacion es del 80% con quimioterapia intensiva, que mejora la supervivencia, pero que tambien aumenta la frecuencia de efectos adversos, incluyendo los neurologicos. Objetivos. Describir la frecuencia y caracteristicas de las complicaciones neurologicas (CN) en pacientes con leucemia aguda linfoide (LAL) y leucemia aguda mieloide (LAM), e identificar los factores asociados a su presencia, la tasa de morbilidad neurologica y la supervivencia. Pacientes y metodos. Estudio retrospectivo de las CN presentes durante el tratamiento y seguimiento de los pacientes con LAL y LAM entre 1997 y 2012 por la unidad de oncohematologia infantil. Variables analizadas: datos demograficos, diagnostico oncologico, tratamiento y CN. Resultados. Se incluyo un total de 157 pacientes, 145 sin infiltracion de sistema nervioso central al diagnostico y ocho con infiltracion (tasa de CN del 14 y 12%, respectivamente). Las CN mas frecuentes fueron: neuropatias (31%), alteracion del nivel de conciencia (27%), convulsiones (22%) y cefalea (12%). Un 40% de los pacientes con CN ha presentado secuelas, pero ninguno ha fallecido como consecuencia de la CN. Se han detectado mas CN en el grupo de edad menor de 6 años con LAL de alto grado, en niveles de gravedad mas altos y en pacientes que habian recibido trasplante de precursores hematopoyeticos, todas ellas con diferencias estadisticamente significativas. Conclusiones. Las complicaciones neurologicas son frecuentes en los pacientes con leucemia aguda, en especial en aquellos con estadio de riesgo alto (sobre todo si son menores de 6 años) y trasplante de precursores hematopoyeticos. La mortalidad asociada es baja.

  19. Needs of family caregivers in home care for older adults.

    PubMed

    Bierhals, Carla Cristiane Becker Kottwitz; Santos, Naiana Oliveira Dos; Fengler, Fernanda Laís; Raubustt, Kamila Dellamora; Forbes, Dorothy Anne; Paskulin, Lisiane Manganelli Girardi

    2017-04-06

    to reveal the felt and normative needs of primary family caregivers when providing instrumental support to older adults enrolled in a Home Care Program in a Primary Health Service in the South of Brazil. using Bradshaw's taxonomy of needs to explore the caregiver's felt needs (stated needs) and normative needs (defined by professionals), a mixed exploratory study was conducted in three steps: Descriptive quantitative phase with 39 older adults and their caregiver, using a data sheet based on patient records; Qualitative exploratory phase that included 21 caregiver interviews, analyzed by content analysis; Systematic observation, using an observation guide with 16 caregivers, analyzed by descriptive statistics. the felt needs were related to information about instrumental support activities and subjective aspects of care. Caregivers presented more normative needs related to medications care. understanding caregivers' needs allows nurses to plan interventions based on their particularities. identificar as necessidades sentidas e normativas dos cuidadores familiares principais no apoio instrumental a idosos registrados em um Programa de Atenção Domiciliar em uma Unidade Básica de Saúde no Sul do Brasil. usando a Taxonomia de Necessidades de Bradshaw para explorar as necessidades sentidas (necessidades declaradas) e normativas (definidas por profissionais), desenvolveu-se um estudo exploratório misto em três etapas: Etapa descritiva quantitativa, envolvendo 39 idosos e seus cuidadores, com a ajuda de um folha de dados baseada no prontuário do paciente; Etapa exploratória qualitativa, baseada em entrevistas com 21 cuidadores, analisadas mediante a análise de conteúdo; Observação sistemática, aplicando um roteiro de observação a 16 cuidadores, com análise estatística descritiva. as necessidades sentidas estavam relacionadas a informações sobre atividades de apoio instrumental e aspectos subjetivos do cuidado. Os cuidadores apresentaram maior número de

  20. Health education with older adults: action research with primary care professionals.

    PubMed

    Mendonça, Francielle Toniolo Nicodemos Furtado de; Santos, Álvaro da Silva; Buso, Ana Luisa Zanardo; Malaquias, Bruna Stephanie Sousa

    2017-01-01

    To assess the development and implementation of permanent education action. Quantitative-qualitative research based on action research in three phases (diagnosis of reality, implementation of activity and evaluation), performed with health professionals and managers of basic health units. The evaluation was on the perception of changes immediately following the activity and after 120 days. In the first phase, 110 professionals took part, 36.4% of whom indicated the existence of groups for older adults at work. In the second phase, 98 professionals participated, pointing out interferences of the group in the life of older adults, items of importance and facilitation in forming groups and developing reality-based activities. The third phase showed, in the quantitative analysis, positive impact of the training, and in the qualitative analysis, reassessment of groups, greater knowledge and confidence in managing groups and increased respect for older adults. Permanent education opens pathways for the construction of differentiated care for older adults based on respect and health promotion. Avaliar o desenvolvimento e implementação de uma ação de educação permanente. Pesquisa quantitativo-qualitativa baseada na pesquisa-ação em 3 fases (diagnóstico da realidade, implementação de atividade e avaliação), realizada com profissionais de saúde e gerentes de unidades básicas. A avaliação se deu pela percepção de mudanças imediatamente à atividade e após 120 dias. Na 1ª fase, participaram 110 profissionais, dos quais 36,4% apontaram a existência de grupos para idosos no trabalho. Na 2ª fase, participaram 98 profissionais, que apontaram interferências do grupo na vida do idoso, itens de importância e facilitação para construção de grupos e atividade baseada na realidade. A 3ª fase mostrou, na análise quantitativa, impacto positivo do treinamento; e, na qualitativa, releitura dos grupos e manejo com mais conhecimento, segurança e respeito ao

  1. Enhanced immunogenicity of a sequence derived from hepatitis B virus surface antigen in a composite peptide that includes the immunostimulatory region from human interleukin 1.

    PubMed Central

    Rao, K V; Nayak, A R

    1990-01-01

    The effect on immunogenicity of coupling the immunostimulatory nonapeptide sequence (residues 163-171) from human interleukin 1 beta (IL-1 beta) to a small immunogen was examined. A 21-amino acid sequence spanning positions 12-32 on the large protein of hepatitis B surface antigen was chosen as a model. Three peptides were synthesized corresponding to the IL-1 beta-derived sequence [peptide IL-(163-171)], the hepatitis B surface antigen-derived sequence [peptide S1-(12-32)] and a composite peptide that included both these sequences separated by a spacer of two glycine residues [peptide S1-(12-32)-IL-(163-171)]. In an in vitro thymocyte proliferation assay, both peptides S1-(12-32)-IL-(163-171) and IL-(163-171) showed comparable activity, whereas peptide S1-(12-32) was inactive. Groups of five to seven mice each from C3H/CH, BALB/c, SJL/J, and C57BL/6 strains were immunized with equimolar amounts of either peptide S1-(12-32), peptide S1-(12-32)-IL-(163-171), or a mixture of peptides S1-(12-32) and IL-(163-171), and sera were screened for anti-S1-(12-32) antibodies. In all strains, peptide S1-(12-32)-IL-(163-171) elicited an increased primary and secondary anti-S1-(12-32) antibody response compared to the other two groups. Further, peptide S1-(12-32)-IL-(163-171) also induced an increased number of responders to primary immunization, though the number of responders was quantitative in all groups following secondary immunization. At least part of the enhanced immunogenicity of the S1-(12-32) sequence in peptide S1-(12-32)-IL-(163-171) appears to be due to augmented T-helper cell activity. These results suggest that coupling of the immunostimulatory IL-1 beta-derived sequence in tandem with an immunogen may confer inbuilt adjuvanticity. PMID:2371286

  2. Cancer pulmonaire: parcours de soins au service de radiothérapie à l'institut national d'oncologie de Rabat

    PubMed Central

    Lachgar, Amine; Sahli, Nadir; Toulba, Ahmedou; Kebdani, Tayeb; Benjaafar, Noureddine

    2015-01-01

    L'objectif de cette étude est d'expliquer la discordance entre le nombre important de patients présentant un cancer du poumon localement avancé demandeurs de consultations en service de radiothérapie et le faible nombre de patients effectivement traité. Il s'agit d'une étude décrivant le circuit de soins des patients admis au service de radiothérapie de l'Institut national d'oncologie de Rabat entre le premier mars 2011 et le 29 février 2012 pour la prise en charge d'un cancer du poumon inopérable et/ou non résécable. On a utilisé pour la collecte des données les dossiers cliniques, le registre des nouveaux patients du bureau des admissions de l'institut ainsi que les registres des rendez-vous de consultation et de traitement du service de radiothérapie. 117 patients ont été collectés. Le stade de la maladie n'a pu être déterminé que chez 102 patients, on a ainsi trouvé 53 cancers non métastatiques et 49 cancers métastatiques. Chez les patients avec un cancer non métastatique une radiothérapie palliative a été réalisée chez 9 patients, chez 2 patients la radiothérapie a été contre indiquée, une chimiothérapie néo-adjuvante a été réalisée chez 7 patients et la radio-chimiothérapie concomitante d'emblée fut proposée à 35 patients, mais 34 patients seulement ont pu avoir leur première séance de radiothérapie à visée curative. Cette étude nous a permis de décrire le circuit de soins de nos patients en repérant les points critiques, auxquels on propose des mesures correctives. PMID:26523190

  3. Une étude rétrospective sur le cancer de l'ovaire avec un recul médian de 42 mois

    PubMed Central

    Raherinantenaina, Fanomezantsoa; Rakotomena, Solonirina Davidà; Hasiniatsy, Nomeharisoa Rodrigue Emile; Rakototiana, Felantsoa Auberlin; Rafaramino, Florine; Ratsimba, Hery Nirina Rakoto

    2015-01-01

    Le cancer de l'ovaire est relativement fréquent mais grave et de mauvais pronostic. Le but de cette étude était de mettre en évidence les aspects épidémiologique, diagnostique, thérapeutique et évolutif de cette pathologie maligne prise en charge dans un pays en développement. Il s'agit d'une étude rétrospective et descriptive de 10 ans (2000- 2009) effectuée dans un CHU de chirurgie générale et d'Oncologie sur 62 patientes ayant développé un cancer de l'ovaire et opérées à visée curative. L’âge moyen des patientes était de 43 ans dont 53,23% avaient plus de 45 ans. Le dosage sanguin du CA-125 était positif chez 10 patientes sur 12. Les tumeurs étaient découvertes à l’échographie dans 87,10% des cas et à la laparotomie dans 12,90%. L'hystérectomie totale avec annexectomie bilatérale était l'intervention la plus pratiquée (64,52%). Les suites opératoires précoces étaient simples. Dix patientes étaient opérées de second regard (16,13%) pour des récidives locorégionales. Les tumeurs épithéliales étaient le type histologique le plus fréquent (93,55%) dont 79% au stade avancé (Ic-IV) et 21% au stade précoce (Ia-Ib). La chimiothérapie adjuvante était administrée chez 22,60% des patientes. Avec un recul médian de 42 mois, 29 patientes étaient perdues de vue. L’évolution était favorable dans 27,42% et dans 25,81% les décès se sont survenus en postopératoire tardif. Le cancer de l'ovaire n’était pas fréquent mais grave compte tenu des stades avancés et du taux élevé des décès postopératoires tardifs qui étaient largement observés chez les patientes privées d'une chimiothérapie adéquate. PMID:26113942

  4. Intranasal Coadministration of Live Lactococci Producing Interleukin-12 and a Major Cow's Milk Allergen Inhibits Allergic Reaction in Mice▿

    PubMed Central

    Cortes-Perez, Naima G.; Ah-Leung, Sandrine; Bermúdez-Humarán, Luis G.; Corthier, Gérard; Wal, Jean-Michel; Langella, Philippe; Adel-Patient, Karine

    2007-01-01

    The Th1/Th2 balance deregulation toward a Th2 immune response plays a central role in allergy. We previously demonstrated that administration of recombinant Lactococcus lactis strains expressing bovine β-lactoglobulin (BLG), a major cow's milk allergen, partially prevents mice from sensitization. In the present study, we aimed to improve this preventive effect by coadministration of L. lactis BLG and a second recombinant L. lactis strain producing biologically active interleukin-12 (IL-12). This L. lactis strain producing IL-12 was previously used to enhance the Th1 immune response in a tumoral murine model (L. G. Bermúdez-Humarán et al., J. Immunol. 175:7297-7302, 2005). A comparison of the administration of either BLG alone or BLG in the presence of IL-12 was conducted. A BLG-specific primary Th1 immune response was observed only after intranasal coadministration of both L. lactis BLG and IL-12-producing L. lactis, as demonstrated by the induction of serum-specific immunoglobulin G2a (IgG2a) concomitant with gamma interferon secretion by splenocytes, confirming the adjuvanticity of IL-12-producing L. lactis. Immunized mice were further sensitized by intraperitoneal administration of purified BLG, and the allergic reaction was elicited by intranasal challenge with purified BLG. Mice pretreated with BLG in either the presence or the absence of IL-12 were rendered completely tolerant to further allergic sensitization and elicitation. Pretreatment with either L. lactis BLG or L. lactis BLG and IL-12-producing L. lactis induces specific anti-BLG IgG2a production in serum and bronchoalveolar lavage (BAL) fluid. Although specific serum IgE was not affected by these pretreatments, the levels of eosinophilia and IL-5 secretion in BAL fluid were significantly reduced after BLG challenge in the groups pretreated with L. lactis BLG and L. lactis BLG-IL-12-producing L. lactis, demonstrating a decreased allergic reaction. Our data demonstrate for the first time (i) the

  5. Fistules scrotales révélant un adénocarcinome mucineux du scrotum: à propos d’un cas

    PubMed Central

    El Alaoui, Abdelilah; El Boté, Hicham; Ziouani, Oussama; Dembele, Oussman; El Sayegh, Hachem; Iken, Ali; Benslimane, Lounis; Nouini, Yassine

    2017-01-01

    Les fistules scrotales sont rares, et souvent secondaires à des lésions de tuberculose. Les adénocarcinomes mucineux sont des tumeurs qui renferment au moins 50% de mucus extracellulaire, et siègent préférentiellement sur le recto sigmoïde, la localisation scrotale est inhabituelle. Nous rapportons un cas d’adénocarcinome mucineux secondaire du scrotum révélé par des fistules scrotales, chez un patient âgé de 54 ans, sans antécédents pathologiques notables, qui présente depuis deux ans des fistules scrotales à répétition, sans autres signes associés. L’examen trouve de multiples fistules scrotales avec issue de pus épais, le toucher rectal est normal. Les explorations urologiques (UIV, UCRM, Cystoscopie, …) sont normales, le bilan infectieux ainsi que la recherche de BK dans les urines et le crachat sont négatives. La biopsie de la peau scrotale est revenue en faveur d’un adénocarcinome mucineux moyennement différencié, dont l’étude immun histochimique est en faveur d’une origine primitive colorectale. L’évolution a été marqué par l’apparition de fistules anales complexes, ayant a l’IRM une caractéristique active, alimentant plusieurs collections pelvi périnéales comportant des bourgeons charnus. Sur le plan thérapeutique et vu la rareté de ce cancer, il n’y a pas de consensus. La résection chirurgicale reste le traitement de choix pour cette affection. La radio chimiothérapie pré opératoire est préconisée pour ce type de cancer mais son rôle n’est pas bien établi. Chez notre patient on a opté pour une radio chimiothérapie néo adjuvante première, avant la réalisation d’une amputation abdomino- périnéale. PMID:28674583

  6. Récidive d'un tératome immature de l'ovaire avec gliomatose péritonéale

    PubMed Central

    Boufettal, Houssine; Samouh, Naïma

    2015-01-01

    Le tératome immature est une tumeur germinale non séminomateuse très rare, dont l’évolution est variable dans les différents cas publiés (récidive, maturation, dégénérescence). Nous rapportons un cas de récidive d'un tératome immature de l'ovaire sous forme d'un tératome mature, après traitement chirurgical conservateur et chimiothérapie. Il s'agit d'une patiente âgée de 25 ans, qui était opérée pour un tératome immature de l'ovaire avec gliomatose péritonéale par une annexectomie droite et des biopsies des granulations péritonéales ainsi qu'une chimiothérapie adjuvante, à base de BEP comprenant bléomycine, étoposide et un sel de platine (cisplatinum). Une rechute était notée 18 mois après le traitement sous forme d'un tératome mature de l'ovaire gauche. Avec un recule de 36 mois, aucune récidive n’était notée. La surveillance des tératomes ovariens associés à une gliomatose péritonéale doit être rapprochée et prolongée. En effet, les tératomes matures peuvent dégénérer ou récidiver. Les tératomes immatures peuvent récidiver au niveau de l'ovaire controlatéral sous forme mature ou immature. Les implants peuvent subir une régression fibreuse ou, exceptionnellement, dégénérer vers une glioblastomatose, de mauvais pronostic. L’échographie pelvienne couplée au doppler reste l'examen de choix pour les masses annexielles. Elle doit être répétée au moindre doute, et complétée par la tomodensitométrie chez ces patientes. PMID:26090012

  7. Costs of topical treatment of pressure ulcer patients.

    PubMed

    Andrade, Cynthia Carolina Duarte; Almeida, Cláudia Fernanda Dos Santos Calixto de; Pereira, Walkíria Euzébio; Alemão, Márcia Mascarenhas; Brandão, Cristina Mariano Ruas; Borges, Eline Lima

    2016-04-01

    To evaluate the costs of a topical treatment of pressure ulcer (PU) patients in a hospital unit for treatment of chronic patients in 2014. This is an activity-based costing study. This method encompasses the identification, measurement and pricing of physical and human resources consumed for dressings. Procedure costs varied between BRL 16.41 and BRL 260.18. For PUs of the same category, of near areas and with the same type of barrier/adjuvant, the cost varied between 3.5% and 614.6%. For most dressings, the cost increased proportionally to the increase of the area and to the development of PU category. The primary barrier accounted for a high percentage of costs among all items required to the application of dressings (human and material resources). Dressings applied in sacral PUs had longer application times. This study allowed us to understand the costs involved in the treatment of PUs, and it may support decision-makers and other cost-effectiveness studies. Realizar uma avaliação do custo do tratamento tópico de pacientes com úlceras por pressão (UP), em uma unidade hospitalar de atendimento a pacientes crônicos no ano de 2014. Trata-se de um estudo de custos baseado no Sistema de custeio Baseado em Atividades. Este método contempla a identificação, mensuração e precificação dos recursos físicos e humanos consumidos para a realização de curativos. Os custos dos procedimentos variaram de R$16,41 a R$260,18. Para UP de mesma categoria, de áreas aproximadas e mesmo tipo de cobertura/adjuvante, a variação entre os custos foi de 3,5% a 614,6%. Para a maioria dos curativos, o custo aumentou proporcionalmente ao aumento da área e à progressão da categoria das UP. A cobertura primária representou elevado percentual nos custos entre todos os itens necessários para realizar os curativos (recursos humanos e materiais). Os curativos realizados nas UP sacrais foram os que apresentaram maiores tempos para execução. Este estudo permitiu conhecer os

  8. Intranasal coadministration of live lactococci producing interleukin-12 and a major cow's milk allergen inhibits allergic reaction in mice.

    PubMed

    Cortes-Perez, Naima G; Ah-Leung, Sandrine; Bermúdez-Humarán, Luis G; Corthier, Gérard; Wal, Jean-Michel; Langella, Philippe; Adel-Patient, Karine

    2007-03-01

    The Th1/Th2 balance deregulation toward a Th2 immune response plays a central role in allergy. We previously demonstrated that administration of recombinant Lactococcus lactis strains expressing bovine beta-lactoglobulin (BLG), a major cow's milk allergen, partially prevents mice from sensitization. In the present study, we aimed to improve this preventive effect by coadministration of L. lactis BLG and a second recombinant L. lactis strain producing biologically active interleukin-12 (IL-12). This L. lactis strain producing IL-12 was previously used to enhance the Th1 immune response in a tumoral murine model (L. G. Bermúdez-Humarán et al., J. Immunol. 175:7297-7302, 2005). A comparison of the administration of either BLG alone or BLG in the presence of IL-12 was conducted. A BLG-specific primary Th1 immune response was observed only after intranasal coadministration of both L. lactis BLG and IL-12-producing L. lactis, as demonstrated by the induction of serum-specific immunoglobulin G2a (IgG2a) concomitant with gamma interferon secretion by splenocytes, confirming the adjuvanticity of IL-12-producing L. lactis. Immunized mice were further sensitized by intraperitoneal administration of purified BLG, and the allergic reaction was elicited by intranasal challenge with purified BLG. Mice pretreated with BLG in either the presence or the absence of IL-12 were rendered completely tolerant to further allergic sensitization and elicitation. Pretreatment with either L. lactis BLG or L. lactis BLG and IL-12-producing L. lactis induces specific anti-BLG IgG2a production in serum and bronchoalveolar lavage (BAL) fluid. Although specific serum IgE was not affected by these pretreatments, the levels of eosinophilia and IL-5 secretion in BAL fluid were significantly reduced after BLG challenge in the groups pretreated with L. lactis BLG and L. lactis BLG-IL-12-producing L. lactis, demonstrating a decreased allergic reaction. Our data demonstrate for the first time (i) the

  9. Le médulloblastome chez l'adulte: à propos de 13 cas et revue de la literature

    PubMed Central

    Drissi, Jamal; Affane, Mariam; Elomrani, Abdelhamid; Khouchani, Mouna

    2015-01-01

    Le médulloblastome est une tumeur neuro-ectodermique primitive maligne. Il s'agit d'une tumeur rare chez l'adulte, représentant moins de 1% des tumeurs cérébrales. Nous proposons une étude rétrospective réalisée au sein du service d'Oncologie-Radiothérapie du CHU Mohamed VI de Marrakech sur une période de 13 ans. Le but de notre travail est de déterminer le profil épidémioclinique, thérapeutique, évolutif ainsi que les facteurs pronostiques de cette entité pathologique avec une revue de la littérature. Notre série comportait 13 patients, 10 hommes et 3 femmes, l’âge médian a été 20,8 ans. Le tableau clinique a été révélé par un syndrome d'hypertension intracrânienne (100%), associée à un syndrome cérébelleux (84%). La localisation était hémisphérique (31%) et vermio-hémisphérique (54%). 31% des patients ont bénéficié d'une exérèse chirurgicale totale. 85% des cas avaient une variante classique et 15% une variante desmoplasique. 30% des cas avaient été classés à «risque standard» et 70% à «haut risque». La chirurgie avait été complétée d'une radiothérapie de l'ensemble du névraxe selon la technique de «jonctions mobiles» dans tous les cas. Le délai moyen était de 73 jours. Une chimiothérapie adjuvante avait été réalisée chez 9 cas. Avec un recul moyen de 21.3 mois, l’évolution a été marquée par une récidive tumorale (4 cas), une toxicité auditive (6 cas) et des troubles cognitifs chez un cas. La prise en charge du médulloblastome doit être multidisciplinaire associant neurochirurgiens et oncologues radiothérapeutes. Cette collaboration est le seul garant d'une amélioration de son pronostic. PMID:26889307

  10. Validation of the Portuguese version of the Evidence-Based Practice Questionnaire

    PubMed Central

    Pereira, Rui Pedro Gomes; Guerra, Ana Cristina Pinheiro; Cardoso, Maria José da Silva Peixoto de Oliveira; dos Santos, Alzira Teresa Vieira Martins Ferreira; de Figueiredo, Maria do Céu Aguiar Barbieri; Carneiro, António Cândido Vaz

    2015-01-01

    OBJECTIVES: to describe the process of translation and linguistic and cultural validation of the Evidence Based Practice Questionnaire for the Portuguese context: Questionário de Eficácia Clínica e Prática Baseada em Evidências (QECPBE). METHOD: a methodological and cross-sectional study was developed. The translation and back translation was performed according to traditional standards. Principal Components Analysis with orthogonal rotation according to the Varimax method was used to verify the QECPBE's psychometric characteristics, followed by confirmatory factor analysis. Internal consistency was determined by Cronbach's alpha. Data were collected between December 2013 and February 2014. RESULTS: 358 nurses delivering care in a hospital facility in North of Portugal participated in the study. QECPBE contains 20 items and three subscales: Practice (α=0.74); Attitudes (α=0.75); Knowledge/Skills and Competencies (α=0.95), presenting an overall internal consistency of α=0.74. The tested model explained 55.86% of the variance and presented good fit: χ2(167)=520.009; p = 0.0001; χ2df=3.114; CFI=0.908; GFI=0.865; PCFI=0.798; PGFI=0.678; RMSEA=0.077 (CI90%=0.07-0.08). CONCLUSION: confirmatory factor analysis revealed the questionnaire is valid and appropriate to be used in the studied context. PMID:26039307

  11. An Analytical Overview of Spirituality in NANDA-I Taxonomies.

    PubMed

    Mesquita, Ana Cláudia; Caldeira, Sílvia; Chaves, Erika; Carvalho, Emilia Campos de

    2017-03-01

    To discuss the approach of spirituality in NANDA-I taxonomies, based on the elements that characterize this phenomenon. This study was based on concepts that are usually adopted in the literature for defining spirituality and on the analysis of the NANDA-I taxonomies from I to III. Spirituality is included in all taxonomies but all three are missing some attributes to guarantee the completeness of this dimension for nursing diagnosis. Taxonomy III makes different approaches to spirituality and some inconsistencies. Contribute to the development and review of the new proposal for taxonomy. Discutir a abordagem à espiritualidade nas taxonomias da NANDA-I, baseada nos elementos que caracterizam este fenômeno. MÉTODOS: Este estudo foi baseado em conceitos usualmente adotados na literatura de enfermagem para definir espiritualidade e na análise das taxonomias da NANDA-I, desde a I à III. A espiritualidade está incluída nas taxonomias, porém estas carecem de atributos do seu conceito. CONCLUSÕES: A taxonomia III faz diferentes abordagens à espiritualidade, porém com algumas inconsistências identificadas. IMPLICAÇÕES PARA A ENFERMAGEM: Esta análise pode contribuir para o desenvolvimento e revisão da taxonomia III. © 2017 NANDA International, Inc.

  12. The Expected Cardiovascular Benefit of Plasma Cholesterol Lowering with or Without LDL-C Targets in Healthy Individuals at Higher Cardiovascular Risk.

    PubMed

    Cesena, Fernando Henpin Yue; Laurinavicius, Antonio Gabriele; Valente, Viviane A; Conceição, Raquel D; Santos, Raul D; Bittencourt, Marcio S

    2017-06-01

    There is controversy whether management of blood cholesterol should be based or not on LDL-cholesterol (LDL-c) target concentrations. To compare the estimated impact of different lipid-lowering strategies, based or not on LDL-c targets, on the risk of major cardiovascular events in a population with higher cardiovascular risk. We included consecutive individuals undergoing a routine health screening in a single center who had a 10-year risk for atherosclerotic cardiovascular disease (ASCVD) ≥ 7.5% (pooled cohort equations, ACC/AHA, 2013). For each individual, we simulated two strategies based on LDL-c target (≤ 100 mg/dL [Starget-100] or ≤ 70 mg/dL [Starget-70]) and two strategies based on percent LDL-c reduction (30% [S30%] or 50% [S50%]). In 1,897 subjects (57 ± 7 years, 96% men, 10-year ASCVD risk 13.7 ± 7.1%), LDL-c would be lowered from 141 ± 33 mg/dL to 99 ± 23 mg/dL in S30%, 71 ± 16 mg/dL in S50%, 98 ± 9 mg/dL in Starget-100, and 70 ± 2 mg/dL in Starget-70. Ten-year ASCVD risk would be reduced to 8.8 ± 4.8% in S50% and 8.9 ± 5.2 in Starget-70. The number of major cardiovascular events prevented in 10 years per 1,000 individuals would be 32 in S30%, 31 in Starget-100, 49 in S50%, and 48 in Starget-70. Compared with Starget-70, S50% would prevent more events in the lower LDL-c tertile and fewer events in the higher LDL-c tertile. The more aggressive lipid-lowering approaches simulated in this study, based on LDL-c target or percent reduction, may potentially prevent approximately 50% more hard cardiovascular events in the population compared with the less intensive treatments. Baseline LDL-c determines which strategy (based or not on LDL-c target) is more appropriate at the individual level. Há controvérsias sobre se o controle do colesterol plasmático deve ou não se basear em metas de concentração de colesterol LDL (LDL-c). Comparar o impacto estimado de diferentes estratégias hipolipemiantes, baseadas ou não em metas de LDL-c, sobre o

  13. Improvement of nursing students' learning outcomes through scenario-based skills training.

    PubMed

    Uysal, Nurcan

    2016-08-08

    presenta los errores comunes de los alumnos en la ejecución de inyecciones intramuscular y subcutánea y su desarrollo de capacidades de acceso intravenoso, tratadas en el examen de laboratorio de habilidades de enfermería. un análisis de los errores más comunes de los alumnos reveló que el más común fue el no seguimiento de los principios de asepsia para las tres habilidades ((intramuscular, inyección subcutánea, acceso intravenoso) en el primer año de la capacitación basada en escenarios. Las notas de desempeño de los alumnos en la prueba aumentaron gradualmente, excepto en el semestre de otoño del año académico 2009-2010. Fue observado que la capacitación basada en escenarios redujo los errores comunes de los alumnos en los exámenes y aumentó su desempeño en las pruebas. tanto los alumnos como los profesores respondieron positivamente a ese método. La capacitación basada en escenarios está disponible para uso en combinación con otros métodos de capacitación. neste estudo se analisou a influência da formação de capacidades baseada em cenários nas capacidades de aprendizagem de alunos. o autor avaliou os textos de exames de laboratório de habilidades de enfermagem produzidos por 605 alunos de segundo ano em cursos de enfermagem durante sete anos. O estudo determinou os erros comuns dos alunos e o trabalho em laboratório adotou o formato baseado em cenários. A eficácia desse método foi avaliada mediante o número de erros que os alunos cometeram e suas notas de desempenho em exames de laboratório. Este estudo apresenta os erros comuns dos alunos na execução de injeções intramuscular e subcutânea e seu desenvolvimento de habilidades de acesso intravenoso, tratadas no exame de laboratório de habilidades de enfermagem. uma análise dos erros mais comuns dos alunos revelou que o mais comum foi o não seguimento dos princípios de assepsia para as três habilidades (intramuscular, injeção subcutânea, acesso intravenoso) no primeiro

  14. Pneumatosis intestinalis after etoposide-based chemotherapy in a patient with metastatic small cell lung cancer: successful conservative management of a rare condition.

    PubMed

    Faria, Luiza Dib Batista Bugiato; Anjos, Carlos Henrique Dos; Fernandes, Gustavo Dos Santos; Carvalho, Igor Fernando da Silva

    2016-01-01

    A 69-year-old male patient, smoker, was diagnosed with small cell lung cancer metastatic to lung, liver and central nervous system. He received chemotherapy with carboplatin AUC 5 on day 1 and etoposide 100mg/m2 on days 1, 2 and 3. During the first cycle, the patient presented with febrile neutropenia and abdominal distension. Chest, abdomen and pelvis computed tomography scan was performed and detected gas dissecting the wall of sigmoid colon extending to the mesosigmoid. Patient had no abdominal pain, nausea, vomiting, and on physical examination he had no peritoneal irritation, tachycardia or hemodynamic instability compatible with perforation or acute abdomen. Therefore, the radiological finding was interpreted as pneumatosis intestinalis caused by chemotherapy with etoposide. Pneumatosis resolved after continuous oxygen therapy. The second cycle was administered after a complete resolution of the clinical condition and etoposide dose was reduced by 30%. The patient experienced a remarkable evolution. RESUMO Paciente do gênero masculino, 69 anos, fumante, diagnosticado com câncer de pulmão de pequenas células, metastático para pulmão, fígado e sistema nervoso central. Foi administrada quimioterapia com carboplatina AUC 5 no dia 1 e etoposídeo 100mg/m2 nos dias 1, 2 e 3. Durante o primeiro ciclo, o paciente apresentou neutropenia febril e distensão abdominal. Tomografias de tórax, abdome e pelve detectaram gás dissecando a parede do cólon sigmoide, com extensão para o mesossigmoide. O paciente não apresentava dor abdominal, náusea, vômito e não tinha sinais de irritação peritoneal, taquicardia ou instabilidade hemodinâmica compatíveis com perfuração ou abdome agudo. O achado radiológico foi interpretado como pneumatose intestinal causada por etoposídeo. A resolução do quadro ocorreu após suplementação de oxigênio. O segundo ciclo foi administrado após resolução completa do quadro, com redução da dose do quimioterápico em 30

  15. [Pineal region tumors in children: is gross-total resection necessary? A single-center experience].

    PubMed

    López-Aguilar, Enrique; Garza-González, María del Carmen; Ortiz-Azpilcueta, Mariana; Sepúlveda-Vildósola, Ana Carolina; Rioscovian-Soto, Ana; de la Cruz-Yañez, Hermilo; Betanzos-Cabrera, Yadira

    2015-01-01

    Introducción: la supervivencia de los niños con tumores de la región pineal se ha incrementado en la última década; estos tienen una evolución insidiosa asociada con los desórdenes endocrinológicos y una alta morbilidad y mortalidad, sobre todo después de la resección. El objetivo es reportar la supervivencia, la morbilidad y mortalidad según el tipo de cirugía, la histología y el tratamiento en un grupo de niños con tumores de la región pineal. Métodos: estudio retrospectivo que incluyó a todos los pacientes con diagnóstico de tumor de la región pineal menores de 17 años de edad que acudieron en un periodo de 10 años a un hospital de pediatría. Se realizó una revisión histopatológica, se determinó la extensión de la resección y se estimó la supervivencia. Resultados: se incluyeron 46 pacientes, 36 de los cuales tenían expediente completo y material de patología adecuado. La resección total se realizó en 24 (66.6 %) y biopsia en 12 (33.3 %); fallecieron 23 pacientes (88 %) y fue el desequilibrio hidroelectrolítico la causa de 14 defunciones (60 %) y la progresión tumoral la causa de las 9 defunciones restantes (39.1 %). La sobrevida a 10 años de los pacientes tratados con resección total y biopsia fue del 52 y 75 %, respectivamente, con una p = 0.7; se presentaron alteraciones endocrinológicas en 13 (36.1%) pacientes de los cuales a 10 (76.9 %) se les realizó la resección de la tumoración. Conclusión: los tumores de la región pineal en niños se pueden tratar con biopsia diagnóstica seguida de tratamiento adyuvante con quimioterapia y radioterapia.

  16. NUTRITIONAL, MICROBIOLOGICAL, AND THERAPEUTIC FACTORS RELATED TO MUCOSITIS IN HEAD AND NECK CANCER PATIENTS: A COHORT STUDY.

    PubMed

    Vidal-Casariego, Alfonso; Fernández-Natal, Isabel; Calleja-Fernández, Alicia; Parras-Padilla, Trinidad; Cano-Rodríguez, Isidoro; Prieto-Alonso, Begoña; Ballesteros-Pomar, María D

    2015-09-01

    Objetivo: el objetivo fue demostrar si la modalidad de tratamiento, el estado nutricional y la flora orofaríngea contribuyen al desarrollo de mucositis en pacientes con cáncer de cabeza y cuello tratados con radioterapia. Métodos: estudio de cohorte de pacientes con cáncer de cabeza y cuello (CyC) tratados con radioterapia. El estado nutricional se evaluó utilizando VGS, IMC e IMM. Se realizó un frotis bucal antes de la radioterapia para el cultivo de bacterias y levaduras. Se evaluó la mucositis usando los criterios de la OMS. Se calcularon el riesgo relativo (RR) y su IC del 95%. Resultados: el estudio incluyó a 35 pacientes, 74,3% hombres, 63,8 (9,9) años de edad, y 34,3% desnutridos. Los tumores estaban localizados en laringe (40,0%), boca (25,7%) y faringe (11,4%). El tratamiento consistió en 66,0 Gy de radiación, quimioterapia (60,0%) y cirugía (57,1%). Se encontraron bacterias en 28,6%, incluyendo Staphylococcus aureus (8,6%) y Escherichia coli (8,6%). Se encontró Candida spp. en el 35,3%. La mucositis fue más frecuente en los pacientes con radioterapia radical [100% vs. 65%, p = 0,01; RR = 1,54 (IC95% 1,12 a 2,12)]. Ni VGS, IMC ni IMM se relacionaron con el desarrollo o la gravedad de la mucositis. Los cultivos positivos para bacterias antes de la radioterapia se relacionaron con mucositis severa [44,4% vs. 12%, p = 0,039; RR = 4,17 (IC95% 1,22 a 14,24)], pero no hubo ninguna relación con la presencia de levaduras. La cirugía no se asoció con la aparición de las cepas estudiadas de bacterias. Conclusión: la colonización bacteriana de la orofaringe antes de la radioterapia puede ser un factor para la mucositis graves en pacientes con cáncer CyC.

  17. Association between an inflammatory-nutritional index and nutritional status in cancer patients.

    PubMed

    Alberici Pastore, Carla; Paiva Orlandi, Silvana; González, María Cristina

    2013-01-01

    Introducción: La caquexia es un síndrome multifactorial caracterizada por la pérdida de peso corporal, grasa y músculo, el aumento de la morbilidad y la mortalidad. El uso de un índice de la contabilidad para los dos niveles de albúmina sérica y la proteína C reactiva podría hacer que la identificación temprana de la caquexia más fácil. Objetivo: Evaluar la variación de una índice inflamatorio- nutricional en relación con el estado nutricional en pacientes con cáncer. Métodos: Estudio descriptivo incluyendo pacientes con cáncer gastrointestinal y los pulmones de un servicio de la quimioterapia pública en Brasil. La albumina y la proteína C reactiva fueron medidos y el estado nutricional se definió por la Evaluación Global Subjetiva. Los análisis estadísticos se realizaron utilizando Stata 9.2(TM). Resultados: Un total de 74 pacientes fueron evaluados, el 58,1% de ellos fueron hombres y el promedio de 63,4 ± 11,9 2013s de edad. Cáncer gastrointestinal era el tipo más frecuente (71,6%). Sólo el 13,7% de los pacientes estaban bien nutridos y el 21,9% estaban gravemente desnutridos. Proteína C reactiva aumentaron significativamente de acuerdo a la declinación del estado nutricional (p=0,03). Cuando la albúmina de los pacientes con inflamación sistémica se evaluó, no hubo variación significativa en relación al estado nutricional (p=0,06). El índice inflamatorio-nutricional varió significativamente en relación al estado nutricional independiente de la inflamación sistémica (p=0,02). Conclusiones: El índice inflamatorio-nutricional puede ser una manera adyuvante para la evaluación nutricional bioquímica y seguimiento en los pacientes con cáncer y la inflamación sistémica.

  18. Angiolymphatic invasion as a prognostic fator in resected N0 pancreatic adenocarcinoma.

    PubMed

    Almeida, Ricardo Vitor Silva de; Pacheco-Jr, Adhemar Monteiro; Silva, Rodrigo Altenfelder; Moricz, André de; Campos, Tércio de

    2017-01-01

    Pancreatic adenocarcinoma remains one of the worst digestive cancers. Surgical resection is the main target when treating a patient with curative intent. To assess angiolymphatic invasion as a prognostic factor in resected pN0 pancreatic cancer. Thirty-eight patients were submitted to pancreatoduodenectomy due to head pancreatic cancer. Tumor size, margins, lymph nodes, pTNM staging, angiolymphatic and perineural invasion were described in the pathologists' reports. Most patients were female. Overall median survival was 13 months. Gemcitabine was the regimen of choice for chemotherapy in selected patients; however, it did not improve overall survival. pR0 resection had better survival compared with pR1. Within the pN0 group, survival was significantly better in patients without angiolymphatic invasion. Angiolymphatic invasion in N0 pancreatoduodenectomy can be demonstrated by the Hematoxylin-Eosin stain and may predict a poor prognosis factor for those patients. Adenocarcinoma pancreático continua sendo um dos piores cânceres do aparelho digestivo. A ressecção cirúrgica é o principal objetivo quando se trata de intenção curativa. Avaliar a invasão angiolinfática como um fator prognóstico no câncer da cabeça do pâncreas ressecado pN0. Trinta e oito pacientes foram submetidos a duodenopancreatectomia por câncer da cabeça do pâncreas. Tamanho do tumor, margens, linfonodos, estadiamento pTNM, invasão angiolinfática e perineural foram descritos nos laudos anatomopatológicos. A maioria foi de mulheres. A sobrevida mediana global foi de 13 meses. Gencitabina foi a droga de escolha para quimioterapia nos pacientes selecionados, entretanto não aumentou a sobrevida global. Pacientes com ressecção pR0 tiveram sobrevida global superior quando comparados com ressecção pR1. Dentro do grupo de pacientes com pN0, a sobrevida foi significativamente melhor no grupo de pacientes que não apresentavam invasão angiolinfática. A invasão angiolinfática da

  19. PubMed

    García Almeida, Jose M; Lupiáñez Pérez, Yolanda; Blanco Naveira, Mercedes; Ruiz Nava, Josefina; Medina, José Antonio; Cornejo Pareja, Isabel; Gómez Pérez, Ana; Molina Vega, María; López-Medina, José A; Tinahones Madueño, Francisco

    2017-06-05

    Introducción: en pacientes con riesgo nutricional, la Sociedad Europea de Clínica y Metabolismo (ESPEN) y Parenteral recomienda suplementos nutricionales durante el tratamiento oncológico para prevenir la pérdida de peso involuntaria.Objetivos: nuestro objetivo es conocer el cumplimiento, la aceptabilidad y la tolerancia de un suplemento hiperproteico, hipercalórico, rico en omega 3 en pacientes oncológicos.Métodos: estudio unicéntrico, observacional y prospectivo en pacientes oncológicos con un suplemento nutricional hiperproteico, hipercalórico, rico en omega 3 y de bajo volumen. Fueron incluidos 30 pacientes con desnutrición o en riesgo de desnutrición. La suplementación duró seis días. Se evaluaron el cumplimiento (envases utilizado), la aceptabilidad (escala Madrid), las variables antropométricas y los acontecimientos adversos (AA) gastrointestinales.Resultados: el 70% fueron hombres, con una edad media de 60 años (rango: 32 a 79) y con neoplasias de pulmón (43,3%), ORL (26,7%) y mama (13,3%), en estadio III-IV (56,7%), tratados con radioterapia (93,3%), quimioterapia (60%) y cirugía (16,7%). El producto fue aceptado por todos los pacientes. Se observó un cumplimiento del 100%. En dos pacientes (6,7%) se observaron AA gastrointestinales (grado II) relacionados con el suplemento; ambos sujetos presentaban patologías gastrointestinales previas. La mediana del peso, índice de masa corporal (IMC) y proteínas ingeridas aumentó durante la suplementación (0,2 kg, 0,1 kg/m2 y 6,2 g). No se observaron diferencias respecto a la ingesta de calorías, lípidos y carbohidratos. Conclusión: la elevada aceptación y cumplimiento del suplemento nutricional específico se asoció con la mejora nutricional de los pacientes oncológicos, pues revirtió la pérdida de peso, sin presentar problemas gastrointestinales severos ni producir desplazamiento de la ingesta.

  20. [In Process Citation].

    PubMed

    Álvarez-Altamirano, Karolina; Mendoza-Hernández, Alma Nubia; Carcoba-Tenorio, Carolina; García-García, José Antonio; Fuchs-Tarlovsky, Vanessa

    2016-03-25

    Introducción y objetivos: la terapia con antioxidantes durante la quimioterapia y radioterapia en pacientes con cáncer cervicouterino es controvertida. Mientras existe evidencia que sugiere que el uso de antioxidantes disminuye los efectos secundarios propios del tratamiento contra el cáncer, hay datos que sugieren que los antioxidantes incrementan el riesgo de recurrencia de cáncer por la afectación de la terapia de los tratamientos. Métodos: se dirigió un estudio clínico controlado en pacientes con cáncer cervicouterino que fueron suplementados con una mezcla de antioxidantes o placebo, con seguimiento por 4 años posteriores al término de su tratamiento antineoplásico para evaluar el efecto de los antioxidantes en la recurrencia. Tomamos datos de niveles de hemoglobina y albúmina. Se analizaron las diferencias entre grupos con la prueba de Chi-cuadrado, la sobrevida se calculó con un análisis multivariado por medio de regresión de COX. Resultados: se dio seguimiento a 103 pacientes con cáncer cervicouterino en etapa clínica IIB y IIIB de los cuales 48% fueron tratados con suplementación de antioxidantes y el 52% con placebo, originalmente y de estos se dio seguimiento a 88 pacientes durante 4 años. El 23,9% de los pacientes tratados presentaron recurrencia por cáncer mientras que el 76,1% no la presentó. El 21,6% de los pacientes presentaron metástasis, el 8% de los pacientes perteneció al grupo de antioxidantes y el 15,9% al grupo placebo (p > 0,05). Implicaciones para los pacientes supervivientes: la suplementación con antioxidantes aparentemente no interfiere con la recurrencia por cáncer, sin embargo no hay evidencia suficiente para probarlo. Posiblemente una dosis distinta sea la clave para un mejor efecto, pero serán necesarios futuros estudios que prueben efectos sobre otro tipo de dosis. Conclusiones: la suplementación con antioxidantes durante el tratamiento de pacientes con cáncer cervicouterino no tiene efectos en la

  1. [Incidence of adverse events associated to the use of short peripheral venous catheters].

    PubMed

    Buenfil-Vargas, Miguel Armando; Espinosa-Vital, Guadalupe Judith; Rodriguez-Sing, Roberta; Miranda-Novales, María Guadalupe

    2015-01-01

    Introducción: la vigilancia de los eventos secundarios al uso de catéteres venosos periféricos es un indicador de calidad de la atención. El objetivo del estudio fue reportar la incidencia y los factores de riesgo para eventos adversos asociados a catéteres cortos periféricos. Métodos: estudio de cohorte prospectiva. Se incluyeron pacientes que tuvieron catéter corto periférico por más de 48 horas. Las variables de resultado fueron la disfunción y la flebitis química o bacteriana. Se registró edad, sexo, enfermedad de base, estado nutricional, sitio y lugar de colocación, calidad de la piel, tipo de soluciones administradas y fijación. En cuanto al análisis estadístico, se calculó la incidencia de los eventos adversos por 100 catéteres y por 1000 días catéter; se realizó análisis univariado y multivariado de los factores de riesgo. Resultados: se incluyeron 410 catéteres, con una mediana de días de uso de tres días. No hubo complicaciones infecciosas: 47 presentaron flebitis química (11.4 %) y 231 disfunción mecánica (56.3 %), la densidad de incidencia fue de 35.6 y 175 por 1000 días catéter respectivamente. En el análisis multivariado los factores asociados con flebitis química fueron lesiones en piel (p = 0.001, RR 3.479), y uso de recubrimiento extra (p = 0.007, RR 4.025); para disfunción mecánica fue administración de quimioterapia (p = 0.026, RR 4.293). Conclusión: la tasa de disfunción fue elevada, lo que lleva a retiro del catéter antes de las 96 horas. No se registraron complicaciones infecciosas.

  2. [Stability study of oxaliplatin and doxorubicin for intraperitoneal administration with hyperthermia].

    PubMed

    Escudero-Ortiz, V; Duart-Duart, M J; Pérez-Ruixo, C; Pérez-Ruixo, J J; Valenzuela, B

    2014-05-01

    Objetivo: Determinar in vitro la estabilidad físico-química de oxaliplatino ydoxorrubicina en las condiciones de hipertermia utilizadas in vivo duranteel tratamiento de pacientes con carcinomatosis peritoneal, tras cirugía citorreductora.Métodos: Se prepararon tres disoluciones: A (oxaliplatino 200 mg/L), B(doxorrubicina 15 mg/L) y C (oxaliplatino 200 mg/L + doxorrubicina 15 mg/L)en glucosa al 5%. Las tres disoluciones se sometieron a la temperaturamáxima alcanzada in vivo (49º C) durante dos horas. La estabilidad física secentró en el control visual de partículas y/o precipitados en las disoluciones,el desprendimiento de gases, olor y color. Para controlar la estabilidad química,se extrajeron muestras cada 15 minutos desde el inicio del estudio yse determinó la concentración remanente de oxaliplatino y doxorrubicina enlas mismas. Las concentraciones de oxaliplatino se determinaron por absorciónatómica con cámara de grafito mientras que doxorrubicina se determinómediante cromatografía líquida de alta resolución. Como criterio deestabilidad química se seleccionó el establecido en la Farmacopea Americanaque establece un margen de variación permitido entre el 90-110% de laconcentración inicial.Resultados: Durante el tiempo de ensayo, no se observó la aparición departículas o precipitados, ni el desprendimiento de gases o cambios decolor en las disoluciones. Las muestras analizadas presentaron una concentraciónremanente de oxaliplatino y doxorrubicina dentro del límite de 90-110%. La estabilidad de las muestras sometidas a dos ciclos de congelación-descongelación tras la hipertermia también se encontró dentro de loslímites especificados.Conclusiones: Las disoluciones A, B y C en glucosa al 5%, son establesfísica y químicamente a 49º C, durante dos horas. En estas condiciones,podrían ser utilizadas con garantías de estabilidad en pacientes con carcinomatosisperitoneal subsidiarios de recibir quimioterapia intraperitonealcon

  3. Clinical development and perspectives of CIMAvax EGF, Cuban vaccine for non-small-cell lung cancer therapy.

    PubMed

    Rodríguez, Pedro C; Rodríguez, Gryssell; González, Gisela; Lage, Agustín

    2010-01-01

    inmunogenicidad con el aumento de la dosis, dividida en dos sitios anatómicos, y además se estableció la correlación entre los títulos de Acs, la concentración de EGF sérico y la supervivencia. En los primeros cuatro ensayos fase I/II, la vacuna se administró después de la quimioterapia (esquema QVV). En el quinto ensayo fase I/II, se lograron mayor supervivencia e inmunogenicidad utilizando un esquema VQV y dividiendo la dosis vacunal en cuatro sitios anatómicos. El ensayo clínico de fase II conforrmó los resultados de los estudios anteriores, así como un perfil de eventos adversos leves a moderados asociados a CIMAvax EGF. Se observó mayor supervivencia en todos los pacientes vacunados en comparación con los controles y la diferencia fue estadísticamente significativa (p <0.05) en el grupo de <60 años. Conclusiones Es necesario evaluar los beneficios de CIMAvax EGF en etapas tempranas del CPCNP y en otras localizaciones tumorales, así como en los pacientes no aptos para recibir quimioterapia. La evidencia de que la vacuna es segura para uso mantenido también debe ser sistematizada. Palabras clave Factor de crecimiento epidérmico, receptor del EGF, cáncer de pulmón de células no pequeñas, tratamiento vacunal, inmunoterapia, vacunas oncológicas

  4. Intra-aortic balloon pump in cardiogenic shock: state of the art.

    PubMed

    Thomaz, Petronio Generoso; Moura, Leonel Adelino; Muramoto, Giovana; Assad, Renato Samy

    2017-01-01

    ínica tem sido baseada em estudos não randomizados e dados de registro. Estudos recentes têm demonstrado que o uso do BIA não reduziu a mortalidade hospitalar (30 dias) em pacientes com IAM e choque cardiogênico, tratados com a estratégia de revascularização precoce do miocárdio como objetivo primário planejado. As diretrizes da Associação Americana de Cardiologia e da Sociedade Europeia de Cardiologia reavaliaram suas recomendações, baseadas nos resultados de metanálises, incluindo o estudo IABP-SCHOCK II Trial, que não evidenciou aumento na sobrevida de pacientes que receberam suporte mecânico com BIA. Este artigo de revisão aborda o impacto clínico do uso do BIA no choque cardiogênico ocasionado pelo IAM.

  5. Incorporando a variabilidade no processo de identificação do modelo de máximo global no Grade of Membership (GoM): considerações metodológicas

    PubMed Central

    Guedes, Gilvan Ramalho; Siviero, Pamila Cristina Lima; Caetano, André Junqueira; Machado, Carla Jorge; Brondízio, Eduardo

    2012-01-01

    A disponibilidade de bases de dados cada vez mais complexas e multidimensionais é um dos principais motivadores para o aumento do número de estudos que utilizam análises multivariadas baseadas em lógica de conjuntos nebulosos. Apesar da disseminação do método Grade of Membership nos trabalhos empíricos brasileiros da área de ciências sociais e saúde, questões relativas à identificabilidade e estabilidade dos parâmetros finais estimados pelo programa GoM 3.4 não foram suficientemente aprofundadas. Dada a relevância de se obterem parâmetros únicos e estáveis, Guedes et al. (2010) propuseram um procedimento empírico para localizar um modelo de máximo global (MG) com parâmetros estáveis. Entretanto, seu localizador de MG não incorpora qualquer medida de variabilidade. Neste artigo, tal limitação é contornada por meio da utilização de uma estatística de ponderação – Máximo Global Ponderado (MGP) – semelhante ao coeficiente de variação. Esse indicador busca não penalizar de forma desproporcional situações nas quais os desvios médios, apesar de diferentes de zero, são muito pequenos. Apresentam-se evidências de que o localizador MGP reduz a distância do modelo identificado à real estrutura latente dos dados em análise, quando comparados ao modelo identificado pelo localizador não ponderado, MG. PMID:23293402

  6. Situação da Mulher na Astronomia Brasileira

    NASA Astrophysics Data System (ADS)

    Silva, Adriana V. R.

    2007-07-01

    O conteúdo desse texto surgiu de uma apresentação de mesmo título que fiz na XXXI Reunião Anual da Sociedade Astronômica Brasileira (SAB) em 2005. Esse tema foi inspirado originalmente pela minha participação no "2nd UIPAP International Conference on Women in Physics" realizado entre 23 e 25 de maio de 2005 no Rio de Janeiro. Essa é uma conferência internacional que acontece de três em três anos, sendo que a primeira ocorreu em 2002 na cidade de Paris, França. Participei dessa conferência como membro da delegação da Sociedade Brasileira de Física e um dos trabalhos que apresentei versava sobre a situação das mulheres na Astronomia brasileira, cujos resultados principais discorro a seguir. A situação das astrônomas, baseada nos dados dos sócios da SAB coletados no final de 2004, é comparada com a das físicas brasileiras e também com as nossas colegas americanas. Os dados identificam ainda uma maior evasão da carreira por parte das mulheres do que os homens. Alguns dos possíveis motivos da evasão são discutidos, como o desejo de constituir família e/ou isolamento. Resultados um tanto preocupantes com relação à distribuição de bolsas de produtividade do CNPq também são apresentados. As principais discussões e estratégias recomendadas nesse congresso são mencionadas de forma resumida ao final.

  7. Eventos de Desconexao na Cauda de Plasma do Cometa P/Halley

    NASA Astrophysics Data System (ADS)

    Voelzke, M. R.; Fahr, H. J.

    2001-08-01

    Observacoes cometárias e de vento solar sao comparadas com o propósito de determinar-se as condicoes do vento solar associadas aos eventos de desconexao (DEs) observados em caudas de plasma cometárias. Os dados cometários sao provenientes do The International Halley Watch Atlas of Large-Scale Phenomena. A análise visual sistemática das imagens do atlas revelou, entre outras estruturas morfológicas, 47 DEs ao longo da cauda de plasma do P/Halley. Estes 47 DEs registrados em 47 imagens distintas permitiram a descoberta de 19 origens de DEs, ou seja, o tempo em que as desconexoes iniciaram foi calculado. Os dados do vento solar sao provenientes de medidas feitas in situ pela sonda espacial IMP-8, as quais foram usadas para elaborar a variacao da velocidade do vento solar, densidade e pressao dinâmica durante o intervalo analisado. O presente trabalho compara as atuais teorias conflitantes, baseadas nos mecanismos de formacao, com o intuito de explicar o fenômeno cíclico dos DEs, ou seja, os efeitos de producao iônica, os efeitos de pressao e os efeitos de reconexao magnética sao analisados. Para cada uma das 19 origens de DEs comparou-se a densidade com a respectiva velocidade do vento solar com o intuito de determinar-se uma possível correlacao entre estas origens e os efeitos de pressao dinâmica. Quando da ocorrência de 6 origens de DEs o IMP-8 nao realizou medidas, nos outros 13 casos 10 origens (77%) mostraram uma anticorrelacao entre velocidade e densidade e apenas 3 (23%) revelaram uma tendência similar entre velocidade e densidade. Portanto, a análise inicial demonstra uma fraca correlacao entre as origens dos DEs e os efeitos de pressao.

  8. Cough: neurophysiology, methods of research, pharmacological therapy and phonoaudiology.

    PubMed

    Balbani, Aracy Pereira Silveira

    2012-04-01

    Introdução: A tosse é o sintoma respiratório mais comum em crianças e adultos.Objetivo: Apresentar uma revisão sobre a neurofisiologia e os métodos para estudo do reflexo da tosse, bem como a farmacoterapia e terapia fonoaudiológica da tosse, baseada nos trabalhos publicados entre 2005 e 2010 e indexados nas bases Medline, Lilacs e Biblioteca Cochrane sob os unitermos “tosse” ou “antitussígenos”.Síntese dos dados: O reflexo da tosse envolve ativação de múltiplos receptores vagais nas vias aéreas e de projeções neurais do núcleo do trato solitário para outras estruturas do sistema nervoso central. Técnicas experimentais permitem estudar o reflexo da tosse ao nível celular e molecular para desenvolver novos agentes antitussígenos. Não há evidências de que antitussígenos isentos de prescrição médica tenham eficácia superior à do placebo para o alívio da tosse. A terapia fonoaudiológica pode beneficiar pacientes com tosse crônica refratária ao tratamento farmacológico, sobretudo quando coexiste movimento paradoxal das pregas vocais.Comentários Finais: A abordagem multidisciplinar tem papel fundamental no diagnóstico etiológico e tratamento da tosse. O otorrinolaringologista deve informar os pacientes sobre os riscos dos antitussígenos de venda livre a fim de prevenir intoxicações e efeitos adversos, especialmente em crianças.

  9. Análise da medição do raio solar em ultravioleta

    NASA Astrophysics Data System (ADS)

    Saraiva, A. C. V.; Giménez de Castro, C. G.; Costa, J. E. R.; Selhorst, C. L.; Simões, P. J. A.

    2003-08-01

    A medição acurada do raio solar em qualquer banda do espectro eletromagnético é de relevância na formulação e calibração de modelos da estrutura e atmosfera solar. Esses modelos atribuem emissão do contínuo do Sol calmo em microondas à mesma região da linha Ha do Hell. Apresentamos a medição do raio solar em UV com imagens do EIT (Extreme Ultraviolet Image Telescope) entre 1996 e 2002, no comprimento de onda 30,9 nm (Ha do Hell), que se forma na região de transição/cromosfera solar. A técnica utilizada para o cálculo do raio UV foi baseada na transformada Wavelet B3spline. Fizemos um banco de dados com 1 imagem por dia durante o período citado. Obtivemos como resultado o raio médio da ordem de 975.61" e uma diminuição do mesmo para o período citado variando em média -0,45" /ano. Comparamos estes dados com os valores obtidos pelo ROI (Radio Observatório de Itapetinga) em 22/48 GHz e Nobeyama Radio Heliograph em 17 GHz mostrando que os raios médios são muito próximos o que indica que a região de formação nessas freqüências é a mesma conforme os modelos. Comparamos os resultados também com outros índices de atividade solar.

  10. Quotidian of accompanying family members in an environment of care: the emergence of hospital tribes.

    PubMed

    Passos, Silvia da Silva Santos; Pereira, Álvaro; Nitschke, Rosane Gonçalves

    2016-01-01

    Compreender o relacionamento no quotidiano dos familiares acompanhantes nos cenários de cuidado que se aproximam da metáfora da tribo no ambiente hospitalar. Estudo qualitativo com dados coletados a partir de entrevistas semiestruturadas e observação com 16 familiares acompanhantes de pessoas hospitalizadas com dependência para o autocuidado. Os dados foram submetidos à análise temática e analisados através da metáfora da tribo proposta pela sociologia compreensiva. Os familiares formam um agrupamento social em torno do cuidado onde encontramos as características das tribos: a ambiência emocional; a solidariedade baseada nos vínculos de simpatia e ajuda mútua; a nebulosa afetual no processo interacional; a lógica da fusão nas relações tácteis e a comunhão/religiosidade no processo de ligação numa identidade coletiva. Os familiares na presença do trágico criam agrupamentos sociais que se assemelham a tribos cujo totem é o cuidado. Understand the quotidian relationships of accompanying family members in an environment of care, which are close to the metaphor of a tribe in hospital environment. METHODQualitative study with data gathered from semi-structured interviews and observations with 16 family members accompanying hospitalized individuals with dependence on self-care. Data were submitted to thematic analysis, and analyzed through the metaphor of "tribe" proposed by comprehensive sociology. Family members build up social clusters around caring, where we find traits typical of tribes: emotional ambience; solidarity based on links of sympathy and mutual assistance; an affectual nebula in the process of interaction; a logic of fusion in tactile relations; and communion/religiosity in the process of connecting in a collective identity. In the presence of tragedy, families build social clusters similar to tribes having care as a totem.

  11. Projeto observatórios virtuais: educação através de telescópios robóticos

    NASA Astrophysics Data System (ADS)

    Santana, P. H. S.; Shida, R. Y.

    2003-08-01

    O principal objetivo do projeto Observatórios Virtuais é o ensino na área de ciências através de atividades práticas desenvolvidas em colaboração entre instituições de pesquisa em astronomia e escolas de ensino médio e fundamental. Este ano deverá ser concluída a implantação do programa piloto de estudos, pesquisas e observação astronômica direta, com utilização em tempo real de telescópios robóticos, que assim funcionarão como "observatórios virtuais". O objetivo pedagógico das atividades práticas baseadas nas imagens atronômicas é desenvolver as habilidades e competências dos alunos no uso do método científico. Para isso, serão realizados projetos interdisciplinares, a partir de observações astronômicas, já que a astronomia é uma área interdisciplinar por excelência. Essas atividades terão níveis diferenciados de complexidade, que podem ser adequados aos vários graus do ensino e realidades regionais. Será dada ênfase ao desenvolvimento e aplicação em São Paulo, onde atua a equipe do IAG/USP. Como resultados apresentados no presente trabalho, temos a criação de um software em português para o processamento de imagens obtidas através de CCDs e a elaboração de material para as atividades educacionais relacionadas.

  12. [Deep brain stimulation: new frontier in the treatment of CNS disorders].

    PubMed

    Gonçalves Ferreira, Antonio

    2014-01-01

    Introdução: O autor faz uma revisão das indicações atuais da estimulação cerebral profunda, dos seus desenvolvimentos e resultados, dos alvos e técnicas utilizados, dos principais neurocirurgiões e centros médicos envolvidos.Material e Métodos: Esta revisão é baseada na experiência do grupo de Neurocirurgia Funcional do Hospital de Santa Maria (Centro Hospitalar Lisboa Norte) desde 1995 e na revisão bibliográfica dos artigos publicados sobre esta matéria desde 1980 indexados na PubMed.Resultados e Discussão: São apresentadas e discutidas as aplicações da estimulação cerebral profunda nos diferentes domínios das neurociências funcionais: Doenças do Movimento, incluindo doença de Parkinson, distonias e tremores, síndrome de Gilles de la Tourette, dor crónica, epilepsia e psicocirurgia nas múltiplas áreas que esta compreende: perturbação obsessiva-compulsiva, depressão grave refratária, comportamento disruptivo com agressividade intratável, deterioração da memória e demência, perturbações do comportamento alimentar (anorexia nervosa, obesidade mórbida) e toxicodependências refratárias (álcool, opioides, cocaína).Conclusões: Na maioria das situações clínicas referidas a estimulação cerebral profunda constitui um recurso terapêutico seguro e eficaz a ter em consideração quando as terapias habituais se mostram insuficientes; nos restantes casos há que reunir maior experiência até adotar o seu uso regular.

  13. [Diagnosis recommendations for late-onset Pompe disease].

    PubMed

    Brito-Avô, Luis; Alves, José Delgado; Costa, João Matos; Valverde, Ana; Santos, Lélita; Araújo, Francisco; Aguiar, Patrício; Marinho, António; Oliveira, Anabela; Gomes, Daniel

    2014-01-01

    Introdução: A Doença de Pompe é uma miopatia autossómica recessiva progressiva e incapacitante, devida ao défice da enzima lisossómica a-glicosidade-ácida. A sua forma tardia tem uma apresentação heterogénea que mimetiza outras doenças neuromusculares, o que dificulta o diagnóstico. Objectivo: Desenvolver recomendações baseadas em consenso para o diagnóstico da forma tardia da doença de Pompe. Material e Métodos: Revisão bibliográfica e análise de um questionário de opinião aplicado a um grupo de especialistas com experiência no diagnóstico de várias miopatias e doenças de sobrecarga lisossomal. Discussão em reunião de consenso. Recomendações: Doentes com miopatia proximal progressiva, fadiga, cãibras e mialgias devem ser submetidos a uma avaliação complementar com determinação de níveis de creatinina fosfoquinase, electromiograma, espirometria dinâmica e, em casos inconclusivos, biópsia muscular. Nos casos suspeitos ou naqueles em que a biópsia muscular não permita outro diagnóstico deve ser determinada a atividade da enzima lisossómica a-glicosidade-ácida através de teste de gota seca (DBS – dried blood spot). A redução da atividade da enzima lisossómica a-glicosidade-ácida requer a confirmação numa segunda amostra e a sequenciação do gene da enzima lisossómica a-glicosidade-ácida.

  14. Green synthesis and evaluation of silver nanoparticles as adjuvant in rabies veterinary vaccine

    PubMed Central

    Asgary, Vahid; Shoari, Alireza; Baghbani-Arani, Fahimeh; Sadat Shandiz, Seyed Ataollah; Khosravy, Mohammad Sadeq; Janani, Alireza; Bigdeli, Razieh; Bashar, Rouzbeh; Cohan, Reza Ahangari

    2016-01-01

    technique. The highest percentage of viability was observed at 15 mg/kg and 20 mg/kg of AgNPs-loaded vaccine concentrations after injecting into the mice. The calculated potencies for alum-containing vaccine and AgNPs-loaded vaccine (dose 15 mg/kg) were 1.897 and 1.303, respectively. MTT assay demonstrated that alum at the concentration of 10 mg/mL was toxic, but AgNPs were not toxic. The in vivo toxicity also elucidated the safety of AgNPs and AgNPs-loaded vaccine in mice and dogs, respectively. Conclusion In the current study, for the first time, the adjuvanticity effect of green synthesized AgNPs on veterinary rabies vaccine potency with no in vivo toxicity was elucidated according to the European Pharmacopeia 8.0. PMID:27536101

  15. Green synthesis and evaluation of silver nanoparticles as adjuvant in rabies veterinary vaccine.

    PubMed

    Asgary, Vahid; Shoari, Alireza; Baghbani-Arani, Fahimeh; Sadat Shandiz, Seyed Ataollah; Khosravy, Mohammad Sadeq; Janani, Alireza; Bigdeli, Razieh; Bashar, Rouzbeh; Cohan, Reza Ahangari

    2016-01-01

    observed at 15 mg/kg and 20 mg/kg of AgNPs-loaded vaccine concentrations after injecting into the mice. The calculated potencies for alum-containing vaccine and AgNPs-loaded vaccine (dose 15 mg/kg) were 1.897 and 1.303, respectively. MTT assay demonstrated that alum at the concentration of 10 mg/mL was toxic, but AgNPs were not toxic. The in vivo toxicity also elucidated the safety of AgNPs and AgNPs-loaded vaccine in mice and dogs, respectively. In the current study, for the first time, the adjuvanticity effect of green synthesized AgNPs on veterinary rabies vaccine potency with no in vivo toxicity was elucidated according to the European Pharmacopeia 8.0.

  16. Impact of neoadjuvant therapy in downstaging of lower rectal adenocarcinoma and the role of pelvic magnetic resonance in staging.

    PubMed

    Magri, Karina Dagre; Bin, Fang Chia; Formiga, Fernanda Bellotti; Manzione, Thiago da Silveira; Gomes, Caroline Merci Caliari de Neves; Candelári, Paulo de Azeredo Passos; Ortiz, Jorge Alberto; Klug, Wilmar Artur; Mandia, José; Capelhuchnik, Peretz

    2016-01-01

    to evaluate the effect of neoadjuvant therapy on the stage (TNM) of patients with rectal adenocarcinoma and validate the use of MRI as a method of determining locoregional stage. we conducted a retrospective study of 157 patients with lower rectum adenocarcinoma, whom we divided into two groups: Group 1, 81 patients (52%) who had undergone surgical treatment initially, with the purpose to analyze the accuracy of locoregional staging by pelvic magnetic resonance imaging throug the comparison of radiological findings with pathological ones; Group 2, 76 patients (48%), who had been submitted to neoadjuvant therapy (chemotherapy and radiation) prior to definitive surgical treatment, so as to evaluate its effects on the stage by comparing clinical and radiological findings with pathology. In group 1, the accuracy of determining tumor depth (T) and lymph node involvement (N) was 91.4% and 82.7%, respectively. In group 2, neoadjuvant therapy decreased the T stage, N stage and TNM stage in 51.3%, 21% and 48.4% of cases, respectively. neoadjuvant therapy in patients with rectal adenocarcinoma is effective in decreasing disease stage, and pelvic magnetic resonance imaging is effective for locoregional staging. avaliar o efeito da terapia neoadjuvante, nos pacientes portadores de adenocarcinoma de reto, sobre o estádio (TNM) e validar o emprego da ressonância magnética como método de determinação do estádio locorregional. estudo retrospectivo de 157 pacientes com diagnóstico de adenocarcinoma de reto baixo, que foram divididos em dois grupos: Grupo 1, 81 pacientes (52%), submetidos ao tratamento cirúrgico de princípio, cuja finalidade foi analisar a acurácia da determinação do estádio locorregional pela ressonância magnética da pelve, através da comparação entre os achados radiológicos e os achados anatomopatológicos; Grupo 2, 76 pacientes (48%), encaminhados à terapia neoadjuvante (quimioterapia e radioterapia), antes do tratamento cirúrgico definitivo

  17. Predictors of hope among women with breast cancer during chemotherapy.

    PubMed

    Balsanelli, Alessandra Cristina Sartore; Grossi, Sonia Aurora Alves

    2016-01-01

    Identifying the predictors of hope in patients with breast cancer during chemotherapy treatment. A prospective longitudinal study. The sample was composed of 122 women who responded to the instruments of hope, anxiety and depression, coping, fatigue, religiosity and self-esteem in the first and last cycle of chemotherapy. These variables were used in adjusting the logistic regression model that characterized multivariate statistics, allowing identification of predictor variables. The increase of hope at the end of chemotherapy treatment was statistically significant (p = 0.012). The delay in undergoing treatment from the onset of breast cancer symptoms, Karnofsky Performance Status, depression, self-esteem and pain were characterized as factors being associated to hope by univariate analysis. Among the variables analyzed, pain was the only predicting factor of hope. Pain was the predicting factor in this sample. Hope increased during treatment and revealed the following associated factors: Karnofsky Performance Status, delay in starting the treatment, depression, self-esteem and pain. This study brought forth a multidisciplinary contribution, allowing for understanding the factors that can influence hope and presenting support to nursing care. The data evidenced conditions of improvement or worsening of hope, which requires interdisciplinary attention in Oncology. Identificar os fatores preditores da esperança nas pacientes com câncer de mama em tratamento quimioterápico. Estudo prospectivo longitudinal. A amostra foi de 122 mulheres que responderam aos instrumentos de esperança, ansiedade e depressão, coping, fadiga, religiosidade e autoestima no primeiro e no último ciclo de quimioterapia. Essas variáveis foram utilizadas no ajuste do modelo de regressão logística que caracterizou a estatística multivariada permitindo a identificação das variáveis preditoras. O aumento da esperança ao final do tratamento quimioterápico foi estatisticamente

  18. [Intratechal Chemotherapy Treatment Through an Ommaya Reservoir Catheter for Meningeal Carcinomatosis: A Single-Centre Experience].

    PubMed

    Lavrador, José Pedro; Simas, Nuno; Oliveira, Edson; Carvalho, Manuel Herculano

    2016-08-01

    Introdução: A carcinomatose meníngea consiste na infiltração de células tumorais ao longo das leptomeninges e espaço subaracnoideu, encontrando-se associada a uma sobrevida média de 2 - 5 meses. As indicações sobre a modalidade mais adequada de tratamento permanecem tema de discussão, sendo fundamental um correto conhecimento da história natural da doença e da dualidade risco-benefício para uma decisão terapêutica interdisciplinar.Material e Métodos: Análise retrospectiva dos doentes com diagnóstico de carcinomatose meníngea com origem em tumores sólidos submetidos a colocação de catéter reservatório de Ommaya no período entre 2006 a 2014 no Serviço de Neurocirurgia do Hospital Santa Maria.Resultados: Foram operados 23 doentes com carcinomatose meníngea (19 mulheres, quatro homens) com idade média de 56,1 ± 2,2 anos. A origem do tumor primário foi: mama – 16 doentes, pulmão – quatro doentes, estômago, bexiga e colo do útero – um doente cada. Não se verificaram complicações tais como infecção, hematomas intracranianos ou fístula de líquor. A sobrevida média dos 21 doentes falecidos à data foi de 26,4 ± 7,7 semanas (mínimo nove dias, máximo 118 semanas). A análise estatística não ajustada revelou que o sexo masculino esteve associado a pior prognóstico (p value = 0,0032), enquanto a análise ajustada mostrou que a origem na mama esteve associada a melhor prognóstico (p value = 0,036) quando comparada com as outras etiologias (HR: 4,36 ± 3,06; 95% IC: 1,10 - 17,25). Um maior tempo de evolução de doença primária até ao diagnóstico esteve associado a melhor prognóstico, apesar de não ter atingido significado estatístico.Discussão: Apesar da colocação de catéter reservatório de Ommaya ser um procedimento com baixo risco de complicações, a resposta à quimioterapia intratecal é limitada e o prognóstico da doença poderá não justificar um procedimento cirúrgico num doente com mau estado

  19. Subjective global assessment and prealbumin levels of esophageal cancer patients undergoing concurrent chemoradiotherapy.

    PubMed

    Pan, Peng; Tao, Guangzhou; Sun, XinChen

    2015-05-01

    Objetivos: Evaluar el estado nutricional de los pacientes sometidos a quimioterapia para cáncer esofagico usando subjetiva evaluación mundial(SGA) y Asociación de prealbumina a niveles de estado nutricional. Métodos: Se realiza un estudio prospectivo en 154 pacientes con cáncer esofágico que fueron tratados con quimiorradioterapia concurrente en centro de Oncología de radiación en Huai ‘an First People’ s Hospital desde enero de 2012 a mayo de 2013. El estado nutricional de los pacientes después de recibir quimiorradioterapia concurrente fueron evaluados utilizando la herramienta de SGA. Albúmina, prealbúmina, proteína sérica total, nutrición y otros parámetros bioquímicos, incluyendo triglicéridos, colesterol total, colesterol y glucosa fueron determinados antes de empezar y después del final de la radioterapia. Resultados: La desnutrición desarrollada en 129 (83,8%) pacientes. Según SGA resultados, 16,2%, 66,2%, y 17,6% de los pacientes fueron clasificados como a, B, o C, respectivamente. La pérdida de grasa subcutánea o atrofia muscular (odds ratio [OR] 11.522); demanda metabolica creciente / estrés (o 8.637); tobillo edema sacro, o ascitis (o -) y la perdida de peso ≥ 5% (o 3) estuvieron significativamente asociados con la malnutrición (SGA B o C; p < 0,001). El nivel de prealbúmina después del final de la radioterapia fue significativamente menor en los pacientes con desnutrición (17 ± 5 g / dl vs. 21 ± 5 g / dl, p = 0,005), pero no mostró diferencia antes de comenzar la radioterapia (24 ± 4 g / dl vs. 22 ± 5 g / dl, p > 0,05). Por otro lado, no hubo diferencia significativa en el plazo de otros parámetros si la nutrición fue antes de comenzar o después del final de la radioterapia (p > 0,05). Conclusiones: La prevalencia de la malnutrición era alta en cáncer de esófago en pacientes sometidos a quimiorradioterapia concurrente. Losresultados sirven de base para la aplicación de la intervención en materia de nutrici

  20. Brachial insertion of fully implantable venous catheters for chemotherapy: complications and quality of life assessment in 35 patients.

    PubMed

    Fonseca, Igor Yoshio Imagawa; Krutman, Mariana; Nishinari, Kenji; Yazbek, Guilherme; Teivelis, Marcelo Passos; Bomfim, Guilherme André Zottele; Cavalcante, Rafael Noronha; Wolosker, Nelson

    2016-01-01

    To prospectively evaluate the perioperative safety, early complications and satisfaction of patients who underwent the implantation of central catheters peripherally inserted via basilic vein. Thirty-five consecutive patients with active oncologic disease requiring chemotherapy were prospectively followed up after undergoing peripheral implantation of indwelling venous catheters, between November 2013 and June 2014. The procedures were performed in the operating room by the same team of three vascular surgeons. The primary endpoints assessed were early postoperative complications, occurring within 30 days after implantation. The evaluation of patient satisfaction was based on a specific questionnaire used in previous studies. In all cases, ultrasound-guided puncture of the basilic vein was feasible and the procedure successfully completed. Early complications included one case of basilic vein thrombophlebitis and one case of pocket infection that did not require device removal. Out of 35 patients interviewed, 33 (94.3%) would recommend the device to other patients. Implanting brachial ports is a feasible option, with low intraoperative risk and similar rates of early postoperative complications when compared to the existing data of the conventional technique. The patients studied were satisfied with the device and would recommend the procedure to others. Avaliar prospectivamente segurança perioperatória, complicações precoces e grau de satisfação de pacientes submetidos ao implante de cateteres centrais de inserção periférica pela veia basílica. Foram acompanhados prospectivamente e submetidos ao implante de cateteres de longa permanência de inserção periférica, entre novembro de 2013 e junho de 2014, 35 pacientes consecutivos com doença oncológica ativa necessitando de quimioterapia. Os procedimentos foram realizados em centro cirúrgico por uma mesma equipe composta por três cirurgiões vasculares. Os desfechos primários avaliados foram as

  1. HD 208905: um sistema múltiplo de estrelas quentes

    NASA Astrophysics Data System (ADS)

    Candeias, J. P.; Daflon, S.; Cunha, K.

    2003-08-01

    Durante o survey de associações OB do disco Galáctico, foi constatada a multiplicidade do sistema HD 208905, pertencentes à associação de Cep OB2. Este objeto está classificado como uma estrela pertencente a um sistema múltiplo, com magnitude mv = 7.0 e tipo espectral B1V. De fato, os espectros de HD 208905 apresentam perfis de absorção triplicados. Dois dos perfis são bastante similares entre si, e são estreitos e bem definidos, sugerindo que as velocidades rotacionais projetadas (v sin i) das duas estrelas são baixas. Os espectros obtidos também apresentam perfis mais alargados que poderiam ser atribuídos a uma terceira componente estelar com v sin i mais alto. A análise de HD 208905 é baseada no estudo da variação da posição relativa dos perfis espectrais de acordo com a fase do sistema. Nossos dados observacionais são um conjunto de espectros de alta resolução obtidos no McDonald Observatory (Universidade do Texas, Austin), Kitt Peak National Observatory e Palomar Observatory, cobrindo o período de 10/91 até 12/95. Inicialmente, calculamos a velocidade radial de cada componente do sistema, considerando o desvio Doppler sofrido por cada estrela. As velocidades radiais medidas foram, em seguida, corrigidas para velocidades radiais heliocêntricas. O passo seguinte constituiu na determinação da periodicidade da série temporal definida pelas medidas das velocidades radiais heliocêntricas através da análise de Fourier. A nossa base de dados não permitiu definir uma solução única para o sistema HD 208905. As possíveis soluções encontradas têm períodos entre 1 e 27 dias e serão apresentadas e discutidas.

  2. Seismic ground motion scenarios in Lower Tagus Valley Basin

    NASA Astrophysics Data System (ADS)

    Borges, José; Torres, Ricardo; Furtado, José; Silva, Hugo; Caldeira, Bento; Pinto, Carlos; Bezzeghoud, Mourad; Carvalho, João

    2013-04-01

    Throughout its history the Lower Tagus Valley (LTV) has been struck by several earthquakes which produced important material damage and loss of lives: The 1st of November 1755 Lisbon earthquake and the 1969 earthquake (Mw=7.3), located in the SW Iberia Margin and the 1344, 1531 and 1909 (M= 6 to 7) with epicenter located inside the LTV basin. Since this region is the most highly populated region in Portugal, it is expected that an earthquake of similar magnitude of those that have occurred in the past will cause an enormous destruction and casualties. This fact makes LTV a high priority area for earthquake research in Portugal. In order to overcome the problems related to the absence of geological outcrops, low slip-rates (<0,4 mm/year) and the processes of sedimentation and erosion, we use in this work seismic reflection profiles, potential field data, soundings, wells and geological cartography to obtain a map of the main seismogenic structures and to characterize their seismic potential [1]. Moreover, a 3D structural model has been developed for de LTV based on Seismic reflection, Seismic Noise and potential field data [2,3]. In order to improve assessment of the seismic hazard in the LTV basin, we simulate long-period (0-1 Hz) ground motion time histories for a suite of scenarios earthquakes (Mw =5.5 to 7) within the basin, using fault geometries and the 3D seismic velocity structure based on the previous mentioned works. References [1] Pinto, Carlos C. (2011). Identification of Seismogenic Structures in the Lower Tagus Basin. Master Thesis, Universidade de Évora, 128 pp. [2] Torres, R.J.G., (2012). Modelo de velocidade da Bacia do Vale do Tejo: uma abordagem baseada no estudo do ruído sísmico ambiental, Master Thesis, Universidade de Évora, 83pp. [3] Furtado, J.A (2010). Confirmação do modelo da estrutura 3D do Vale Inverior do Tejo a partir de dados de ruído sísmico ambiente, Master Thesis, Universidade de Évora, 136pp.

  3. SERUM LEPTIN LEVENS AND HEPATOCELLULAR CARCINOMA: REVIEW ARTICLE.

    PubMed

    Andrighetto, Luiza Vitelo; Poziomyck, Aline Kirjner

    2016-01-01

    Hepatocellular carcinoma is one of the most frequent types of malignant tumors in the world. There is growing evidence of the relationship between it development and obesity. The mechanism that links obesity to cancer is still not fully understood; however, it is essential to the understanding the adipose tissue in metabolic changes related to obesity and hepatocellular carcinoma. To review the influence of serum leptin levels in patients with hepatocelular carcinoma. Systematic review of the literature based on the methodology of the Cochrane Institute. The search for articles was in the database: Science Direct, Scielo, Medline, Lilacs e Pubmed. The key words used were hepatocellular carcinoma, leptin, adipokine. After evaluation of individual studies, were selected seven studies. The results previously studied are still inconsistent and contradictory, and leptin can be effectively involved in the occurrence and development of hepatocellular carcinoma. Therefore, it is necessary to develop prospective, well-designed and conducted focusing on the role and specific mechanisms of this hormone in patients with hepatocellular carcinoma, so that new correlations can be properly supported. O carcinoma hepatocelular é um dos tipos mais frequentes de tumores malignos no mundo. Há crescentes evidências da relação entre o seu desenvolvimento e a obesidade. O mecanismo que os relaciona ainda não é completamente entendido. Entretanto é essencial a compreensão do tecido adiposo nas alterações metabólicas relacionadas à obesidade e ao câncer. Revisar a influência dos níveis séricos de leptina em pacientes com carcinoma hepatocelular. Trata-se de revisão bibliográfica baseada na metodologia do Instituto Cochrane; a busca de dados foi realizada na base de dados Science Direct, Scielo, Medline, Lilacs e Pubmed, empregando as seguintes descritores: hepatocellular carcinoma, leptin, adipokine. Após avaliação individual dos artigos selecionaram-se sete estudos

  4. Velocity and structural model of the Lower Tagus Basin according to the study of environmental seismic noise

    NASA Astrophysics Data System (ADS)

    Gomes Torres, Ricardo Jorge; Furtado, José Augusto; Gonçalves Silva, Hugo; Borges, José Fernando; Caldeira, Bento; Bezzeghoud, Mourad; Carvalho, João

    2013-04-01

    ] Torres, R.J.G., (2012). Modelo de velocidade da Bacia do Vale do Tejo: uma abordagem baseada no estudo do ruído sísmico ambiental, Master Thesis, Universidade de Évora, 83pp. [3] Nakamura, Y., 1989. A method for dynamic characteristics estimations of subsurface using microtremors on the ground surface, Quarterly Report, RTRI, Japan, v. 30, p. 25-33. [4] J.A. Furtado, Confirmação do modelo da estrutura 3D do Vale Inverior do Tejo a partir de dados de ruído sísmico ambiente, Master Thesis, Universidade de Évora, 136pp, 2010.

  5. Transferências orbitais dentro do modelo quase bicircular no sistema Terra-Lua-Sol

    NASA Astrophysics Data System (ADS)

    Corrêa, A. A.; de Almeida Prado, A. F. B.; Stuchi, T. J.; Beaugé, C.

    2003-08-01

    O problema quase bicircular planar consiste na determinação da dinâmica de um corpo, de massa desprezível, que se move sob o campo gravitacional de três corpos. No caso estudado, o quarto corpo é considerado um satélite artificial e os demais são a Terra, a Lua e o Sol, formando o sistema de três corpos. Este modelo permite a construção de uma hamiltoniana similar a do problema restrito de três corpos (PRTC), incluindo termos periódicos não autônomos, provenientes da presença do Sol, portanto pode ser entendido como uma perturbação ao PRTC. Suas órbitas periódicas aparecem isoladas e possuem o mesmo período solar. Os pontos de equilíbrio colineares possuem o mesmo caráter de estabilidade linear dos pontos lagrangianos (L1, L2 e L3) do PRTC, sendo do tipo sela x centro x centro, instável na direção x e estáveis nas direções y e z. As órbitas periódicas tridimensionais ao redor do ponto colinear é chamada órbita Halo. O objetivo deste trabalho é determinar órbitas de transferências de baixo consumo de combustível para um veículo espacial partindo de uma órbita de estacionamento ao redor da Terra em direção a uma órbita Halo do ponto L1, situado entre a Terra e Lua. Esta tarefa pode ser transformada no problema de valor de contorno: dado um ponto inicial na órbita de estacionamento, um ponto final na órbita halo e o tempo de transferência, deseja-se obter a trajetória que liga estes dois pontos e que minimize os incrementos de velocidade do veículo. Essas transferências são realizadas baseadas no método de Lambert e analisadas de modo a fornecer um baixo consumo. Posteriormente, é feita uma comparação de consumo com as órbitas de transferência equivalentes do PRTC.

  6. A distância e o conteúdo estelar da região HII gigante G333.1-0.4 - vínculos para a taxa de formação estelar da galáxia

    NASA Astrophysics Data System (ADS)

    Figuerêdo, E.; Damineli, A.; Blum, R.; Conti, P.

    2003-08-01

    Neste trabalho apresentamos imagens de alta resolução angular da região HII gigante G333.1-0.4 obtidas através dos filtros J, H e K no telescópio de 4-m do CTIO. Este trabalho faz parte de um estudo de regiões HII gigantes no infravermelho próximo que tem por objetivo estudar a natureza da formação de estrelas massivas e traçar a estrutura espiral de nossa galáxia. Nossa determinação da distância é baseada no método da paralaxe espectroscópica de estrelas OB localizadas na seqüência principal de idade zero (ZAMS) do Diagrama HR. No caso de G333.1-0.4, a magnitude aparente das estrelas localizadas na ZAMS indica que a distância não pode ser maior do que o limite inferior determinado por técnica rádio (2,8 kpc). Resultados semelhantes foram encontrados para regiões estudadas anteriormente, reforçando a idéia de que a taxa de formação estelar na Via Láctea é menor do que o determinado a partir de dados rádio. Nossos resultados mais recentes sobre o conteúdo estelar de G333.1-0.4 revelaram vários objetos que possuem cores bastante avermelhadas (H-K > 2,0). Nós identificamos estes objetos usando os diagramas cor-cor e cor-magnitude dos aglomerados. Estes objetos apresentam um forte excesso em emissão na banda K e possivelmente se tratam de estrelas do tipo OB envolvidas por um disco/envelope circumestelar espesso. O estudo da função de massa inical desta região, em conjunto com resultados de nossos trabalhos anteriores, aponta para uma IMF independente da posição galática. A contagem de estrelas nos fornece um valor para o número de fótons no contínuo de Lyman que corrobora com a afirmação de que G333.1-0.4 se encontra mais próxima da menor distância determinada por rádio.

  7. Controle orbital de satélites artificiais com propulsão e uso de gravidade lunar

    NASA Astrophysics Data System (ADS)

    Torres, K. S.; de Almeida Prado, A. F. B.

    2003-08-01

    A redução do custo de combustível de uma manobra é atualmente a grande prioridade de todos os programas espaciais existentes no mundo. As manobras assistidas pela gravidade são uma ótima forma de se contornar o problema pois proporcionam economias com vasto impacto no custo final da missão. Neste trabalho é feito um estudo particular do controle orbital de um satélite artificial da Terra usando a gravidade da Lua. O objetivo é estudar uma técnica econômica para uma mudança de plano de um satélite que está em órbita em volta da Terra. A idéia principal desta abordagem é enviar primeiramente o veículo espacial em direção à Lua usando uma manobra mono-impulsiva para que assim o campo gravitacional da Lua possa fazer a mudança de plano desejada (sem custo de combustível) e só então retornar o veículo aos valores iniciais de semi-eixo e excentricidade usando uma manobra bi-impulsiva tipo Hohmann. Para tanto, é assumido que a espaçonave inicia em uma órbita circular coplanar à órbita da lua em torno da Terra e a meta é colocá-la em uma órbita similar que difere da órbita inicial somente pela inclinação. São usadas equações analíticas baseadas na abordagem Patched Conics para se calcular a variação na velocidade, momento angular, energia e inclinação do veículo espacial que realiza esta manobra. Várias simulações são feitas para se avaliar as economias de combustível envolvidas.

  8. HOW TO EVALUATE SCIENTIFIC PRODUCTION.

    PubMed

    Antunes, Alberto Azoubel

    2015-01-01

    To conduct a critical analysis of the two main bibliometric indexes used by science: the impact factor and the H index. Research was conducted on PubMed using the keywords: impact factor, Bibliometrics and H index. The citations of articles tend to follow a curve in which the articles published in a given year increase sharply to a peak occurring between two and six years after its publication. From this peak citations decline over time. The analysis of the scientific merit should not be based on only in bibliometric measure, but in the association of various parameters. The impact factor and the H index is mainly based on the number of citations of scientific papers, and this parameter, although important, should not be used alone, nor overvalued in the evaluation of teaching merit. Realizar análise crítica dos dois principais índices bibliométricos utilizados pela ciência: o fator de impacto e o índice H. Foi realizada pesquisa no Pubmed utilizando as palavras-chave: impact factor, bibliometrics, H index. As citações dos artigos tendem a seguir uma curva em que os artigos publicados em determinado ano aumentam agudamente para um pico que ocorre entre dois e seis anos após sua publicação. A partir deste pico, as citações declinam ao longo do tempo. A análise do mérito científico não deve ser baseada em apenas uma medida bibliométrica, mas em associação de medidas. O FI e o índice H se baseiam fundamentalmente no número de citações dos artigos científicos, e este parâmetro, apesar de importante, não deve ser utilizado sozinho e tampouco supervalorizado na avaliação do mérito docente.

  9. Aerobic program in persons with stroke: a systematic review.

    PubMed

    Francica, Juliana V; Bigongiari, Aline; Mochizuki, Luis; Miranda, Maria Luiza J; Rodrigues, Bruno

    2014-01-01

    Introdução: O objetivo deste estudo foi realizar uma revisão sistemática sobre o exercício após acidente vascular cerebral.Material e Métodos: Para isso, foi realizada uma revisão sistemática de ensaios clínicos randomizados e controlados publicados no PubMed e PEDro. Os critérios para inclusão dos artigos foram: Estudos - ensaios clínicos randomizados ou controlados; participantes - adultos de qualquer idade com diagnóstico clínico de acidente vascular cerebral; intervenções - qualquer treino físico aeróbio que vise melhorar a capacidade e/ou função cardiovascular. Dois revisores independentes categorizaram os ensaios selecionados, avaliaram a qualidade metodológica e extraíram os dados relevantes. A análise realizada foi dos vários protocolos usados tanto para a avaliaçãoe treino de indivíduos pós-acidente vascular cerebral.Resultados: De acordo com estudos clínicos analisados, uma vasta gama de instrumentos foi utilizada para medir a capacidade funcional dos pacientes. Ergometria e ergoespirometria foram os principais dispositivos da avaliação da capacidade cardiovascular. Treino\\exercício na bicicleta ergométrica foi a estratégia de treino mais comumente usada, e fisioterapia convencional (baseada em alongamentos, fortalecimentos, treino de equilíbrio, coordenação e marcha) foi a terapia de controle mais frequente.Discussão: A duração do programa variou de 4 semanas a 6 meses, a frequência semanal média foi de três sessões por semana, enquanto que a intensidade do treinamento variou de 40 a 80% da frequência cardíaca máxima ou VO2 máximo. A duração de sessões de treino variou entre 25 minutos a 1 hora.Conclusão: O treino físico é uma ferramenta promissora para o tratamento de pacientes pós-AVC, tanto em termos de melhoria da capacidade funcional e da capacidade cardiovascular. No entanto, mais estudos são necessários para ampliar a área de atuação terapêutica nesta população.

  10. [Primary and secondary outcomes in oncology clinical trials: definitions and uses].

    PubMed

    Vaz-Carneiro, António; Luz, Ricardo; Borges, Margarida; Costa, João

    2014-01-01

    Introdução: A prova de eficácia de uma intervenção terapêutica em oncologia consegue-se através de ensaios clínicos rigorosamente conduzidos. Um dos factores metodológicos mais importantes é a selecção de indicadores clínicos de eficácia (outcomes), necessários ao cálculo das chamadas medidas de associação que permitem a definição de eficácia terapêutica. Material e Métodos: Foi feita uma revisão narrativa baseada em alguns dos documentos de agências reguladoras internacionais, assim como documentos de consenso entre as sociedades científicas oncológicas, procurando listar e avaliar criticamente cada um dos indicadores utilizados em ensaios clínicos oncológicos. Resultados: Identificaram-se como indicadores mais importantes a sobrevivência global, a sobrevivência livre de progressão/sobrevivência livre de doença, a toxicidade/qualidade de vida e taxa objectiva de resposta tumoral. Discussão: A selecção do outcome primário deve basear-se no conceito de eficácia terapêutica, mas também na toxicidade relativa da terapêutica experimental, na sobrevivência esperada após progressão da doença, na existência de fármacos alternativos já estudados com indicações idênticas e até a prevalência da patologia em causa. Conclusão: A selecção de indicadores em ensaios clínicos oncológicos reveste-se de especial importância e a sua selecção deve ser bem fundamentada, dependendo da doença, dos doentes e do fármaco em estudo.

  11. Correlação de longo alcance em sistemas binários de raios-x usando remoção de flutuações

    NASA Astrophysics Data System (ADS)

    Pereira, M. G.; Moret, M. A.; Zebende, G. F.; Nogueira, E., Jr.

    2003-08-01

    Neste trabalho é proposta uma metodologia de analise de series temporais de fontes astrofísicas, baseada no método proposto por Peng et al. (1994) e Liu et al. (1999), o qual consiste na idéia de que uma série temporal correlacionada pode ser mapeada por um processo de busca de auto-similaridades em diversas escalas de tempo n. Removendo as eventuais tendências e integrando o sinal observado, é obtida uma medida do desvio médio quadrático das flutuações do sinal integrado F(n)~na, onde a representa o fator de escala associado com a auto-similaridade da correlação de longo alcance do sinal. Baseado nos valores obtidos de a, é possível distinguir entre os casos de sinais não-correlacionados, tipo ruído branco (a = 0,5), sinal anti-persistentes (a < 0,5) e sinal persistente (a > 0,5). Usando esta metodologia, foram analisadas 129 curvas de luz de sistemas binários de raios-X, provenientes do banco de dados públicos de observações feitas pelo instrumento All Sky Monitor, a bordo do satélite Rossi X-Ray Timing Explorer (ASM-RXTE). Foram identificadas a presença de a'0,5 em mais de 90% dos sistemas estudados, implicando em dizer que as flutuações de intensidade observadas apresentam correlação de auto-similaridade, sem entretanto, indícios de apresentarem uma escala de tempo característica das flutuações de intensidade. Sistemas onde são observadas erupções (flares), apresentam sistematicamente a > 0,5, característica esta, possivelmente associada com persistência das flutuações de densidade de disco ou taxa de acréscimo de massa. Os sistemas com curvas de luz onde nao são observadas as erupções apresentam uma distribuição normal centrada em a~0,62+/-0,10. Referências ¾ Peng, C.-K., Buldyrev, S.V., Havlin, S., Simons, M., Stanley, H.E., e Goldberg, A.L., Phys. Rev. E, (49), 1685 (1994). ¾ Liu, Y., Gopikrishnan, P., Cizeau, P., Meyer, M., Peng,C.-K., e Stanley, H.E., Phys. Rev. E, (60), 1390 (1999).

  12. Development of a virtual learning environment for cardiorespiratory arrest training.

    PubMed

    Silva, Anazilda Carvalho da; Bernardes, Andrea; Évora, Yolanda Dora Martinez; Dalri, Maria Célia Barcellos; Silva, Alexandre Ribeiro da; Sampaio, Camila Santana Justo Cintra

    2016-01-01

    To develop a Virtual Learning Environment (VLE) aiming at the training of nursing team workers and emergency vehicle drivers in Basic Life Support (BLS) to attend Cardiorespiratory arrest, and to evaluate the quality of its contents among specialists in the area of Emergency and Urgent care. Applied research of technological development. The methodology used was based on the Instructional Design Model (ADDIE), which structures the teaching-learning planning in different stages (analysis, design, development, implementation and evaluation). The VLE was composed of texts elaborated from bibliographic research, links, edited video from a simulation scenario in the laboratory and questions to evaluate the fixation of the content, organized in modules. After its development, it was evaluated as adequate to satisfy the needs of the target public, by eight expert judges, which was made available for electronic access. The VLE has potential as a tool for training and qualification in BLS, as it can be easily integrated with other pedagogical approaches and strategies with active methodologies. Desenvolver um Ambiente Virtual de Aprendizagem (AVA) visando à capacitação de trabalhadores da equipe de enfermagem e condutores de veículo de emergência em Suporte Básico de Vida (SBV) no atendimento à Parada Cardiorrespiratória, e avaliar a qualidade do seu conteúdo junto a especialistas na área de Urgência e Emergência. Pesquisa aplicada, de produção tecnológica. A metodologia utilizada foi baseada no Modelo de Design Instrucional (ADDIE), que estrutura o planejamento de ensino-aprendizagem em estágios distintos (analysis, design, development, implementation and evaluation). O AVA foi composto por textos elaborados a partir de pesquisa bibliográfica, links, vídeo construído a partir de um cenário de simulação em laboratório e questões para avaliar a fixação do conteúdo, organizados em módulos. Após a sua construção, foi avaliado como adequado para

  13. Is there any link between accreditation programs and the models of organizational excellence?

    PubMed

    Berssaneti, Fernando Tobal; Saut, Ana Maria; Barakat, Májida Farid; Calarge, Felipe Araujo

    2016-01-01

    To evaluate whether accredited health organizations perform better management practices than non-accredited ones. The study was developed in two stages: a literature review, and a study of multiple cases in 12 healthcare organizations in the state of São Paulo, Brazil. It surveyed articles comparing hospital accreditation with the EFQM (European Foundation for Quality Management) model of excellence in management. According to the pertinent literature, the accreditation model and the EFQM model are convergent and supplementary in some aspects. With 99% confidence, one can say that there is evidence that accredited organizations scored better in the evaluation based on the EFQM model in comparison to non-accredited organizations. This result was also confirmed in the comparison of results between the categories Facilitators and Results in the EFQM model. There is convergence between the accreditation model and the EFQM excellence model, suggesting that accreditation helps the healthcare sector to implement the best management practices already used by other business sectors. Avaliar se as organizações de saúde acreditadas possuem melhores práticas de gestão do que as não acreditadas. A pesquisa foi dividida em duas etapas: revisão da literatura e estudo de casos múltiplos com 12 organizações de saúde, localizadas no estado de São Paulo ‒ Brasil. Foram pesquisados artigos que comparavam a acreditação hospitalar com o modelo de excelência em gestão da EFQM (European Foundation for Quality Management), sendo que a literatura pertinente considera que o modelo de acreditação e o modelo da EFQM são convergentes e, ao mesmo tempo, complementares em determinados aspectos. Com 99% de confiança, pode-se afirmar que há evidência de que as organizações com acreditação obtiveram uma pontuação maior na avaliação baseada no modelo EFQM comparativamente às organizações não acreditadas. Este resultado também se confirmou na comparação dos

  14. Recent surgical advances in Peyronie's Disease.

    PubMed

    Gaspar, Sandro; Santos Dias, José; Martins, Francisco; Lopes, Tomé

    2016-02-01

    Introdução: A doença de Peyronie, uma doença fibrótica da túnica albuginea do pénis tem estado associada a encurtamento peniano e a algum grau de disfunção eréctil. Afeta a qualidade de vida do doente, levando a stress psicológico, mental e físico. A deformidade peniana perturba a vida sexual do doente, levando a episódios de depressão, disfunções sexuais e a ansiedade associada ao ato sexual. A etiologia da doença de Peyronie permanece por esclarecer. Material e Métodos: A pesquisa na literatura foi efetuada nas bases de dados da Medline, Embase e Cochrane no mês de Janeiro de 2015 no sentido de identificar artigos relacionados com a doença de Peyronie, nomeadamente o tratamento cirúrgico, técnicas, resultados bem como tratamentos complementares. Publicações que não envolvessem humanos não foram consideradas. Identificámos artigos originais, artigos de revisão e editoriais acerca do assunto em questão. Todos os artigos publicados na língua inglesa foram selecionados para screening. Os critérios de elegibilidade para inclusão envolveram a relevância associada ao tema. Resultados: Existe uma variedade de deformidades penianas associada com a doença de Peyronie que ainda não têm uma solução não cirúrgica que seja eficaz. Apresentamos uma atualização das técnicas cirúrgicas atuais bem como o algoritmo de tratamento associada a esta doença. Discussão: Todos os tratamentos cirúrgicos têm como objetivo a correção da curvatura, a preservação da função eréctil e do comprimento peniano, bem como o de minimizar a morbilidade. Conclusão: Até à data não existem estudos de medicina baseada na evidência que determinem o melhor tratamento cirúrgico para a doença de Peyronie. Após o diagnóstico, a reconstrução cirúrgica deve ter como objetivo um pénis funcional, com uma retificação da sua curvatura que permita o acto sexual.

  15. Care path of person with stroke: from onset to rehabilitation.

    PubMed

    Faria, Ana da Conceição Alves; Martins, Maria Manuela Ferreira Pereira da Silva; Schoeller, Soraia Dornelles; Matos, Leandro Oliveira de

    2017-01-01

    to describe the care path of the person with stroke goes through and to identify the important events in this path. qualitative descriptive exploratory research, using the semi-structured interview technique based on Meleis's Middle-Range Theory. The sample was composed of 13 people who became dependent after a stroke and were admitted to two hospital units in the region of Vale do Ave, Portugal. Data were collected between January and October 2013. Content analysis was used to analyze the data. The data revealed that the person's care path goes from recognition of the symptoms to preparation for hospital discharge. Adapting to the new situation of dependence brings the need for new competencies. The research aims to contribute to the improvement of nursing care regarding care for people with stroke including onset, recovery and rehabilitation, and home care. Descrever o percurso da pessoa com Acidente Vascular Encefálico e identificar os acontecimentos significativos neste percurso. Abordagem qualitativa e natureza exploratória- descritiva, valeu-se da técnica de entrevista semiestruturada baseada na Teoria de Médio Alcance de Meleis. Participaram 13 pessoas que se tornaram dependentes devido à Acidente Vascular Encefálico e recorreram a duas Unidades da região do Vale do Ave, Portugal. A colheita de dados deu-se durante Janeiro a Outubro de 2013. Para análise dos dados foi utilizada a análise de conteúdo. Os dados revelaram que o trajeto da pessoa vai desde o reconhecimento dos sintomas até à preparação da alta hospitalar. A dependência traz a necessidade de adquirir competências para se adaptar à nova situação. Espera-se contribuir para a melhoria dos cuidados de enfermagem no atendimento das pessoas acometidas com Acidente Vascular Encefálico, desde o acometimento, recuperação e reabilitação, até aos cuidados domiciliares.

  16. Procedures for measuring and verifying gastric tube placement in newborns: an integrative review.

    PubMed

    Dias, Flávia de Souza Barbosa; Emidio, Suellen Cristina Dias; Lopes, Maria Helena Baena de Moraes; Shimo, Antonieta Keiko Kakuda; Beck, Ana Raquel Medeiros; Carmona, Elenice Valentim

    2017-07-10

    de duas distâncias morfológicas e os de aplicação de duas fórmulas, uma baseada no peso e outra na altura. Para técnicas de verificação do posicionamento, encontrou-se traçado eletromagnético, atividade elétrica do diafragma, detecção de CO2, solução de índigo carmim, ausculta do epigástrio, aspiração de secreção gástrica, inspeção da cor, avaliação de pH, enzimas e bilirrubina. o método de mensuração que utiliza as medidas do nariz ao lóbulo da orelha ao ponto médio entre apêndice xifoide e cicatriz umbilical apresenta melhores evidências. As equações baseadas em peso e altura necessitam ser testadas experimentalmente. O retorno de secreção na aspiração da sonda, avaliação da cor e do pH da secreção são indicadores confiáveis na identificação do posicionamento da sonda gástrica, e são as técnicas atualmente indicadas. investigar, en la literatura, evidencias sobre procedimientos de medición de la sonda gástrica en recién nacidos y de verificación de su posicionamiento, procedimientos alternativos al examen radiológico. revisión integradora de la literatura en las bases Biblioteca Cochrane, LILACS, CINAHL, EMBASE, MEDLINE y Scopus, utilizando los descriptores "intubación gastrointestinal" y "recién nacido" en artículos originales. diecisiete publicaciones fueron incluidas y categorizadas en "método de medición" o "técnica de verificación del posicionamiento". Como métodos de medición, fueron encontrados los de medida de dos distancias morfológicas y los de aplicación de dos fórmulas (una basada en el peso y otra en la altura). Para las técnicas de verificación del posicionamiento, se encontró: trazado electromagnético, actividad eléctrica del diafragma, detección de CO2, solución de índigo carmín, auscultación del epigastrio, aspiración de secreción gástrica, inspección del color, evaluación de pH, enzimas y bilirrubina. el método de medición que utiliza las medidas de la nariz al l

  17. DIETARY MANAGEMENT FOR DYSLIPIDEMIA IN LIVER TRANSPLANT RECIPIENTS.

    PubMed

    Pinto, Andressa S; Chedid, Marcio F; Guerra, Léa T; Cabeleira, Daiane D; Kruel, Cleber D P

    2016-01-01

    os efeitos de uma intervenção dietética no perfil lipídico de pacientes transplantados hepáticos dislipidêmicos em acompanhamento ambulatorial. Foram incluídos todos os pacientes adultos transplantados hepáticos com dislipidemia e em acompanhamento ambulatorial em nossa instituição. Avaliação antropométrica, anamnese alimentar, composição corporal (bioimpedância) e cálculo do metabolismo basal (calorimetria indireta) foram realizados. Pacientes foram atendidos por uma nutricionista e uma dieta individualizada baseada no metabolismo basal e consistindo de 25% do valor energético em gorduras totais e menos de 200 mg/dia de colesterol foi prescrita. Colesterol total (CT), HDL-colesterol (HDL), LDL-colesterol (LDL), triglicerídeos (TG) e medidas antropométricas foram medidos antes do início da dieta, sendo repetidos seis meses após o início da intervenção dietética. Cinquenta e três pacientes concluíram o seguimento e tinham idade 59±10 anos e 29 eram homens (51,8%). CT pré-intervenção=238,9±30; pós-intervenção=165,1±35, p<0.001; LDL pré-intervenção=154±33; pós-intervenção=90±29, p<0.001 e TG pré-intervenção=168, IQR=151-200; pós-intervenção=137, IQR=94-177, p=<0.001 sofreram modificações significativas seis meses após a intervenção. Antes do estudo, nenhum dos pacientes apresentava níveis séricos normais para o CT, e apenas 12 pacientes (22,7%) tinham níveis séricos ótimo ou quase ótimos para o LDL. Seis meses após o início da intervenção, 45 pacientes (84,9%) alcançaram níveis séricos normais de CT e 50 (94,4%) níveis séricos ótimos ou quase ótimos de LDL. Os níveis séricos de HDL e as medidas antropométricas não sofreram modificações significativas. Aconselhamento dietético com prescrição de dieta individualizada baseada no cálculo do metabolismo basal mostrou-se efetivo no manejo da dislipidemia em pacientes transplantados hepáticos em seguimento ambulatorial. Assim, todos os

  18. Kinetics of Hypotension during 50 Sessions of Resistance and Aerobic Training in Hypertensive Patients: a Randomized Clinical Trial.

    PubMed

    Damorim, Igor Rodrigues; Santos, Tony Meireles; Barros, Gustavo Willames Pimentel; Carvalho, Paulo Roberto Cavalcanti

    2017-04-01

    Resistance and aerobic training are recommended as an adjunctive treatment for hypertension. However, the number of sessions required until the hypotensive effect of the exercise has stabilized has not been clearly established. To establish the adaptive kinetics of the blood pressure (BP) responses as a function of time and type of training in hypertensive patients. We recruited 69 patients with a mean age of 63.4 ± 2.1 years, randomized into one group of resistance training (n = 32) and another of aerobic training (n = 32). Anthropometric measurements were obtained, and one repetition maximum (1RM) testing was performed. BP was measured before each training session with a digital BP arm monitor. The 50 training sessions were categorized into quintiles. To compare the effect of BP reduction with both training methods, we used two-way analysis of covariance (ANCOVA) adjusted for the BP values obtained before the interventions. The differences between the moments were established by one-way analysis of variance (ANOVA). The reductions in systolic (SBP) and diastolic BP (DBP) were 6.9 mmHg and 5.3 mmHg, respectively, with resistance training and 16.5 mmHg and 11.6 mmHg, respectively, with aerobic training. The kinetics of the hypotensive response of the SBP showed significant reductions until the 20th session in both groups. Stabilization of the DBP occurred in the 20th session of resistance training and in the 10th session of aerobic training. A total of 20 sessions of resistance or aerobic training are required to achieve the maximum benefits of BP reduction. The methods investigated yielded distinct adaptive kinetic patterns along the 50 sessions. Os treinamentos de força e aeróbio são indicados para o tratamento adjuvante da hipertensão. Entretanto, o número de sessões necessárias até estabilização do efeito hipotensor com o exercício ainda não está claramente estabelecido. Estabelecer a cinética adaptativa das respostas tensionais em função do

  19. Atrial Function in Patients with Breast Cancer After Treatment with Anthracyclines.

    PubMed

    Yaylali, Yalin Tolga; Saricopur, Ahmet; Yurtdas, Mustafa; Senol, Hande; Gokoz-Dogu, Gamze

    2016-11-01

    Atrial electromechanical delay (EMD) is used to predict atrial fibrillation, measured by echocardiography. The aim of this study was to assess atrial EMD and mechanical function after anthracycline-containing chemotherapy. Fifty-three patients with breast cancer (48 ± 8 years old) who received 240 mg/m2of Adriamycin, 2400 mg/m2 of cyclophosphamide, and 960 mg/m2 of paclitaxel were included in this retrospective study, as were 42 healthy subjects (47 ± 9 years old). Echocardiographic measurements were performed 11 ± 7 months (median 9 months) after treatment with anthracyclines. Left intra-atrial EMD (11.4 ± 6.0 vs. 8.1 ± 4.9, p=0.008) and inter-atrial EMD (19.7 ± 7.4 vs. 14.7 ± 6.5, p=0.001) were prolonged; LA passive emptying volume and fraction were decreased (p=0.0001 and p=0.0001); LA active emptying volume and fraction were increased (p=0.0001 and p=0.0001); Mitral A velocity (0.8 ± 0.2 vs. 0.6 ± 0.2, p=0.0001) and mitral E-wave deceleration time (201.2 ± 35.6 vs. 163.7 ± 21.8, p=0.0001) were increased; Mitral E/A ratio (1.0 ± 0.3 vs. 1.3 ± 0.3, p=0.0001) and mitral Em (0.09 ± 0.03 vs. 0.11 ± 0.03, p=0.001) were decreased; Mitral Am (0.11 ± 0.02 vs. 0.09 ± 0.02, p=0.0001) and mitral E/Em ratio (8.8 ± 3.2 vs. 7.6 ± 2.6, p=0.017) were increased in the patients. In patients with breast cancer after anthracycline therapy: Left intra-atrial, inter-atrial electromechanical intervals were prolonged. Diastolic function was impaired. Impaired left ventricular relaxation and left atrial electrical conduction could be contributing to the development of atrial arrhythmias. Atraso eletromecânico atrial (AEA) é utilizado para prever fibrilação atrial, medido pela ecocardiografia. O propósito deste estudo era verificar o AEA e a função mecânica após quimioterapia com antraciclinas. Cinquenta e três pacientes com câncer de mama (48 ± 8 anos) que receberam 240 mg/m2 de adriamicina, 2400 mg/m2 de ciclofosfamida, e 960 mg/m2 de paclitaxel foram

  20. BREAST CANCER METASTASIS IN THE STOMACH: WHEN THE GASTRECTOMY IS INDICATED ?

    PubMed

    Rodrigues, Marcus Vinicius Rozo; Tercioti-Junior, Valdir; Lopes, Luiz Roberto; Coelho-Neto, João de Souza; Andreollo, Nelson Adami

    2016-01-01

    the absence of other secondary involvement and control of the primary lesion. A neoplasia de mama é o tumor maligno mais comum na população feminina tendo o trato gastrointestinal, e mais especificamente o estômago, como local incomum para metástases. Analisar uma série de casos com esse tumor e propor medidas que possam diagnosticá-lo com maior precocidade. Foram analisados retrospectivamente 12 pacientes com diagnóstico de neoplasia gástrica secundária a câncer de mama, confirmado por biópsia e imunoistoquímica. Foram analisados idade do diagnóstico, tipo histológico do tumor primário, intervalo de tempo entre o diagnóstico do tumor e a metástase, tratamento e sobrevida. A idade média foi de 71,3 anos (40-86 anos). Em média, o diagnóstico da metástase gástrica foi de sete anos após o diagnóstico da lesão primaria (0-13 anos). Nove casos tiveram metástases em outros órgãos, sendo os ossos os locais mais acometidos. Evidenciou-se positividade de anticorpo CK7 em 90,9% casos, receptor de estrógeno em 91,67%, receptor de progesterona em 66,67% e BRST2 em 41,67%. A ausência de CK20 foi de 88,89%. Oito casos foram tratados com quimioterapia associada ou não ao bloqueio hormonal e em quatro foi indicada ressecção cirúrgica sendo em três gastrectomia total e em um caso gastrectomia subtotal. A sobrevida média foi de 14,58 meses. Em doentes com história prévia de câncer de mama apresentando diagnóstico endoscópico de neoplasia gástrica, é necessário considerar a possibilidade de metástase. A confirmação é feita por estudo imunoistoquímico e a gastrectomia deve ser orientada diante da ausência de outros locais de acometimento secundário e controle da lesão primária.

  1. Estimated costs of advanced lung cancer care in a public reference hospital.

    PubMed

    Knust, Renata Erthal; Portela, Margareth Crisóstomo; Pereira, Claudia Cristina de Aguiar; Fortes, Guilherme Bastos

    2017-08-17

    coorte de 277 pacientes matriculados no Instituto Nacional do Câncer em 2011. Os custos foram estimados sob a perspectiva do hospital como prestador de serviços de referência para o SUS. Insumos e procedimentos utilizados foram identificados e quantificados, por paciente, sendo a eles atribuídos valores monetários, consolidados por fases da assistência definidas. As análises tiveram caráter descritivo com custos em reais (R$). Em termos globais, a coorte representou um custo de R$2.473.559,91, sendo 71,5% relacionados à atenção ambulatorial e 28,5% as internações. Na atenção ambulatorial, predominaram os custos com radioterapia (34%) e quimioterapia (22%). Os resultados apontaram para custos menores na fase inicial de tratamento (7,2%) e custos muito elevados na fase de manutenção (61,6%). Por fim, identificaram-se diferenças estatisticamente significativas das médias dos custos por faixas etárias, níveis de escolaridade, desempenho físico e tipo histológico. Este estudo fornece um retrato atual, útil e relevante sobre os custos de pacientes com câncer de pulmão não pequenas células assistidos em um hospital público de referência e provê elementos sobre a magnitude do problema do câncer no âmbito da saúde pública. Os resultados ratificam a importância do tratamento radioterápico e das internações como principais componentes de custo do tratamento. Apesar de algumas perdas de seguimento avalia-se que, para cerca de 80% dos pacientes incluídos no estudo, as estimativas aqui apresentadas sejam satisfatoriamente fidedignas ao cuidado da doença, sob a perspectiva de um prestador de referência do SUS, fornecendo elementos para a gestão do serviço, bem como para estudos que redundem em formas mais racionais de alocação de recursos.

  2. DEVELOPMENT OF METRICS FOR PROTOCOLS AND OTHER TECHNICAL PRODUCTS.

    PubMed

    Veiga, Daniela Francescato; Ferreira, Lydia Masako

    2015-01-01

    To develop a proposal for metrics for protocols and other technical products to be applied in assessing the Postgraduate Programs of Medicine III - Capes. The 2013 area documents of all the 48 Capes areas were read. From the analysis of the criteria used by the areas at the 2013's Triennal Assessment, a proposal for metrics for protocols and other technical products was developed to be applied in assessing the Postgraduate Programs of Medicine III. This proposal was based on the criteria of Biological Sciences I and Interdisciplinary areas. Only seven areas have described a scoring system for technical products. The products considered and the scoring varied widely. Due to the wide range of different technical products which could be considered relevant, and that would not be punctuated if they were not previously specified, it was developed, for the Medicine III, a proposal for metrics in which five specific criteria to be analyzed: Demand, Relevance/Impact, Scope, Complexity and Adherence to the Program. Based on these criteria, each product can receive 10 to 100 points. This proposal can be applied to the item Intellectual Production of the evaluation form, in subsection "Technical production, patents and other relevant production". The program will be scored as Very Good when it reaches mean ≥150 points/permanent professor/quadrennium; Good, mean between 100 and 149 points; Regular, mean between 60 and 99 points; Weak mean between 30 and 59 points; Insufficient, up to 29 points/permanent professor/quadrennium. Desenvolver proposta de métricas para protocolos e outras produções técnicas a serem aplicadas na avaliação dos Programas de Pós-Graduação da Área Medicina III da Capes. Foram lidos os documentos de área de 2013 de todas as 48 Áreas da Capes. A partir da análise dos critérios utilizados por elas na avaliação trienal 2013, foi desenvolvida uma proposta de métricas para protocolos e outras produções técnicas. Esta proposta foi baseada

  3. COST-EFFECTIVENESS OF PERIOPERATIVE IMMUNONUTRITION IN GASTROINTESTINAL ONCOLOGIC SURGERY: A SYSTEMATIC REVIEW.

    PubMed

    Reis, Audrey Machado Dos; Kabke, Geórgia Brum; Fruchtenicht, Ana Valéria Gonçalves; Barreiro, Taiane Dias; Moreira, Luis Fernando

    2016-01-01

    defesas. Avaliar a imunonutrição em pacientes oncológicos que são operados por doenças do aparelho digestivo e avaliar a relação custo-eficácia desta suplementação. Revisão sistemática da literatura baseada nas bases de dados PubMed, Lilacs e SciELO. A busca foi realizada com combinação de descritores em inglês e português relacionados ao tema da revisão: [immunonutrition, arginine, omega-3, nucleotides] combinado com [costs, cost-effective, cost-effectiveness] e [gastrointestinal cancer surgery, oesophageal, gastric or pancreatic surgery]. Para análise de custos, moedas usadas nos artigos foram todas convertidas para dólar americano. Seis estudos randomizados prospectivos foram incluídos nesta revisão. O custo-benefício foi positivo na maioria dos estudos, sugerindo que este tipo de dieta reduz significativamente os custos hospitalares nos países do hemisfério norte. Contudo, estudos similares de custo-benefício devem ser realizados para definir o real custo-benefício em nosso meio.

  4. Informal and paid care for Brazilian older adults (National Health Survey, 2013).

    PubMed

    Lima-Costa, Maria Fernanda; Peixoto, Sérgio Viana; Malta, Deborah Carvalho; Szwarcwald, Célia Landmann; Mambrini, Juliana Vaz de Melo

    2017-06-01

    nenhuma. Os fatores sociodemográficos foram idade (60-64, 65-74, ≥ 75 anos), sexo e número de moradores no domicílio (1, 2, ≥ 3). A análise multivariada foi baseada nas regressões logísticas binomial e multinomial. A ajuda informal predominou (81,8%), seguida pela remunerada (5,8%) ou mista (6,8%) e nenhuma (5,7%). A propensão ao recebimento da ajuda por qualquer fonte aumentou gradativamente com o número de moradores no domicílio, independentemente da idade e do sexo (OR = 4,85 e 9,74 para 2 e ≥ 3 moradores, respectivamente). A idade apresentou associação positiva e o sexo masculino apresentou associação negativa com o recebimento de qualquer ajuda. O número de moradores no domicílio apresentou associação mais forte com a ajuda informal (OR = 10,94 para ≥ 3 moradores), em comparação à ajuda remunerada (OR = 5,48) e mista (OR = 4,16). O cuidado informal é a principal fonte de ajuda domiciliar aos idosos com limitações funcionais. Em um contexto de rápido envelhecimento populacional e diminuição do tamanho das famílias, os resultados reforçam a necessidade de políticas para garantir o cuidado domiciliar aos idosos com limitações funcionais.

  5. Effectiveness of teaching strategies on the development of critical thinking in undergraduate nursing students: a meta-analysis.

    PubMed

    Oliveira, Larissa Bertacchini de; Díaz, Leidy Johanna Rueda; Carbogim, Fábio da Costa; Rodrigues, Adriano Rogério Baldacin; Püschel, Vilanice Alves de Araújo

    2016-04-01

    To evaluate the effectiveness of teaching strategies used for development of critical thinking (CT) in undergraduate nursing students. Systematic review with meta-analysis based on the recommendations of the Joanna Briggs Institute . Searches were conducted in the following databases: PubMed, CINAHL, EMBASE, Web of Science, SCOPUS, LILACS, Cochrane CENTRAL, PsycINFO, ERIC, and a database of theses from four continents. The initial selection and evaluation of studies and assessment of methodological quality was performed by two reviewers independently. Twelve randomized clinical trials were included in the study. In the meta-analysis of the four studies included that evaluated the strategy of problem-based learning (PBL), compared to lectures, the effectiveness of PBL was demonstrated with statistical significance (SMD = 0.21 and 95% CI = 0.01 to 0.42; p = 0.0434) for the development of CT in undergraduate nursing students, and the studies were homogeneous (chi-square = 6.10, p = 0.106). The effectiveness of PBL was demonstrated in the increase of overall CT scores. Further studies need to be conducted in order to develop, implement and evaluate teaching strategies that are guided in high methodological rigor, and supported in theoretical models of teaching and learning. Avaliar a efetividade das estratégias de ensino utilizadas para o desenvolvimento do pensamento crítico (PC) em estudantes de graduação em Enfermagem. Revisão sistemática com metanálise baseada nas recomendações do Joanna Briggs Institute. A busca foi realizada nas bases de dados PubMed, CINAHL, EMBASE, Web of Science, SCOPUS, LILACS, Cochrane CENTRAL, PsycINFO e ERIC e de banco de teses dos quatro continentes. A seleção e avaliação inicial dos estudos e a avaliação da qualidade metodológica foi realizada por dois revisores de forma independente. Incluídos 12 ensaios clínico randomizados. Na metanálise, dos quatro estudos incluídos que avaliaram a estratégia do Problem Based

  6. Attitude and knowledge about foot health: a spanish view.

    PubMed

    López-López, Daniel; García-Mira, Ricardo; Palomo-López, Patricia; Sánchez-Gómez, Rubén; Ramos-Galván, José; Tovaruela-Carrión, Natalia; García-Sánchez, Matilde

    2017-04-06

    to explore attitudes towards patients' self-reported data about foot health-related beliefs from a behavioural and attitudinal perspective. a sample of 282 participants of a mean age of 39.46 ± 16.026 came to a health centre where self-reported demographic, clinical characteristics and beliefs relating to foot health data were registered, informants' completed all the stages of the research process. the results of the analysis revealed an 8-factor factorial structure based on (1) podiatric behaviours, (2) the intention to carry out protective behaviour, (3) attitudinal beliefs, (4) normative beliefs, (5) needs, (6) apathy, (7) self-care, and (8) the general perception of foot health. They all explained 62.78% of the variance, and were considered as independent variables in a regression analysis to determine which provided the best explanations for the importance attributed to foot health. the participants in the study revealed a positive attitude in relation to foot health care and responsible behaviour. explorar as atitudes em relação aos dados auto-relatados dos pacientes sobre crenças relacionadas à saúde do pé, desde uma perspectiva comportamental e atitudinal. uma amostra de 282 participantes com idade média de 39,46 ± 16,026 chegaram a um centro de saúde onde foram registradas características demográficas, clínicas e crenças auto-relatadas referentes a dados de saúde do pé, os quais completaram todas as fases do processo de pesquisa. os resultados da análise revelaram uma estrutura fatorial de 8 fatores baseada em (1) comportamentos podiátricos, (2) a intenção de realizar comportamentos protetores, (3) crenças atitudinais, (4) crenças normativas, (6) apatia, (7) autocuidado, e (8) a percepção geral da saúde do pé. Todos eles explicaram 62,78% da variância e foram considerados como variáveis ​​independentes em uma análise de regressão para determinar quais forneceram as melhores explicações para a importância atribuída

  7. A causa das estações do ano: modelos mentais

    NASA Astrophysics Data System (ADS)

    de Campos, J. A. S.; de Araujo, J. F. S.

    2003-08-01

    A década de 70 do século passado foi marcada pelo estudo das concepções alternativas que os alunos trazem para a sala de aula. A identificação destas concepções foi o ponto de partida para promover a mudança conceitual, onde as pré-concepções seriam trocadas pelas concepções científicas. Na década seguinte, surgiram muitas propostas de estratégias educacionais para facilitar esta troca, na sua maioria baseadas na idéia do conflito cognitivo, proposta por Piaget. Entretanto, os resultados pouco animadores conduziram à percepção de que a mudança conceitual é um processo mais complexo. Pelas idéias da Ciência Cognitiva, a mudança conceitual é uma mudança progressiva dos modelos mentais que o aluno tem sobre o mundo físico, através de enriquecimento e revisão. A causa das Estações do Ano é um tópico sobre o qual a maioria dos estudantes apresenta concepções alternativas. Os autores fizeram um levantamento sobre as pré-concepções encontradas em trabalhos sobre o tema (16 referências), procurando encontrar elementos comuns que indicassem a presença de modelos mentais específicos. As pré-concepções encontradas na literatura foram obtidas usando-se diversas metodologias (desde entrevistas clínicas até questionários de múltipla escolha) e envolvendo alunos e professores de diferentes regiões geográficas. A partir de uma análise aprofundada de cada trabalho, e utilizando-se a técnica das Redes Sistêmicas, chegou-se a conclusão que as diversas pré-concepções identificadas (em torno de 50), poderiam ser representadas por 6 modelos mentais, onde a explicação da causa das estações do ano tem um mecanismo causal responsável. Os mecanismos causais identificados foram: a dependência da distância, a dependência da orientação, a dependência conjunta da distância e orientação, a dependência da obstrução, a dependência da velocidade e a dependência da inclinação dos raios solares. Foram ainda identificadas

  8. [Contribution for the validation of the Portuguese version of EQ-5D].

    PubMed

    Ferreira, Pedro Lopes; Ferreira, Lara Noronha; Pereira, Luis Nobre

    2013-01-01

    Introdução: O EQ-5D permite a junção de duas componentes essenciais de qualquer medida de qualidade de vida relacionada com a saúde a ser usada em avaliações económicas de custo-utilidade: (i) um perfil descrevendo o estado de saúde em termos de domínios ou dimensões; e (ii) um valor numérico associado ao estado de saúde anteriormente descrito.Objectivo: A versão portuguesa do questionário EQ-5D foi finalizada em 1998, com base em normas de orientação definidas pelo Grupo EuroQol, incluindo os procedimentos de tradução e retroversão. Apesar da sua larga utilização em Portugal, até agora ainda não tinham sido publicados os estudos que conduziram inicialmente à versão portuguesa e à garantia de aceitabilidade, fiabilidade e validade. O propósito do presente artigo é, assim, documentar estes primeiros valores referentes à versão portuguesa do EQ-5D.Material e Métodos: Foram utilizadas três amostras diferentes: uma primeira com 1.500 indivíduos representativa da populaçãoportuguesa; uma segunda com 140 indivíduos apenas destinada ao teste da fiabilidade; e uma terceira amostra com 643 indivíduos doentes com cataratas, asma, doença pulmonar obstrutiva crónica ou artrite reumatoide.Resultados: A aceitabilidade foi avaliada pelo número de respostas em falta. Foi também encontrado um marcado efeito de teto com grande parte da amostra a não reportar quaisquer problemas nas dimensões do EQ-5D.Discussão: A validade de construção foi testada pela análise do grau com que valores baixos de EQ-5D estavam positivamente associados ao aumento da idade, ao ser do sexo feminino, e ao estar doente, assim como a valores de dimensões da escala SF-36v2. A validade convergente foi baseada nas correlações entre valores do EQ-5D e outras escalas específicas de condição de saúde. O EQ-5D apresentou correlações moderadas a altas com outras medidas de estado de saúde e de qualidade de vida relacionada com a saúde, específicas de cada

  9. Preimplantation genetic diagnosis associated to Duchenne muscular dystrophy.

    PubMed

    Bianco, Bianca; Christofolini, Denise Maria; Conceição, Gabriel Seixas; Barbosa, Caio Parente

    2017-09-21

    DMD e G.T.S., 39 anos, buscaram aconselhamento genético sobre o processo de diagnóstico genético pré-implantação. O casal relatou que tiveram um filho de 6 anos que morreu devido a complicações da distrofia muscular de Duchenne. Os pacientes realizaram quatro ciclos de injeção intracitoplásmica de espermatozoides (ICSI) e oito biópsias de embriões foram analisadas por reação em cadeia da polimerase (PCR) para análise de mutação específica, seguida hibridação genômica comparativa baseada em microarranjos ( array CGH) para a pesquisa de aneuploidias. O diagnóstico genético pré-implantação revelou que dois embriões haviam herdado a mutação materna no gene DMD , um embrião tinha uma alteração cromossômica e cinco embriões eram normais. Um blastocisto foi transferido e resultou em gravidez bem sucedida. Os outros embriões permanecem vitrificados. Concluímos que a análise de embriões utilizando técnicas associadas de PCR e CGH array mostrou-se segura para a seleção de embriões em casos de doenças ligadas ao X, como a distrofia muscular de Duchenne.

  10. THE ROLE OF METABOLIC SURGERY FOR PATIENTS WITH OBESITY GRADE I ANDCLINICALLY UNCONTROLLED TYPE 2 DIABETES.

    PubMed

    Campos, Josemberg; Ramos, Almino; Szego, Thomaz; Zilberstein, Bruno; Feitosa, Heládio; Cohen, Ricardo

    2016-07-07

    Metabolic Risk Score defined by the surgical societies. Roux-en-Y gastric bypass (RYGB), because of its well known safety and efficacy and longer follow-up studies, is the main surgical technique indicated for patients eligible for surgery through the Metabolic Risk Score. The vertical sleeve gastrectomy may be considered if there is an absolute contraindication for the RYGB. T2DM patients should be evaluated by the multiprofessional team that will assess surgical eligibility, preoperative work up, follow up and long term monitoring for micro and macrovascular complications. Mesmo considerando o avanço do tratamento clínico ocorrido nos últimos 20 anos, com novos e mais eficientes medicamentos, os dados ainda são desanimadores quanto ao controle da obesidade e da diabete melito tipo 2(DMT2),com grande parcela de doentes em tratamento clínico ficando fora da meta desejada de controle. Apresentar proposta de Escore de Risco Metabólico para melhor orientar a indicação cirúrgica do diabete em pacientes com índice de massa corpórea (IMC) mais baixo nos quais o uso de procedimento cirúrgico para obesidade ainda é controverso. Foi realizada pesquisa nas bases de dados PubMed, Medline, PubMed Central, Scielo e Lilacs entre 2003-2015 correlacionando os descritores:cirurgia metabólica, obesidade e diabete melito tipo 2. Adicionalmente, representantes das sociedades envolvidas emitiram opiniões em pontos nos quais não existia na literatura trabalhos com graus de evidência elevados. Foram encontrados 45 artigos relacionadosque foram analisados pelos critérios da medicina baseada em evidências.As opiniões agrupadas procuraram responder as seguintes questões: Porque cirurgia metabólica e não bariátrica?;Mecanismos envolvidos no controle glicêmico; IMC como critério isolado de indicação cirúrgica para o DMT2 não controlado; Resultados de estudos de cirurgia metabólica em IMC<35 kg/m2; Segurança da cirurgia metabólica em pacientes com IMC<35 kg/m2; Efeitos

  11. THE ROLE OF METABOLIC SURGERY FOR PATIENTS WITH OBESITY GRADE I AND TYPE 2 DIABETES NOT CONTROLLED CLINICALLY.

    PubMed

    Campos, Josemberg; Ramos, Almino; Szego, Thomaz; Zilberstein, Bruno; Feitosa, Heládio; Cohen, Ricardo

    Metabolic Risk Score defined by the surgical societies. Roux-en-Y gastric bypass (RYGB), because of its well known safety and efficacy and longer follow-up studies, is the main surgical technique indicated for patients eligible for surgery through the Metabolic Risk Score. The vertical sleeve gastrectomy may be considered if there is an absolute contraindication for the RYGB. T2DM patients should be evaluated by the multiprofessional team that will assess surgical eligibility, preoperative work up, follow up and long term monitoring for micro and macrovascular complications. Mesmo considerando o avanço do tratamento clínico ocorrido nos últimos 20 anos, com novos e mais eficientes medicamentos, os dados ainda são desanimadores quanto ao controle da obesidade e da diabete melito tipo 2 (DMT2),com grande parcela de doentes em tratamento clínico ficando fora da meta desejada de controle. Apresentar proposta de Escore de Risco Metabólico para melhor orientar a indicação cirúrgica do diabete em pacientes com índice de massa corpórea (IMC) mais baixo nos quais o uso de procedimento cirúrgico para obesidade ainda é controverso. Foi realizada pesquisa nas bases de dados Pubmed, Medline, Pubmed Central, Scielo e Lilacs entre 2003-2015 correlacionando os descritores:cirurgia metabólica, obesidade e diabete melito tipo 2. Adicionalmente, representantes das sociedades envolvidas emitiram opiniões em pontos nos quais não existia na literatura trabalhos com graus de evidência elevados. Foram encontrados 45 artigos relacionados que foram analisados pelos critérios da medicina baseada em evidências. As opiniões agrupadas procuraram responder as seguintes questões: Porque cirurgia metabólica e não bariátrica?; Mecanismos envolvidos no controle glicêmico; IMC como critério isolado de indicação cirúrgica para o DMT2 não controlado; Resultados de estudos de cirurgia metabólica em IMC<35 kg/m2; Segurança da cirurgia metabólica em pacientes com IMC<35 kg/m2

  12. Assessment in the primary care of the State of São Paulo, Brazil: incipient actions in sexual and reproductive health.

    PubMed

    Nasser, Mariana Arantes; Nemes, Maria Ines Battistella; Andrade, Marta Campagnoni; Prado, Rogério Ruscitto do; Castanheira, Elen Rose Lodeiro

    2017-08-17

    the highest correlation with the other ones. The implementation of sexual and reproductive health in primary health care in the services studied is incipient. The revision of the purpose of the work, the dissemination of technologies, and the investing in permanent education are needed. The evaluative framework built can be used by the sexual and reproductive health program services and management in primary health care, thereby contributing to their actions. Avaliar o desempenho em saúde sexual e reprodutiva de serviços de atenção primária à saúde do Sistema Único de Saúde, no estado de São Paulo. Construiu-se quadro avaliativo para a saúde sexual e reprodutiva com a categorização de 99 indicadores em três domínios: promoção à saúde sexual e reprodutiva (25), prevenção e assistência às doenças sexualmente transmissíveis/aids (43), e atenção à saúde reprodutiva (31). Esse quadro foi aplicado para avaliar as respostas dos serviços ao questionário Avaliação da Qualidade da Atenção Básica em Municípios de São Paulo (QualiAB), em 2010. Calcularam-se as porcentagens de respostas positivas aos indicadores e o desempenho na dimensão saúde sexual e reprodutiva, segundo os domínios; e verificou-se sua contribuição para o escore geral em saúde sexual e reprodutiva (Friedman), participação relativa (Dunn) e correlação (Spearman). Participaram 2.735 serviços, localizados em 586 municípios (distribuídos nos 17 departamentos regionais de saúde paulistas), dos quais 70,6% municípios com menos de 100.000 habitantes. A média geral do desempenho desses serviços para saúde sexual e reprodutiva é 56,8%. As ações são caracterizadas por: pré-natal com início e exames adequados, melhor organização para puerpério imediato do que tardio, e planejamento reprodutivo seletivo para alguns contraceptivos; prevenção baseada em proteção específica, limites na prevenção da sífilis congênita, no tratamento de doen

  13. Use of health services by Brazilian older adults with and without functional limitation.

    PubMed

    Silva, Alexandre Moreira de Melo; Mambrini, Juliana Vaz de Melo; Peixoto, Sérgio Viana; Malta, Deborah Carvalho; Lima-Costa, Maria Fernanda

    2017-06-01

    idosos brasileiros com e sem limitação funcional. As análises principais foram baseadas em amostra nacional representativa de 23.815 participantes da Pesquisa Nacional de Saúde com 60 anos ou mais. A limitação funcional foi definida pela dificuldade para realizar pelo menos uma entre dez atividades básicas ou instrumentais da vida diária. Potenciais variáveis de confusão incluíram fatores predisponentes e facilitadores do uso de serviços de saúde. A prevalência da limitação funcional foi de 30,1% (IC95% 29,2-31,4). O número de consultas médicas e a ocorrência de hospitalizações nos últimos 12 meses apresentaram associações estatisticamente significantes com a limitação funcional, tanto entre usuários do sistema público (OR = 2,48 [IC95% 2,13-2,88] para três ou mais consultas e OR = 2,58 [IC95% 2,15-3,09] para uma ou mais hospitalizações) quanto do sistema privado (OR = 2,56 [IC95% 1,50-4,36] e OR = 2,22 [IC95% 1,64-3,00], respectivamente). A propensão ao uso da unidade básica de saúde foi maior entre usuários do sistema privado com limitações funcionais (OR = 2,01 [IC95% 1,12-3,59]). Entre sete indicadores da qualidade da atenção médica recebida, na percepção dos usuários dos sistemas público e privado, somente dois apresentaram associação com a limitação funcional. Os usuários do sistema público com limitações funcionais fizeram pior avaliação da liberdade para escolha do médico e do tempo de espera para a consulta, em comparação aos usuários do mesmo sistema sem essas limitações (OR = 0,81 [IC95% 0,67-0,99] e OR = 0,76 [IC95% 0,62-0,93], respectivamente). Idosos com limitações funcionais utilizam mais serviços de saúde em comparação aos seus pares sem essas limitações. A magnitude da associação entre a limitação funcional e o número de consultas médicas e de hospitalizações foi semelhante nos sistemas público e privado de saúde.

  14. The genesis of the AIDS policy and AIDS Space in Brazil (1981-1989).

    PubMed

    Barros, Sandra Garrido de; Vieira-da-Silva, Ligia Maria

    2016-07-21

    para a formulação de uma política específica. O Espaço Aids constituiu-se como produto do encontro da trajetória de agentes de diversos campos sociais (médico, científico, político e burocrático). Um espaço específico de relações, que possibilitou a formulação de uma política para o controle da epidemia da aids, mas onde também estava em disputa a autoridade de falar sobre o significado da doença, suas formas de prevenção e tratamento. A análise mostrou como as estruturas (governos democráticos no estado de São Paulo e no âmbito nacional, com sanitaristas assumindo posições importantes) e a ausência de terapia específica contribuíram para que agentes sociais com disposições e formações diversas formulassem uma política que priorizou inicialmente a prevenção. A ascensão do movimento sanitário, a constituição do SUS e a dominância do campo médico no Espaço Aids contribuíram para a valorização do tratamento, como parte das medidas de controle da epidemia. Essas condições possibilitaram a formulação de uma política baseada na integralidade das ações, articulando prevenção e tratamento, na década seguinte, com importante participação da burocracia estatal e de pesquisadores.

  15. Biochemical and biophysical investigation of surfactant in neonatal gastric aspirate at birth.

    PubMed

    Bangyozova, Maya; Jordanova, Albena; Tsanova, Asya; Jekova, Neli; Chakarov, Decho; Doumanov, Jordan; Christova, Emilia; Lalchev, Zdravko

    2013-01-01

    Introdução: A melhor abordagem para detecção de deficiência de surfactante em recém-nascidos prematuros no nascimento permanece pouco clara e a decisão de aplicar surfactante exógeno é baseada principalmente no desenvolvimento de sinais clínicos e radiológicos da síndrome de angústia respiratória neonatal (NRDS). Objetivos: Estudamos as propriedades bioquímicas e biofísicas do aspirado gástrico (GA) de crianças nascidas prematuramente com NRDS e saudáveis nascidos a termo, com o objetivo de encontrar um método acessível para avaliação da maturidade do surfactante no nascimento. Material e Métodos: Quarenta e sete recém-nascidos, divididos em dois grupos foram incluídos no estudo. O primeiro grupo composto por 34 crianças saudáveis nascidas a termo (após 37 semanas de gestação). O segundo grupo incluiu 13 recém-nascidos prematuros (idade entre 26 - 32 semanas de gestação) desenvolveram sinais clínicos de NRDS para os quais foram tratados por ventilação assistida e surfactante exógeno. A análise bioquímica da proteína e lipídio da GA coletado no nascimento foi realizado. A composição de ácidos graxos das amostras GA foi determinada pelo detector de cromatografia de massa seletiva (GS-MSD) análise. As características da superfície (de equilíbrio, os valores máximo e mínimo de tensão de superfície) das amostras de AG foram medidos utilizando o método de gota pendente. Os dados foram comparados entre os grupos, utilizando o teste t de Student ou teste de Mann-Whitney análise. Os valores foram considerados significativamente diferentes se o valor de p ≤ 0,05. Resultados: A concentração média de fosfolipídeos em GA dos prematuros foi menor (295,7 g / ml vs 374,5 mg / ml) do que em crianças a termo e do conteúdo médio de proteína foi menor no GA dos bebês prematuros que o termo recém-nascidos (574,5 ng / ml vs 641,5 ug / ml). A medição das características de superfície dinâmicas da GA mostraram

  16. Social representations of the health care of the Mbyá-Guarani indigenous population by health workers.

    PubMed

    Falkenberg, Mirian Benites; Shimizu, Helena Eri; Bermudez, Ximena Pamela Díaz

    2017-02-06

    medicina tradicional e da biomedicina, mas observam-se alguns avanços na perspectiva da intermedicalidade. Fronteiras étnicas estabelecidas entre os trabalhadores e os indígenas, baseadas em suas representações de cultura e família, da mesma maneira que a falta de infraestrutura e os modos de organização do trabalho em saúde são percebidos como fatores que dificultam o cuidado em contextos de interculturalidade. é preciso estabelecer novas bases para o processo de cuidar em saúde indígena, a partir da compreensão das necessidades representadas, negociadas entre sujeitos individuais e coletivos e os profissionais nas instituições de saúde em um diálogo intercultural de múltiplas vozes. analizar las representaciones sociales de la atención de la salud del grupo étnico Mbyá-Guaraní por equipos multidisciplinarios del Distrito Sanitario Especial Indígena en la costa sur del estado de Rio Grande do Sul (Distrito Sanitário Especial Indígena Litoral Sul do Rio Grande do Sul), Brasil. se utilizó un método cualitativo basado en la teoría de las representaciones sociales. Los datos fueron recogidos a través de entrevistas semi-estructuradas con 20 trabajadores de la salud y por observación de los participantes. Las entrevistas fueron analizadas con el programa ALCESTE, que realiza un análisis de contenido léxico utilizando técnicas cuantitativas para el tratamiento de datos textuales. hubo desacuerdos en los conceptos y prácticas de atención médica entre medicina tradicional y biomedicina; sin embargo, se han logrado algunos avances en el área de la intermedicina. Las barreras étnicas establecidas entre los trabajadores de la salud y los pueblos indígenas basados en sus representaciones de la cultura y la familia, junto con la falta de infraestructura y organización de las acciones de salud, son percibidas como factores que obstaculizan la atención sanitaria en un contexto intercultural. es necesario establecer una nueva base para el proceso

  17. Culture-bound syndromes in migratory contexts: the case of Bolivian immigrants.

    PubMed

    Roldán-Chicano, María Teresa; Fernández-Rufete, José; Hueso-Montoro, César; García-López, María Del Mar; Rodríguez-Tello, Javier; Flores-Bienert, María Dolores

    2017-07-10

    ís de origem, são mantidas pelo grupo estudado. As formas de cuidado para esses problemas de saúde são adaptadas aos recursos do novo contexto e baseadas em interações com o ambiente doméstico, a biomedicina e a medicina tradicional. Foi constatada a necessidade de que os profissionais de saúde reconheçam que a eficácia de determinadas terapias se dá no âmbito das crenças culturais e não no âmbito da comprovação científica. describir los síndromes de filiación cultural que mantienen los inmigrantes bolivianos en el nuevo contexto migratorio y analizar los procesos de atención de estos padecimientos. diseño de investigación de carácter cualitativo con enfoque metodológico etnográfico. Muestra: 27 inmigrantes bolivianos. Las estrategias para recoger datos fueron las entrevistas en profundidad y la observación participante. Los datos se categorizaron y ordenaron en esquemas lógicos manualmente y a través del programa ATLAS-ti v.5. el susto, los "wayras", el amartelo, el pasmo de sol, el pasmo de luna y el pasmo de sereno son algunos de los síndromes de carácter folk que los inmigrantes bolivianos padecen y tratan en el nuevo contexto migratorio. en el nuevo entorno, el colectivo estudiado mantiene síndromes de filiación cultural comunes en su país de origen. Las formas de atención de éstos padecimientos se adaptan a los recursos del nuevo contexto y se basan en transacciones con el ámbito doméstico, la biomedicina y la medicina tradicional. Se constata la necesidad de que el profesional sanitario reconozca que la efectividad percibida de ciertas terapias opera dentro del ámbito de las creencias culturales y no en el de la evidencia científica.

  18. Cultural adaptation and validation of an instrument on barriers for the use of research results.

    PubMed

    Ferreira, Maria Beatriz Guimarães; Haas, Vanderlei José; Dantas, Rosana Aparecida Spadoti; Felix, Márcia Marques Dos Santos; Galvão, Cristina Maria

    2017-03-02

    confirmada, la escala investiga las barreras para la utilización de resultados de investigación en la práctica clínica. El análisis factorial confirmatorio demostró que la versión del instrumento para el portugués brasileño está adecuadamente ajustado a la estructura dimensional originalmente propuesta por los autores de la escala. Fueron observadas diferencias estadísticamente significantes entre los enfermeros con título de maestría o doctorado, con características favorables a la Práctica Basada en Evidencias, y actuantes en institución con cultura organizacional dirigida hacia tal aproximación. La fiabilidad presentó correlación fuerte (r variando entre 0,77 y 0,84, p<0,001) y la consistencia interna fue adecuada (alfa de Cronbach variando entre 0,77 y 0,82). la versión para el portugués brasileño del instrumento The Barriers Scale se mostró válida y confiable en el grupo estudiado. realizar adaptação cultural do instrumento The Barriers to Research Utilization Scale, e analisar propriedades métricas de validade e confiabilidade da sua versão para o português brasileiro. pesquisa metodológica conduzida por meio do processo de adaptação cultural (tradução e retrotradução), validade de face e conteúdo, validade de construto (dimensionalidade e grupos conhecidos) e análise da confiabilidade (consistência interna e teste-reteste). A amostra foi composta de 335 enfermeiros, desses, 43 participaram da etapa reteste. a validade da versão adaptada do instrumento foi confirmada, a escala investiga as barreiras para a utilização de resultados de pesquisa na prática clínica. A análise fatorial confirmatória demonstrou que a versão do instrumento para o português brasileiro está adequadamente ajustada à estrutura dimensional originalmente proposta pelos autores da escala. Observou-se diferenças estatisticamente significantes entre os enfermeiros mestres ou doutores, com características favoráveis a Prática Baseada em Evid

  19. The situation of nursing education in Latin America and the Caribbean towards universal health.

    PubMed

    Cassiani, Silvia Helena De Bortoli; Wilson, Lynda Law; Mikael, Sabrina de Souza Elias; Peña, Laura Morán; Grajales, Rosa Amarilis Zarate; McCreary, Linda L; Theus, Lisa; Agudelo, Maria Del Carmen Gutierrez; Felix, Adriana da Silva; Uriza, Jacqueline Molina de; Gutierrez, Nathaly Rozo

    2017-05-11

    ,63, indicando que os estudantes têm mais experiências clínicas nos cenários hospitalares. Os resultados sugeriram necessidade de aprimoramento relacionada ao acesso à Internet; tecnologia da informação; acesso para portadores de deficiências; avaliação do programa, do corpo docente e dos estudantes; e aos métodos de ensino/aprendizagem. há heterogeneidade na educação em enfermagem na América Latina e no Caribe. Os currículos de enfermagem incluem, geralmente, os princípios e valores da Saúde Universal e da atenção primária à saúde, bem como aqueles princípios subjacentes às modalidades de educação transformativa, como o desenvolvimento de pensamento crítico e complexo, a solução de problemas, a tomada de decisão clínica baseada em evidências, e aprendizagem contínua. No entanto, é preciso promover uma mudança de paradigma na educação em enfermagem que inclua mais treinamento na atenção primária à saúde. evaluar la situación de la educación en enfermería y analizar en qué grado los programas de educación de enfermería a nivel de grado en América Latina y el Caribe están preparando a los graduados para contribuir al logro de la Salud Universal. se llevó a cabo un estudio transversal, cuantitativo, descriptivo y exploratorio en 25 países. participaron en el estudio 246 escuelas de enfermería. El porcentaje de profesores con títulos de doctorado fue de 31,3%; pero, si se excluye a Brasil esta cifra se reduce a 8,3%. La proporción de la experiencia clínica adquirida en los servicios de atención primaria de salud en relación con la adquirida en servicios hospitalarios fue de 0,63, lo que indica que los estudiantes adquieren la mayor parte de su experiencia clínica en entornos hospitalarios. Los resultados mostraron una necesidad de mejorar el acceso a internet; la tecnología de la información; la accesibilidad para las personas discapacitadas; la evaluación de los programas, de los profesores y de los estudiantes; y los m

  20. EFFECTIVE INDICATORS FOR SCIENCE INTERNATIONALIZATION.

    PubMed

    Cunha-Melo, José Renan da

    2015-01-01

    ções, explorando o potencial para cooperação internacional interdisciplinar de cada laboratório, departamento, universidade ou instituto. Procura de indicadores que possam avaliar o grau de internacionalização das universidades e institutos de pesquisa em vários níveis interconectados: organizacional, regional, setorial e global e para definição de políticas nas áreas de ciência, tecnologia inovação e educação superior. A pesquisa científica ainda é realizada individualmente, mas está atualmente muito mais intimamente integrada a outros processos sociais. O cientista não é mais um estranho que tem permissão para entregar-se ao seu passatempo de fazer aquilo que bem entende. Internacionalização da pesquisa e da educação médica, embora esteja entre os tópicos de maior reconhecimento como sendo necessidade do mundo globalizado, é atividade difícil de ser avaliada. Os governantes parecem ter entendido que as sociedades do conhecimento, induzindo a política econômica baseada no conhecimento pode resultar em progresso econômico e social das nações. Esse fato tem motivado de forma crescente o incentivo às ações que visam a abordagem de problemas globais (e.g. saúde, mudanças climáticas) pelo financiamento da pesquisa que gera conhecimento novo. É consenso que a internacionalização da ciência é desejável e necessária para o desenvolvimento sustentável das nações. Entretanto ela não pode ser feita somente incentivando e fomentando a ida de estudantes e pesquisadores para o exterior. É preciso, em adição, oferecer condições a professores pesquisadores e estudantes estrangeiros para que possam atuar em colaboração com os brasileiros e elevar o país aos padrões científicos internacionais.

  1. Cardiovascular Risk Stratification and Statin Eligibility Based on the Brazilian vs. North American Guidelines on Blood Cholesterol Management.

    PubMed

    Cesena, Fernando Henpin Yue; Laurinavicius, Antonio Gabriele; Valente, Viviane A; Conceição, Raquel D; Santos, Raul D; Bittencourt, Marcio S

    2017-06-01

    íduos saudáveis em prevenção primária: avaliar a relação entre o risco cardiovascular segundo a V Diretriz Brasileira de Dislipidemias e o risco calculado pelas pooled cohort equations (PCE); comparar a proporção de indivíduos elegíveis para estatinas, de acordo com diferentes critérios. Em indivíduos de 40 a 75 anos submetidos consecutivamente a avaliação rotineira de saúde em um único centro, quatro critérios de elegibilidade para estatina foram definidos: BR-1, BR-2 (LDL-c acima ou pelo menos 30 mg/dL acima da meta preconizada pela diretriz brasileira, respectivamente), EUA-1 e EUA-2 (risco estimado pelas PCE em 10 anos ≥ 5,0% ou ≥ 7,5%, respectivamente). Foram estudados 13.947 indivíduos (48 ± 6 anos, 71% homens). A maioria dos indivíduos de risco intermediário ou alto pela V Diretriz apresentou risco calculado pelas PCE baixo e mais de 70% daqueles considerados de alto risco o foram devido à presença de fator agravante. Foram elegíveis para estatina 24%, 17%, 4% e 2% das mulheres pelos critérios BR-1, BR-2, EUA-1 e EUA-2, respectivamente (p < 0,01). Os respectivos valores para os homens foram 75%, 58%, 31% e 17% (p < 0,01). Oitenta e cinco por cento das mulheres e 60% dos homens elegíveis para estatina pelo critério BR-1 não seriam candidatos pelo critério EUA-1. Comparada à diretriz norte-americana, a V Diretriz Brasileira considera uma proporção substancialmente maior da população como elegível para estatina em prevenção primária. Isso se relaciona com discrepâncias entre o risco estratificado pela diretriz brasileira e o calculado pelas PCE, particularmente devido à reclassificação de risco baseada em fatores agravantes.

  2. Perceptional gaps among women, husbands and family members about intentions for birthplace: a cross-sectional study.

    PubMed

    Shimpuku, Yoko; Madeni, Frida Elikana; Horiuchi, Shigeko; Leshabari, Sebalda Charles

    2017-01-30

    (BIQ), medindo o conhecimento, atitude, percepcão de controle comportamental, normas subjetivas e intenção para lugar de parto. Análise descritivas, ANOVA, Qui-quadrado e regressão linear múltipla foram utilizados para analisar os dados. o modelo de regressão mostrou que o conhecimento, percepcão de controle comportamental e normas subjetivas previram intenção de lugar de parto (R2 = 0,28). Enquanto 81% das mulheres grávidas pensavam que seus maridos eram os decisores para seu parto, apenas 38% dos maridos e 37% dos membros da família concordaram. As mulheres grávidas tiveram escores significativamente mais baixos sobre o item "Vou me preparar para o parto com a minha família", em comparação com os maridos (p < 0,01) e outros membros da família (p < 0,001). Proporcionar preparação para o parto baseada em evidencias e a redução das lacunas de percepção identificadas podem melhorar a intenção das mulheres para dar à luz em unidades de saúde. las mujeres son más propensas a dar a luz en un centro de salud cuando sus familias están de acuerdo con el lugar de parto. Sin embargo, en las zonas rurales de Tanzania, las mujeres son a menudo marginadas de la toma de decisiones. Este estudio predijo la intención del lugar de parto y los factores identificados para reducir la brecha de percepción entre las mujeres embarazadas, esposos y miembros de la familia. encuesta transversal explicativa llevada a cabo en tres aldeas en el noreste de Tanzania. Los participantes fueron 138 mujeres embarazadas y sus familias, que respondieron al Cuestionario sobre Intención del Parto (BIQ), que mide el conocimiento, la actitud, percepción de control del comportamiento, las normas subjetivas y la intención de lugar de parto. Se utilizaron análisis descriptivo, ANOVA, Chi-cuadrado y regresión lineal múltiple para analizar los datos. el modelo de regresión mostró que el conocimiento, la percepción de control del comportamiento, y las normas subjetivas

  3. Practical Astronomical Activities during Daytime. (Spanish Title: Actividades Astronómicas Prácticas Diurnas.) Atividades Astronômicas Práticas Diurnas

    NASA Astrophysics Data System (ADS)

    Jackson, Eric

    2009-12-01

    relacionadas al mal tiempo. El problema de no tener suficientes actividades prácticas, la sensación de poseer conocimientos inadecuados, la necesidad de disponer de equipamiento astronómico y experiencia suelen ser demasiado intimidantes para que los profesores introduzcan la materia en sus clases. Si la Astronomía iba a ser introducida, entonces era preciso encontrar una forma de resolver estas dificultades. Nuestro grupo, trabajando con maestros y alumnos dentro de un marco constructivista, encontró que los principios de la Astronomía pueden ser descubiertos durante el día, en cuanto los alumnos están en la escuela. Trabajando de forma cooperativa los alumnos midieron y registraron observaciones de sus propias sombras causadas por los movimientos de la estrella más próxima, el Sol, y nuestro planeta Tierra. Debido a que los alumnos se involucraran tan personalmente en las actividades, estuvieron mucho más interesados en los resultados del estudio. La Astronomía pasó a ser un desafío para el maestro y sus alumnos cuando aplicaron sus experiencias diurnas a la observación nocturna desde sus casas, reportada después en clase. Estas atividades astronômicas diurnas surgiram de uma investigação feita na Nova Zelândia por um grupo de professores e astrônomos a respeito dos problemas do ensino da Astronomia. Este trabalho mostrou que a Astronomia é geralmente considerada uma disciplina difícil de ensinar, tradicionalmente baseada em livros, filmes e modelos. Os mais afortunados podem ter feito alguma visita a um observatório ou planetário, e os mais avançados podem talvez ter tentado uma sessão de observação noturna, as quais sofrem às vezes de dificuldades relacionadas ao tempo. O problema de não dispor de suficientes atividades práticas, a sensação de possuir conhecimentos inadequados, a necessidade de dispor de equipamento astronômico e experiência tem sido, em geral, demasiado intimidante para que os professores introduzam a matéria nas suas